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Kühne L, Knöbl P, Eller K, Thaler J, Sperr WR, Gleixner K, Osterholt T, Kaufeld J, Menne J, Buxhofer-Ausch V, Mühlfeld A, Seelow E, Schreiber A, Todorova P, Cukoski S, Jabs WJ, Özcan F, Gäckler A, Schönfelder K, Seibert FS, Westhoff T, Schwenger V, Eichenauer DA, Völker LA, Brinkkoetter PT. Management of immune thrombotic thrombocytopenic purpura without therapeutic plasma exchange. Blood 2024; 144:1486-1495. [PMID: 38838300 DOI: 10.1182/blood.2023023780] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Revised: 05/24/2024] [Accepted: 05/26/2024] [Indexed: 06/07/2024] Open
Abstract
ABSTRACT Immune thrombotic thrombocytopenic purpura (iTTP) is a rare, life-threatening autoimmune disorder caused by a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13 (ADAMTS13) deficiency. Caplacizumab, an anti-von Willebrand factor nanobody, is approved for iTTP treatment, reducing the need for therapeutic plasma exchange (TPE) and improving platelet count recovery and survival. We conducted a retrospective study on 42 acute iTTP cases in Austria and Germany, treated with a modified regimen aimed at avoiding TPE if platelet count increased after the first caplacizumab dose. Baseline characteristics and patient outcomes were compared with a control group of 59 patients with iTTP receiving frontline treatment with TPE, caplacizumab, and immunosuppression. The main outcome was the time to platelet count normalization. Secondary outcomes included clinical response, exacerbation, refractory iTTP, iTTP-related deaths, and the time to platelet count doubling. The median time to platelet count normalization was similar between the 2 cohorts (3 and 4 days; P = .31). There were no significant differences in clinical response, exacerbations, refractoriness, iTTP-related deaths, or time to platelet count doubling, reflecting the short-term treatment response. Four patients did not respond to the first caplacizumab dose, and TPE was subsequently initiated. Cytomegalovirus infection, HIV/hepatitis B virus coinfection, an ovarian teratoma with associated antiplatelet antibodies, and multiple platelet transfusions before the correct diagnosis may have impeded the immediate treatment response in these patients. In conclusion, caplacizumab and immunosuppression alone, without TPE, rapidly controlled thrombotic microangiopathy and achieved a sustained clinical response in iTTP. Our study provides a basis for TPE-free iTTP management in experienced centers via shared decision-making between patients and treating physicians.
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Affiliation(s)
- Lucas Kühne
- Department II of Internal Medicine and Center for Molecular Medicine Cologne, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Paul Knöbl
- Division of Hematology and Hemostasis, Department of Medicine 1, Medical University of Vienna, Vienna, Austria
| | - Kathrin Eller
- Division of Nephrology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
| | - Johannes Thaler
- Division of Hematology and Hemostasis, Department of Medicine 1, Medical University of Vienna, Vienna, Austria
| | - Wolfgang R Sperr
- Division of Hematology and Hemostasis, Department of Medicine 1, Medical University of Vienna, Vienna, Austria
| | - Karoline Gleixner
- Division of Hematology and Hemostasis, Department of Medicine 1, Medical University of Vienna, Vienna, Austria
| | - Thomas Osterholt
- Department II of Internal Medicine and Center for Molecular Medicine Cologne, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Jessica Kaufeld
- Department of Nephrology and Hypertension, Medical School Hannover, Hannover, Germany
| | - Jan Menne
- KRH Klinikum Mitte-Location Siloah, Hannover, Germany
| | - Veronika Buxhofer-Ausch
- Department of Internal Medicine I with Hematology, Stem Cell Transplantation, Hemostaseology and Medical Oncology, Ordensklinikum Linz Elisabethinnen, Linz, Austria
- Medical Faculty, Johannes Kepler University Linz, Linz, Austria
| | - Anja Mühlfeld
- Division of Nephrology, Department of Medicine, Uniklinik RWTH Aachen, Aachen, Germany
| | - Evelyn Seelow
- Department of Nephrology and Intensive Care Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Adrian Schreiber
- Department of Nephrology and Intensive Care Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Polina Todorova
- Department II of Internal Medicine and Center for Molecular Medicine Cologne, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Sadrija Cukoski
- Department II of Internal Medicine and Center for Molecular Medicine Cologne, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Wolfram J Jabs
- Department of Nephrology, Vivantes Klinikum im Friedrichshain, Berlin, Germany
| | - Fedai Özcan
- Klinik für Nephrologie, Klinikum Dortmund, Universität Witten-Herdecke, Campus Dortmund, Dortmund, Germany
| | - Anja Gäckler
- Department of Nephrology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Kristina Schönfelder
- Department of Nephrology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Felix S Seibert
- Medical Department 1, Marien Hospital Herne-Universitätsklinikum der Ruhr-Universität Bochum, Herne, Germany
| | - Timm Westhoff
- Medical Department 1, Marien Hospital Herne-Universitätsklinikum der Ruhr-Universität Bochum, Herne, Germany
| | - Vedat Schwenger
- Department of Nephrology, Klinikum Stuttgart, Stuttgart, Germany
| | - Dennis A Eichenauer
- Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Dusseldorf, University of Cologne, Cologne, Germany
| | - Linus A Völker
- Department II of Internal Medicine and Center for Molecular Medicine Cologne, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
- Cluster of Excellence Cellular Stress Response in Aging-associated Diseases (CECAD), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Paul T Brinkkoetter
- Department II of Internal Medicine and Center for Molecular Medicine Cologne, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
- Cluster of Excellence Cellular Stress Response in Aging-associated Diseases (CECAD), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
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Mishra AP, Sahoo SK, Kanungo G, Sahoo LK, Mishra S, Mishra C. Therapeutic Plasma Exchange in Neurological Conditions: An Observation from the Eastern Part of India. Ann Afr Med 2024; 23:649-655. [PMID: 39279168 PMCID: PMC11556484 DOI: 10.4103/aam.aam_65_24] [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: 04/18/2024] [Accepted: 06/18/2024] [Indexed: 09/18/2024] Open
Abstract
INTRODUCTION Therapeutic plasma exchange (TPE) is an extracorporeal process of separation of plasma from the cellular components of blood and its replacement with analogous fluids. This process is effective in treatment of disease conditions from dysregulation of the humoral immune system by removal of various humoral pathogenic substances like antibodies, immune complexes, monoclonal proteins, toxins or cytokine(s) and/or the replenishment of a specific plasma factor. AIM AND OBJECTIVE To evaluate major indications of therapeutic plasma exchange in neurological disorders. To identify major complications associated and factors associated with premature cessation of the therapeutic plasma exchange cycle. Materials and Methods: This is a hospital based retrospective study conducted by analyzing medical records of patients, who had undergone therapeutic plasma exchange (TPE) for various neurological disorders at IMS & SUM hospital. Medical records total 118 patients who underwent TPE from January 2016 to December 2021 were analyzed. The demographic data, blood group pattern and indications for TPE were enumerated from the records. Various complications of TPE and reasons for incomplete TPE cycle were documented and analyzed. RESULTS A total of 508 TPE procedures were performed on 118 patients. In this study 61 patients were male and 57 patients were female. O-blood group was commonest blood group among the patients. GBS is the commonest indication of TPE. 57.6 % of patients could complete all sessions TPE cycle. Blockage of vascular access is the commonest cause of incomplete TPE session. Cramps (33%) and mild transient hypotension (27.1%0 were the commonest complications observed. CONCLUSION TPE is a safe and effective treatment option for various immune-mediated neurological disorders and should be considered in managing these disorders.
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Affiliation(s)
- Ajit Prasad Mishra
- Department of Neurology, IMS and SUM Hospital, Bhubaneswar, Odisha, India
| | | | - Girijanandini Kanungo
- Department of Transfusion Medicine, IMS and SUM Hospital, Bhubaneswar, Odisha, India
| | - Lulup Kumar Sahoo
- Department of Neurology, IMS and SUM Hospital, Bhubaneswar, Odisha, India
| | - Shubhankar Mishra
- Department of Neurology, IMS and SUM Hospital, Bhubaneswar, Odisha, India
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Demeter F, Bihari G, Vadicsku D, Sinkovits G, Kajdácsi E, Horváth L, Réti M, Müller V, Iványi Z, Gál J, Gopcsa L, Reményi P, Szathmáry B, Lakatos B, Szlávik J, Bobek I, Prohászka ZZ, Förhécz Z, Masszi T, Vályi-Nagy I, Prohászka Z, Cervenak L. Anti-Inflammatory Cytokine Profiles in Thrombotic Thrombocytopenic Purpura-Differences Compared to COVID-19. Int J Mol Sci 2024; 25:10007. [PMID: 39337495 PMCID: PMC11432022 DOI: 10.3390/ijms251810007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2024] [Revised: 09/11/2024] [Accepted: 09/13/2024] [Indexed: 09/30/2024] Open
Abstract
Thromboinflammation/immunothrombosis plays a role in several diseases including thrombotic thrombocytopenic purpura (TTP) and COVID-19. Unlike the extensive research that has been conducted on COVID-19 cytokine storms, the baseline and acute phase cytokine profiles of TTP are poorly characterized. Moreover, we compared the cytokine profiles of TTP and COVID-19 to identify the disease-specific/general characteristics of thromboinflammation/immunothrombosis. Plasma concentrations of 33 soluble mediators (SMs: cytokines, chemokines, soluble receptors, and growth factors) were measured by multiplex bead-based LEGENDplex™ immunoassay from 32 COVID-19 patients (32 non-vaccinated patients in three severity groups), 32 TTP patients (remission/acute phase pairs of 16 patients), and 15 control samples. Mainly, the levels of innate immunity-related SMs changed in both diseases. In TTP, ten SMs decreased in both remission and acute phases compared to the control, one decreased, and two increased only in the acute phase compared to remission, indicating mostly anti-inflammatory changes. In COVID-19, ten pro-inflammatory SMs increased, whereas one decreased with increasing severity compared to the control. In severe COVID-19, sixteen SMs exceeded acute TTP levels, with only one higher in TTP. PCA identified CXCL10, IL-1RA, and VEGF as the main discriminators among their cytokine profiles. The innate immune response is altered in both diseases. The cytokine profile of TTP suggests a distinct pathomechanism from COVID-19 and supports referring to TTP as thromboinflammatory rather than immunothrombotic, emphasizing thrombosis over inflammation as the driving force of the acute phase.
