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Complement Inhibition Using Eculizumab to Overcome Platelet Transfusion Refractoriness in Patients with Severe Thrombocytopenia

ABSTRACT: Complement Inhibition Using Eculizumab to Overcome Platelet Transfusion Refractoriness in Patients with Severe Thrombocytopenia

PROVIDER: PRJNA938238 | ENA |

REPOSITORIES: ENA

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Complement Inhibition Using Eculizumab to Overcome Platelet Transfusion Refractoriness in Patients with Severe Thrombocytopenia

Project description:Complement Inhibition Using Eculizumab to Overcome Platelet Transfusion Refractoriness in Patients with Severe Thrombocytopenia

| PRJNA938237 | ENA

A pilot trial of complement inhibition using eculizumab to overcome platelet transfusion refractoriness in human leukocyte antigen allo-immunized patients.

Project description:Heavily transfused patients frequently develop human leukocyte antigen (HLA) allo-immunization resulting in platelet transfusion refractoriness and a high risk for life-threatening thrombocytopenia. Data suggest complement activation leading to the destruction of platelets bound by HLA allo-antibodies may play a pathophysiologic role in platelet refractoriness. Here we conducted a pilot trial to investigate the use of eculizumab, a monoclonal antibody that binds and inhibits C5 complement, to treat platelet transfusion refractoriness in allo-immunized patients with severe thrombocytopenia. A single eculizumab infusion was administered to 10 eligible patients, with four (40%) patients overcoming platelet refractories assessed measuring the corrected platelet count increment (CCI) 10-60 min and 18-24 h post transfusion. Responding patients had a reduction in the requirement for subsequent platelet transfusions and had higher post-transfusion platelet increments for 14 days following eculizumab administration. Remarkably, three of the four responders met CCI criteria for response despite receiving HLA-incompatible platelets. Our results suggest that eculizumab has the ability to overcome platelet transfusion refractoriness in patients with broad HLA allo-immunization. This study establishes proof of principle that complement inhibition can treat platelet transfusion refractoriness, laying the foundation for a large multicentre trial to assess the overall efficacy of this approach (ClinicalTrials.gov, identifier: NCT02298933).

| S-EPMC7192788 | biostudies-literature

Proteomic study of apheresis platelets made HLA class I deficient for transfusion of refractory patients

Project description:Refractoriness can occur after repeated PLT transfusions because of alloimmunization to HLA class I antigens on transfused PLTs and generation of anti-HLA antibodies that bind to the foreign PLTs and initiate their destruction. Such refractoriness can be overcome by provision of HLA-matched PLTs from HLA typed donors. However, since the procedure is both expensive and time-consuming, an alternative approach is to deplete PLTs of HLA class I molecules by a brief treatment with citric acid, on ice at low pH. This is shown to be feasible without damaging PLT function

2022-02-14 | PXD027893 | Pride

Platelet proteomics profiling in transfusion adverse events

Project description:Blood platelets destined for transfusion release panoply of molecules during preparation and storage. The leukoreduction process made the transfusion safer but did not completely abolish the adverse events. The rationale is to study the proteome profile of platelet components SDA-PC (platelet pellets) involved in transfusion adverse events.

2019-02-13 | PXD008886 | Pride

Platelet proteomics profiling in transfusion adverse events, part 2

Project description:Blood platelets destined for transfusion release panoply of molecules during preparation and storage. The leukoreduction process made the transfusion safer but did not completely abolish the adverse events. The rationale is to study the proteome profile of platelet components PPC (platelet pellets) involved in transfusion adverse events.

2019-02-13 | PXD003510 | Pride

Serum Proteomics of Severe Fever with Thrombocytopenia Syndrome Patients

Project description:Dabie bandavirus, also termed as severe fever with thrombocytopenia syndrome virus (SFTSV), was first isolated in China in 2010. At this time, the virus was found to have spread to South Korea, Japan, and other countries. A high case fatality rate is reported for SFTS, ranging from 12–50% within various sources. Several omics for clinical studies among SFTS patients as well as studies of cultured SFTSV have attempted to characterize the relevant molecular biology and epidemiology of the disease. However, a global serum proteomics analysis among SFTS patients has not yet been reported to date. Thrombocytopenia and multiple organ failure are the major immediate causes of death among SFTS patients. In this study, serum proteomic changes related to thrombocytopenia, abnormal immune response, and inflammatory activation were documented in SFTS patients. These findings provide useful information forunderstanding the clinical manifestations of SFTS.

2022-10-13 | PXD033989 | Pride

Transfusion transmitted hepatitis E

Project description:Risk of transfusion-transmitted hepatitis E virus infection by pool tested platelet and plasma transfusions

| PRJEB46178 | ENA

Evidence of Listeria monocytogenes infection following platelet transfusion

Project description:Evidence of Listeria monocytogenes infection following platelet transfusion

| PRJEB62146 | ENA

Severe fever with thrombocytopenia syndrome virus

Project description:Research of Severe fever with thrombocytopenia syndrome

| PRJNA1056441 | ENA

Comparison of Interleukin-11 and rhTPO for Recurrent Colorectal Cancer Patients With Thrombocytopenia

Project description:This randomized controlled clinical phase II study was designed to compare the effect of rhTPO with rhIL-11 in improving thrombocytopenia in patients with recurrent colorectal cancer who underwent radiotherapy and with thrombocytopenia.

| 2295813 | ecrin-mdr-crc

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