|
1
|
Zhang C, Charland D, O'Hearn K, Steele M, Klaassen RJ, Speckert M. Childhood autoimmune hemolytic anemia: A scoping review. Eur J Haematol 2024; 113:273-282. [PMID: 38894537 DOI: 10.1111/ejh.14253] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Revised: 05/24/2024] [Accepted: 06/04/2024] [Indexed: 06/21/2024]
Abstract
BACKGROUND AND OBJECTIVE Autoimmune hemolytic anemia (AIHA) is a rare but important cause of morbidity in pediatric hematology patients. Given its rarity, there is little high-quality evidence on which to base the investigation and management of pediatric AIHA. This scoping review aims to summarize the current evidence and highlight key gaps to inform future studies. METHODS This review searched MEDLINE and the Cochrane CENTRAL Trials Register from 2000 to November 03, 2023. Experimental and observational studies reporting AIHA diagnostic criteria, laboratory workup, or treatment/management in populations with at least 20% of patients ≤18 years were included. RESULTS Forty-three studies were included, with no randomized controlled trials identified. AIHA diagnostic criteria, diagnostic tests, and treatments were highly variable. First-line treatment approaches include corticosteroids, intravenous immunoglobulin, or both. Approaches to AIHA resistance to first-line therapy were widely variable between studies, but most commonly included rituximab and/or cyclosporine. CONCLUSIONS We identify a heterogenous group of observational studies into this complex, immune-mediated disorder. Standardized definitions and classifications are needed to guide collaborative efforts needed to study this rare disease. The work done by the CEREVANCE group provides an important paradigm for future studies.
Collapse
Affiliation(s)
- Caseng Zhang
- Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
- Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada
| | - Danielle Charland
- Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
- Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada
| | - Katie O'Hearn
- Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada
| | - MacGregor Steele
- Department of Pediatrics, Section of Pediatric Hematology, Alberta Children's Hospital, University of Calgary, Calgary, Alberta, Canada
| | - Robert J Klaassen
- Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
- Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada
- Division of Hematology Oncology, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada
| | - Matthew Speckert
- Division of Hematology Oncology, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada
| |
Collapse
|
|
2
|
Chen DX, Wu Y, Zhang SF, Yang XJ. Refractory autoimmune hemolytic anemia in a patient with systemic lupus erythematosus and ulcerative colitis: A case report. World J Clin Cases 2024; 12:2286-2292. [PMID: 38808337 PMCID: PMC11129137 DOI: 10.12998/wjcc.v12.i13.2286] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Revised: 02/06/2024] [Accepted: 03/27/2024] [Indexed: 04/25/2024] Open
Abstract
BACKGROUND Ulcerative colitis (UC) and systemic lupus erythematosus (SLE) are both systemic immunoreactive diseases, and their pathogenesis depends on the interaction between genes and environmental factors. There are no reports of UC with SLE in China, but six cases of SLE with UC have been reported in China. The combination of these two diseases has distinct effects on the pathogenesis of both diseases. CASE SUMMARY A female patient (30 years old) came to our hospital due to dull umbilical pain, diarrhea and mucous bloody stool in August 2018 and was diagnosed with UC. The symptoms were relieved after oral administration of mesalazine (1 g po tid) or folic acid (5 mg po qd), and the patient were fed a control diet. On June 24, 2019, the patient was admitted for treatment due to anemia and tinnitus. During hospitalization, the patient had repeated low-grade fever and a progressively decreased Hb level. Blood tests revealed positive antinuclear antibody test, positive anti-dsDNA antibody, 0.24 g/L C3 (0.9-1.8 g/L), 0.04 g/L C4 (0.1-0.4 g/L), 32.37 g/L immunoglobulin (8-17 g/L), and 31568.1 mg/24 h total 24-h urine protein (0-150 mg/24 h). The patient was diagnosed with SLE involving the joints, kidneys and blood system. Previously reported cases of SLE were retrieved from PubMed to characterize clinicopathological features and identify prognostic factors for SLE. CONCLUSION The patient was discharged in remission after a series of treatments, such as intravenous methylprednisolone sodium succinate, intravenous human immunoglobulin, cyclophosphamide injection, and plasma exchange. After discharge, the patient took oral prednisone acetate tablets, cyclosporine capsules, hydroxychloroquine sulfate tablets and other treatments for symptoms and was followed up regularly for 1 month, after which the patient's condition continued to improve and stabilize.
Collapse
Affiliation(s)
- Dai-Xing Chen
- Department of Digestive System, Chongqing Traditional Chinese Medicine Hospital, Chongqing 400021, China
| | - Yue Wu
- Department of Digestive System, Chongqing Traditional Chinese Medicine Hospital, Chongqing 400021, China
| | - Sui-Feng Zhang
- Department of Digestive System, Chongqing Traditional Chinese Medicine Hospital, Chongqing 400021, China
| | - Xiao-Jun Yang
- Department of Digestive System, Chongqing Traditional Chinese Medicine Hospital, Chongqing 400021, China
| |
Collapse
|
|
3
|
Kashiwagi R, Ishida M, Onodera K, Aoki S, Iseki M, Miura T, Ohtsuka H, Mizuma M, Nakagawa K, Kamei T, Unno M. Laparoscopic excision of accessory spleen for recurrent autoimmune hemolytic anemia after splenectomy: a case report. Surg Case Rep 2024; 10:110. [PMID: 38700738 PMCID: PMC11068696 DOI: 10.1186/s40792-024-01884-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2023] [Accepted: 04/01/2024] [Indexed: 05/06/2024] Open
Abstract
BACKGROUND Splenectomy is indicated in cases of autoimmune hemolytic anemia (AIHA), which are refractory to medical management. In post-splenectomy, there exists a theoretical risk of AIHA recurrence, especially if an accessory spleen undergoes compensatory hypertrophy. In this context, we present a unique case of recurrent AIHA managed through laparoscopic excision of the accessory spleen (LEAS). CASE PRESENTATION A 60-year-old male underwent laparoscopic splenectomy (LS) for AIHA refractory to standard medical therapies. Following the surgery, there was a marked improvement in hemolytic anemia symptoms, and oral steroid therapy was terminated 7 months post-LS. Nonetheless, a year after the LS, the patient exhibited a marked decline in hemoglobin levels, dropping to a concerning 5.8 g/dl, necessitating the reintroduction of oral steroids. A subsequent contrast-enhanced computed tomography (CT) scan unveiled an enlarged accessory spleen. The patient then underwent LEAS, during which the accessory spleen, obscured within adipose tissue, proved challenging to visualize laparoscopically. This obstacle was surmounted utilizing intraoperative ultrasonography (US), enabling successful excision of the accessory spleen. The post-surgical period progressed without complications, and the steroid dosage was reduced to one-twelfth of its initial preoperative quantity. CONCLUSIONS Recurrent AIHA can be instigated by post-splenectomy compensatory hypertrophy of the accessory spleen. Ensuring comprehensive splenic tissue excision is crucial in AIHA management to obviate recurrent stemming from hypertrophic remnants. In scenarios of AIHA recurrence tied to an enlarged accessory spleen, LEAS stands as a viable and effective therapeutic modality.
Collapse
Affiliation(s)
- Ryosuke Kashiwagi
- Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryomachi, Aobaku, Sendai, Miyagi, 980-8574, Japan
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan
| | - Masaharu Ishida
- Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryomachi, Aobaku, Sendai, Miyagi, 980-8574, Japan
| | - Koichi Onodera
- Department of Hematology, Tohoku University Hospital, 1-1 Seiryomachi, Aobaku, Sendai, Miyagi, 980-8574, Japan
| | - Shuichi Aoki
- Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryomachi, Aobaku, Sendai, Miyagi, 980-8574, Japan
| | - Masahiro Iseki
- Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryomachi, Aobaku, Sendai, Miyagi, 980-8574, Japan
| | - Takayuki Miura
- Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryomachi, Aobaku, Sendai, Miyagi, 980-8574, Japan
| | - Hideo Ohtsuka
- Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryomachi, Aobaku, Sendai, Miyagi, 980-8574, Japan
| | - Masamichi Mizuma
- Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryomachi, Aobaku, Sendai, Miyagi, 980-8574, Japan
| | - Kei Nakagawa
- Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryomachi, Aobaku, Sendai, Miyagi, 980-8574, Japan
| | - Takashi Kamei
- Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryomachi, Aobaku, Sendai, Miyagi, 980-8574, Japan
| | - Michiaki Unno
- Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryomachi, Aobaku, Sendai, Miyagi, 980-8574, Japan.
| |
Collapse
|
|
4
|
Namineni N, Waldron C, Tormey C, Goshua G. Severe, Refractory Primary Warm Autoimmune Hemolytic Anemia Requiring 90 Erythrocyte Transfusions. ANNALS OF INTERNAL MEDICINE. CLINICAL CASES 2024; 3:e231141. [PMID: 38725710 PMCID: PMC11081177 DOI: 10.7326/aimcc.2023.1141] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/12/2024]
Abstract
A previously healthy 60-year-old man presented to the hospital with a hemoglobin of 3.5 g/dL. He was diagnosed with severe warm autoimmune hemolytic anemia (wAIHA) with reticulocytopenia on hospital day 1 that was not responsive to steroids, immune globulin, and rituximab. Over a 42-day hospital stay, the patient remained continuously transfusion-dependent with a ninety red cell unit requirement for his refractory disease. He was trialed on therapeutic plasma exchange before ultimately undergoing inpatient splenectomy that led to a response within hours. He remains in complete remission at six months of follow-up.
Collapse
Affiliation(s)
| | | | - Christopher Tormey
- Department of Laboratory Medicine, Yale School of Medicine, New Haven, CT
| | - George Goshua
- Section of Hematology, Department of Internal Medicine, Yale School of Medicine, New Haven, CT
| |
Collapse
|
|
5
|
Cvetković Z, Pantić N, Cvetković M, Virijević M, Sabljić N, Marinković G, Milosavljević V, Pravdić Z, Suvajdžić-Vuković N, Mitrović M. The Role of the Spleen and the Place of Splenectomy in Autoimmune Hemolytic Anemia-A Review of Current Knowledge. Diagnostics (Basel) 2023; 13:2891. [PMID: 37761258 PMCID: PMC10527817 DOI: 10.3390/diagnostics13182891] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Revised: 09/04/2023] [Accepted: 09/06/2023] [Indexed: 09/29/2023] Open
Abstract
Autoimmune hemolytic anemia (AIHA) is a rare, very heterogeneous, and sometimes life-threatening acquired hematologic disease characterized by increased red blood cell (RBC) destruction by autoantibodies (autoAbs), either with or without complement involvement. Recent studies have shown that the involvement of T- and B-cell dysregulation and an imbalance of T-helper 2 (Th2) and Th17 phenotypes play major roles in the pathogenesis of AIHA. AIHA can be primary (idiopathic) but is more often secondary, triggered by infections or drug use or as a part of other diseases. As the location of origin of autoAbs and the location of autoAb-mediated RBC clearance, as well as the location of extramedullary hematopoiesis, the spleen is crucially involved in all the steps of AIHA pathobiology. Splenectomy, which was the established second-line therapeutic option in corticosteroid-resistant AIHA patients for decades, has become less common due to increasing knowledge of immunopathogenesis and the introduction of targeted therapy. This article provides a comprehensive overview of current knowledge regarding the place of the spleen in the immunological background of AIHA and the rapidly growing spectrum of novel therapeutic approaches. Furthermore, this review emphasizes the still-existing expediency of laparoscopic splenectomy with appropriate perioperative thromboprophylaxis and the prevention of infection as a safe and reliable therapeutic option in the context of the limited availability of rituximab and other novel therapies.
Collapse
Affiliation(s)
- Zorica Cvetković
- Department of Hematology, University Hospital Medical Center Zemun, 11080 Belgrade, Serbia
- Medical Faculty, University of Belgrade, 11000 Belgrade, Serbia
| | - Nikola Pantić
- Clinic for Hematology, University Clinical Center of Serbia, 11000 Belgrade, Serbia
| | - Mirjana Cvetković
- Clinic for Hematology, University Clinical Center of Serbia, 11000 Belgrade, Serbia
| | - Marijana Virijević
- Medical Faculty, University of Belgrade, 11000 Belgrade, Serbia
- Clinic for Hematology, University Clinical Center of Serbia, 11000 Belgrade, Serbia
| | - Nikica Sabljić
- Clinic for Hematology, University Clinical Center of Serbia, 11000 Belgrade, Serbia
| | - Gligorije Marinković
- Department of Hematology, University Hospital Medical Center Zemun, 11080 Belgrade, Serbia
| | - Vladimir Milosavljević
- Department for HPB Surgery, University Hospital Medical Center Bežanijska Kosa, 11070 Belgrade, Serbia
| | - Zlatko Pravdić
- Clinic for Hematology, University Clinical Center of Serbia, 11000 Belgrade, Serbia
| | - Nada Suvajdžić-Vuković
- Medical Faculty, University of Belgrade, 11000 Belgrade, Serbia
- Clinic for Hematology, University Clinical Center of Serbia, 11000 Belgrade, Serbia
| | - Mirjana Mitrović
- Medical Faculty, University of Belgrade, 11000 Belgrade, Serbia
- Clinic for Hematology, University Clinical Center of Serbia, 11000 Belgrade, Serbia
| |
Collapse
|
|
6
|
Rodríguez-Rodríguez S, Álvarez-Blanco JM, Sánchez-Díaz S, Rangel-Patiño J, Sierra-Salazar A, Apodaca-Chávez E, Demichelis-Gómez R. Are accessory spleen screening and resection in refractory immune cytopenia an effective strategy or a waste of resources? Ann Hematol 2023; 102:2309-2315. [PMID: 37439893 DOI: 10.1007/s00277-023-05360-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Accepted: 07/04/2023] [Indexed: 07/14/2023]
Abstract
Splenectomy remains an effective treatment for refractory immune cytopenia (RIC), which encompasses immune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA). Accessory spleens (AS) have been described without identifying specific risk factors. We retrospectively analyzed patients with RIC after splenectomy who underwent splenic scintigraphy (SS) at our institution. Seventy-one patients were included. Sixty-two patients had ITP, five had AIHA, and four had Evans syndrome. Seventy-five percent (n = 53) were women. Eleven patients (15.5%) had an AS detected by SS. A complete response (CR) to first-line steroids (odds ratio (OR) 5.75, 95% confidence interval (CI) 1.37-24.14, p = 0.017) and the absence of Howell-Jolly bodies (HJB) in peripheral blood smear (PBS) (OR 11.37, 95% CI 2.70-47.85, p = 0.001) were found to be risk factors. Patients with both elements had a higher rate of AS (83.3%) when compared to those with one or no factors (p < 0.001). Eight patients (73%) underwent an accessory splenectomy: seven (87.5%) achieved a CR, and none had perioperative complications. The presence of HJB in PBS changed from 25 to 87.5% after accessory splenectomy. We recommend the search for an AS via SS in patients with RIC due to ITP, who had a CR to corticosteroids and the absence of HJB in PBS. Accessory splenectomy is a safe and effective procedure.