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Affiliation(s)
- Flóra Demeter
- Department of Internal Medicine and Haematology, Semmelweis University, 1088 Budapest, Hungary
| | - György Bihari
- Department of Internal Medicine and Haematology, Semmelweis University, 1088 Budapest, Hungary
| | - Dorina Vadicsku
- Department of Internal Medicine and Haematology, Semmelweis University, 1088 Budapest, Hungary
| | - György Sinkovits
- Department of Internal Medicine and Haematology, Semmelweis University, 1088 Budapest, Hungary
| | - Erika Kajdácsi
- Department of Internal Medicine and Haematology, Semmelweis University, 1088 Budapest, Hungary
- Research Group for Immunology and Hematology, Semmelweis University—HUN-REN-SU (Office for Supported Research Groups), 1085 Budapest, Hungary
| | - Laura Horváth
- Department of Internal Medicine and Haematology, Semmelweis University, 1088 Budapest, Hungary
| | - Marienn Réti
- Department of Haematology and Stem Cell Transplantation, Central Hospital of Southern Pest National Institute of Haematology and Infectious Diseases, 1097 Budapest, Hungary
| | - Veronika Müller
- Department of Pulmonology, Semmelweis University, 1083 Budapest, Hungary
| | - Zsolt Iványi
- Department of Anaesthesiology and Intensive Therapy, Semmelweis University, 1085 Budapest, Hungary
| | - János Gál
- Department of Anaesthesiology and Intensive Therapy, Semmelweis University, 1085 Budapest, Hungary
| | - László Gopcsa
- Department of Haematology and Stem Cell Transplantation, Central Hospital of Southern Pest National Institute of Haematology and Infectious Diseases, 1097 Budapest, Hungary
| | - Péter Reményi
- Department of Haematology and Stem Cell Transplantation, Central Hospital of Southern Pest National Institute of Haematology and Infectious Diseases, 1097 Budapest, Hungary
| | - Beáta Szathmáry
- Department of Infectology, Central Hospital of Southern Pest, National Institute of Haematology and Infectious Diseases, 1097 Budapest, Hungary
| | - Botond Lakatos
- Department of Infectology, Central Hospital of Southern Pest, National Institute of Haematology and Infectious Diseases, 1097 Budapest, Hungary
| | - János Szlávik
- Department of Infectology, Central Hospital of Southern Pest, National Institute of Haematology and Infectious Diseases, 1097 Budapest, Hungary
| | - Ilona Bobek
- Department of Anaesthesiology and Intensive Therapy, Central Hospital of Southern Pest, National Institute of Haematology and Infectious Diseases, 1097 Budapest, Hungary
| | - Zita Z. Prohászka
- Department of Internal Medicine and Haematology, Semmelweis University, 1088 Budapest, Hungary
| | - Zsolt Förhécz
- Department of Internal Medicine and Haematology, Semmelweis University, 1088 Budapest, Hungary
| | - Tamás Masszi
- Department of Internal Medicine and Haematology, Semmelweis University, 1088 Budapest, Hungary
| | - István Vályi-Nagy
- Department of Haematology and Stem Cell Transplantation, Central Hospital of Southern Pest National Institute of Haematology and Infectious Diseases, 1097 Budapest, Hungary
| | - Zoltán Prohászka
- Department of Internal Medicine and Haematology, Semmelweis University, 1088 Budapest, Hungary
- Research Group for Immunology and Hematology, Semmelweis University—HUN-REN-SU (Office for Supported Research Groups), 1085 Budapest, Hungary
| | - László Cervenak
- Department of Internal Medicine and Haematology, Semmelweis University, 1088 Budapest, Hungary
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Mina-Osorio P, Tran MH, Habib AA. Therapeutic Plasma Exchange Versus FcRn Inhibition in Autoimmune Disease. Transfus Med Rev 2024; 38:150767. [PMID: 37867088 DOI: 10.1016/j.tmrv.2023.150767] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2023] [Revised: 08/31/2023] [Accepted: 09/01/2023] [Indexed: 10/24/2023]
Abstract
Therapeutic plasma exchange (TPE or PLEX) is used in a broad range of autoimmune diseases, with the goal of removing autoantibodies from the circulation. A newer approach for the selective removal of immunoglobulin G (IgG) antibodies is the use of therapeutic molecules targeting the neonatal Fc receptor (FcRn). FcRn regulates IgG recycling, and its inhibition results in a marked decrease in circulating autoantibodies of the IgG subtype. The difference between FcRn inhibition and PLEX is often questioned. With anti-FcRn monoclonal antibodies (mAbs) and fragments only recently entering this space, limited data are available regarding long-term efficacy and safety. However, the biology of FcRn is well understood, and mounting evidence regarding the efficacy, safety, and potential differences among compounds in development is available, allowing us to compare against nonselective plasma protein depletion methods such as PLEX. FcRn inhibitors may have distinct advantages and disadvantages over PLEX in certain scenarios. Use of PLEX is preferred over FcRn inhibition where removal of antibodies other than IgG or when concomitant repletion of missing plasma proteins is needed for therapeutic benefit. Also, FcRn targeting has not yet been studied for use in acute flares or crisis states of IgG-mediated diseases. Compared with PLEX, FcRn inhibition is associated with less invasive access requirements, more specific removal of IgG versus other immunoglobulins without a broad impact on circulating proteins, and any impacts on other therapeutic drug levels are restricted to other mAbs. In addition, the degree of IgG reduction is similar with FcRn inhibitors compared with that afforded by PLEX. Here we describe the scientific literature regarding the use of PLEX and FcRn inhibitors in autoimmune diseases and provide an expert discussion around the potential benefits of these options in varying clinical conditions and scenarios.
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Affiliation(s)
| | - Minh-Ha Tran
- Department of Pathology, School of Medicine, University of California, Irvine, Irvine, CA, USA
| | - Ali A Habib
- Department of Neurology, School of Medicine, University of California, Irvine, Irvine, CA, USA
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Katyal N, Katsumoto TR, Ramachandran KJ, Yunce M, Muppidi S. Plasma Exchange in Patients With Myositis due to Immune Checkpoint Inhibitor Therapy. J Clin Neuromuscul Dis 2023; 25:89-93. [PMID: 37962196 PMCID: PMC10645099 DOI: 10.1097/cnd.0000000000000457] [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] [Indexed: 11/15/2023]
Abstract
ABSTRACT Immune checkpoint inhibitors used to treat malignancies may lead to various immune-related adverse events (irAEs) including conditions such as myositis and myasthenia gravis (MG). Here, we describe 2 cases of myositis treated effectively with therapeutic plasma exchange (PLEX). A 64-year-old man with thymic cancer developed leg weakness and dyspnea 1 month after the second dose of nivolumab with moderate weakness in proximal and distal muscles, with elevated creatine kinase levels. Another 77-year-old man with Stage IIIB squamous cell carcinoma of the lung developed progressive proximal muscle weakness and became nonambulatory after cycle 2 of durvalumab with persistently high creatine kinase levels despite prednisone treatment. Electrophysiology revealed irritative myopathy without evidence of neuromuscular junction dysfunction and MG antibody testing was nonrevealing. With PLEX, both patients noticed rapid improvement in strength. PLEX in conjunction with other immunosuppressive agents can result in rapid improvement in irAE-myositis even in patients without associated MG.
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Affiliation(s)
- Nakul Katyal
- Department of Neurology, Stanford University School of Medicine, Stanford, CA
| | - Tamiko R. Katsumoto
- Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA
| | - Kavitha J. Ramachandran
- Division of Oncology, Department of Medicine, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA; and
| | - Muharrem Yunce
- Department of Pathology, Stanford University School of Medicine, Stanford, CA
| | - Srikanth Muppidi
- Department of Neurology, Stanford University School of Medicine, Stanford, CA
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Zhang F, Zhang B, Fan R, Cheng T, Hu X, Liu Y, Cen X, Bu Y, Cao J, Chen F, Chen J. Clinical efficacy of plasma exchange in systemic lupus erythematosus during pregnancy. Immun Inflamm Dis 2023; 11:e1041. [PMID: 37904711 PMCID: PMC10566447 DOI: 10.1002/iid3.1041] [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: 04/12/2023] [Revised: 09/11/2023] [Accepted: 09/20/2023] [Indexed: 11/01/2023] Open
Abstract
OBJECTIVE To investigate the clinical efficacy of plasma exchange (PE) with or without prednisone and hydroxychloroquine (HCQ) for the treatment of systemic lupus erythematosus (SLE) during pregnancy. METHODS The clinical characteristics of 14 pregnant women with SLE admitted to our hospital were retrospectively analyzed, including 7 only treated with prednisone and HCQ (non-PE group) as well as 7 combined PE (PE group). The delivery situations of 14 patients were recorded. Data like erythrocyte sedimentation rate (ESR), urine protein, platelet count, and SLEDAI scores were compared between two groups before treatment and 3, 6, and 12 months after delivery. RESULTS Three patients in the non-PE group ended in miscarriage while all patients in the PE group were delivered successfully. Eleven successfully delivered fetuses in the two groups were healthy, and the Apgar scores were over 8. The ESR of the PE group was significantly lower than that of the non-PE group at 6 and 12 months after delivery, while there was no statistical difference in ESR between the two groups before treatment and 3 months after delivery. The ESR and urine protein were significantly higher in the non-PE group at months 3, 6, and 12 postpartum. There was a significant decrease in disease activity postpartum in the PE group compared to predelivery disease activity. The change in platelet counts between the two groups significantly increased over time in the PE group, while SLEDAI scores decreased. CONCLUSIONS The combination of PE and oral prednisone and HCQ is possibly a more effective treatment than oral prednisone and HCQ alone for patients with active SLE during pregnancy. This treatment option reduces pregnancy loss and promotes the patients' postpartum condition to a certain extent.
