• CAR-T
• Eltrombopag
• TPO-RA
• Thrombocytopenia
• Toxicity

• Chemotherapy induced thrombocytopenia
• chemotherapy toxicity
• eltrombopag
• romiplostim
• thrombopoietin

• Humans
• Receptors, Thrombopoietin/agonists
• Thrombocytopenia/chemically induced
• Thrombocytopenia/drug therapy
• Thrombopoietin/therapeutic use
• Recombinant Fusion Proteins/therapeutic use
• Recombinant Fusion Proteins/adverse effects
• Hydrazines/therapeutic use
• Benzoates/therapeutic use
• Antineoplastic Agents/adverse effects
• Antineoplastic Agents/therapeutic use
• Receptors, Fc/therapeutic use
• Pyrazoles/therapeutic use
• Pyrazoles/adverse effects
• Platelet Count
• Neoplasms/drug therapy
• Thiazoles
• Thiophenes

• avatrombopag
• chemotherapy‐induced thrombocytopenia
• persistent
• romiplostim
• thrombopoietin receptor agonist

• Humans
• Thrombocytopenia/chemically induced
• Antineoplastic Agents/adverse effects
• Neoplasms/drug therapy
• Neoplasms/complications
• Thiazoles
• Thiophenes

• 1K23HL159313 NHLBI NIH HHS
• 1K23HL159313 NHLBI NIH HHS

• adverse effects
• chemotherapy-induced cytopenia
• cytopenia
• growth factors

• Humans
• Neutropenia/chemically induced
• Neutropenia/drug therapy
• Antineoplastic Agents/adverse effects
• Antineoplastic Agents/therapeutic use
• Anemia/chemically induced
• Anemia/drug therapy
• Thrombocytopenia/chemically induced
• Neoplasms/drug therapy
• Intercellular Signaling Peptides and Proteins/therapeutic use
• Granulocyte Colony-Stimulating Factor/therapeutic use
• Receptors, Thrombopoietin/agonists
• Cytopenia

• autologous stem cell transplantation (asct)
• investigator-initiated study
• multiple myeloma (mm)
• platelet transfusion
• romiplostim
• thrombocytopenia

• eltrombopag
• hematopoietic cell transplantation
• recombinant human thrombopoietin
• romiplostim
• thrombocytopenia
• thrombopoietin receptor agonists

• chemotherapy
• peptibody
• platelet growth factors
• romiplostim
• thrombocytopenia
• thrombopoietin receptor agonists

• Humans
• Receptors, Fc/therapeutic use
• Thrombopoietin/therapeutic use
• Thrombopoietin/adverse effects
• Recombinant Fusion Proteins/therapeutic use
• Recombinant Fusion Proteins/adverse effects
• Recombinant Fusion Proteins/administration & dosage
• Thrombocytopenia/drug therapy
• Thrombocytopenia/chemically induced
• Antineoplastic Agents/adverse effects
• Antineoplastic Agents/therapeutic use
• Neoplasms/drug therapy
• Platelet Count
• Receptors, Thrombopoietin/agonists
• Treatment Outcome

• P30 CA008748 NCI NIH HHS

• Avatrombopag
• Bleeding
• Chemotherapy
• Chemotherapy-induced thrombocytopenia
• Nadir CIT
• Persistent CIT
• Romiplostim
• Supportive care
• Thrombocytopenia
• Thrombopoietin
• Thrombopoietin receptor agonist

• Humans
• Thrombocytopenia/chemically induced
• Thrombocytopenia/drug therapy
• Receptors, Thrombopoietin/agonists
• Antineoplastic Agents/adverse effects
• Neoplasms/complications
• Neoplasms/drug therapy
• Risk

• K23 HL159313 NHLBI NIH HHS

• chemotherapy
• guidelines
• platelets
• thrombocytopenia

• Bile ducts
• Hodgkin disease
• bilirubin
• cholestasis

• K23 HL159313 NHLBI NIH HHS

• Cirrhosis
• Liver transplantation
• Perioperative period
• Platelet
• Thrombopoietin pre-treatment