Collapse
Affiliation(s)
- Sergio Rodríguez-Rodríguez
- Hematology and Oncology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15, Belisario Domínguez, Tlalpan, 14080, Mexico City, ZC, Mexico
| | - José Miguel Álvarez-Blanco
- Hematology and Oncology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15, Belisario Domínguez, Tlalpan, 14080, Mexico City, ZC, Mexico
| | - Susana Sánchez-Díaz
- Hematology and Oncology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15, Belisario Domínguez, Tlalpan, 14080, Mexico City, ZC, Mexico
| | - Juan Rangel-Patiño
- Hematology and Oncology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15, Belisario Domínguez, Tlalpan, 14080, Mexico City, ZC, Mexico
| | - Ana Sierra-Salazar
- Hematology and Oncology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15, Belisario Domínguez, Tlalpan, 14080, Mexico City, ZC, Mexico
| | - Elia Apodaca-Chávez
- Hematology and Oncology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15, Belisario Domínguez, Tlalpan, 14080, Mexico City, ZC, Mexico
| | - Roberta Demichelis-Gómez
- Hematology and Oncology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15, Belisario Domínguez, Tlalpan, 14080, Mexico City, ZC, Mexico.
| |
Collapse
|
|
7
|
Mehrotra H, Otrock ZK. Clinical and laboratory characteristics of patients with cold agglutinin disease: A retrospective analysis at a tertiary medical center. Asian J Transfus Sci 2023; 17:229-233. [PMID: 38274972 PMCID: PMC10807533 DOI: 10.4103/ajts.ajts_65_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Revised: 05/05/2023] [Accepted: 05/21/2023] [Indexed: 01/27/2024] Open
Abstract
BACKGROUND Cold agglutinin disease (CAD) is relatively rare and has primarily been reported as retrospective case series. AIM We reviewed our experience with CAD to shed light on this disease. STUDY SETTINGS AND DESIGN This was a retrospective review of all patients with CAD managed at our institution between 2007 and 2018. MATERIALS AND METHODS The study was approved by our institutional review board. We extracted patients' demographic, clinical, and laboratory data, blood transfusions, and outcomes from their electronic medical records. STATISTICAL ANALYSIS USED Statistical analysis was performed using SPSS version 17. The method of Kaplan-Meier was used to plot survival curves. RESULTS Forty-eight patients fulfilled the inclusion criteria for CAD. The median age of patients was 73.1 (range, 43-99) years; 36 (75%) were female. The majority (n = 38; 79.2%) of patients were Caucasians. Most patients (n = 25, 52.1%) presented with symptomatic anemia. Eight patients were asymptomatic. The median hemoglobin level was 8.6 g/dL (range, 3-12 g/dL); 7 (14.6%) patients had concurrent thrombocytopenia. Lactate dehydrogenase was elevated in 40/47 (85.1%) patients and haptoglobin was below normal in 35/46 (76.1%) patients. Coagulopathy was observed in 19 (52.8%) of 36 patients. Sixteen (33.3%) patients required blood transfusion during admission at the time of diagnosis with a median number of 3.5 red blood cell units. Twenty-five (52.1%) patients were alive after a median follow-up of 50.1 months. The 5-year and 10-year survival was estimated at 58.2% and 30.8%, respectively. CONCLUSION CAD poses considerable burden on patients and health-care systems. Patients vary widely in their disease severity and course.
Collapse
Affiliation(s)
- Harshita Mehrotra
- Department of Pathology and Laboratory Medicine, Henry Ford Hospital, Detroit, MI, USA
| | - Zaher K. Otrock
- Department of Pathology and Laboratory Medicine, Henry Ford Hospital, Detroit, MI, USA
- Department of Pathology, Wayne State University School of Medicine, Detroit, MI, USA
| |
Collapse
|
|
8
|
Sayed NI, Basantwani S, Bhalerao C, Nair U, Navalkar P. Cardiopulmonary bypass surgery-cold alert! Ann Card Anaesth 2023; 26:223-226. [PMID: 37706393 PMCID: PMC10284479 DOI: 10.4103/aca.aca_78_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2021] [Revised: 09/04/2021] [Accepted: 09/12/2021] [Indexed: 09/15/2023] Open
Abstract
The term "cold agglutinin (CA)" refers to a group of disorders caused by anti-erythrocyte autoantibodies that preferentially bind RBCs at cold temperatures (4°C-18°C). CAs contribute to 10 to 15% of autoimmune hemolytic anemia. We report a case of CAs diagnosed intraoperatively during emergency mitral valve replacement.
Collapse
Affiliation(s)
- Nazmeen I Sayed
- Department of Anaesthesiology, Lokmanya Tilak Municipal Medical College and General Hospital, Navi Mumbai, India
| | - Shakuntala Basantwani
- Department of Anaesthesiology, Lokmanya Tilak Municipal Medical College and General Hospital, Navi Mumbai, India
| | - Chetana Bhalerao
- Fellow in Regional Anaesthesia Department of Anaesthesiology, Ganga Medical Centre and Hospitals Pvt Ltd, Coimbatore, India
| | - Usha Nair
- Clinical Associate Critical Care Medicine D Y Patil Hospital, Navi Mumbai, India
| | - Priyanka Navalkar
- Cardiac Perfusionist K G Somaiya Hospital and Research Centre, Mumbai, India
| |
Collapse
|
|
9
|
Philips CA, Kedarisetty CK. Palliative Care for Patients with End-Stage Liver Disease. J Clin Exp Hepatol 2023; 13:319-328. [PMID: 36950499 PMCID: PMC10025682 DOI: 10.1016/j.jceh.2022.08.003] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2022] [Accepted: 08/07/2022] [Indexed: 02/17/2023] Open
Abstract
End-stage liver disease (ESLD) is the culmination of progression of chronic liver disease to cirrhosis, decompensation, and chronic liver failure, featuring portal hypertension or hepatocellular failure-related complications. Liver transplantation offers improved long-term survival for these patients but is negatively influenced by donor availability, financial constraints in developing countries, active substance abuse, progression of disease or malignancy on wait-list, sepsis and extrahepatic organ involvement. In this context, palliative care (PC), an interdisciplinary medical practice that aim to prevent and relieve suffering, offers best possible quality of life and is not limited to end-of-life care. It also encompasses achievable goals such as symptom control and aggressive disease-modifying treatments or interventions that beneficially alter the natural course of the disease to offer curative intend. In this narrative review, we discuss the prognostic factors that define disease course in ESLD, various indications and challenges in PC for advanced cirrhosis and management options for major symptom burden in patients with ESLD based on evidence-based best practice.
Collapse
Key Words
- ACLF
- ACLF, acute-on-chronic liver failure
- CPT, Child–Pugh–Turcotte
- ESLD, end-stage liver disease
- HE, hepatic encephalopathy
- INR, international normalized ratio
- LSM, liver stiffness measurement
- LT, liver transplantation
- MELD, model for end stage liver disease
- PC, palliative care
- TE, transient elastography
- TIPS, transjugular intrahepatic portosystemic shunt
- ascites
- cirrhosis
- end of life care
- hepatic encephalopathy
- hyponatremia
- portal hypertension
- sepsis
Collapse
Affiliation(s)
- Cyriac A. Philips
- Department of Clinical and Translational Hepatology and the Monarch Liver Laboratory, Rajagiri Hospital, Aluva, Kerala, India
| | - Chandan K. Kedarisetty
- Department of Hepatology and Liver Transplantation, Gleneagles Global Hospital, Hyderabad, India
| |
Collapse
|
|
10
|
Ammon Shimano K, Noel P. Immunohematologic Disorders. Clin Immunol 2023. [DOI: 10.1016/b978-0-7020-8165-1.00062-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/08/2023]
|
|
11
|
Huang HE, Lin KM, Lin JC, Lin YT, He HR, Wang YW, Yu SF, Chen JF, Cheng TT. Danazol in Refractory Autoimmune Hemolytic Anemia or Immune Thrombocytopenia: A Case Series Report and Literature Review. Pharmaceuticals (Basel) 2022; 15:1377. [PMID: 36355549 PMCID: PMC9692819 DOI: 10.3390/ph15111377] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Revised: 11/03/2022] [Accepted: 11/07/2022] [Indexed: 09/16/2023] Open
Abstract
Danazol is a treatment option for autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP). Three patients with AIHA and eight patients with ITP between 2008 and 2022 were enrolled in the Rheumatology Outpatient Clinic of Chang Gung Memorial Hospital, Kaohsiung. Those patients were refractory or intolerant to conventional therapy and were treated with danazol. All the patients received an initial dose of danazol (200-400 mg). The observation period was 6 months. Three patients (100%) with AIHA and six (75%) with ITP achieved treatment response after 6 months of danazol therapy. The dose of glucocorticoid for responders could be reduced to ≤5 mg/day of prednisolone, and the immunosuppressants, except hydroxychloroquine and azathioprine for systemic lupus erythematosus, could be discontinued. Adverse events were acne in two (18.2%) patients and transient dose-related liver function impairment in one (9.1%) patient in the current series. Danazol therapy appears to be a favorable alternative for refractory AIHA and ITP by altering the erythrocyte membrane to resist osmotic lysis and protecting platelets against complement-mediated lysis. In this report, we also performed a literature review and searched the PubMed/Cochrane Library for articles published from 1984 to January 2022 on danazol therapy for patients with AIHA and ITP.
Collapse
Affiliation(s)
- Hsu-En Huang
- Division of Rheumatology, Allergy and Immunology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi 613, Taiwan
| | - Ko-Ming Lin
- Division of Rheumatology, Allergy and Immunology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi 613, Taiwan
| | - Jing-Chi Lin
- Division of Rheumatology, Allergy and Immunology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi 613, Taiwan
| | - Yu-Ting Lin
- Division of Rheumatology, Allergy and Immunology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
| | - Hsiao-Ru He
- Division of Rheumatology, Allergy and Immunology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
| | - Yu-Wei Wang
- Division of Rheumatology, Allergy and Immunology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
| | - Shan-Fu Yu
- Division of Rheumatology, Allergy and Immunology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi 613, Taiwan
- School of Medicine, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
| | - Jia-Feng Chen
- Division of Rheumatology, Allergy and Immunology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
- School of Medicine, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
| | - Tien-Tsai Cheng
- Division of Rheumatology, Allergy and Immunology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
- School of Medicine, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
| |
Collapse
|
|
12
|
Pacillo L, Giardino G, Amodio D, Giancotta C, Rivalta B, Rotulo GA, Manno EC, Cifaldi C, Palumbo G, Pignata C, Palma P, Rossi P, Finocchi A, Cancrini C. Targeted treatment of autoimmune cytopenias in primary immunodeficiencies. Front Immunol 2022; 13:911385. [PMID: 36052091 PMCID: PMC9426461 DOI: 10.3389/fimmu.2022.911385] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2022] [Accepted: 07/15/2022] [Indexed: 11/14/2022] Open
Abstract
Primary Immunodeficiencies (PID) are a group of rare congenital disorders of the immune system. Autoimmune cytopenia (AIC) represents the most common autoimmune manifestation in PID patients. Treatment of AIC in PID patients can be really challenging, since they are often chronic, relapsing and refractory to first line therapies, thus requiring a broad variety of alternative therapeutic options. Moreover, immunosuppression should be fine balanced considering the increased susceptibility to infections in these patients. Specific therapeutic guidelines for AIC in PID patients are lacking. Treatment choice should be guided by the underlying disease. The study of the pathogenic mechanisms involved in the genesis of AIC in PID and our growing ability to define the molecular underpinnings of immune dysregulation has paved the way for the development of novel targeted treatments. Ideally, targeted therapy is directed against an overexpressed or overactive gene product or substitutes a defective protein, restoring the impaired pathway. Actually, the molecular diagnosis or a specific drug is not always available. However, defining the category of PID or the immunological phenotype can help to choose a semi-targeted therapy directed towards the suspected pathogenic mechanism. In this review we overview all the therapeutic interventions available for AIC in PID patients, according to different immunologic targets. In particular, we focus on T and/or B cells targeting therapies. To support decision making in the future, prospective studies to define treatment response and predicting/stratifying biomarkers for patients with AIC and PID are needed.