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Affiliation(s)
- Fen Zhang
- Department of RheumatologyThe Second Hospital of Shanxi Medical UniversityTaiyuan CityShanxi ProvinceChina
| | - Bing‐Ying Zhang
- Department of Respiratory MedicineXinzhou People's HospitalXinzhou CityShanxi ProvinceChina
| | - Ru Fan
- Department of RheumatologyThe Second Hospital of Shanxi Medical UniversityTaiyuan CityShanxi ProvinceChina
| | - Ting Cheng
- Department of RheumatologyThe Second Hospital of Shanxi Medical UniversityTaiyuan CityShanxi ProvinceChina
| | - Xiao‐Rong Hu
- Department of RheumatologyThe Second Hospital of Shanxi Medical UniversityTaiyuan CityShanxi ProvinceChina
| | - Yu‐Qing Liu
- Department of RheumatologyThe Second Hospital of Shanxi Medical UniversityTaiyuan CityShanxi ProvinceChina
| | - Xing Cen
- Department of RheumatologyThe Second Hospital of Shanxi Medical UniversityTaiyuan CityShanxi ProvinceChina
| | - Yu‐Jie Bu
- Department of RheumatologyThe Second Hospital of Shanxi Medical UniversityTaiyuan CityShanxi ProvinceChina
| | - Jian‐Ping Cao
- Department of RheumatologyThe Second Hospital of Shanxi Medical UniversityTaiyuan CityShanxi ProvinceChina
| | - Feng‐Wu Chen
- State Key Laboratory of Multiphase Flow in Power EngineeringXi'an Jiaotong UniversityXi'anShanxi ProvinceChina
| | - Jun‐Wei Chen
- Department of RheumatologyThe Second Hospital of Shanxi Medical UniversityTaiyuan CityShanxi ProvinceChina
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David S, Russell L, Castro P, van de Louw A, Zafrani L, Pirani T, Nielsen ND, Mariotte E, Ferreyro BL, Kielstein JT, Montini L, Brignier AC, Kochanek M, Cid J, Robba C, Martin-Loeches I, Ostermann M, Juffermans NP. Research priorities for therapeutic plasma exchange in critically ill patients. Intensive Care Med Exp 2023; 11:26. [PMID: 37150798 PMCID: PMC10164453 DOI: 10.1186/s40635-023-00510-w] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Accepted: 04/10/2023] [Indexed: 05/09/2023] Open
Abstract
Therapeutic plasma exchange (TPE) is a therapeutic intervention that separates plasma from blood cells to remove pathological factors or to replenish deficient factors. The use of TPE is increasing over the last decades. However, despite a good theoretical rationale and biological plausibility for TPE as a therapy for numerous diseases or syndromes associated with critical illness, TPE in the intensive care unit (ICU) setting has not been studied extensively. A group of eighteen experts around the globe from different clinical backgrounds used a modified Delphi method to phrase key research questions related to "TPE in the critically ill patient". These questions focused on: (1) the pathophysiological role of the removal and replacement process, (2) optimal timing of treatment, (3) dosing and treatment regimes, (4) risk-benefit assumptions and (5) novel indications in need of exploration. For all five topics, the current understanding as well as gaps in knowledge and future directions were assessed. The content should stimulate future research in the field and novel clinical applications.
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Affiliation(s)
- Sascha David
- Institute of Intensive Care Medicine, University Hospital Zurich, Zurich, Switzerland.
- Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany.
| | - Lene Russell
- Department of Intensive Care, Copenhagen University Hospital Gentofte, Copenhagen, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Pedro Castro
- Medical Intensive Care Unit, Hospital Clínic of Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Andry van de Louw
- Medical Intensive Care Unit, Penn State Health Hershey Medical Center, Hershey, PA, USA
| | - Lara Zafrani
- Medical Intensive Care Unit, Saint-Louis Hospital, AP-HP, University of Paris Cité, Paris, France
| | - Tasneem Pirani
- King's College Hospital, General and Liver Intensive Care, London, UK
| | - Nathan D Nielsen
- Division of Pulmonary, Critical Care and Sleep Medicine & Section of Transfusion Medicine and Therapeutic Pathology, University of New Mexico School of Medicine, Albuquerque, USA
| | - Eric Mariotte
- Medical Intensive Care Unit, Saint-Louis Hospital, AP-HP, University of Paris Cité, Paris, France
| | - Bruno L Ferreyro
- Department of Medicine, Sinai Health System and University Health Network, Toronto, Canada
| | - Jan T Kielstein
- Medical Clinic V, Nephrology, Rheumatology, Blood Purification, Academic Teaching Hospital Braunschweig, Brunswick, Germany
| | - Luca Montini
- Department of Intensive Care Medicine and Anesthesiology, "Fondazione Policlinico Universitario Agostino Gemelli IRCCS" Università Cattolica del Sacro Cuore, Rome, Italy
| | - Anne C Brignier
- Apheresis Unit, Saint-Louis Hospital, AP-HP, University of Paris Cite, Paris, France
| | - Matthias Kochanek
- Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO), University of Cologne, Cologne, Germany
| | - Joan Cid
- Apheresis and Cellular Therapy Unit, Department of Hemotherapy and Hemostasis, ICMHO, Clínic Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Chiara Robba
- IRCCS per Oncologia e Neuroscienze, Genoa, Italy
- Dipartimento di Scienze Chirurgiche Diagnostiche ed Integrate, Universita' di Genova, Genoa, Italy
| | - Ignacio Martin-Loeches
- Department of Intensive Care Medicine, Multidisciplinary Intensive Care Research Organization (MICRO), St. James's Hospital, Dublin, D08 NHY1, Ireland
- Department of Clinical Medicine, School of Medicine, Trinity College Dublin, Dublin, D02 PN91, Ireland
- Institut D'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Hospital Clinic, Universidad de Barcelona, Ciberes, Barcelona, Spain
| | - Marlies Ostermann
- Department of Intensive Care, Guy's & St Thomas' Hospital, King's College London, London, UK
| | - Nicole P Juffermans
- Department of Intensive Care, OLVG Hospital, Amsterdam, The Netherlands
- Laboratory of Translational Intensive Care, Erasmus MC, Rotterdam, The Netherlands
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Foettinger F, Pilz G, Wipfler P, Harrer A, Kern JM, Trinka E, Moser T. Immunomodulatory Aspects of Therapeutic Plasma Exchange in Neurological Disorders—A Pilot Study. Int J Mol Sci 2023; 24:ijms24076552. [PMID: 37047524 PMCID: PMC10095570 DOI: 10.3390/ijms24076552] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Revised: 03/26/2023] [Accepted: 03/29/2023] [Indexed: 04/03/2023] Open
Abstract
Therapeutic plasma exchange (TPE) is used for drug-resistant neuroimmunological disorders, but its mechanism of action remains poorly understood. We therefore prospectively explored changes in soluble, humoral, and cellular immune components associated with TPE. We included ten patients with neurological autoimmune disorders that underwent TPE and assessed a panel of clinically relevant pathogen-specific antibodies, total serum immunoglobulin (Ig) levels, interleukin-6 (IL-6, pg/mL), C-reactive protein (CRP, mg/dL), procalcitonin (PCT, µg/L) and major lymphocyte subpopulations (cells/µL). Blood was collected prior to TPE (pre-TPE, baseline), immediately after TPE (post-TPE), as well as five weeks (follow-up1) and 130 days (follow-up2) following TPE. Pathogen-specific antibody levels were reduced by −86% (p < 0.05) post-TPE and recovered to 55% (follow-up1) and 101% (follow-up2). Ig subclasses were reduced by −70–89% (p < 0.0001) post-TPE with subsequent complete (IgM/IgA) and incomplete (IgG) recovery throughout the follow-ups. Mean IL-6 and CRP concentrations increased by a factor of 3–4 at post-TPE (p > 0.05) while PCT remained unaffected. We found no alterations in B- and T-cell populations. No adverse events related to TPE occurred. TPE induced a profound but transient reduction in circulating antibodies, while the investigated soluble immune components were not washed out. Future studies should explore the effects of TPE on particular cytokines and assess inflammatory lymphocyte lineages to illuminate the mode of action of TPE beyond autoantibody removal.
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Thrombotic thrombocytopenic purpura (TTP) in Human immunodeficiency virus (HIV) infected patients: New twists on an old disease. AIDS 2022; 36:1345-1354. [PMID: 35608117 DOI: 10.1097/qad.0000000000003257] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVE Investigate the presence of inflammation, endothelial dysfunction and complement activation in patients with HIV-associated thrombotic thrombocytopenic purpura (HIV-TTP) to support the hypothesis that these processes probably contribute to the development of this thrombotic microangiopathy. DESIGN A prospective, investigational cohort study of 35 consecutive patients diagnosed with HIV-associated TTP presenting to three academic, tertiary care hospitals in Johannesburg, South Africa over 2 years. METHODS The patients with HIV-TTP received therapeutic plasma therapy and supportive treatment. Demographic data, the results of routine investigations and patient outcomes were recorded. Peripheral blood samples were collected prior to and on completion of plasma therapy and the following additional parameters were assessed at both time points: activity of the von Willebrand factor (VWF) cleaving protease, a-disintegrin-and-metalloproteinase-with-thrombospondin-motifs 13 (ADAMTS-13) and the presence of ADAMTS-13 autoantibodies, levels of pro-inflammatory cytokines, interleukin-6 and tumour necrosis factor-alpha, and two endothelial cell adhesion molecules. Complement activation was assessed by sequential measurement of C3 and C4 as well as levels of the complement inhibitor, factor H. RESULTS The inflammatory and endothelial activation markers were significantly (P < 0.001) elevated in the cohort of patients prior to plasma therapy compared with levels on discharge. Complement was activated and normalized with therapy. The ADAMTS-13 levels were reduced with significant auto-antibodies to this protease at presentation. CONCLUSION Inflammation in HIV mediates endothelial damage and complement activation. This study proposes that these processes are probably contributory to the development of HIV-TTP, which can therefore be characterized in part as a complementopathy, resembling TTP-like syndrome.