• cancer
• chemotherapy
• hetrombopag
• thrombocytopenia
• thrombopoietin

• TPO-RA
• Thrombocytopenia
• avatrombopag
• chemotherapy induced thrombocytopenia
• eltrombopag
• romiplostim
• thrombopoietin
• thrombopoietin receptor agonist

• Humans
• Antineoplastic Agents/adverse effects
• Benzoates/adverse effects
• Neoplasms/complications
• Neoplasms/drug therapy
• Purpura, Thrombocytopenic, Idiopathic/drug therapy
• Receptors, Fc/therapeutic use
• Receptors, Thrombopoietin/agonists
• Recombinant Fusion Proteins/adverse effects
• Thrombocytopenia/chemically induced
• Thrombocytopenia/drug therapy

• K23 HL159313 NHLBI NIH HHS

• National Nature Science Foundation of China

Even though cytopenia caused by either chemotherapy or radiotherapy is a common complication in cancer patients, chemoradiotherapy remains an essential treatment for the majority of patients. The purpose of this study was to look into the clinical efficacy and cost-effectiveness of recombinant human thrombopoietin (rhTPO) in treating chemo- or chemoradiotherapy-induced grade II, III, and IV thrombocytopenia. From December 2019 to November 2020, 233 lung cancer patients admitted to our hospital with chemotherapy- or chemoradiotherapy-induced thrombocytopenia were enrolled and treated with rhTPO. The study's findings revealed a significant disparity in the use of concurrent chemoradiotherapy in patients with grade II, III, and IV thrombocytopenia. All costs, including rhTPO treatment costs, platelet costs, drug costs, and nondrug costs, tended to rise as the severity of thrombocytopenia increased. In the treatment of chemotherapy or radiotherapy-induced thrombocytopenia, rhTPO has shown good clinical efficacy. In the treatment of grade II thrombocytopenia, rhTPO has a favorable economic evaluation. As a result, early intervention and thrombocytopenia treatment should be provided, which warrants further clinical investigation.

Currently, there are no approved options to prevent or treat chemotherapy-induced thrombocytopenia (CIT). We performed a systematic literature review and meta-analysis on use of thrombopoietic agents for CIT.

We searched Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, PubMed, EMBASE, ClinicalTrials.gov, and health technology assessments from January 1995 to March 2021 for studies evaluating thrombopoietic agents for CIT, including recombinant human thrombopoietin (rhTPO), megakaryocyte growth and development factor (MGDF), romiplostim, and eltrombopag. Random effects meta-analyses were conducted for efficacy and safety endpoints.

We screened 1503 titles/abstracts, assessed 138 articles, and abstracted data from 39 publications (14 recombinant human thrombopoietin, 7 megakaryocyte growth and development factor, 9 romiplostim, 8 eltrombopag, and 1 romiplostim/eltrombopag). Random effects meta-analyses of data from multiple studies comparing thrombopoietic agents versus control (comparator, placebo, or no treatment) showed that thrombopoietic agents did not significantly improve chemotherapy dose delays and/or reductions (21.1% vs 40.4%, P = 0.364), grade 3/4 thrombocytopenia (39.3% vs 34.8%; P = 0.789), platelet transfusions (16.7% vs 31.7%, P = 0.111), grade ≥ 2 bleeding (6.7% vs 16.5%; P = 0.250), or thrombosis (7.6% vs 12.5%; P = 0.131). However, among individual studies comparing thrombopoietic agents with placebo or no treatment, thrombopoietic agents positively improved outcomes in some studies, including significantly increasing mean peak platelet counts (186 x 10⁹/L with rhTPO vs 122 x 10⁹/L with no treatment; P < 0.05) in one study and significantly increasing platelet count at nadir (56 x 10⁹/L with rhTPO vs 28 x 10⁹/L with not treatment; P < 0.05) in another study. Safety findings included thrombosis (n = 23 studies) and bleeding (n = 11), with no evidence of increased thrombosis risk with thrombopoietic agents.