Collapse
Affiliation(s)
- Lucia Pacillo
- Academic Department of Pediatrics (DPUO), Immune and Infectious Diseases Division, Research Unit of Primary Immunodeficiencies, IRCCS Bambino Gesù Children’s Hospital, Rome, Italy
- Department of Systems Medicine, University of Tor Vergata, Rome, Italy
| | - Giuliana Giardino
- Pediatric Section, Department of Translational Medical Sciences, Federico II University, Naples, Italy
| | - Donato Amodio
- Academic Department of Pediatrics (DPUO), Research Unit of Clinical Immunology and Vaccinology, IRCCS Bambino Gesù Children’s Hospital, Rome, Italy
| | - Carmela Giancotta
- Academic Department of Pediatrics (DPUO), Research Unit of Clinical Immunology and Vaccinology, IRCCS Bambino Gesù Children’s Hospital, Rome, Italy
| | - Beatrice Rivalta
- Academic Department of Pediatrics (DPUO), Immune and Infectious Diseases Division, Research Unit of Primary Immunodeficiencies, IRCCS Bambino Gesù Children’s Hospital, Rome, Italy
- Department of Systems Medicine, University of Tor Vergata, Rome, Italy
| | - Gioacchino Andrea Rotulo
- Academic Department of Pediatrics (DPUO), Research Unit of Clinical Immunology and Vaccinology, IRCCS Bambino Gesù Children’s Hospital, Rome, Italy
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, Italy
| | - Emma Concetta Manno
- Academic Department of Pediatrics (DPUO), Research Unit of Clinical Immunology and Vaccinology, IRCCS Bambino Gesù Children’s Hospital, Rome, Italy
| | - Cristina Cifaldi
- Academic Department of Pediatrics (DPUO), Immune and Infectious Diseases Division, Research Unit of Primary Immunodeficiencies, IRCCS Bambino Gesù Children’s Hospital, Rome, Italy
| | - Giuseppe Palumbo
- Department of Onco Hematology, IRCCS Bambino Gesù Children’s Hospital, Rome, Italy
| | - Claudio Pignata
- Pediatric Section, Department of Translational Medical Sciences, Federico II University, Naples, Italy
| | - Paolo Palma
- Department of Systems Medicine, University of Tor Vergata, Rome, Italy
- Academic Department of Pediatrics (DPUO), Research Unit of Clinical Immunology and Vaccinology, IRCCS Bambino Gesù Children’s Hospital, Rome, Italy
| | - Paolo Rossi
- Department of Systems Medicine, University of Tor Vergata, Rome, Italy
- Academic Department of Pediatrics (DPUO), Research Unit of Clinical Immunology and Vaccinology, IRCCS Bambino Gesù Children’s Hospital, Rome, Italy
| | - Andrea Finocchi
- Academic Department of Pediatrics (DPUO), Immune and Infectious Diseases Division, Research Unit of Primary Immunodeficiencies, IRCCS Bambino Gesù Children’s Hospital, Rome, Italy
- Department of Systems Medicine, University of Tor Vergata, Rome, Italy
| | - Caterina Cancrini
- Academic Department of Pediatrics (DPUO), Immune and Infectious Diseases Division, Research Unit of Primary Immunodeficiencies, IRCCS Bambino Gesù Children’s Hospital, Rome, Italy
- Department of Systems Medicine, University of Tor Vergata, Rome, Italy
- *Correspondence: Caterina Cancrini,
| |
Collapse
|
|
13
|
Calhoun B, Moore A, Dickey A, Shoemaker DM. Systemic loxoscelism induced warm autoimmune hemolytic anemia: clinical series and review. Hematology 2022; 27:543-554. [PMID: 35544675 DOI: 10.1080/16078454.2022.2065086] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
OBJECTIVES Describe the development of warm autoimmune hemolytic anemia warm (AIHA) secondary to a brown recluse spider (Loxosceles reclusa) bite is known as systemic loxoscelism; and review epidemiology, clinical manifestations, diagnostic work-up, pathophysiology, and treatment options associated with warm AIHA secondary to systemic loxoscelism. METHODS Cases series of two cases of warm AIHA due to systemic loxoscelism and a review of the current literature: epidemiology, clinical manifestations, diagnostic work-up, pathophysiology, and treatment options associated with warm AIHA secondary to systemic loxoscelism. RESULTS Presented here are two cases of warm AIHA due to systemic loxoscelism. Each patient was generally healthy appearing and presented with symptomatic anemia in the setting of brown recluse spider bites. Both patients were eventually found to have warm AIHA. Upon recognition of the diagnosis, the patients were started on corticosteroids and aggressive intravenous fluid hydration. In addition, they received transfusions of packed red blood cells. Their clinical courses improved, and they recovered to eventually be discharged home. CONCLUSION Envenomation by a brown recluse spider, Loxosceles reclusa, can result in systemic loxoscelism which can cause warm AIHA. The diagnosis of warm AIHA is confirmed by the direct antiglobulin/Coomb's test. Warm AIHA can be a life-threatening disease process. Hemodynamic support with intravenous fluids and RBC transfusion is the initial step in the management of these patients. Corticosteroids are the mainstay of current management. Second line treatments include rituximab. Rarely patients require splenectomy for refractory disease. Corticosteroids should be tapered over a three-month period.
Collapse
Affiliation(s)
- Brandon Calhoun
- Division of Infectious Diseases, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, MO, USA
| | - Andrew Moore
- SEHealth Cancer Center, SEHealth, Cape Girardeau, MO, USA
| | - Andrew Dickey
- SEHealth Cancer Center, SEHealth, Cape Girardeau, MO, USA
| | - D Matthew Shoemaker
- Division of Infectious Diseases, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, MO, USA
| |
Collapse
|
|
14
|
Autoimmune Hemolytic Anemia in Children: Laboratory Investigation, Disease Associations, and Treatment Strategies. J Pediatr Hematol Oncol 2022; 44:71-78. [PMID: 35235549 DOI: 10.1097/mph.0000000000002438] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Accepted: 01/25/2022] [Indexed: 01/19/2023]
Abstract
Autoimmune hemolytic anemia is a relatively uncommon pediatric clinical condition. As such, the evaluation and management of these cases can be challenging for even the most seasoned pediatrician. In this review, the 3 major forms of autoimmune hemolytic anemia in children will be discussed: warm autoimmune hemolytic anemia, cold agglutinin disease, and paroxysmal cold hemoglobinuria. After a general description of the laboratory approach to these entities, the pathophysiology of these disease processes, including important disease associations, will be described, and treatment strategies will be discussed. This will provide the reader with a rational approach to identifying and managing pediatric patients with these uncommon autoimmune conditions.
Collapse
|
|
15
|
Wang S, Wang D, Duan Y, Zhou Z, Gao W, Zhang L. Cellular Nanosponges for Biological Neutralization. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2022; 34:e2107719. [PMID: 34783078 DOI: 10.1002/adma.202107719] [Citation(s) in RCA: 46] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Revised: 11/06/2021] [Indexed: 06/13/2023]
Abstract
Biological neutralization represents a general strategy that deploys therapeutic agents to bind with harmful molecules or infectious pathogens, block their bioactivity, and thus prevent them from causing the diseases. Here, a comprehensive review of using cell-membrane-coated nanoparticles, namely "cellular nanosponges," as host decoys for a wide range of biological neutralization applications is provided. Compared to traditional neutralization strategies, the cellular nanosponges stand out by mimicking susceptible host cells rather than accommodating the structures of the causative agents for the design of therapeutics. As all pathological agents must interact with host cells for bioactivity, nanosponges bypass the diversity of these agents and create function-driven and broad-spectrum neutralization solutions. The review focuses on the recent progress of using this new nanomedicine platform for neutralization against five primary pathological agents, including bacterial toxins, chemical toxicants, inflammatory cytokines, pathological antibodies, and viruses. Existing studies have established cellular nanosponges as versatile tools for biological neutralization. A thorough review of the cellular nanosponge technology is expected to inspire more refined cellular nanosponge designs and unique neutralization applications to address unsolved medical problems.
Collapse
Affiliation(s)
- Shuyan Wang
- Department of NanoEngineering, Chemical Engineering Program, Moores Cancer Center, University of California San Diego, La Jolla, CA, 92093, USA
| | - Dan Wang
- Department of NanoEngineering, Chemical Engineering Program, Moores Cancer Center, University of California San Diego, La Jolla, CA, 92093, USA
| | - Yaou Duan
- Department of NanoEngineering, Chemical Engineering Program, Moores Cancer Center, University of California San Diego, La Jolla, CA, 92093, USA
| | - Zhidong Zhou
- Department of NanoEngineering, Chemical Engineering Program, Moores Cancer Center, University of California San Diego, La Jolla, CA, 92093, USA
| | - Weiwei Gao
- Department of NanoEngineering, Chemical Engineering Program, Moores Cancer Center, University of California San Diego, La Jolla, CA, 92093, USA
| | - Liangfang Zhang
- Department of NanoEngineering, Chemical Engineering Program, Moores Cancer Center, University of California San Diego, La Jolla, CA, 92093, USA
| |
Collapse
|
|
16
|
Hwang SR, Saliba AN, Wolanskyj-Spinner AP. Immunotherapy-associated Autoimmune Hemolytic Anemia. Hematol Oncol Clin North Am 2022; 36:365-380. [PMID: 35339260 DOI: 10.1016/j.hoc.2021.11.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
Over the past decade, the role of immunotherapy treatment in cancer has expanded; specifically, indications for immune checkpoint inhibitors (ICI) have multiplied and are used as first-line therapy. ICIs include cytotoxic T-lymphocyte-associated protein 4 and programmed cell death protein 1 inhibitors, as monotherapies or in combination. Autoimmune hemolytic anemia (AIHA) has emerged as a rare yet serious immune-related adverse event in ICI use. This review describes diagnosis and management of immunotherapy related AIHA (ir-AIHA) including an algorithmic approach based on severity of anemia. Suggested mechanisms are discussed, guidance on ICI resumption provided and prognosis reviewed including risk of recurrence.
Collapse
Affiliation(s)
- Steven R Hwang
- Division of Hematology, Department of Medicine, Mayo Clinic, 200 First street Southwest, Rochester, Minnesota 55905, USA; Division of Medical Oncology, Department of Oncology, Mayo Clinic, 200 First Street Southwest, Rochester, Minnesota 55905, USA
| | - Antoine N Saliba
- Division of Hematology, Department of Medicine, Mayo Clinic, 200 First street Southwest, Rochester, Minnesota 55905, USA; Division of Medical Oncology, Department of Oncology, Mayo Clinic, 200 First Street Southwest, Rochester, Minnesota 55905, USA
| | - Alexandra P Wolanskyj-Spinner
- Division of Hematology, Department of Medicine, Mayo Clinic, 200 First street Southwest, Rochester, Minnesota 55905, USA; Mayo Clinic Alix School of Medicine, Mayo Clinic College of Medicine and Science, 200 First Street Southwest, Rochester, Minnesota 55905, USA.
| |
Collapse
|
|
17
|
Yui JC, Brodsky RA. Updates in the Management of Warm Autoimmune Hemolytic Anemia. Hematol Oncol Clin North Am 2022; 36:325-339. [DOI: 10.1016/j.hoc.2021.11.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
|
|
18
|
|
|
19
|
Saafan M, El-Ashwah S, Jamal E, F. Khalifa RI, Denewer M, M. Saleh L, Emarah Z, A. Saleh G, Sheta H, M. Taalab M, Azmy E, Shamaa S, Mabed M. Exacerbation of Autoimmune Hemolytic Anemia after COVID-19 in a Relapsed/Refractory Hodgkin Lymphoma Patient: A Case Report. JOURNAL OF MEDICAL SCIENCES 2022. [DOI: 10.3923/jms.2022.78.82] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
|
|
20
|
Yao M, Zhang J, Li Y, Lv L, Jia L, Yang C, Huang Y, Liu H, Wang J, Chen M, Zhang H. Combination of low-dose rituximab, bortezomib and dexamethasone for the treatment of autoimmune hemolytic anemia. Medicine (Baltimore) 2022; 101:e28679. [PMID: 35089216 PMCID: PMC8797600 DOI: 10.1097/md.0000000000028679] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2021] [Accepted: 12/31/2021] [Indexed: 01/05/2023] Open
Abstract
Autoimmune hemolytic anemia (AIHA) therapy may be associated with severe complications such as diabetes, hypertension, obesity, osteoporosis, peptic ulcers, infection, and some other diseases. To reduce those effects, we used low-dose rituximab, bortezomib and dexamethasone (LowR-BD regimen) to treat AIHA. The purpose of this study was to evaluate the efficacy and safety of this regimen.Seven patients with warm AIHA (wAIHA) admitted from March 2020 to October 2020 were treated with LowR-BD regimen: Rituximab 100 mg by intravenous infusion on day 1 combined with bortezomib 1.3 mg/m2 by subcutaneous injection on day 2 plus dexamethasone 20 mg by intravenous infusion on days 2, 3. Clinical efficacy and safety were assessed at the regular reexamination of relevant indicators and follow-up.After 4 cycles of the LowR-BD regimen, the overall response rate (ORR) was 85.71% with a complete response (CR) of 28.57% and a partial response (PR) of 57.14%. After a median follow-up of 12 (range 7-13) months, 5 patients achieved CR and 2 patients had PR status, including 1 patient who did not respond to LowR-BD treatment and reached CR after using methylprednisolone combined with cyclophosphamide. One patient relapsed and achieved PR after retreatment of 2 cycles LowR-BD regimen. The patients tolerated the treatment well and did not complain of apparently adverse reactions except a patient with Sjogren's syndrome and bronchiectasis who developed a severe infection during treatment.Low-dose rituximab combined with bortezomib and dexamethasone is effective and relatively safe in patients with wAIHA.