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Ouyang S, Yin W, Zeng Q, Li B, Zhang J, Duan W, Li Y, Liang Y, Wang J, Tan H, Yang H. Lymphoplasma Exchange Improves Myasthenia Gravis Exacerbations: A Retrospective Study in a Chinese Center. Front Immunol 2022; 13:757841. [PMID: 35514988 PMCID: PMC9063637 DOI: 10.3389/fimmu.2022.757841] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Accepted: 03/16/2022] [Indexed: 12/04/2022] Open
Abstract
Background Lymphoplasma exchange (LPE), a technique combining plasma exchange with leukapheresis, is emerging as promising treatment for autoimmune diseases. Data on the efficacy and safety of LPE in myasthenia gravis (MG) therapy are scarce. In this study, we aimed to comprehensively review the clinical efficacy, safety, and immunological characteristics of LPE therapy in MG patients. Study Design and Methods A Chinese cohort of 276 generalized MG patients in state of exacerbation, including impeding crisis, myasthenia crisis, and preparation for thoracic exsection between January 2014 and December 2020, were evaluated in this study. Results A total of 276 patients with a median age of 45.5 ± 16.7 years underwent a total of 635 LPE sessions. Clinical scales of Quantitative Myasthenia Gravis (QMG) scores, Myasthenia Gravis Specific Manual Muscle Testing (MMT) scores, activities of daily living (ADL) scores, and quality of life (QOL) scores were improved during 4 weeks’ follow-up. Adverse effects occurred in 20 out of 276 patients, with 14 patients having one adverse event each. Independent predictive factors for good response to LPE therapy were symptom onset before LPE therapy ≤3 days and age on LPE therapy <50 years of age. LPE decreased the serum levels of antibodies, immunoglobulins, and complements 4 weeks after the first replacement, with decreased levels of interleukin (IL)-17A and interferon (IFN)-γ and increased level of IL-10. Conclusion LPE is an effective treatment for MG patients in state of exacerbation and preparation for thymectomy. Early use of LPE on early-onset MG may have good therapeutic effects. The potential mechanism for LPE is the polarization of cytokines from IL-17A, IFN-γ, into IL-10.
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Affiliation(s)
- Song Ouyang
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, China
- Medical Center of Neurology, The First Hospital of Changsha City, South China University, Changsha, China
| | - Weifan Yin
- The Second Xiangya Hospital, Central South University, Changsha, China
- *Correspondence: Huan Yang, ; Weifan Yin,
| | - Qiuming Zeng
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, China
| | - Bijuan Li
- Department of Blood Transfusion, Xiangya Hospital, Central South University, Changsha, China
| | - Jian Zhang
- Department of Pathology, University of Iowa, Iowa City, IA, United States
| | - Weiwei Duan
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, China
| | - Yi Li
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, China
| | - Yong Liang
- Medical Center of Neurology, The First Hospital of Changsha City, South China University, Changsha, China
| | - Jiaqi Wang
- Medical Center of Neurology, The First Hospital of Changsha City, South China University, Changsha, China
| | - Hong Tan
- Medical Center of Neurology, The First Hospital of Changsha City, South China University, Changsha, China
| | - Huan Yang
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, China
- *Correspondence: Huan Yang, ; Weifan Yin,
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Wu CL, Chao CH, Lin SW, Chien YY, Huang WY, Weng WC, Su FC, Wei YC. Case Report: Plasma Biomarkers Reflect Immune Mechanisms of Guillain-Barré Syndrome. Front Neurol 2021; 12:720794. [PMID: 34539561 PMCID: PMC8446349 DOI: 10.3389/fneur.2021.720794] [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: 06/05/2021] [Accepted: 08/02/2021] [Indexed: 11/13/2022] Open
Abstract
This case series reported a group of patients with Guillain-Barré syndrome (GBS) and their plasma cytokine changes before and after immunotherapy. We aimed to understand GBS's pathogenesis and pathophysiology through observing the interval differences of the representative cytokines, which were the thymus and activation regulated chemokine (TARC) for T-cell chemotaxis, CD40 ligand (CD40L) for cosimulation of B and T cells, activated complement component C5/C5a, and brain-derived neurotrophic factor (BDNF) for survival and regenerative responses to nerve injuries. The fluorescence magnetic bead-based multiplexing immunoassay simultaneously quantified the five cytokines in a single sample. From June 2018 to December 2019, we enrolled five GBS patients who had completed before-after blood cytokine measurements. One patient was diagnosed with paraneoplastic GBS and excluded from the following cytokine analysis. The BDNF level decreased consistently in all the patients and made it a potential biomarker for the acute stage of GBS. Interval changes of the other four cytokines were relatively inconsistent and possibly related to interindividual differences in the immune response to GBS triggers, types of GBS variants, and classes of antiganglioside antibodies. In summary, utilizing the multiplexing immunoassay helps in understanding the complex immune mechanisms of GBS and the variation of immune responses in GBS subtypes; this method is feasible for identifying potential biomarkers of GBS.
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Affiliation(s)
- Chia-Lun Wu
- Department of Neurology, Chang Gung Memorial Hospital, Keelung City, Taiwan
- School of Medicine, Chang Gung University, Taoyuan City, Taiwan
| | - Chung-Hao Chao
- Department of Neurology, Chang Gung Memorial Hospital, Keelung City, Taiwan
| | - Shun-Wen Lin
- Department of Neurology, Chang Gung Memorial Hospital, Keelung City, Taiwan
| | - Yu-Yi Chien
- Department of Neurology, Chang Gung Memorial Hospital, Keelung City, Taiwan
- School of Medicine, Chang Gung University, Taoyuan City, Taiwan
| | - Wen-Yi Huang
- Department of Neurology, Chang Gung Memorial Hospital, Keelung City, Taiwan
- School of Medicine, Chang Gung University, Taoyuan City, Taiwan
| | - Wei-Chieh Weng
- Department of Neurology, Chang Gung Memorial Hospital, Keelung City, Taiwan
- School of Medicine, Chang Gung University, Taoyuan City, Taiwan
| | - Feng-Chieh Su
- Department of Neurology, Chang Gung Memorial Hospital, Keelung City, Taiwan
| | - Yi-Chia Wei
- Department of Neurology, Chang Gung Memorial Hospital, Keelung City, Taiwan
- Community Medicine Research Center, Chang Gung Memorial Hospital, Keelung City, Taiwan
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12
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Kalampokini S, Artemiadis A, Zis P, Hadjihannas L, Parpas G, Kyrri A, Hadjigeorgiou GM. Osmotic demyelination syndrome improving after immune-modulating treatment: Case report and literature review. Clin Neurol Neurosurg 2021; 208:106811. [PMID: 34358802 DOI: 10.1016/j.clineuro.2021.106811] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 06/30/2021] [Accepted: 07/01/2021] [Indexed: 10/20/2022]
Abstract
BACKGROUND Osmotic demyelination syndrome (ODS), which embraces central pontine and extrapontine myelinolysis, is an uncommon neurological disorder that occurs due to plasma osmotic changes. CASE PRESENTATION We present the case of a 55-year-old man, who presented with severe hyponatremia due to repeated vomiting, antidepressant treatment and consumption of large amounts of water. Fifteen days after sodium correction, the patient showed fluctuation of vigilance, dysarthria and dysphagia, tremor, cogwheel rigidity, bilateral facial palsy, ophthalmoplegia and tetraparesis. A brain MRI scan revealed extrapontine and later on pontine myelinolysis. He received intravenous steroids and subsequently immunoglobulin. His status began to improve gradually after completion of immunoglobulin and at three month-follow-up had no neurological deficit. LITERATURE REVIEW A comprehensive literature search of all reported ODS cases that received immunoglobulin, steroids or plasmapheresis was conducted in the electronic databases PubMed and Web of science. CONCLUSIONS Improvement was seen in most cases that received immunoglobulin either during treatment or in the first days after treatment. With regard to steroids, although most cases reported improvement in the following months their effect on the outcome is unclear. Most cases treated with plasmapheresis reported favorable outcome at variable follow-up time. Immunoglobulin and steroids have immunomodulatory effects, which could contribute to promotion of myelin repair in ODS. Plasmapheresis has effects on the immune system beyond removing myelinotoxins from the circulation. More evidence is required to support their use in ODS. However, in view of the disease severity, these therapeutic choices should be considered in the clinical management of ODS.