Our analyses generate the hypothesis that thrombopoietic agents may benefit patients with CIT. Further studies with well-characterized bleeding and platelet thresholds are warranted to explore the possible benefits of thrombopoietic agents for CIT.

• Anemia/drug therapy
• Antineoplastic Agents/therapeutic use
• Hemorrhage/drug therapy
• Humans
• Receptors, Fc/therapeutic use
• Recombinant Fusion Proteins/adverse effects
• Recombinant Proteins/adverse effects
• Thrombocytopenia/chemically induced
• Thrombocytopenia/drug therapy
• Thrombopoiesis
• Thrombopoietin/adverse effects

• P30 CA008748 NCI NIH HHS
• Amgen Inc.

Several therapeutic agents can cause thrombocytopenia by either immune-mediated or non-immune-mediated mechanisms. Non-immune-mediated thrombocytopenia is due to direct toxicity of drug molecules to platelets or megakaryocytes. Immune-mediated thrombocytopenia, on the other hand, involves the formation of antibodies that react to platelet-specific glycoprotein complexes, as in classic drug-induced immune thrombocytopenia (DITP), or to platelet factor 4, as in heparin-induced thrombocytopenia (HIT) and vaccine-induced immune thrombotic thrombocytopenia (VITT). Clinical signs include a rapid drop in platelet count, bleeding or thrombosis. Since the patient's condition can deteriorate rapidly, prompt diagnosis and management are critical. However, the necessary diagnostic tests are only available in specialized laboratories. Therefore, the most demanding step in treatment is to identify the agent responsible for thrombocytopenia, which often proves difficult because many patients are taking multiple medications and have comorbidities that can themselves also cause thrombocytopenia. While DITP is commonly associated with an increased risk of bleeding, HIT and VITT have a high mortality rate due to the high incidence of thromboembolic complications. A structured approach to drug-associated thrombocytopenia/thrombosis can lead to successful treatment and a lower mortality rate. In addition to describing the treatment of DITP, HIT, VITT, and vaccine-associated immune thrombocytopenia, this review also provides the pathophysiological and clinical information necessary for correct patient management.

Chemotherapy-induced thrombocytopenia (CIT) is a common complication of the treatment of non-hematologic malignancies. Many patient-related variables (e.g., age, tumor type, number of prior chemotherapy cycles, amount of bone marrow tumor involvement) determine the extent of CIT. CIT is related to the type and dose of chemotherapy, with regimens containing gemcitabine, platinum, or temozolomide producing it most commonly. Bleeding and the need for platelet transfusions in CIT are rather uncommon except in patients with platelet counts below 25x10⁹/L in whom bleeding rates increase significantly and platelet transfusions are the only treatment. Nonetheless, platelet counts below 70x10⁹/L present a challenge. In patients with such counts, it is important to exclude other causes of thrombocytopenia (medications, infection, thrombotic microangiopathy, post-transfusion purpura, coagulopathy and immune thrombocytopenia). If these are not present, the common approach is to reduce chemotherapy dose intensity or switch to other agents. Unfortunately decreasing relative dose intensity is associated with reduced tumor response and remission rates. Thrombopoietic growth factors (recombinant human thrombopoietin, pegylated human megakaryocyte growth and development factor, romiplostim, eltrombopag, avatrombopag and hetrombopag) improve pretreatment and nadir platelet counts, reduce the need for platelet transfusions, and enable chemotherapy dose intensity to be maintained. National Comprehensive Cancer Network guidelines permit their use but their widespread adoption awaits adequate phase III randomized, placebo-controlled studies demonstrating maintenance of relative dose intensity, reduction of platelet transfusions and bleeding, and possibly improved survival. Their potential appropriate use also depends on consensus by the oncology community as to what constitutes an appropriate pretreatment platelet count as well as identification of patient-related and treatment variables that might predict bleeding.