Collapse
Affiliation(s)
- Mingkang Yao
- Department of Clinical Medicine, Jining Medical University, Jining, Shandong Province, China
- Department of Hematology, Affiliated Hospital of Jining Medical University, Jining, Shandong Province, China
- Institute of Blood and Marrow Transplantation, Jining Medical University, Jining, Shandong Province, China
| | - Jingjing Zhang
- Department of Hematology, Affiliated Hospital of Jining Medical University, Jining, Shandong Province, China
- Institute of Blood and Marrow Transplantation, Jining Medical University, Jining, Shandong Province, China
| | - Ying Li
- Department of Hematology, Affiliated Hospital of Jining Medical University, Jining, Shandong Province, China
- Institute of Blood and Marrow Transplantation, Jining Medical University, Jining, Shandong Province, China
| | - Linlin Lv
- Department of Hematology, Affiliated Hospital of Jining Medical University, Jining, Shandong Province, China
- Institute of Blood and Marrow Transplantation, Jining Medical University, Jining, Shandong Province, China
| | - Lu Jia
- Department of Hematology, Affiliated Hospital of Jining Medical University, Jining, Shandong Province, China
- Institute of Blood and Marrow Transplantation, Jining Medical University, Jining, Shandong Province, China
| | - Chunyan Yang
- Department of Hematology, Affiliated Hospital of Jining Medical University, Jining, Shandong Province, China
- Institute of Blood and Marrow Transplantation, Jining Medical University, Jining, Shandong Province, China
| | - Yu Huang
- Department of Hematology, Affiliated Hospital of Jining Medical University, Jining, Shandong Province, China
- Institute of Blood and Marrow Transplantation, Jining Medical University, Jining, Shandong Province, China
| | - Haihui Liu
- Department of Hematology, Affiliated Hospital of Jining Medical University, Jining, Shandong Province, China
- Institute of Blood and Marrow Transplantation, Jining Medical University, Jining, Shandong Province, China
| | - Jian Wang
- Department of Hematology, Affiliated Hospital of Jining Medical University, Jining, Shandong Province, China
- Institute of Blood and Marrow Transplantation, Jining Medical University, Jining, Shandong Province, China
| | - Mingtai Chen
- Institute of Blood and Marrow Transplantation, Jining Medical University, Jining, Shandong Province, China
- Medical Research Center, Affiliated Hospital of Jining Medical University, Jining, Shandong Province, China
| | - Hao Zhang
- Department of Hematology, Affiliated Hospital of Jining Medical University, Jining, Shandong Province, China
- Institute of Blood and Marrow Transplantation, Jining Medical University, Jining, Shandong Province, China
| |
Collapse
|
|
21
|
Garg SK, Garg P. Autoimmune Hemolytic Anemia in Intensive Care Unit and Blood Transfusion: Lesson Learnt-A Case Report. Indian J Crit Care Med 2021; 25:1201-1202. [PMID: 34916757 PMCID: PMC8645826 DOI: 10.5005/jp-journals-10071-23999] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Clinicians are often in a difficult situation while managing severe anemia due to autoimmune hemolysis in intensive care unit (ICU). It is hard to get properly cross-matched blood due to the presence of autoantibody in the patient's serum. Still, such patients should not be devoid of transfusion. How to cite this article: Garg SK, Garg P. Autoimmune Hemolytic Anemia in Intensive Care Unit and Blood Transfusion: Lesson Learnt—A Case Report. Indian J Crit Care Med 2021;25(10):1201–1202.
Collapse
Affiliation(s)
- Sunil K Garg
- Department of Critical Care, NMC Healthcare, Dubai, United Arab Emirates
| | - Pragya Garg
- Department of Critical Care, NMC Healthcare, Dubai, United Arab Emirates
| |
Collapse
|
|
22
|
Dei Zotti F, Qiu A, La Carpia F, Moriconi C, Hudson KE. A New Murine Model of Primary Autoimmune Hemolytic Anemia (AIHA). Front Immunol 2021; 12:752330. [PMID: 34867985 PMCID: PMC8634489 DOI: 10.3389/fimmu.2021.752330] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Accepted: 10/21/2021] [Indexed: 11/13/2022] Open
Abstract
Loss of humoral tolerance to red blood cells (RBCs) can lead to autoimmune hemolytic anemia (AIHA), a severe, and sometimes fatal disease. Patients with AIHA present with pallor, fatigue, decreased hematocrit, and splenomegaly. While secondary AIHA is associated with lymphoproliferative disorders, infections, and more recently, as an adverse event secondary to cancer immunotherapy, the etiology of primary AIHA is unknown. Several therapeutic strategies are available; however, there are currently no licensed treatments for AIHA and few therapeutics offer treatment-free durable remission. Moreover, supportive care with RBC transfusions can be challenging as most autoantibodies are directed against ubiquitous RBC antigens; thus, virtually all RBC donor units are incompatible. Given the severity of AIHA and the lack of treatment options, understanding the cellular and molecular mechanisms that facilitate the breakdown in tolerance would provide insight into new therapeutics. Herein, we report a new murine model of primary AIHA that reflects the biology observed in patients with primary AIHA. Production of anti-erythrocyte autoantibodies correlated with sex and age, and led to RBC antigen modulation, complement fixation, and anemia, as determined by decreased hematocrit and hemoglobin values and increased reticulocytes in peripheral blood. Moreover, autoantibody-producing animals developed splenomegaly, with altered splenic architecture characterized by expanded white pulp areas and nearly diminished red pulp areas. Additional analysis suggested that compensatory extramedullary erythropoiesis occurred as there were increased frequencies of RBC progenitors detectable in the spleen. No significant correlations between AIHA onset and inflammatory status or microbiome were observed. To our knowledge, this is the first report of a murine model that replicates observations made in humans with idiopathic AIHA. Thus, this is a tractable murine model of AIHA that can serve as a platform to identify key cellular and molecular pathways that are compromised, thereby leading to autoantibody formation, as well as testing new therapeutics and management strategies.
Collapse
Affiliation(s)
- Flavia Dei Zotti
- Columbia University Irving Medical Center, Department of Pathology and Cell Biology, New York, NY, United States
| | - Annie Qiu
- Columbia University Irving Medical Center, Department of Pathology and Cell Biology, New York, NY, United States
| | - Francesca La Carpia
- Columbia University Irving Medical Center, Department of Pathology and Cell Biology, New York, NY, United States
| | - Chiara Moriconi
- Columbia University Irving Medical Center, Department of Pathology and Cell Biology, New York, NY, United States
| | - Krystalyn E Hudson
- Columbia University Irving Medical Center, Department of Pathology and Cell Biology, New York, NY, United States
| |
Collapse
|
|
23
|
Autoimmune Hemolytic Anemia in Chronic Lymphocytic Leukemia: A Comprehensive Review. Cancers (Basel) 2021; 13:cancers13225804. [PMID: 34830959 PMCID: PMC8616265 DOI: 10.3390/cancers13225804] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2021] [Revised: 11/06/2021] [Accepted: 11/11/2021] [Indexed: 12/19/2022] Open
Abstract
Simple Summary This review analyzes the occurrence, clinical characteristics, and prognostic impact and treatment of autoimmune hemolytic anemia (AIHA) in chronic lymphocytic leukemia (CLL). Autoimmune hemolytic anemia is observed in about 10% of CLL. Pathogenesis is multifactorial involving humoral, cellular, and innate immunity, so the different mechanisms are well described in this review which also focuses on drugs associated to CLL-AIHA and on difficulties to diagnose it. There is a comprehensive revision of the main published casistics and then of the treatments; in particular the paper analyzes the main chemo-immunotherapeutic agents used in this setting. Since the therapy depends on the presence and severity of clinical symptoms, disease status, and comorbidities, treatment is nowadays more individualized in CLL and also in CLL-AIHA. Patients not responding to corticosteroids and rituximab are treated with CLL-specific drugs as per current guidelines according to age and comorbidities and new targeted agents against BCR and BCL-2 which can be given orally and have few side effects, are very effective both in progressive CLL and in situations such as AIHA. Abstract Chronic lymphocytic leukemia (CLL) patients have a greater predisposition to develop autoimmune complications. The most common of them is autoimmune hemolytic anemia (AIHA) with a frequency of 7–10% of cases. Pathogenesis is multifactorial involving humoral, cellular, and innate immunity. CLL B-cells have damaged apoptosis, produce less immunoglobulins, and could be responsible for antigen presentation and releasing inflammatory cytokines. CLL B-cells can act similar to antigen-presenting cells activating self-reactive T helper cells and may induce T-cell subsets imbalance, favoring autoreactive B-cells which produce anti-red blood cells autoantibodies. Treatment is individualized and it depends on the presence and severity of clinical symptoms, disease status, and comorbidities. Corticosteroids are the standardized first-line treatment; second-line treatment comprises rituximab. Patients not responding to corticosteroids and rituximab should be treated with CLL-specific drugs as per current guidelines according to age and comorbidities. New targeted drugs (BTK inhibitors and anti BCL2) are recently used after or together with steroids to manage AIHA. In the case of cold agglutinin disease, rituximab is preferred, because steroids are ineffective. Management must combine supportive therapies, including vitamins; antibiotics and heparin prophylaxis are indicated in order to minimize infectious and thrombotic risk.
Collapse
|
|
24
|
Ghobrial S, Gonzalez CE, Kaufman S, Yazigi N, Matsumoto C, Fishbein T, Hawksworth J, Ekong UD, Kroemer A, Khan K. Anti-plasma cell treatment in refractory autoimmune hemolytic anemia in a child with multivisceral transplant. Pediatr Transplant 2021; 25:e14045. [PMID: 34092010 DOI: 10.1111/petr.14045] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Revised: 04/15/2021] [Accepted: 05/03/2021] [Indexed: 11/30/2022]
Abstract
BACKGROUND Warm-antibody AIHA is known to complicate solid organ (SOT) and HSCT, the disease maybe refractory to standard therapy. Immunosuppressive therapies as well as IVIG, and rituximab have been the main stay of treatment. Over the past decade, B-lymphocyte targeted, anti-CD-20 antibody has been recognized in the treatment of autoimmune diseases and utilized in AIHA. Bortezomib, a proteasome inhibitor that causes apoptosis of plasma cells, is an appealing targeted therapy in secondary AIHA and has demonstrated efficacy in HSCT patients. From our experience, we advocate for early targeted therapy that combines B cell with plasma cell depletion. CASE REPORT We describe a 4-year-old-girl with stage III neuroblastoma, complicated with intestinal necrosis needing multivisceral transplant developed warm AIHA 1-year after transplantation, and following an adenovirus infection. She received immunoglobulin therapy, rituximab, sirolimus, plasmapheresis, and long-term prednisolone with no sustained benefit while developing spinal fractures related to the latter therapy. She received bortezomib for intractable AIHA in combination with rituximab with no appreciable adverse effects. Three years later the child remains in remission with normal reticulocyte and recovered B cells. In the interim, she required chelation therapy for iron overload related to blood transfusion requirement during the treatment of AIHA. CONCLUSION We propose early targeted anti-plasma cell therapy with steroid burst, IVIG, rituximab, and possible plasmapheresis may reduce morbidity in secondary refractory w-AIHA.
Collapse
Affiliation(s)
- Shahira Ghobrial
- MedStar Georgetown University Hospital, Transplant Institute, Washington, DC, USA
| | | | - Stuart Kaufman
- MedStar Georgetown University Hospital, Transplant Institute, Washington, DC, USA
| | - Nada Yazigi
- MedStar Georgetown University Hospital, Transplant Institute, Washington, DC, USA
| | - Cal Matsumoto
- MedStar Georgetown University Hospital, Transplant Institute, Washington, DC, USA
| | - Thomas Fishbein
- MedStar Georgetown University Hospital, Transplant Institute, Washington, DC, USA
| | - Jason Hawksworth
- MedStar Georgetown University Hospital, Transplant Institute, Washington, DC, USA
| | - Udeme D Ekong
- MedStar Georgetown University Hospital, Transplant Institute, Washington, DC, USA
| | - Alexander Kroemer
- MedStar Georgetown University Hospital, Transplant Institute, Washington, DC, USA
| | - Khalid Khan
- MedStar Georgetown University Hospital, Transplant Institute, Washington, DC, USA
| |
Collapse
|
|
25
|
Kompotiatis P, Manohar S, Alkhateeb HB, Hogan WJ, Nath KA, Leung N. Hemoglobinuria in the Early Poststem-Cell-Transplant Period: Risk Factors and Association with Outcomes. KIDNEY360 2021; 2:1569-1575. [PMID: 35372983 PMCID: PMC8785790 DOI: 10.34067/kid.0002262021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/05/2021] [Accepted: 08/06/2021] [Indexed: 02/04/2023]
Abstract
Background Information on risk factors of hemoglobinuria after hematopoietic stem-cell transplant (HSCT) and its association with AKI, mortality, and engraftment is limited. Methods We conducted a retrospective cohort study on all consecutive adults that underwent HSCT from January 6, 1999, to November 6, 2017. The study included 6039 patients that underwent bone marrow transplantation (BMT), umbilical cord blood, and peripheral blood stem-cell transplantation (PBSCT). Results Early post-HSCT, AKI occurred in 393 (7%) patients, and 52 (0.9%) patients had post-HSCT hemoglobinuria. Post-HSCT hemoglobinuria was associated with graft type (BMT+Cord), underlying disease (lymphoma, acute leukemia), and fludarabine-based conditioning regimen. Post-HSCT hemoglobinuria was associated with early (48-72 hours) post-HSCT AKI. Graft type (BMT+Cord) was associated with AKI among patients with hemoglobinuria. AKI in patients with hemoglobinuria was associated with delayed platelet engraftment and delayed WBC engraftment but not 100-day mortality. Conclusion Close monitoring is recommended in this patient group to facilitate a good engraftment outcome.