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Affiliation(s)
- Stefania Kalampokini
- Medical School, University of Cyprus, Nicosia, Cyprus; Department of Neurology, Nicosia General Hospital, Nicosia, Cyprus.
| | - Artemios Artemiadis
- Medical School, University of Cyprus, Nicosia, Cyprus; Department of Neurology, Nicosia General Hospital, Nicosia, Cyprus
| | - Panagiotis Zis
- Medical School, University of Cyprus, Nicosia, Cyprus; Department of Neurology, Nicosia General Hospital, Nicosia, Cyprus
| | - Linos Hadjihannas
- Department of Internal medicine, Nicosia General Hospital, Nicosia, Cyprus
| | - Giorgos Parpas
- Department of Internal medicine, Nicosia General Hospital, Nicosia, Cyprus
| | - Artemis Kyrri
- Department of Internal medicine, Nicosia General Hospital, Nicosia, Cyprus
| | - Georgios M Hadjigeorgiou
- Medical School, University of Cyprus, Nicosia, Cyprus; Department of Neurology, Nicosia General Hospital, Nicosia, Cyprus
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May FNJ, Rees MT, Griffin S, Fildes JE. Understanding immunological response to desensitisation strategies in highly sensitised potential kidney transplant patients. Transplant Rev (Orlando) 2021; 35:100596. [DOI: 10.1016/j.trre.2021.100596] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2020] [Revised: 01/06/2021] [Accepted: 01/08/2021] [Indexed: 01/18/2023]
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Rodríguez-Pintó I, Lozano M, Cid J, Espinosa G, Cervera R. Plasma exchange in catastrophic antiphospholipid syndrome. Presse Med 2019; 48:347-353. [PMID: 31694791 DOI: 10.1016/j.lpm.2019.10.003] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Plasma exchange is a well-established therapeutic procedure commonly used in many autoimmune disorders. The beneficial effects of plasma exchange are thought to occur through the elimination of pathogenic mediators found in plasma, including autoantibodies, complement components, and cytokines. The catastrophic antiphsopholipid syndrome (CAPS) is a life-threatening variant of the antiphospholipid syndrome (APS) where several thrombosis take place in a short period of time in patients with circulating antiphospholipid antibodies. The triple therapy with anticoagulation, corticosteroids and plasma exchange or intravenous immunoglobulins has been proposed in CAPS. CAPS is a rare disease precluding the conduction of formal clinical trials. However, the observation of a better clinical course of patients who received this treatment supports their use. Plasma exchange has become an established therapeutic procedure in CAPS but there are no studies regarding the better approach and thus its use relies on the experience of the physicians in charge. The current article aims to review potential mechanisms of action of plasma exchange and the technical aspects of this procedure and will focus on its current role in CAPS, the experience published in treating this condition and the treatment protocol that we use in our institution.
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Affiliation(s)
- Ignasi Rodríguez-Pintó
- Hospital Universitari Mutua de Terrassa, Systemic Autoimmune Disease Unit, Barcelona, Catalonia, Spain
| | - Miquel Lozano
- Hospital Clínic, Department of Haemotherapy and Hemostasis, Barcelona, Catalonia, Spain
| | - Joan Cid
- Hospital Clínic, Department of Haemotherapy and Hemostasis, Barcelona, Catalonia, Spain
| | - Gerard Espinosa
- Hospital Clínic, Department of Autoimmune Diseases, Barcelona, Catalonia, Spain
| | - Ricard Cervera
- Hospital Clínic, Department of Autoimmune Diseases, Barcelona, Catalonia, Spain.
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15
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Prendecki M, Pusey C. Plasma exchange in anti-glomerular basement membrane disease. Presse Med 2019; 48:328-337. [DOI: 10.1016/j.lpm.2019.03.017] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2019] [Accepted: 03/11/2019] [Indexed: 12/31/2022] Open
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Salvadori M, Tsalouchos A. Therapeutic apheresis in kidney transplantation: An updated review. World J Transplant 2019; 9:103-122. [PMID: 31750088 PMCID: PMC6851502 DOI: 10.5500/wjt.v9.i6.103] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2019] [Revised: 10/02/2019] [Accepted: 10/15/2019] [Indexed: 02/05/2023] Open
Abstract
Therapeutic apheresis is a cornerstone of therapy for several conditions in transplantation medicine and is available in different technical variants. In the setting of kidney transplantation, immunological barriers such as ABO blood group incompatibility and preformed donor-specific antibodies can complicate the outcome of deceased- or living- donor transplantation. Postoperatively, additional problems such as antibody-mediated rejection and a recurrence of primary focal segmental glomerulosclerosis can limit therapeutic success and decrease graft survival. Therapeutic apheresis techniques find application in these issues by separating and selectively removing exchanging or modifying pathogenic material from the patient by an extracorporeal aphaeresis system. The purpose of this review is to describe the available techniques of therapeutic aphaeresis with their specific advantages and disadvantages and examine the evidence supporting the application of therapeutic aphaeresis as an adjunctive therapeutic option to immunosuppressive agents in protocols before and after kidney transplantation.
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Affiliation(s)
- Maurizio Salvadori
- Department of Transplantation Renal Unit, Careggi University Hospital, Florence 50139, Italy
| | - Aris Tsalouchos
- Nephrology and Dialysis Unit, Saints Cosmas and Damian Hospital, Pescia 51017, Italy
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17
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Stork L, Ellenberger D, Beißbarth T, Friede T, Lucchinetti CF, Brück W, Metz I. Differences in the Reponses to Apheresis Therapy of Patients With 3 Histopathologically Classified Immunopathological Patterns of Multiple Sclerosis. JAMA Neurol 2019; 75:428-435. [PMID: 29404583 DOI: 10.1001/jamaneurol.2017.4842] [Citation(s) in RCA: 48] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Importance Plasma exchange and immunoadsorption are second-line apheresis therapies for patients experiencing multiple sclerosis relapses. Early active multiple sclerosis lesions can be classified into different histopathological patterns of demyelination. Pattern 1 and 2 lesions show T-cell- and macrophage-associated demyelination, and pattern 2 is selectively associated with immunoglobulin and complement deposits, suggesting a humoral immune response. Pattern 3 lesions show signs of oligodendrocyte degeneration. Thus it is possible that pathogenic heterogeneity might predict therapy response. Objective To evaluate the apheresis response in relation to histopathologically defined immunopathological patterns of multiple sclerosis. Design, Setting and Participants This single-center cohort study recruited 69 patients nationwide between 2005 and 2016. All included patients had a diagnosis of early active inflammatory demyelination consistent with multiple sclerosis; were classified into patterns 1, 2, or 3 based on brain biopsy analysis; and underwent apheresis treatments. Patients who had concomitant severe disease, neuromyelitis optica, or acute disseminated encephalomyelitis were excluded. Main Outcomes and Measures The primary therapy outcome was a functionally relevant improvement of the relapse-related neurological deficit. Radiological and Expanded Disability Status Scale changes were secondary outcome parameters. Results The mean (SD) age of patients was 36.6 (13.3) years; 46 of the 69 participants (67%) were female. Overall, 16 patients (23%) exhibited pattern 1 lesions, 40 (58%) had pattern 2 lesions, and 13 (19%) had pattern 3 lesions. A functional therapy response was observed in 5 of the 16 patients with pattern 1 disease (31%) and 22 of the 40 patients with pattern 2 disease (55%), but none of the 13 patients with pattern 3 disease exhibited improvement (pattern 2 vs 3 P < .001). Radiological improvements were found in 4 (25%), 22 (56%), and 1 (11%) of patients with patterns 1, 2, and 3, respectively. The respective rates of response measured by changes in Expanded Disability Status Scale scores were 25%, 40%, and 0%. Brainstem involvement was a negative predictive factor for the functional therapy response (logarithmic odds ratio [logOR], -1.43; 95% CI, -3.21 to 0.17; P = .03), while immunoadsorption (as compared with plasma exchange) might be a positive predictive factor (logOR, 3.26; 95% CI, 0.75 to 8.13; P = .01). Conclusions and Relevance This cohort study provides evidence that the response to apheresis treatment is associated with immunopathological patterns. Patients with both patterns 1 and 2 improved clinically after apheresis treatment, but pattern 2 patients who showed signs of a humoral immune response benefited most. Apheresis appears unlikely to benefit patients with pattern 3 lesions.
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Affiliation(s)
- Lidia Stork
- Institute of Neuropathology, University Medical Center Goettingen, Goettingen, Germany
| | - David Ellenberger
- Department of Medical Statistics, University Medical Center Goettingen, Goettingen, Germany
| | - Tim Beißbarth
- Department of Medical Statistics, University Medical Center Goettingen, Goettingen, Germany
| | - Tim Friede
- Department of Medical Statistics, University Medical Center Goettingen, Goettingen, Germany
| | | | - Wolfgang Brück
- Institute of Neuropathology, University Medical Center Goettingen, Goettingen, Germany
| | - Imke Metz
- Institute of Neuropathology, University Medical Center Goettingen, Goettingen, Germany
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Kahovec C, Levin MC. Stabilization Without Rituximab After Disease Activation in an Alemtuzumab-Treated Patient with Multiple Sclerosis and a Literature Overview. Int J MS Care 2019; 21:125-128. [PMID: 31191177 DOI: 10.7224/1537-2073.2018-030] [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: 11/18/2022]
Abstract
There has been an increasing number of reports describing B-cell-associated disease activation in patients with multiple sclerosis after alemtuzumab treatment. Herein, 4.5 months after a first alemtuzumab infusion, a 33-year-old female patient had altered gait and vision loss associated with gadolinium enhancement of the optic nerves and chiasm on brain magnetic resonance imaging. The patient's blood showed normal B-cell counts concurrent with abnormally low T-cell counts. The patient stabilized after receiving steroids and prolonged plasma exchange without the use of rituximab. This case report adds to the growing body of literature of B-cell-associated disease activation after alemtuzumab infusion and provides a therapeutic strategy to stabilize patients when rituximab is not readily available or if contraindications to its use exist.
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Wyble AJ, Moore SC, Yates SG. Weathering the storm: A case of thyroid storm refractory to conventional treatment benefiting from therapeutic plasma exchange. J Clin Apher 2018; 33:678-681. [PMID: 30321468 DOI: 10.1002/jca.21658] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2018] [Revised: 08/05/2018] [Accepted: 08/07/2018] [Indexed: 12/28/2022]
Abstract
Thyroid storm is a severe manifestation of thyrotoxicosis characterized by systemic organ dysfunction secondary to a hypermetabolic state. Although antithyroid drugs, steroids, beta-blockers, antipyretics, and cholestyramine are the standard of care, some patients inadequately respond to these conventional therapies. Therapeutic plasma exchange has been previously utilized as a treatment modality in patients with a poor response to routine therapies or with contraindications to them. Herein, we report our experience with the management of a case of thyroid storm refractory to conventional treatment but responsive to therapeutic plasma exchange.