Chemotherapy‐induced thrombocytopenia (CIT) is common during treatment with antineoplastic therapies and may adversely impact chemotherapy dose intensity. There is no approved therapy for CIT. In our recent phase II randomized study, romiplostim led to correction of platelet counts in 85% of treated patients and allowed resumption of chemotherapy, with low rates of recurrent CIT in the first two cycles or 8 weeks of chemotherapy. However, there is a lack of long‐term data on the efficacy and safety of romiplostim in CIT.

To analyze efficacy and safety of romiplostim in the patients in the phase 2 study, who received romiplostim for ≥1 year.

Twenty‐one patients remained on romiplostim for ≥1 year. We analyzed the effect of romiplostim on platelet counts, absolute neutrophil counts, and hemoglobin, as well as impact on ongoing chemotherapy. We also tracked venous or arterial thrombotic events.

During the study period, romiplostim was effective in preventing reduction of chemotherapy dose intensity due to CIT. Fourteen of the 20 (70%) analyzable patients experienced no episode of CIT, 4 subjects experienced a single chemotherapy dose delay due CIT, and 2 patients required a chemotherapy dose reduction. Platelet counts were preserved throughout the duration of the extension analysis. One patient experienced a proximal deep vein thrombosis, and one patient experienced multiple tumor‐related ischemic events.

Long‐term use of romiplostim for treatment of CIT was effective and safe, with no evidence of resistance or increased risk of thrombosis.

• Carboplatin-based regimens
• FOLFOX/FOLFIRI-based regimens
• Meta-analysis
• Overall survival
• Progression-free survival
• Relative dose intensity

• Antineoplastic Combined Chemotherapy Protocols/adverse effects
• Carboplatin
• Humans
• Pancreatic Neoplasms

• immune thrombocytopenia
• pharmacodynamics
• pharmacokinetics
• structure
• thrombopoietin receptor agonist

• Clinical Trials as Topic
• Humans
• Purpura, Thrombocytopenic, Idiopathic/drug therapy
• Purpura, Thrombocytopenic, Idiopathic/immunology
• Receptors, Fc/chemistry
• Recombinant Fusion Proteins/chemistry
• Recombinant Fusion Proteins/pharmacokinetics
• Thrombopoietin/chemistry
• Thrombopoietin/pharmacokinetics

• P30 CA008748 NCI NIH HHS

• Chemotherapy
• bleeding
• chemotherapy-induced thrombocytopenia
• eltrombopag
• romiplostim
• supportive care
• thrombocytopenia
• thrombopoietin
• thrombopoietin receptor agonist

• anticoagulation
• antifibrinolytic
• antiplatelet
• cancer
• thrombocytopenia
• thrombopoietin receptor agonist
• tranexamic acid

• ITP
• Immune thrombocytopenia
• Romiplostim
• Thrombopoietin
• Thrombopoietin receptor agonist

• CIT
• Thrombocytopenia
• adverse event
• chemotherapy
• chemotherapy-induced thrombocytopenia
• hematologic malignancy
• incidence
• solid tumor
• toxicity

• AKR-501
• Avatrombopag maleate
• TPO-RA
• chemotherapy-induced thrombocytopenia
• chronic liver disease
• immune thrombocytopenia
• thrombocytopenia
• thrombopoietin
• thrombopoietin receptor agonist

• CIT
• Chemotherapy dose delay
• FOLFIRI
• FOLFOX4
• mCRC

The thrombopoietin receptor agonists (TPO-RAs) are a class of platelet growth factors used to treat immune thrombocytopenia (ITP) in children and adults. Romiplostim is a peptide TPO-RA approved for over a decade to treat adults with ITP but was just recently US Food and Drug Administration approved to manage ITP in children 1 year of age and older who have had an inadequate response to corticosteroids, intravenous immunoglobulin, or splenectomy. Like the small molecule TPO-RA eltrombopag, romiplostim offers a high clinical response rate in pediatric patients with ITP, but requires use over an extended, and possibly indefinite, duration. This review is a critical appraisal of the role of romiplostim in pediatric ITP, discussing the safety and efficacy of this agent in clinical trials of children and adults and defining the patients most likely to benefit from romiplostim treatment. The treating hematologist is additionally provided guidance with treatment goals, dosing strategies, toxicity management, and indications for discontinuation.