Collapse
Affiliation(s)
| | - Sandhya Manohar
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota
| | | | | | - Karl A. Nath
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota
| | - Nelson Leung
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota,Division of Hematology, Mayo Clinic, Rochester, Minnesota
| |
Collapse
|
|
26
|
Moon GS, Choi YU, Shim H, Jang JY. Autoimmune Hemolytic Anemia Combined with Sepsis After Abdominal Trauma Surgery. JOURNAL OF ACUTE CARE SURGERY 2021. [DOI: 10.17479/jacs.2021.11.2.82] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022] Open
Abstract
Intra-abdominal infection is a common, serious complication in patients undergoing emergency abdominal surgery following blunt abdominal trauma. Infectious conditions increase the incidence of autoimmune hemolytic anemia (AIHA), but reports of AIHA occurring after abdominal trauma surgery are rare. Therefore, we report a case of sepsis due to fasciitis and AIHA after abdominal trauma surgery which was successfully managed following the appropriate treatment of both conditions.
Collapse
|
|
27
|
Ma C, Feng Y, Yang L, Wang S, Sun X, Tai S, Guan X, Wang D, Yu Y. In vitro Immunomodulatory Effects of Human Umbilical Cord-Derived Mesenchymal Stem Cells on Peripheral Blood Cells from Warm Autoimmune Hemolytic Anemia Patients. Acta Haematol 2021; 145:63-71. [PMID: 34284381 DOI: 10.1159/000506759] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2019] [Accepted: 02/24/2020] [Indexed: 11/19/2022]
Abstract
INTRODUCTION Autoimmune hemolytic anemia is a potentially lethal disease characterized by autoimmune hemolysis. Although human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) have been reported as a promising therapy, there is limited evidence regarding warm autoimmune hemolytic anemia (wAIHA) patients. This study aimed to investigate the potential therapeutic effects of hUC-MSCs via immune regulation in wAIHA patients. METHODS Peripheral blood mononuclear cells (PBMCs) from 10 wAIHA patients and 8 healthy controls were isolated from peripheral blood and cultured for 3 days with or without the presence of hUC-MSCs; PBMCs were co-cultured with hUC-MSCs using Transwell assays. The supernatant cytokine levels were measured after culture through AimPlex Multiple Immunoassays for Flow, including IL-2, IL-4, IL-10, IFN-γ, TNF-α, and IL-17A. The percentages of regulatory T cells, regulatory B cells, and Th1/Th2 in PBMCs were also assessed before and after culturing. RESULTS In the wAIHA group, hUC-MSCs could upregulate the Treg and Breg proportions after culturing for 3 days, and the Treg and Breg percentages increased after co-culturing with hUC-MSCs in the wAIHA group compared with PBMC cultured alone for 3 days (8.29 ± 8.59 vs. 6.82 ± 1.32, 3.82 ± 1.87 vs. 1.75 ± 1.20, respectively). Compared with the PBMC wAIHA group, the levels of TNF-α (2.13 ± 2.07 vs. 16.20 ± 21.13 pg/mL, p = 0.019) and IL-10 (10.51 ± 18.42 vs. 37.78 ± 44.20 pg/mL, p = 0.012) were significantly elevated in the PBMC + hUC-MSCs wAIHA group. CONCLUSION The hUC-MSCs contributed to the increasing proportion of regulatory cell populations in PBMCs of wAIHA patients, thereby potentially regulating autoimmune response; thus, hUC-MSCs may be a promising approach for wAIHA treatment.
Collapse
Affiliation(s)
- Chunya Ma
- Department of Blood Transfusion, First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Yannan Feng
- Department of Blood Transfusion, First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Lu Yang
- Department of Blood Transfusion, First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Shufang Wang
- Department of Blood Transfusion, First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Xiaolin Sun
- Department of Blood Transfusion, First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Shengfei Tai
- Department of Blood Transfusion, First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Xiaozhen Guan
- Department of Blood Transfusion, First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Deqing Wang
- Department of Blood Transfusion, First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Yang Yu
- Department of Blood Transfusion, First Medical Center of Chinese PLA General Hospital, Beijing, China
| |
Collapse
|
|
28
|
Huda Z, Jahangir A, Sahra S, Rafay Khan Niazi M, Anwar S, Glaser A, Jahangir A. A Case of COVID-19-Associated Autoimmune Hemolytic Anemia With Hyperferritinemia in an Immunocompetent Host. Cureus 2021; 13:e16078. [PMID: 34345558 PMCID: PMC8324606 DOI: 10.7759/cureus.16078] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/30/2021] [Indexed: 01/02/2023] Open
Abstract
We report an interesting case of a middle-aged gentleman who presented with diabetic ketoacidosis (DKA) and tested polymerase chain reaction (PCR) positive for COVID-19 infection. His hospital stay was complicated by acute kidney injury, hematuria, and normocytic anemia. Initial chest x-ray demonstrated bibasilar opacities. D-dimer and C-reactive protein were elevated. During his hospital stay, his hemoglobin decreased from 13.4 g/dL to 9 g/dL, and further workup demonstrated ferritin of 49,081 ng/mL with lactate dehydrogenase of 1665 U/L. He was treated with prednisone and folic acid for autoimmune hemolytic anemia (AIHA). Ferritin was downtrended, and hemoglobin stabilized. As demonstrated by this case report and prior literature review, COVID-19 infection can be associated with AIHA.
Collapse
Affiliation(s)
- Zoha Huda
- Medicine, The City University of New York (CUNY) School of Medicine, New York, USA
| | - Abdullah Jahangir
- Internal Medicine, Staten Island University Hospital, Northwell Health, New York, USA
| | - Syeda Sahra
- Internal Medicine, Northwell Health, New York, USA
| | | | - Shamsuddin Anwar
- Internal Medicine, Staten Island University Hospital, Northwell Health, New York, USA
| | | | | |
Collapse
|
|
29
|
Nasse SA. Autoimmune haemolytic anaemia: emergency blood transfusion. BMJ Case Rep 2021; 14:14/5/e242378. [PMID: 34011642 DOI: 10.1136/bcr-2021-242378] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
A 50-year-old woman, with a background of autoimmune haemolytic anaemia, presented to the emergency department with lethargy and shortness of breath. Investigations revealed a haemoglobin level of 50 g/L. High dose steroids were administered and blood transfusion prescribed. However, the blood transfusion was delayed due to a positive antibody screen and concerns regarding administering blood when the patient was pyrexic. The delay resulted in a significant deterioration in the patient's clinical state with her haemoglobin level falling to 26 g/L 24 hours later. She was urgently transfused with blood and made a full recovery. This report analyses the delays for transfusion and how these could have been minimised. First, guidelines advise that emergency blood should be considered in life-threatening circumstances. Second, fever is not always a contraindication for transfusion, particularly in an emergency setting.
Collapse
|
|
30
|
Inhibition of complement C1s in patients with cold agglutinin disease: lessons learned from a named patient program. Blood Adv 2021; 4:997-1005. [PMID: 32176765 DOI: 10.1182/bloodadvances.2019001321] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2019] [Accepted: 01/27/2020] [Indexed: 12/12/2022] Open
Abstract
Cold agglutinin disease (CAD) causes predominantly extravascular hemolysis and anemia via complement activation. Sutimlimab is a novel humanized monoclonal antibody directed against classical pathway complement factor C1s. We aimed to evaluate the safety and efficacy of long-term maintenance treatment with sutimlimab in patients with CAD. Seven CAD patients treated with sutimlimab as part of a phase 1B study were transitioned to a named patient program. After a loading dose, patients received biweekly (once every 2 weeks) infusions of sutimlimab at various doses. When a patient's laboratory data showed signs of breakthrough hemolysis, the dose of sutimlimab was increased. Three patients started with a dose of 45 mg/kg, another 3 with 60 mg/kg, and 1 with a fixed dose of 5.5 g every other week. All CAD patients responded to re-treatment, and sutimlimab increased hemoglobin from a median initial level of 7.7 g/dL to a median peak of 12.5 g/dL (P = .016). Patients maintained near normal hemoglobin levels except for a few breakthrough events that were related to underdosing and which resolved after the appropriate dose increase. Four of the patients included were eventually treated with a biweekly 5.5 g fixed-dose regimen of sutimlimab. None of them had any breakthrough hemolysis. All patients remained transfusion free while receiving sutimlimab. There were no treatment-related serious adverse events. Overlapping treatment with erythropoietin, rituximab, or ibrutinib in individual patients was safe and did not cause untoward drug interactions. Long-term maintenance treatment with sutimlimab was safe, effectively inhibited hemolysis, and significantly increased hemoglobin levels in re-exposed, previously transfusion-dependent CAD patients.
Collapse
|
|
31
|
Westermann-Clark E, Meehan CA, Meyer AK, Dasso JF, Amre D, Ellison M, Patel B, Betensky M, Hauk CI, Mayer J, Metts J, Leiding JW, Sriaroon P, Kumar A, Ayala I, Walter JE. Primary Immunodeficiency in Children With Autoimmune Cytopenias: Retrospective 154-Patient Cohort. Front Immunol 2021; 12:649182. [PMID: 33968040 PMCID: PMC8100326 DOI: 10.3389/fimmu.2021.649182] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2021] [Accepted: 03/01/2021] [Indexed: 11/13/2022] Open
Abstract
Background Primary immunodeficiency is common among patients with autoimmune cytopenia. Objective The purpose of this study is to retrospectively identify key clinical features and biomarkers of primary immunodeficiency (PID) in pediatric patients with autoimmune cytopenias (AIC) so as to facilitate early diagnosis and targeted therapy. Methods Electronic medical records at a pediatric tertiary care center were reviewed. We selected 154 patients with both AIC and PID (n=17), or AIC alone (n=137) for inclusion in two cohorts. Immunoglobulin levels, vaccine titers, lymphocyte subsets (T, B and NK cells), autoantibodies, clinical characteristics, and response to treatment were recorded. Results Clinical features associated with AIC-PID included splenomegaly, short stature, and recurrent or chronic infections. PID patients were more likely to have autoimmune hemolytic anemia (AIHA) or Evans syndrome than AIC-only patients. The AIC-PID group was also distinguished by low T cells (CD3 and CD8), low immunoglobulins (IgG and IgA), and higher prevalence of autoantibodies to red blood cells, platelets or neutrophils. AIC diagnosis preceded PID diagnosis by 3 years on average, except among those with partial DiGeorge syndrome. AIC-PID patients were more likely to fail first-line treatment. Conclusions AIC patients, especially those with Evans syndrome or AIHA, should be evaluated for PID. Lymphocyte subsets and immune globulins serve as a rapid screen for underlying PID. Early detection of patients with comorbid PID and AIC may improve treatment outcomes. Prospective studies are needed to confirm the diagnostic clues identified and to guide targeted therapy.