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Affiliation(s)
- Aaron J Wyble
- Department of Pathology, Division of Transfusion Medicine, University of Texas Medical Branch, Galveston, Texas
| | - Steven C Moore
- Department of Emergency Medicine, Henry Ford Hospital, Detroit, Michigan
| | - Sean G Yates
- Department of Pathology, Division of Transfusion Medicine, University of Texas Medical Branch, Galveston, Texas
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Meguri Y, Asada N, Nakasako Y, Kondo E, Kambara Y, Yamamoto A, Masunari T, Sezaki N, Ikeda G, Toji T, Yoshino T, Kiguchi T. A case report of TAFRO syndrome successfully treated by immunosuppressive therapies with plasma exchange. Ann Hematol 2018; 98:537-539. [PMID: 30054706 PMCID: PMC6342888 DOI: 10.1007/s00277-018-3456-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2018] [Accepted: 07/22/2018] [Indexed: 01/12/2023]
Affiliation(s)
- Yusuke Meguri
- Department of Hematology and Oncology, Chugoku Central Hospital, 148-13 Miyuki-Cho Kamiiwanari, Fukuyama, Hiroshima, 720-0001, Japan
- Department of Hematology and Oncology, Okayama University Hospital, Okayama, Japan
| | - Noboru Asada
- Department of Hematology and Oncology, Okayama University Hospital, Okayama, Japan
| | - Yukio Nakasako
- Department of Nephrology, Chugoku Central Hospital, Fukuyama, Japan
| | - Eisei Kondo
- Department of General Medicine, Okayama University Hospital, Okayama, Japan
| | - Yui Kambara
- Department of Hematology and Oncology, Chugoku Central Hospital, 148-13 Miyuki-Cho Kamiiwanari, Fukuyama, Hiroshima, 720-0001, Japan
| | - Akira Yamamoto
- Department of Hematology and Oncology, Chugoku Central Hospital, 148-13 Miyuki-Cho Kamiiwanari, Fukuyama, Hiroshima, 720-0001, Japan
| | - Taro Masunari
- Department of Hematology and Oncology, Chugoku Central Hospital, 148-13 Miyuki-Cho Kamiiwanari, Fukuyama, Hiroshima, 720-0001, Japan
| | - Nobuo Sezaki
- Department of Hematology and Oncology, Chugoku Central Hospital, 148-13 Miyuki-Cho Kamiiwanari, Fukuyama, Hiroshima, 720-0001, Japan
| | - Genyo Ikeda
- Department of Respiratory Medicine, Chugoku Central Hospital, Fukuyama, Japan
| | - Tomohiro Toji
- Department of Pathology, Chugoku Central Hospital, Fukuyama, Japan
| | - Tadashi Yoshino
- Department of Pathology, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Okayama, Japan
| | - Toru Kiguchi
- Department of Hematology and Oncology, Chugoku Central Hospital, 148-13 Miyuki-Cho Kamiiwanari, Fukuyama, Hiroshima, 720-0001, Japan.
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Peruzzi L, Albiani R, Giancaspero K. Plasma exchange in kidney transplantation: Still a valuable option for nephrotic syndrome recurrence. Transfus Apher Sci 2017; 56:525-530. [PMID: 28830667 DOI: 10.1016/j.transci.2017.07.010] [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: 10/19/2022]
Abstract
About 30% of the cases of steroid resistant nephrotic syndrome display a genetically determined disease and will not recur after kidney transplant; the other cases with fully or partially immunological pathogenesis display a high risk of post transplant recurrence. Although lots of studies were carried out in the last 50 years the pathogenetic mechanism is still obscure and the therapeutic approach mostly empirical. The cornerstones principles of the therapies are based on removal of a still undefined "permeability factor" through plasma-exchange or other apheresis techniques and inhibition of its synthesis by the immunological system through different drugs. The probability of successfully inducing persistant remission is nowadays around 30%through the different schemes experimented so far which mostly include plasmapheresis. Rituximab in the last years has significantly increased the efficacy of the treatments. Non responders are rapidly evolving to graft loss and will most probably recur also in subsequent transplant. Apart from genetics no other risk factors are predictive for recurrence.
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Affiliation(s)
- Licia Peruzzi
- Pediatric Nephrology Unit, Regina Margherita Children's Hospital, Città della Salute e della Scienza di Torino, Turin, Italy.
| | - Roberto Albiani
- Apheresis Unit, Regina Margherita Children's Hospital, Città della Salute e della Scienza di Torino, Turin, Italy
| | - Karol Giancaspero
- Apheresis Unit, Regina Margherita Children's Hospital, Città della Salute e della Scienza di Torino, Turin, Italy
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Martirosyan A, Petrek M, Kishore A, Manukyan G. Immunomodulatory effects of therapeutic plasma exchange on monocytes in antiphospholipid syndrome. Exp Ther Med 2016; 12:1189-1195. [PMID: 27446342 DOI: 10.3892/etm.2016.3441] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2015] [Accepted: 02/18/2016] [Indexed: 11/06/2022] Open
Abstract
Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by thrombosis and recurrent fetal loss, with the persistent presence of antiphospholipid antibodies (aPLs). aPLs exert their pathogenic effect via the overproduction of tissue factor and activation of complement and several cell types, including endothelial cells, platelets and notably monocytes. As a result, a hypercoagulable state develops leading to APS-associated obstetric complications and fetal loss. Despite being far from optimal, treatment of APS usually includes heparin and low dose aspirin. Recently, plasma exchange (PE) therapy was successfully used in patients with APS with obstetric complications who did not respond to the standard treatment. Therefore, the present study investigated the mechanism underlying PE action, and aimed to determine whether PE affects the functional activity of APS monocytes by examining the expression of 11 mRNA transcripts encoding cytokines, signaling molecules and transcription factors. Monocytes were collected prior to and following the PE treatment from women with APS who experienced recurrent pregnancy losses, as well as from healthy volunteers. Compared with control cells, APS monocytes showed deregulated expression of interleukin (IL)-1β, IL-6, IL-23, chemokine (C-C motif) ligand 2 (CCL2), C-X-C motif chemokine 10 (CXCL10), toll-like receptor 2, and signal transducer and activator of transcription 3. PE treatment resulted in increased IL-1β, IL-6, IL-23, CCL2, P2X7 and tumor necrosis factor-α mRNA transcripts in APS monocytes, restoring the mRNA expression levels to within normal ranges. Furthermore, PE therapy counterbalanced the expression levels of CCL2 and CXCL10, the levels of which are indicative of T helper cell 1/2 balance. The results of the present study indicate that the altered transcriptional profile in APS monocytes was restored by the immunomodulatory effect of plasmapheresis.
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Affiliation(s)
- Anush Martirosyan
- Department of Pathological Physiology, Faculty of Medicine and Dentistry, Palacky University, Olomouc 77520, Czech Republic; Group of Molecular and Cellular Immunology, Institute of Molecular Biology, National Academy of Sciences, Yerevan 0014, Armenia
| | - Martin Petrek
- Department of Pathological Physiology, Faculty of Medicine and Dentistry, Palacky University, Olomouc 77520, Czech Republic
| | - Amit Kishore
- Department of Pathological Physiology, Faculty of Medicine and Dentistry, Palacky University, Olomouc 77520, Czech Republic
| | - Gayane Manukyan
- Department of Pathological Physiology, Faculty of Medicine and Dentistry, Palacky University, Olomouc 77520, Czech Republic; Group of Molecular and Cellular Immunology, Institute of Molecular Biology, National Academy of Sciences, Yerevan 0014, Armenia
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Gafoor VA, Jose J, Saifudheen K, Musthafa M. Plasmapheresis in neurological disorders: Experience from a tertiary care hospital in South India. Ann Indian Acad Neurol 2015; 18:15-9. [PMID: 25745304 PMCID: PMC4350207 DOI: 10.4103/0972-2327.144301] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2014] [Revised: 07/17/2014] [Accepted: 07/18/2014] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND Therapeutic plasma exchange (PE) or plasmapheresis is the treatment of choice in many neurological disorders. Even though it is safe in experienced hands, there is a major concern about its safety among physicians. OBJECTIVES To analyze our experience with 230 patients who underwent PE for various neurological disorders. MATERIALS AND METHODS Retrospective review of PE procedures done during a period of 48 months, from July 2007 to June 2011 in a tertiary care teaching hospital in South India. Indications, clinical results and technical factors are discussed. RESULTS The main indication for PE was GBS (203 patients; 88.3%). Age of patients ranged from 14-65 (mean = 42.3 years). The most common complications were paraesthesias and/or cramps (36.1%) and hypotension (32.2%). Four pregnant patients who underwent PE had good recovery with one intrauterine death. There was no mortality. CONCLUSION The analysis of 240 cases of PE done in our department shows that the procedure is safe, with only minimal procedure related complications and no mortality.