• TPO
• children
• immune thrombocytopenia
• pediatric
• platelets
• romiplostim
• thrombopoietin
• thrombopoietin receptor agonist

• Bone marrow involvement
• castrate-resistant metastatic prostate cancer
• docetaxel
• severe pancytopenia

• Aged
• Antineoplastic Agents/therapeutic use
• Docetaxel/therapeutic use
• Humans
• Male
• Pancytopenia/diagnostic imaging
• Pancytopenia/drug therapy
• Prostate-Specific Antigen/blood
• Prostatic Neoplasms, Castration-Resistant/blood
• Prostatic Neoplasms, Castration-Resistant/diagnostic imaging
• Prostatic Neoplasms, Castration-Resistant/drug therapy
• Severity of Illness Index
• Treatment Outcome

5-Fluorouracil (5-FU) is an antimetabolite chemotherapy widely used for the treatment of various cancers. However, many cancer patients experience hematological side effects following 5-FU treatment. Here, we investigated the protective effects of 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) as a mitigator against 5-FU-induced hematologic toxicity, including neutropenia, monocytopenia, thrombocytopenia, and thrombocytosis, in Balb/c mice injected with 5-FU (100 mg/kg, i.p.). Administration of PLAG significantly and dose-dependently reduced the duration of neutropenia and improved the nadirs of absolute neutrophil counts (ANCs). Moreover, while the ANCs of all mice in the control fell to the severely neutropenic range, none of the mice in the PLAG 200 and 400 mg/kg-treated groups experienced severe neutropenia. Administration of PLAG significantly delayed the mean first day of monocytopenia and reduced the duration of monocytopenia. PLAG also effectively reduced extreme changes in platelet counts induced by 5-FU treatment, thus preventing 5-FU-induced thrombocytopenia and thrombocytosis. PLAG significantly decreased plasma levels of the chemokine (C–X–C motif) ligand 1 (CXCL1), CXCL2, interleukin (IL)-6, and C-reactive protein (CRP), which were elevated consistently with the occurrence time of neutropenia, monocytopenia, and thrombocytopenia. When compared with olive oil and palmitic linoleic hydroxyl glycerol (PLH), only PLAG effectively mitigated 5-FU-induced hematological toxicity, indicating that it has a distinctive mechanism of action. In conclusion, PLAG may have therapeutic potential as a mitigator for 5-FU-induced neutropenia and other hematological disorders.

• 5-Fluorouracil
• PLAG
• chemotherapy-induced hematological toxicity
• monocytopenia
• neutropenia
• thrombocytopenia
• thrombocytosis

• Eltrombopag
• Mechanism of action
• Megakaryopoiesis
• Romiplostim
• Thrombocytopenia

Chemotherapy-induced thrombocytopenia (CIT) leads to delay or reduction in cancer treatment. There is no approved treatment.

We conducted a phase II randomized trial of romiplostim versus untreated observation in patients with solid tumors with CIT. Before enrollment, patients had platelets less than 100,000/μL for at least 4 weeks, despite delay or dose reduction of chemotherapy. Patients received weekly titrated romiplostim with a target platelet count of 100,000/μL or more, or were monitored with usual care. The primary end point was correction of platelet count within 3 weeks. Twenty-three patients were treated in a randomization phase, and an additional 37 patients were treated in a single-arm, romiplostim phase. Resumption of chemotherapy without recurrent CIT was a secondary end point.