Collapse
Affiliation(s)
- Emma Westermann-Clark
- Division of Allergy and Immunology, Department of Pediatrics, Morsani College of Medicine, University of South Florida, Tampa, FL, United States.,Division of Allergy and Immunology, Department of Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, United States
| | - Cristina Adelia Meehan
- Division of Allergy and Immunology, Department of Pediatrics, Morsani College of Medicine, University of South Florida, Tampa, FL, United States
| | - Anna K Meyer
- Division of Allergy and Immunology, Department of Pediatrics, National Jewish Health, Denver, CO, United States.,Graduate Medical Education, University of Colorado, Denver, CO, United States
| | - Joseph F Dasso
- Division of Allergy and Immunology, Department of Pediatrics, Morsani College of Medicine, University of South Florida, Tampa, FL, United States.,Department of Biology, University of Tampa, Tampa, FL, United States
| | - Devendra Amre
- Division of Allergy and Immunology, Department of Pediatrics, Morsani College of Medicine, University of South Florida, Tampa, FL, United States
| | - Maryssa Ellison
- Division of Allergy and Immunology, Department of Pediatrics, Morsani College of Medicine, University of South Florida, Tampa, FL, United States
| | - Bhumika Patel
- Division of Allergy and Immunology, Department of Pediatrics, Morsani College of Medicine, University of South Florida, Tampa, FL, United States
| | - Marisol Betensky
- Cancer and Blood Disorders Institute, Johns Hopkins All Children's Hospital, St Petersburg, FL, United States.,Division of Hematology, Department of Pediatrics Johns Hopkins All Children's Hospital, St. Petersburg, FL, United States
| | - Charles Isaac Hauk
- Cancer and Blood Disorders Institute, Johns Hopkins All Children's Hospital, St Petersburg, FL, United States
| | - Jennifer Mayer
- Cancer and Blood Disorders Institute, Johns Hopkins All Children's Hospital, St Petersburg, FL, United States
| | - Jonathan Metts
- Cancer and Blood Disorders Institute, Johns Hopkins All Children's Hospital, St Petersburg, FL, United States
| | - Jennifer W Leiding
- Division of Allergy and Immunology, Department of Pediatrics, Morsani College of Medicine, University of South Florida, Tampa, FL, United States.,Division of Allergy/Immunology, Department of Pediatrics Johns Hopkins All Children's Hospital, St. Petersburg, FL, United States
| | - Panida Sriaroon
- Division of Allergy and Immunology, Department of Pediatrics, Morsani College of Medicine, University of South Florida, Tampa, FL, United States.,Division of Allergy/Immunology, Department of Pediatrics Johns Hopkins All Children's Hospital, St. Petersburg, FL, United States
| | - Ambuj Kumar
- Research Methodology and Biostatistics Core, Morssani College of Medicine, University of South Florida, Tampa, FL, United States
| | - Irmel Ayala
- Cancer and Blood Disorders Institute, Johns Hopkins All Children's Hospital, St Petersburg, FL, United States.,Division of Hematology, Department of Pediatrics Johns Hopkins All Children's Hospital, St. Petersburg, FL, United States
| | - Jolan E Walter
- Division of Allergy and Immunology, Department of Pediatrics, Morsani College of Medicine, University of South Florida, Tampa, FL, United States.,Division of Allergy/Immunology, Department of Pediatrics Johns Hopkins All Children's Hospital, St. Petersburg, FL, United States.,Division of Allergy and Immunology, Massachusetts General Hospital for Children, Boston, MA, United States
| |
Collapse
|
|
32
|
Tranekær S, Hansen DL, Frederiksen H. Epidemiology of Secondary Warm Autoimmune Haemolytic Anaemia-A Systematic Review and Meta-Analysis. J Clin Med 2021; 10:jcm10061244. [PMID: 33802848 PMCID: PMC8002719 DOI: 10.3390/jcm10061244] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Revised: 03/09/2021] [Accepted: 03/14/2021] [Indexed: 12/15/2022] Open
Abstract
Background: Warm autoimmune haemolytic anaemia (wAIHA) is a haemolytic disorder, most commonly seen among adults and is classified as either primary or secondary to an underlying disease. We describe the age and sex distribution and the proportion of secondary wAIHA. Method: We retrieved 2635 published articles, screened abstracts and titles, and identified 27 articles eligible for full-text review. From these studies, we extracted data regarding number of patients, sex distribution, age at diagnosis, number of patients with secondary wAIHA, and whether the patients were diagnosed through local or referral centres. All data were weighted according to the number of included patients in each study. Results: 27 studies including a total of 4311 patients with wAIHA, of which 66% were females, were included. The median age at diagnosis was 68.7 years, however, wAIHA affected all ages. The mean proportion of secondary wAIHA was 49%, most frequently secondary to systemic lupus erythematosus. The proportions of secondary wAIHA reported from primary vs. referral centres were 35% vs. 59%, respectively. Conclusion: This review consolidates previously reported gender distribution. The higher proportion of secondary wAIHA in referral centres suggests that the most severely affected patients are disproportionally more frequent in such facilities.
Collapse
Affiliation(s)
- Stinne Tranekær
- Haematological Research Unit, Department of Clinical Research, University of Southern, 5230 Odense M, Denmark; (S.T.); (D.L.H.)
- Department of Haematology, Odense University Hospital, 5000 Odense C, Denmark
| | - Dennis Lund Hansen
- Haematological Research Unit, Department of Clinical Research, University of Southern, 5230 Odense M, Denmark; (S.T.); (D.L.H.)
- Department of Haematology, Odense University Hospital, 5000 Odense C, Denmark
| | - Henrik Frederiksen
- Haematological Research Unit, Department of Clinical Research, University of Southern, 5230 Odense M, Denmark; (S.T.); (D.L.H.)
- Department of Haematology, Odense University Hospital, 5000 Odense C, Denmark
- Correspondence:
| |
Collapse
|
|
33
|
Richards AL, Qiu A, Dei Zotti F, Sheldon K, Usaneerungrueng C, Gruber DR, Hudson KE. Autoantigen presentation by splenic dendritic cells is required for RBC-specific autoimmunity. Transfusion 2021; 61:225-235. [PMID: 33151564 PMCID: PMC9092285 DOI: 10.1111/trf.16191] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2019] [Revised: 08/29/2020] [Accepted: 09/26/2020] [Indexed: 11/26/2022]
Abstract
BACKGROUND Failure of humoral tolerance to red blood cell (RBC) antigens may lead to autoimmune hemolytic anemia (AIHA), a severe and sometimes fatal disease. Previous studies have shown that although tolerance is robust in HOD mice, autoantibodies are generated upon adoptive transfer of OTII CD4+ T cells, which are specific for an epitope contained within the HOD antigen. These data imply that antigen-presenting cells (APCs) are presenting RBC-derived autoantigen(s) and are capable of driving T-cell activation. Given that multiple APCs participate in erythrophagocytosis, we used a transgenic approach to determine which cellular subsets were required for autoantigen presentation and subsequent autoreactive T-cell activation. STUDY DESIGN AND METHODS HOD mice, which express an RBC-specific antigen consisting of hen egg lysozyme, ovalbumin, and human blood group molecule Duffy, were bred with IAbfl/fl and Cre-expressing transgenic animals to generate mice that lack I-Ab expression on particular cell subsets. OTII CD4+ T cell proliferation was assessed in vivo in HOD+ I-Abfl/fl xCre+ mice and in vitro upon coculture with sorted APCs. RESULTS Analysis of HOD+ I-Abfl/fl xCre+ mice demonstrated that splenic conventional dendritic cells (DCs), but not macrophages or monocytes, were required for autoantigen presentation to OTII CD4+ T cells. Subsequent in vitro coculture experiments revealed that both CD8+ and CD8- DC subsets participate in erythrophagocytosis, present RBC-derived autoantigen and stimulate autoreactive T-cell proliferation. CONCLUSION These data suggest that if erythrocyte T-cell tolerance fails, DCs are capable of initiating autoimmune responses. As such, targeting DCs may be a fruitful strategy for AIHA therapies.
Collapse
Affiliation(s)
| | - Annie Qiu
- Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY
| | - Flavia Dei Zotti
- Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY
| | | | | | | | - Krystalyn E. Hudson
- Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY
- KEH was at Bloodworks NW Research Institute prior to transitioning to Columbia University Irving Medical Center
| |
Collapse
|
|
34
|
Pelle MC, Tassone B, Ricchio M, Mazzitelli M, Davoli C, Procopio G, Cancelliere A, La Gamba V, Lio E, Matera G, Quirino A, Barreca GS, Trecarichi EM, Torti C. Late-onset myocardial infarction and autoimmune haemolytic anaemia in a COVID-19 patient without respiratory symptoms, concomitant with a paradoxical increase in inflammatory markers: a case report. J Med Case Rep 2020; 14:246. [PMID: 33339534 PMCID: PMC7746982 DOI: 10.1186/s13256-020-02595-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2020] [Accepted: 11/19/2020] [Indexed: 01/03/2023] Open
Abstract
BACKGROUND In December 2019, a new coronavirus (named severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) spread from China, causing a pandemic in a very short time. The main clinical presentation of SARS-CoV-2 infection (COVID-19, coronavirus disease-2019) is pneumonia, but several cardiovascular complications may also occur (e.g., acute coronary syndromes, pulmonary embolism, stroke, arrhythmias, heart failure and cardiogenic shock). Direct or indirect mechanisms induced by SARS-CoV-2 could be implicated in the pathogenesis of these events. CASE PRESENTATION We report herein the third case of COVID-19 autoimmune haemolytic anaemia (AIHA) reported so far, which occurredwithout any other possible explanations in a Caucasian patient. The patient also suffered from ST-elevation myocardial injury. CONCLUSIONS Both complications occurred quite late after COVID-19 diagnosis and were probably precipitated by systemic inflammation, as indicated by a significant delayed increase in inflammatory markers, including interleukin-6 (IL-6).
Collapse
Affiliation(s)
- Maria Chiara Pelle
- Infectious and Tropical Disease Unit, Department of Medical and Surgical Sciences, "Magna Graecia" University of Catanzaro, Viale Europa, 88100, Catanzaro, Italy.
| | - Bruno Tassone
- Infectious and Tropical Disease Unit, Department of Medical and Surgical Sciences, "Magna Graecia" University of Catanzaro, Viale Europa, 88100, Catanzaro, Italy
| | - Marco Ricchio
- Infectious and Tropical Disease Unit, Department of Medical and Surgical Sciences, "Magna Graecia" University of Catanzaro, Viale Europa, 88100, Catanzaro, Italy
| | - Maria Mazzitelli
- Infectious and Tropical Disease Unit, Department of Medical and Surgical Sciences, "Magna Graecia" University of Catanzaro, Viale Europa, 88100, Catanzaro, Italy
| | - Chiara Davoli
- Infectious and Tropical Disease Unit, Department of Medical and Surgical Sciences, "Magna Graecia" University of Catanzaro, Viale Europa, 88100, Catanzaro, Italy
| | - Giada Procopio
- Infectious and Tropical Disease Unit, Department of Medical and Surgical Sciences, "Magna Graecia" University of Catanzaro, Viale Europa, 88100, Catanzaro, Italy
| | - Anna Cancelliere
- Infectious and Tropical Disease Unit, Department of Medical and Surgical Sciences, "Magna Graecia" University of Catanzaro, Viale Europa, 88100, Catanzaro, Italy
| | - Valentina La Gamba
- Infectious and Tropical Disease Unit, Department of Medical and Surgical Sciences, "Magna Graecia" University of Catanzaro, Viale Europa, 88100, Catanzaro, Italy
| | - Elena Lio
- Infectious and Tropical Disease Unit, Department of Medical and Surgical Sciences, "Magna Graecia" University of Catanzaro, Viale Europa, 88100, Catanzaro, Italy
| | - Giovanni Matera
- Department of Health Sciences, Unit of Clinical Microbiology, University "Magna Graecia", Catanzaro, Italy
| | - Angela Quirino
- Department of Health Sciences, Unit of Clinical Microbiology, University "Magna Graecia", Catanzaro, Italy
| | | | - Enrico Maria Trecarichi
- Infectious and Tropical Disease Unit, Department of Medical and Surgical Sciences, "Magna Graecia" University of Catanzaro, Viale Europa, 88100, Catanzaro, Italy
| | - Carlo Torti
- Infectious and Tropical Disease Unit, Department of Medical and Surgical Sciences, "Magna Graecia" University of Catanzaro, Viale Europa, 88100, Catanzaro, Italy
| |
Collapse
|
|
35
|
Rituximab Use in Warm and Cold Autoimmune Hemolytic Anemia. J Clin Med 2020; 9:jcm9124034. [PMID: 33322221 PMCID: PMC7763062 DOI: 10.3390/jcm9124034] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Revised: 12/06/2020] [Accepted: 12/09/2020] [Indexed: 01/22/2023] Open
Abstract
Autoimmune hemolytic anemia is a rare condition characterized by destruction of red blood cells with and without involvement of complement. It is associated with significant morbidity and mortality. In warm autoimmune hemolytic anemia, less than 50% of patients remain in long-term remission following initial steroid therapy and subsequent therapies are required. Cold agglutinin disease is a clonal hematologic disorder that requires therapy in the majority of patients and responds poorly to steroids and alkylators. Rituximab has a favorable toxicity profile and has demonstrated efficacy in autoimmune hemolytic anemia in first-line as well as relapsed settings. Rituximab is the preferred therapy for steroid refractory warm autoimmune hemolytic anemia (wAIHA) and as part of the first- and second-line treatment of cold agglutinin disease. This article reviews the mechanism of action of rituximab and the current literature on its role in the management of primary and secondary warm autoimmune hemolytic anemia and cold agglutinin disease.