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Affiliation(s)
- V Abdul Gafoor
- Department of Neurology, Medical College, Calicut, Kerala, India
| | - James Jose
- Department of Neurology, Medical College, Calicut, Kerala, India
| | - K Saifudheen
- Department of Neurology, Medical College, Calicut, Kerala, India
| | - Mohamed Musthafa
- Department of Neurology, Medical College, Calicut, Kerala, India
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Should Plasma Exchange Be Offered to Patients With Multiple Sclerosis–Associated Optic Neuritis? J Neuroophthalmol 2015; 35:86-9. [DOI: 10.1097/wno.0000000000000197] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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25
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Connelly-Smith LS, Linenberger ML. Therapeutic Apheresis for Patients with Cancer. Cancer Control 2015; 22:60-78. [DOI: 10.1177/107327481502200109] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Affiliation(s)
- Laura S. Connelly-Smith
- Seattle Cancer Care Alliance, School of Medicine, University of Washington, Seattle, Washington
- Division of Hematology, School of Medicine, University of Washington, Seattle, Washington
| | - Michael L. Linenberger
- Seattle Cancer Care Alliance, School of Medicine, University of Washington, Seattle, Washington
- Division of Hematology, School of Medicine, University of Washington, Seattle, Washington
- Fred Hutchinson Cancer Research Center, Seattle, Washington
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Bose N, Kanzariya H. Role of therapeutic apheresis and phlebotomy techniques in anaesthesia and critical care. Indian J Anaesth 2014; 58:672-8. [PMID: 25535434 PMCID: PMC4260318 DOI: 10.4103/0019-5049.144685] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
Therapeutic transfusion techniques such as apheresis and phlebotomy are frequently used in intensive care units. Use of the apheresis technique for the treatment of various diseases in critically ill patients is growing day by day. There are increasing evidences for using apheresis as a primary therapy or as an adjunct to other therapies for various diseases such as thrombotic thrombocytopenic purpura, haemolytic uremic syndrome, drug toxicities, autoimmune disease, sepsis and fulminant hepatic failure. Apheresis is an invasive procedure. It has significant physiologic consequences, so the care of these patients requires continuous supervision. Phlebotomy is performed as an intervention for some disease management. Its use is nowadays restricted to conditions such as polycythaemia, haemochromatosis and porphyria cutanea tarda. In this review, we have looked at various indications, procedure and complications of apheresis and phlebotomy in critical care unit.
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Affiliation(s)
- Neeta Bose
- Department of Anesthesia, Gujarat Medical Education and Research Society, Gotri, Vadodara, Gujarat, India
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27
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Zhan Y, Zou S, Hua F, Li F, Ji L, Wang W, Ye Y, Sun L, Chen H, Cheng Y. High-dose dexamethasone modulates serum cytokine profile in patients with primary immune thrombocytopenia. Immunol Lett 2014; 160:33-38. [DOI: 10.1016/j.imlet.2014.03.002] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2013] [Revised: 01/19/2014] [Accepted: 03/10/2014] [Indexed: 10/25/2022]
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Plasma exchange as a complementary approach to snake bite treatment: An academic emergency department’s experiences. Transfus Apher Sci 2013; 49:494-8. [DOI: 10.1016/j.transci.2013.03.006] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2012] [Revised: 02/18/2013] [Accepted: 03/05/2013] [Indexed: 12/18/2022]
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Abstract
The initial description of therapeutic plasma exchange (TPE) in an animal model was published almost 100 years ago. Since that time, this treatment has been applied to a wide variety of diseases but limited research has been published examining the mechanisms of action of TPE. The therapeutic effects of TPE could include the removal of pathological substances from the blood, such as monoclonal paraproteins and autoantibodies, as well as the replacement of deficient plasma components when plasma is used as a replacement fluid. Beyond these potential mechanisms, other possible mechanisms include possible alterations in lymphocyte proliferation and function that could sensitize these cells to immunosuppressant and chemotherapeutic agents and alterations in the immune system including changes in B and T cell numbers and activation, increased T suppressor function, and alteration in T-helper cell type 1/2 (Th1/Th2) ratio. Much remains unknown about the mechanisms of action of TPE, indicating a need for basic research into this therapy.
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Affiliation(s)
- Hollie M Reeves
- Department of Pathology - Clinical, University Hospitals Case Medical Center, Cleveland, OH, USA
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30
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Abstract
Abstract
Plasma exchange is a therapeutic procedure used to treat a variety of diseases through the bulk removal of plasma. To apply this treatment to patients appropriately, it is essential to understand the methods to remove plasma, its effects on normal plasma constituents, the role of replacement fluids in the treatment, and the risks associated with the procedure. To facilitate the appropriate evidence-based use of plasma exchange and to encourage research, the American Society for Apheresis has published guidelines providing practical guidance and information to those responsible for ordering or providing this treatment.
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A FACTOR FOUND IN THE IGG FRACTION OF SERUM OF PATIENTS WITH PARANEOPLASTIC BILATERAL DIFFUSE UVEAL MELANOCYTIC PROLIFERATION CAUSES PROLIFERATION OF CULTURED HUMAN MELANOCYTES. Retina 2012; 32:1959-66. [DOI: 10.1097/iae.0b013e3182618bab] [Citation(s) in RCA: 56] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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32
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Jamshidian A, Gharagozloo M. Can plasma exchange therapy induce regulatory T lymphocytes in multiple sclerosis patients? Clin Exp Immunol 2012; 168:75-7. [PMID: 22385241 DOI: 10.1111/j.1365-2249.2011.04547.x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023] Open
Abstract
Plasma exchange is used increasingly as an individual therapeutic decision for treating of severe, steroid-resistant relapses of multiple sclerosis (MS). However, given that its mechanism of action in this CD4(+) T cell-mediated autoimmune disease remains unknown, it is not yet considered as a routine therapy for this prevalent neuroimmune disorder. In this regard, we hypothesized that plasma exchange, by depleting the body of inflammatory mediators that acts as providers of co-stimulatory signals for the adaptive immune system, provides the immune system with an exceptional break for de-novo recognition of autoantigens in a tolerogenic manner. This may lead to an increase in the frequency and function of myelin-specific regulatory T cells. For evaluating this we suggest some in vitro and in vivo studies to analyse the effects of varied dilutions of normal and MS plasmas on the induction of regulatory T cells or on the function of isolated and purified regulatory T cells. Clarifying the effects of therapeutic plasma exchange on regulatory T cells as the major controllers of autoimmune responses may provide us with strong evidence to use this procedure as a disease-modifying treatment in remission phase for reducing the rate and severity of future attacks, in addition to more trustworthy therapy in severe relapses of MS.
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Affiliation(s)
- A Jamshidian
- Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
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Van Laecke S, Nagler EVT, Vanholder R. Thrombotic microangiopathy: a role for magnesium? Thromb Haemost 2012; 107:399-408. [PMID: 22274299 DOI: 10.1160/th11-08-0593] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2011] [Accepted: 12/01/2011] [Indexed: 12/15/2022]
Abstract
Despite advances in more recent years, the pathophysiology and especially treatment modalities of thrombotic microangiopathy (TMA) largely remain enigmatic. Disruption of endothelial homeostasis plays an essential role in TMA. Considering the proven causal association between magnesium and both endothelial function and platelet aggregability, we speculate that a magnesium deficit could influence the course of TMA and the related haemolytic uraemic syndrome and thrombotic thrombocytopenic purpura. A predisposition towards TMA is seen in many conditions with both extracellular and intracellular magnesium deficiency. We propose a rationale for magnesium supplementation in TMA, in analogy with its evidence-based therapeutic application in pre-eclampsia and suggest, based on theoretical grounds, that it might attenuate the development of TMA, minimise its severity and prevent its recurrence. This is based on several lines of evidence from both in vitro and in vivo data showing dose-dependent effects of magnesium supplementation on nitric oxide production, platelet aggregability and inflammation. Our hypothesis, which is further amenable to assessment in animal models before therapeutic applications in humans are implemented, could be explored both in vitro and in vivo to decipher the potential role of magnesium deficit in TMA and of the effects of its supplementation.
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Affiliation(s)
- Steven Van Laecke
- Department of Nephrology, Ghent University Hospital, Ghent, Belgium.
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34
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Evidence for the role of B cells and immunoglobulins in the pathogenesis of multiple sclerosis. Neurol Res Int 2011; 2011:780712. [PMID: 21961063 PMCID: PMC3179868 DOI: 10.1155/2011/780712] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2011] [Accepted: 07/27/2011] [Indexed: 01/06/2023] Open
Abstract
The pathogenesis of multiple sclerosis (MS) remains elusive. Recent reports advocate greater involvement of B cells and immunoglobulins in the initiation and propagation of MS lesions at different stages of their ontogeny. The key role of B cells and immunoglobulins in pathogenesis was initially identified by studies in which patients whose fulminant attacks of demyelination did not respond to steroids experienced remarkable functional improvement following plasma exchange. The positive response to Rituximab in Phase II clinical trials of relapsing-remitting MS confirms the role of B cells. The critical question is how B cells contribute to MS. In this paper, we discuss both the deleterious and the beneficial roles of B cells and immunoglobulins in MS lesions. We provide alternative hypotheses to explain both damaging and protective antibody responses.
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35
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Jaben EA, Pulido JS, Pittock S, Markovic S, Winters JL. The potential role of plasma exchange as a treatment for bilateral diffuse uveal melanocytic proliferation: a report of two cases. J Clin Apher 2011; 26:356-61. [PMID: 21898575 DOI: 10.1002/jca.20310] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2011] [Accepted: 07/15/2011] [Indexed: 01/04/2023]
Abstract
Bilateral diffuse uveal melanocytic proliferation (BDUMP) is a rare paraneoplastic syndrome associated with gynecologic malignancies in women and pancreatic or lung carcinomas in men. The clinical presentation consists of the rapid onset of decreased visual acuity due to bilateral serous retinal detachment and cataracts. Pathologically, there is diffuse uveal thickening and proliferation of uveal melanocytes. The onset of blindness is often rapid, with some patients presenting with blindness. We describe the cases of two women with gynecologic malignancies who were treated with plasma exchange (PE) for BDUMP. After a course of five to seven procedures, their ocular disease stabilized. One patient has maintained her vision more than 1 year following the completion of the course of PE. The other patient, who also received treatment with corticosteroids, in addition to the PE, reported stable vision on telephone follow-up 9 months after presentation. These cases suggest that PE may be a treatment option in this rare paraneoplastic syndrome which has otherwise been reported to invariably result in vision loss.