The mean platelet count at enrollment was 62,000/μL. In the randomization phase, 14 of 15 romiplostim-treated patients (93%) experienced correction of their platelet count within 3 weeks, compared with one of eight control patients (12.5%; P < .001). Including all romiplostim-treated patients (N = 52), the mean platelet count at 2 weeks of treatment was 141,000/μL. The mean platelet count in the eight observation patients at 3 weeks was 57,000/μL. Forty-four patients who achieved platelet correction with romiplostim resumed chemotherapy with weekly romiplostim. Only three patients (6.8%) experienced recurrent reduction or delay of chemotherapy because of isolated CIT.

This prospective trial evaluated treatment of CIT with romiplostim. Romiplostim is effective in correcting CIT, and maintenance allows for resumption of chemotherapy without recurrence of CIT in most patients.

Avatrombopag is an orally-administered small molecule thrombopoietin receptor agonist. It was the third thrombopoietin receptor agonist approved for the treatment of immune thrombocytopenia and the first approved to treat periprocedural thrombocytopenia in patients with chronic liver disease (thereby providing an alternative to blood transfusions for these patients). Unlike eltrombopag, avatrombopag does not require a 4 hr food-restricted window around its use and it has not been associated with hepatotoxicity in ITP patients or portal vein thrombosis in patients with chronic liver disease. In ITP patients it can often be dosed less frequently than once daily. It is overall well-tolerated with a side-effect profile similar to placebo in randomized clinical trials. This article will review the clinical development, efficacy, safety, and pharmacology of avatrombopag for use in patients with ITP and thrombocytopenia of chronic liver disease.

• avatrombopag
• hematologic agents
• hemorrhage
• idiopathic
• liver cirrhosis
• liver diseases
• purpura
• receptors
• surgery
• thrombocytopenia
• thrombopoietin

• ITP
• avatrombopag
• eltrombopag
• immune thrombocytopenia
• platelets
• romiplostim
• thrombopoietin
• thrombopoietin receptor agonist

Patients with idiopathic thrombocytopenic purpura (ITP) have low platelet counts and an increased risk of complications. Therefore, these patients generally require high-dose immunoglobulin therapy and platelet transfusion. However, thrombopoietin receptor agonists (TPO-RAs) have recently become available for use in the preoperative treatment strategy for intractable ITP. Recent studies have also reported radiofrequency ablation (RFA) or tissue biopsy as perioperative management for thrombocytopenia using TPO-RA. However, no report has described the use of TPO-RA in a case of hepatectomy.

A 76-year-old man presented with intrahepatic cholangiocarcinoma (IHCC) complicated with ITP. His platelet count was 3.5 × 10⁴/μL. To increase platelet levels prior to surgery, romiplostim was administered subcutaneously (70 μg per week for 3 weeks) and eltrombopag was administered orally (25 mg per day for 23 days), as TPO-RA. His platelet count increased to 14.1 × 10⁴/μL. The patient was successfully and safely treated with left hemi-hepatectomy and TPO-RA as preoperative platelet management.

This case suggests that TPO-RA can be effective, and could serve as a new treatment option in the preoperative management of ITP.

• Idiopathic thrombocytopenic purpura
• Intrahepatic cholangiocarcinoma
• Left hemi-hepatectomy
• Thrombopoietin receptor agonist

• Cancer
• Chemotherapy-induced thrombocytopenia
• Thrombocytopenia

• Antineoplastic Agents/adverse effects
• Antineoplastic Agents/therapeutic use
• Humans
• Neoplasms/complications
• Neoplasms/drug therapy
• Retrospective Studies
• Thrombocytopenia/chemically induced
• Thrombocytopenia/etiology
• Thrombocytopenia/therapy

• desmopressin
• eltrombopag
• operative
• platelets
• romiplostim
• surgical procedures
• thrombopoietin