Collapse
|
|
36
|
Morigi A, Casadei B, Argnani L, Stefoni V, Sergio E, Cavo M, Zinzani PL. Successful stem cell harvest and autologous transplantation in a patient with cold agglutinin syndrome and aggressive lymphoma. Leuk Lymphoma 2020; 62:1007-1009. [PMID: 33274685 DOI: 10.1080/10428194.2020.1855342] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Affiliation(s)
- Alice Morigi
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italia.,Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Istituto di Ematologia "Seràgnoli", Università degli Studi, Bologna, Italia
| | - Beatrice Casadei
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italia.,Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Istituto di Ematologia "Seràgnoli", Università degli Studi, Bologna, Italia
| | - Lisa Argnani
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italia.,Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Istituto di Ematologia "Seràgnoli", Università degli Studi, Bologna, Italia
| | - Vittorio Stefoni
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italia.,Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Istituto di Ematologia "Seràgnoli", Università degli Studi, Bologna, Italia
| | - Emanuela Sergio
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italia
| | - Michele Cavo
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italia.,Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Istituto di Ematologia "Seràgnoli", Università degli Studi, Bologna, Italia
| | - Pier Luigi Zinzani
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italia.,Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Istituto di Ematologia "Seràgnoli", Università degli Studi, Bologna, Italia
| |
Collapse
|
|
37
|
Kasinathan G, Sathar J. Mixed-type autoimmune hemolytic anaemia presenting as multiple thromboses: A case report. Ann Med Surg (Lond) 2020; 60:323-326. [PMID: 33204423 PMCID: PMC7653202 DOI: 10.1016/j.amsu.2020.11.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2020] [Revised: 11/01/2020] [Accepted: 11/01/2020] [Indexed: 11/13/2022] Open
Abstract
Autoimmune hemolytic anaemia (AIHA) is a heterogenous disorder characterised by the presence of IgG or IgM pathological autoantibodies that target antigens of erythrocytes resulting in active hemolysis. Case presentation: A 40-year-old gentleman presented to a medical centre with chest pain and right sided hemiparesis for a week. He was pale and jaundiced. The power of the right upper and lower limbs was 3/5. His spleen was palpable. His complete blood count revealed macrocytic anaemia of 7.6 g/dL. The brain Magnetic Resonance Imaging (MRI) showed left fronto-parietal infarction. The right cardiac and left carotid angiogram revealed thromboses involving the right coronary and left internal carotid artery respectively. At the cardiology department, he was transfused with two units of red blood cells without his anemia being investigated and a stent was deployed to the left internal carotid artery. He was referred to the hematology department in which his peripheral blood smear revealed hemolysis and his direct antiglobulin test was positive. He responded to a course of steroids and direct oral anticoagulation and is in complete remission for the past 18 months. Conclusion: It is always imperative to investigate the cause of anaemia and consider hemolysis in a patient presenting with multiple unexplained thromboses.
Collapse
Affiliation(s)
- Ganesh Kasinathan
- Department of Haematology, Ampang Hospital, Ampang, Selangor, Malaysia
| | - Jameela Sathar
- Department of Haematology, Ampang Hospital, Ampang, Selangor, Malaysia
| |
Collapse
|
|
38
|
A case of Evans syndrome secondary to COVID-19. BLOOD TRANSFUSION = TRASFUSIONE DEL SANGUE 2020; 19:85-88. [PMID: 33263526 DOI: 10.2450/2020.0221-20] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Subscribe] [Scholar Register] [Received: 07/02/2020] [Accepted: 08/31/2020] [Indexed: 11/21/2022]
|
|
39
|
New Insights in Autoimmune Hemolytic Anemia: From Pathogenesis to Therapy Stage 1. J Clin Med 2020; 9:jcm9123859. [PMID: 33261023 PMCID: PMC7759854 DOI: 10.3390/jcm9123859] [Citation(s) in RCA: 55] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2020] [Revised: 11/20/2020] [Accepted: 11/24/2020] [Indexed: 12/15/2022] Open
Abstract
Autoimmune hemolytic anemia (AIHA) is a highly heterogeneous disease due to increased destruction of autologous erythrocytes by autoantibodies with or without complement involvement. Other pathogenic mechanisms include hyper-activation of cellular immune effectors, cytokine dysregulation, and ineffective marrow compensation. AIHAs may be primary or associated with lymphoproliferative and autoimmune diseases, infections, immunodeficiencies, solid tumors, transplants, and drugs. The direct antiglobulin test is the cornerstone of diagnosis, allowing the distinction into warm forms (wAIHA), cold agglutinin disease (CAD), and other more rare forms. The immunologic mechanisms responsible for erythrocyte destruction in the various AIHAs are different and therefore therapy is quite dissimilar. In wAIHA, steroids represent first line therapy, followed by rituximab and splenectomy. Conventional immunosuppressive drugs (azathioprine, cyclophosphamide, cyclosporine) are now considered the third line. In CAD, steroids are useful only at high/unacceptable doses and splenectomy is uneffective. Rituximab is advised in first line therapy, followed by rituximab plus bendamustine and bortezomib. Several new drugs are under development including B-cell directed therapies (ibrutinib, venetoclax, parsaclisib) and inhibitors of complement (sutimlimab, pegcetacoplan), spleen tyrosine kinases (fostamatinib), or neonatal Fc receptor. Here, a comprehensive review of the main clinical characteristics, diagnosis, and pathogenic mechanisms of AIHA are provided, along with classic and new therapeutic approaches.
Collapse
|
|
40
|
Michalak SS, Olewicz-Gawlik A, Rupa-Matysek J, Wolny-Rokicka E, Nowakowska E, Gil L. Autoimmune hemolytic anemia: current knowledge and perspectives. Immun Ageing 2020; 17:38. [PMID: 33292368 PMCID: PMC7677104 DOI: 10.1186/s12979-020-00208-7] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2020] [Accepted: 11/10/2020] [Indexed: 02/07/2023]
Abstract
Autoimmune hemolytic anemia (AIHA) is an acquired, heterogeneous group of diseases which includes warm AIHA, cold agglutinin disease (CAD), mixed AIHA, paroxysmal cold hemoglobinuria and atypical AIHA. Currently CAD is defined as a chronic, clonal lymphoproliferative disorder, while the presence of cold agglutinins underlying other diseases is known as cold agglutinin syndrome. AIHA is mediated by autoantibodies directed against red blood cells (RBCs) causing premature erythrocyte destruction. The pathogenesis of AIHA is complex and still not fully understood. Recent studies indicate the involvement of T and B cell dysregulation, reduced CD4+ and CD25+ Tregs, increased clonal expansions of CD8 + T cells, imbalance of Th17/Tregs and Tfh/Tfr, and impaired lymphocyte apoptosis. Changes in some RBC membrane structures, under the influence of mechanical stimuli or oxidative stress, may promote autohemolysis. The clinical presentation and treatment of AIHA are influenced by many factors, including the type of AIHA, degree of hemolysis, underlying diseases, presence of concomitant comorbidities, bone marrow compensatory abilities and the presence of fibrosis and dyserthropoiesis. The main treatment for AIHA is based on the inhibition of autoantibody production by mono- or combination therapy using GKS and/or rituximab and, rarely, immunosuppressive drugs or immunomodulators. Reduction of erythrocyte destruction via splenectomy is currently the third line of treatment for warm AIHA. Supportive treatment including vitamin supplementation, recombinant erythropoietin, thrombosis prophylaxis and the prevention and treatment of infections is essential. New groups of drugs that inhibit immune responses at various levels are being developed intensively, including inhibition of antibody-mediated RBCs phagocytosis, inhibition of B cell and plasma cell frequency and activity, inhibition of IgG recycling, immunomodulation of T lymphocytes function, and complement cascade inhibition. Recent studies have brought about changes in classification and progress in understanding the pathogenesis and treatment of AIHA, although there are still many issues to be resolved, particularly concerning the impact of age-associated changes to immunity.
Collapse
Affiliation(s)
- Sylwia Sulimiera Michalak
- Department of Pharmacology and Toxicology Institute of Health Sciences, Collegium Medicum, University of Zielona Gora, Zielona Góra, Poland.
| | - Anna Olewicz-Gawlik
- Department of Anatomy and Histology Institute of Health Sciences, Collegium Medicum, University of Zielona Gora, Zielona Góra, Poland
- Department of Infectious Diseases, Hepatology and Acquired Immune Deficiencies, Poznan University of Medical Sciences, Poznan, Poland
- Department of Immunology, Poznan University of Medical Sciences, Poznan, Poland
| | - Joanna Rupa-Matysek
- Department of Hematology and Bone Marrow Transplantation, Poznan University of Medical Sciences, Poznań, Poland
| | - Edyta Wolny-Rokicka
- Department of Radiotherapy, Multidisciplinary Hospital, Gorzów Wielkopolski, Poland
| | - Elżbieta Nowakowska
- Department of Pharmacology and Toxicology Institute of Health Sciences, Collegium Medicum, University of Zielona Gora, Zielona Góra, Poland
| | - Lidia Gil
- Department of Hematology and Bone Marrow Transplantation, Poznan University of Medical Sciences, Poznań, Poland
| |
Collapse
|
|
41
|
Jain NA, Zhao S, Wei L, Rogers KA, Otterson GA, Wang TF, Owen DH. Association Between RBC Antigen Allo-Antibodies and Immune-Related Adverse Events During Immune Checkpoint Inhibitor Treatment for Advanced Cancers. Cancer Manag Res 2020; 12:11743-11749. [PMID: 33235503 PMCID: PMC7680604 DOI: 10.2147/cmar.s264166] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Accepted: 10/01/2020] [Indexed: 11/23/2022] Open
Abstract
Introduction Immune checkpoint inhibitors (ICI) have become a primary treatment modality for patients with a variety of malignancies. Given their increasing use, it is essential to be familiar with their immune-related adverse events (irAEs). Here we report a severe case of autoimmune hemolytic anemia (AIHA) associated with cold agglutinin precipitated by pembrolizumab, and a retrospective study of patients treated with ICI utilizing an institutional database where we analyzed the patterns of anti-RBC testing and their ability to predict irAE. Methods Patients treated with at least one dose of ICI (PD-1, PD-L1, CTLA-4 inhibitors) for advanced cancer between November 2012 and September 2017 at our institution were included. Electronic Medical Records were reviewed to abstract data. Medians and 95% CIs were estimated using Kaplan–Meier method and differences compared using the Log Rank test. Fisher’s exact test and Chi square test were used to analyze clinical associations. Results We identified 1065 patients who received at least one dose of ICI: 180/1065 (17%) underwent direct antiglobulin test (DAT) or allo-antibody (alloAb) testing at any time; 127/1065 (12%) had either DAT or alloAb testing pre-ICI; 129 had either DAT or alloAb testing after ICI initiation; and 76 had either DAT or alloAb testing at both time points. There was a significant association between positive alloAb pre-ICI and the development of irAE while on ICI (p = 0.04). Conclusion Given the increasing use of ICI, oncologists should be aware of potential irAEs with ICI. We found an association between the presence of an alloAb pre-ICI and the development of irAE, indicating that this previous non-self antigen response may predict immune adverse events. A larger prospective study is needed for systematic evaluation of the association between alloAb testing and irAE, and whether routine testing may inform clinical decision-making for patients.
Collapse
Affiliation(s)
- Natasha A Jain
- Division of Medical Oncology, The Ohio State University, Columbus, OH, USA.,Division of Hematology, The Ohio State University, Columbus, OH, USA
| | - Songzhu Zhao
- Center for Biostatistics, The Ohio State University, Columbus, OH, USA
| | - Lai Wei
- Center for Biostatistics, The Ohio State University, Columbus, OH, USA
| | - Kerry A Rogers
- Division of Medical Oncology, The Ohio State University, Columbus, OH, USA.,Division of Hematology, The Ohio State University, Columbus, OH, USA
| | - Gregory A Otterson
- Division of Medical Oncology, The Ohio State University, Columbus, OH, USA
| | - Tzu-Fei Wang
- Division of Hematology, The Ohio State University, Columbus, OH, USA
| | - Dwight H Owen
- Division of Medical Oncology, The Ohio State University, Columbus, OH, USA
| |
Collapse
|
|
42
|
Ray GK, Mishra D, Jena RK, Mahapatra S, Palai S, Parida AA. Clinical Profile and Severity of Hemolysis in Adult Patients of Primary Autoimmune Hemolytic Anemia and Their Response to Steroid: A Prospective Cohort Study from Single Institution. Indian J Hematol Blood Transfus 2020; 37:119-125. [PMID: 33707844 DOI: 10.1007/s12288-020-01326-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2020] [Accepted: 07/29/2020] [Indexed: 11/29/2022] Open
Abstract
Autoimmune hemolytic anaemia (AIHA) has traditionally been classified based on the temperature sensitivity of the autoagglutinins as warm (WAIHA), cold (CAIHA) and mixed type. Autoagglutinin may be of IgG or IgM type. The present prospective study was conducted to evaluate the profile of clinical picture, severity of haemolysis, treatment response of steroid. This study on patients of adult primary AIHA was conducted by taking complete history followed by detail physical examination. Laboratory investigations were performed to establish haemolytic anaemia and to assess severity of haemolysis. Immunehematological work up including blood grouping, direct antiglobulin test (DAT), IAT, antibody screening, adsorption elution was performed to diagnose type of AIHA. All cases were followed up to assess the response to prednisolone. All the data were collected and analysed by SPSS 19. Out of 62 primary AIHA cases, female were affected more than male (41:21). WAIHA is most common type (42, 67.8%) followed by mixed (20.9%) and cold AIHA (11.3%). Severity of haemolysis showed significant correlation with the DAT strength and not with type of AIHA. (P < 0.05) On oral prednisolone, 22 cases attended complete remission, while relapse, drug dependency and partial remission was achieved in 13, 9, 3 cases respectively. Severity of haemolysis in AIHA is directly related with DAT strength. WAIHA is most common type and can be managed with oral prednisolone (cr 45.2%), without red cell transfusion in most of cases. Mixed type AIHA cases were presented mostly with severe haemolysis, with minimum therapeutic response to prednisolone and maximum relapse/drug dependency.