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Affiliation(s)
- Elizabeth A Jaben
- Department of Laboratory Medicine and Pathology, Division of Transfusion Medicine, Mayo Clinic, Rochester, MN, USA
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36
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Thomas MR, Machin SJ, Mackie I, Scully MA. B cell activating factor is elevated in acute idiopathic thrombotic thrombocytopenic purpura. Br J Haematol 2011; 155:620-2. [DOI: 10.1111/j.1365-2141.2011.08730.x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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Qureshi A, Niazi JH, Kallempudi S, Gurbuz Y. Label-free capacitive biosensor for sensitive detection of multiple biomarkers using gold interdigitated capacitor arrays. Biosens Bioelectron 2010; 25:2318-23. [PMID: 20381333 DOI: 10.1016/j.bios.2010.03.018] [Citation(s) in RCA: 91] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2010] [Revised: 03/02/2010] [Accepted: 03/16/2010] [Indexed: 02/08/2023]
Abstract
In this study, a highly sensitive and label-free multianalyte capacitive immunosensor was developed based on gold interdigitated electrodes (GID) capacitor arrays to detect a panel of disease biomarkers. C-reactive protein (CRP), TNFalpha, and IL6 have strong and consistent relationships between markers of inflammation and future cardiovascular risk (CVR) events. Early detection of a panel of biomarkers for a disease could enable accurate prediction of a disease risk. The detection of protein biomarkers was based on relative change in capacitive/dielectric properties. Two different lab-on-a-chip formats were employed for multiple biomarker detection on GID-capacitors. In format I, capacitor arrays were immobilized with pure forms of anti-CRP, -TNFalpha, and -IL6 antibodies in which each capacitor array contained a different immobilized antibody. Here, the CRP and IL6 were detected in the range 25 pg/ml to 25 ng/ml and 25 pg/ml to 1 ng/ml for TNFalpha in format I. Sensitive detection was achieved with chips co-immobilized (diluted) with equimolar mixtures of anti-CRP, -IL6, and -TNFalpha antibodies (format II) in which all capacitors in an array were identical and tested for biomarkers with sequential incubation. The resulting response to CRP, IL6, and TNFalpha in format II for all biomarkers was found to be within 25 pg/ml to 25 ng/ml range. The capacitive biosensor for panels of inflammation and CVR markers show significant clinical value and provide great potential for detection of biomarker panel in suspected subjects for early diagnosis.
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Affiliation(s)
- Anjum Qureshi
- Faculty of Engineering & Natural Sciences, Sabanci University, Orhanli, Tuzla 34956, Istanbul, Turkey
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High versus standard dose methylprednisolone in the acute phase of idiopathic thrombotic thrombocytopenic purpura: a randomized study. Ann Hematol 2009; 89:591-6. [PMID: 20033409 DOI: 10.1007/s00277-009-0877-5] [Citation(s) in RCA: 89] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2009] [Accepted: 11/23/2009] [Indexed: 12/28/2022]
Abstract
Therapeutic plasma exchange (PE) is the accepted therapy for thrombotic thrombocytopenic purpura (TTP). Because not all patients achieve remission, other treatment modalities have been used in addition to PE, but no randomized clinical trial evaluated their efficacy. The aim of this multicentric study was to compare the effectiveness of standard- versus high-dose methylprednisolone as an adjunctive treatment to PE in the acute phase of TTP. Sixty patients with idiopathic TTP were randomized to receive methylprednisolone 1 mg/kg/die intravenous or 10 mg/kg/die for 3 days, thereafter, 2.5 mg/kg/die in addition to PE. Both dosages of steroids were well tolerated. At the end of induction therapy (day 23), the percentage of patients failing to achieve complete remission was significantly higher in the standard dose (16 of 30) than in the high-dose group (seven of 30). Also, the number of cases without a good response at day 9 and the number of deaths were higher in the standard-dose arm, but the differences did not reach the statistical significance. Results of present study indicate that the association of PE with high-dose instead of standard-dose steroids reduces the percentage of TTP patients that fail to achieve complete remission.
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McLeod BC. Therapeutic apheresis: history, clinical application, and lingering uncertainties. Transfusion 2009; 50:1413-26. [DOI: 10.1111/j.1537-2995.2009.02505.x] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
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40
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Erickson YO, Samia NI, Bedell B, Friedman KD, Atkinson BS, Raife TJ. Elevated procalcitonin and C-reactive protein as potential biomarkers of sepsis in a subpopulation of thrombotic microangiopathy patients. J Clin Apher 2009; 24:150-4. [PMID: 19591197 DOI: 10.1002/jca.20205] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Thrombotic microangiopathy (TMA) comprises a group of microvascular thrombosis syndromes associated with multiple pathogenic factors. Deficient activity of ADAMTS13 is a pathogenic factor in a subset of TMA patients that provides a strong rationale for plasma exchange treatment. However, the subset of TMA patients with normal ADAMTS13 activity remains a heterogeneous group of patients in which the appropriate treatment is not well understood. In addition to the common forms of TMA thrombotic thrombocytopenic purpura and the hemolytic uremic syndrome, the differential diagnosis of TMA may include sepsis, autoimmune disorders, and disseminated intravascular coagulation. Optimal treatment of TMA depends on timely recognition of treatable pathogenic factors. We hypothesized that sepsis is a rapidly identifiable pathogenic factor in a subset of TMA patients. To test this hypothesis, we retrospectively measured the rapid biomarkers of sepsis C-reactive protein (CRP) and procalcitonin (PCT), in a repository of pretreatment plasma samples from 61 TMA patients treated with plasma exchange. Levels were analyzed in 31 severely ADAMTS13-deficient and 30 ADAMTS13-normal patients. None of the 31 patients with severe deficiency of ADAMTS13 had elevated PCT. However, 11 of 30 (37%) non-ADAMTS13-deficient patient samples were strongly positive for PCT. These patient samples also had a >10-fold higher median CRP level than patients with normal PCT. We conclude that rapid assays may help identify sepsis in a subset of TMA patients.
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Affiliation(s)
- Yasuko O Erickson
- The Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA
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Synergistic interactions between interferon-gamma and TRAIL modulate c-FLIP in endothelial cells, mediating their lineage-specific sensitivity to thrombotic thrombocytopenic purpura plasma-associated apoptosis. Blood 2008; 112:340-9. [PMID: 18339897 DOI: 10.1182/blood-2007-10-119552] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Microvascular endothelial cell (MVEC) injury coupled to progression of platelet microthrombi facilitated by ADAMTS13 deficiency is characteristic of idiopathic and HIV-linked thrombotic thrombocytopenic purpura (TTP). Cytokines capable of inducing MVEC apoptosis in vitro are up-regulated in both TTP and HIV infection. However, the concentrations of these cytokines required to elicit EC apoptosis in vitro are 2- to 3-log-fold greater than present in patient plasmas. We report that clinically relevant levels of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and interferon (IFN)-gamma act in synergy to induce apoptosis in dermal MVECs, but have no effect on large-vessel ECs or pulmonary MVECs. This reflects the tissue distribution of TTP lesions in vivo. Sensitivity to TTP plasma or TRAIL plus IFN-gamma is paralleled by enhanced ubiquitination of the caspase-8 regulator cellular FLICE-like inhibitory protein (c-FLIP), targeting it for proteasome degradation. c-FLIP silencing with anti-FLIP short interfering RNA (siRNA) in pulmonary MVECs rendered them susceptible to TTP plasma- and cytokine-mediated apoptosis, while up-regulation of c-FLIP by gene transfer partially protected dermal MVECs from such injury. TTP plasma-mediated apoptosis appears to involve cytokine-induced acceleration of c-FLIP degradation, sensitizing cells to TRAIL-mediated caspase-8 activation and cell death. Suppression of TRAIL or modulation of immunoproteasome activity may have therapeutic relevance in TTP.
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Song Y, Wang D, Li H, Hao F, Ma J, Xia Y. Severe acute arsine poisoning treated by plasma exchange. Clin Toxicol (Phila) 2007; 45:721-7. [PMID: 17849251 DOI: 10.1080/15563650701502675] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
INTRODUCTION Exposure to arsine gas can cause fatal hemolysis and multiorgan damage. Whole blood exchange transfusion and hemodialysis have been recommended to treat severe acute arsine poisoning, but are associated with significant complications and sub-optimal outcomes. Plasma exchange is another method of blood purification technique but there are no data on its use in acute arsine poisoning. This retrospective study evaluated the clinical and effects and arsenic clearance from the use of plasma exchange treatment of patients with acute arsine poisoning. METHODS Data from patients with severe acute arsine poisoning, treated with plasma exchange from December 2000 to December 2005 were collected and analyzed. Measured laboratory factors, performed before and after plasma exchange treatment included routine biochemistry and hematology tests as well as arsenic concentrations in blood, urine, and discarded plasma. RESULTS During the study period, 12 patients with severe acute arsine poisoning were treated with plasma exchange. Plasma exchange was performed one or two times on each patient, during which the replacement fluid was fresh frozen plasma (total volume ranged from 1,400 to 4,000 mL). The range of concentrations of arsenic in discarded plasma was 27.7 to 88.7 mg/L and the range of total arsenic removed by plasma exchange was 55.4 to 177.4 mg. Plasma exchange appears to rapidly terminate arsine-induced hemolysis and favorably modify damage to the kidneys and other organs. Laboratory factors that showed significant association with treatment response were creatine kinase, lactate dehydrogenase, blood urea nitrogen, total bilirubin, and heart-related enzymes. All patients recovered from the poisoning and were in good condition at a 2 to 3 months follow-up. CONCLUSIONS Plasma exchange appears to be an effective treatment intervention for patients with severe acute arsine poisoning. It is suggested that it be used as early as possible.
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Affiliation(s)
- Yuguo Song
- Department of Occupational Diseases and Clinical Toxicology, Beijing Chaoyang Hospital, Beijing, People's Republic of China.
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Rojnuckarin P, Watanaboonyongcharoen P, Akkawat B, Intragumtornchai T. The role of pulse dexamethasone in acquired idiopathic thrombotic thrombocytopenic purpura. J Thromb Haemost 2006; 4:1148-50. [PMID: 16689774 DOI: 10.1111/j.1538-7836.2006.01879.x] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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