Collapse
Affiliation(s)
- Gopal Krushna Ray
- Department of Transfusion Medicine, Sriram Chandra Bhanja Medical College and Hospital, Cuttack, Odisha India
| | - Debasish Mishra
- Department of Transfusion Medicine, Sriram Chandra Bhanja Medical College and Hospital, Cuttack, Odisha India
| | - Rabindra Kumar Jena
- Department of Clinical Hematology, Sriram Chandra Bhanja Medical College and Hospital, Cuttack, Odisha India
| | - Smita Mahapatra
- Department of Transfusion Medicine, Sriram Chandra Bhanja Medical College and Hospital, Cuttack, Odisha India
| | - Sabita Palai
- Department of Transfusion Medicine, Sriram Chandra Bhanja Medical College and Hospital, Cuttack, Odisha India
| | - Ansuman Abhishek Parida
- Department of Pharmacology, Sriram Chandra Bhanja Medical College and Hospital, Cuttack, Odisha India
| |
Collapse
|
|
43
|
Severe Autoimmune Hemolytic Anemia in COVID-19 İnfection, Safely Treated with Steroids. Mediterr J Hematol Infect Dis 2020; 12:e2020053. [PMID: 32670531 PMCID: PMC7340241 DOI: 10.4084/mjhid.2020.053] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2020] [Accepted: 06/23/2020] [Indexed: 12/19/2022] Open
|
|
44
|
Wong ASL, Gruber DR, Richards AL, Sheldon K, Qiu A, Hay A, Hudson KE. Tolerization of recent thymic emigrants is required to prevent RBC-specific autoimmunity. J Autoimmun 2020; 114:102489. [PMID: 32507505 DOI: 10.1016/j.jaut.2020.102489] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2020] [Revised: 05/11/2020] [Accepted: 05/13/2020] [Indexed: 11/18/2022]
Abstract
Autoimmune hemolytic anemia (AIHA) leads to accelerated destruction of autologous red blood cells (RBCs) by autoantibodies. AIHA is a severe and sometimes fatal disease. While there are several therapeutic strategies available, there are currently no licensed treatments for AIHA and few therapeutics result in treatment-free durable remission. The etiology of primary AIHA is unknown; however, secondary AIHA occurs concurrently with lymphoproliferative disorders and infections. Additionally, AIHA is the second most common manifestation of primary immunodeficiency disorders and has been described as a side effect of checkpoint inhibitor therapy. Given the severity of AIHA and the lack of treatment options, understanding the initiation of autoimmunity is imperative. Herein, we utilized a well-described model of RBC biology to dissect how RBC-specific autoreactive T cells become educated against RBC autoantigens. We show that, unlike most autoantigens, T cells do not encounter RBC autoantigens in the thymus. Instead, when they leave the thymus as recent thymic emigrants (RTEs), they retain the ability to positively respond to RBC autoantigens; only after several weeks in circulation do RTEs become nonresponsive. Together, these data suggest that any disruption in this process would lead to breakdown of tolerance and initiation of autoimmunity. Thus, RTEs and this developmental process are potential targets to prevent and treat AIHA.
Collapse
Affiliation(s)
| | | | | | | | - Annie Qiu
- Columbia University Irving Medical Center, Department of Pathology and Cell Biology, New York, NY, USA
| | - Ariel Hay
- University of Virginia, Charlottesville, VA, USA
| | - Krystalyn E Hudson
- Columbia University Irving Medical Center, Department of Pathology and Cell Biology, New York, NY, USA.
| |
Collapse
|
|
45
|
Lopez C, Kim J, Pandey A, Huang T, DeLoughery TG. Simultaneous onset of COVID-19 and autoimmune haemolytic anaemia. Br J Haematol 2020; 190:31-32. [PMID: 32369626 PMCID: PMC7267644 DOI: 10.1111/bjh.16786] [Citation(s) in RCA: 90] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Affiliation(s)
- Chris Lopez
- Legacy Health System, Internal Medicine, Portland, OR, USA
| | - Jeremy Kim
- Legacy Health System, Internal Medicine, Portland, OR, USA
| | - Apurva Pandey
- Knight Cancer Institute, Oregon Health Sciences University, Portland, OR, USA
| | - Ted Huang
- Knight Cancer Institute, Oregon Health Sciences University, Portland, OR, USA
| | - Thomas G DeLoughery
- Knight Cancer Institute, Oregon Health Sciences University, Portland, OR, USA
| |
Collapse
|
|
46
|
Fang LW, Pan H, Shi J. [Ibrutinib treatment for 2 cases of relapsed/refractory autoimmune hemolytic anemia: a pilot study]. ZHONGHUA XUE YE XUE ZA ZHI = ZHONGHUA XUEYEXUE ZAZHI 2020; 41:412-416. [PMID: 32536139 PMCID: PMC7342072 DOI: 10.3760/cma.j.issn.0253-2727.2020.05.009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/10/2020] [Indexed: 11/20/2022]
Abstract
Objective: To explore the efficacy and safety of ibrutinib treatment for relapsed/refractory (R/R) primary autoimmune hemolytic anemia (AIHA) . Methods: Two cases of primary AIHA with relapse events were refractory to glucocorticoid, anti-CD20 monoclonal antibody, immunosuppressive drugs, and splenectomy (case 1 only) . Ibrutinib treatment was administered at an initial dose of 280 mg/d (420 mg/d for case 1 from the 3rd to 8th week) . Results: Both patients achieved transfusion independence and HGB>20 g/L above baseline after 2 weeks (partial response) . For case 1, HGB concentration restored to 113 g/L but with incomplete hemolysis recovery after 10 weeks; HGB reached the level of 118 g/L, also with incomplete hemolysis recovery, after 6 weeks in case 2. They all acquired complete response with incomplete hemolysis recovery (CRi) . The responses sustained 14 weeks and 10 weeks after follow-up at 16 weeks and 12 weeks, respectively. During the treatment, hematologic and nonhematologic toxicity is mild and acceptable. Conclusion: Ibrutinib alone is effective for the 2 R/R primary AIHA cases. We need further clinical trial to identify its efficacy and safety.
Collapse
Affiliation(s)
- L W Fang
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Scienes and Peking Union Medical College, Tianjin 300020, China
| | - H Pan
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Scienes and Peking Union Medical College, Tianjin 300020, China
| | - J Shi
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Scienes and Peking Union Medical College, Tianjin 300020, China
| |
Collapse
|
|
47
|
Deng J, Zhou F, Wong CY, Huang E, Zheng E. Efficacy of therapeutic plasma exchange for treatment of autoimmune hemolytic anemia: A systematic review and meta‐analysis of randomized controlled trials. J Clin Apher 2020; 35:294-306. [DOI: 10.1002/jca.21790] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2020] [Revised: 04/24/2020] [Accepted: 04/25/2020] [Indexed: 12/27/2022]
Affiliation(s)
- Jiawen Deng
- Faculty of Health Sciences McMaster University Hamilton Ontario Canada
| | - Fangwen Zhou
- Faculty of Health Sciences McMaster University Hamilton Ontario Canada
| | - Chi Yi Wong
- Faculty of Health Sciences McMaster University Hamilton Ontario Canada
| | - Emma Huang
- Faculty of Health Sciences McMaster University Hamilton Ontario Canada
| | - Elena Zheng
- Faculty of Applied Health Sciences University of Waterloo Waterloo Ontario Canada
| |
Collapse
|
|
48
|
Yahya HA, Khan N, Barta S, Nejati R. A Rare Association: Autoimmune Hemolytic Anemia With Indolent T-Cell Prolymphocytic Leukemia. Cureus 2020; 12:e7994. [PMID: 32523849 PMCID: PMC7274264 DOI: 10.7759/cureus.7994] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
Abstract
The association of warm autoimmune hemolytic anemia (wAIHA) with various lymphoproliferative disorders is well reported in the literature. But the association of wAIHA with T-cell prolymphocytic leukemia (T-PLL), a very rare lymphoproliferative disorder, has never been reported. A 71-year-old man was in his usual state of health until three years ago when he developed intermittent bouts of worsening anemia associated with mild peripheral blood lymphocytosis. He was diagnosed with wAIHA and steroid therapy was initiated, resulting in an improvement in the hemoglobin level of the patient. His lymphocyte count remained persistently elevated but he did not develop any malignancy-related signs or symptoms. A diagnosis of ‘indolent’ T-cell prolymphocytic leukemia (small cell variant) was made by combining distinctive clinical, morphologic, immunophenotypic, and cytogenetic analysis. His wAIHA went into complete remission and steroid therapy was successfully tapered off. He has not required any treatment for his T-PLL during the last two years' follow-up.
Collapse
Affiliation(s)
- Hafiz A Yahya
- Pathology, Fox Chase Cancer Center, Philadelphia, USA
| | - Nadia Khan
- Hematology/Oncology, Fox Chase Cancer Center, Temple University Health System, Philadelphia, USA
| | - Stefan Barta
- Hematology/Oncology, Abramson Cancer Center, University of Pennsylvania, Philadelphia, USA
| | - Reza Nejati
- Pathology/Hematopathology, Fox Chase Cancer Center, Philadelphia, USA
| |
Collapse
|
|
49
|
Tauseef A, Asghar MS, Zafar M, Ahmed I, Dawood M, Shaikh T, Khan N, Alam T. Cold autoimmune hemolytic anemia: a rare association with triple-positive breast cancer. J Community Hosp Intern Med Perspect 2020; 9:499-502. [PMID: 32002158 PMCID: PMC6968714 DOI: 10.1080/20009666.2019.1698262] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2019] [Accepted: 09/18/2019] [Indexed: 11/16/2022] Open
Abstract
A 45-year-old Asian woman was presented with fever, easy fatigability, shortness of breath, cervical and axillary lymphadenopathy and other signs and symptoms of anemia. After all the baseline work-up, the patient was investigated for Mono-coombs C3d levels, which were elevated, suggesting the diagnosis of Cold autoimmune hemolytic anemia (Cold AIHA). An Ultrasound-guided true-cut biopsy was done to determine the primary cause associated with it, which showed the presence of tumor cells arranged in cords and clusters. They have dark staining cells with mitotic activity, suggestive of breast carcinoma as an association of Cold AIHA. Estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) were sent, which came out to be positive. So, the patient was diagnosed with Cold AIHA in association with triple-positive breast cancer.
Collapse
Affiliation(s)
- Abubakar Tauseef
- Resident Physician in Internal Medicine Department, Dow University Hospital, Karachi, Pakistan
| | - Muhammad Sohaib Asghar
- Resident Physician in Internal Medicine Department, Dow University Hospital, Karachi, Pakistan
| | - Maryam Zafar
- Resident Physician in Internal Medicine Department, Dow University Hospital, Karachi, Pakistan
| | - Iftekhar Ahmed
- Resident Physician in Internal Medicine Department, Dow University Hospital, Karachi, Pakistan
| | | | - Tooba Shaikh
- Resident Physician in Internal Medicine Department, Dow University Hospital, Karachi, Pakistan
| | - Narmin Khan
- Resident Physician in Internal Medicine Department, Dow University Hospital, Karachi, Pakistan
| | | |
Collapse
|
|
50
|
Li X, Cai S, Zhong Z, Wang H, Wang L, You Y, Zhang M. Role of autoimmune hemolytic anemia as an initial indicator for chronic myeloid leukemia: A case report. Medicine (Baltimore) 2020; 99:e19256. [PMID: 32118733 PMCID: PMC7478578 DOI: 10.1097/md.0000000000019256] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2019] [Revised: 12/09/2019] [Accepted: 01/20/2020] [Indexed: 11/25/2022] Open
Abstract
INTRODUCTION We report here the case of a patient with chronic myeloid leukemia (CML) in the chronic phase who was diagnosed 1 year after receiving a diagnosis of autoimmune hemolytic anemia (AIHA). The objective was to assess if the CML patient progressed from AIHA and explore the underlying factors of the poor outcome after the achievement of molecular complete remission (MCR). PATIENT CONCERNS A patient with AIHA underwent splenectomy because of poor response to immune inhibitors. The spleen biopsy showed reactive hyperplasia. DIAGNOSIS The patient was diagnosed with CML because of over-expression of the BCR-ABL (P210) gene in the bone marrow (BM), 1 year after receiving the diagnosis of AIHA. INTERVENTIONS The splenectomy was performed as the patient was unresponsive to the standard treatments consisting of immunoglobulin and dexamethasone. The removed spleen was sent for pathological examination. After she was diagnosed with CML, she received imatinib treatment. OUTCOMES The spleen biopsy confirmed the translocation of 22q11/9q34. No BCR-ABL kinase domain mutation was detected and there was no expression of the WT1 or EVI1 genes. After splenectomy, the number of peripheral white blood cells was consistently higher than normal during the total therapy time for CML even though she showed MCR. Two years after CML was diagnosed, the patient died from severe infection. The BM gene array analysis displayed 3 types of chromosomal abnormalities: gain (14q32.33), uniparental disomy (UPD) Xp11.22-p11.1), and UPD Xp11.1-q13.1. LESSONS AIHA may be a clinical phase of CML progression in this patient. Both splenectomy and prolonged oral tyrosine kinase inhibitors may have contributed to the high risk of infection and her subsequent death. In addition, the gain of chromosome 14q32.33 may be related to her poor outcome.
Collapse
Affiliation(s)
- Xiang Li
- Institution of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan
| | - Sisi Cai
- Institution of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan
| | - Zhaodong Zhong
- Institution of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan
| | - Hongxiang Wang
- Institution of Hematology, The central hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Li Wang
- Institution of Hematology, The central hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yong You
- Institution of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan
| | - Min Zhang
- Institution of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan
| |
Collapse
|