DETERMINATION OF OPTIMAL PROPHYLACTIC PLATELET DOSE STRATEGY TO PREVENT BLEEDING

确定预防出血的最佳预防性血小板剂量策略

• 批准号: 7375524
• 负责人: ROBERT D WOODSON
• 金额: $ 4.78万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7375524
• 关键词: DETERMINATION; OPTIMAL; PROPHYLACTIC; PLATELET; DOSE

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. [from CRISP website (edited)] Study I: Thrombotic thrombocytopenic purpura (TTP) is a rare disorder of unknown cause that causes multi-organ dysfunction due to occlusion of small blood vessels by microthrombi. Over the past three decades plasma therapy has reduced the death rate from nearly 100% to about 20%. Although most patients recover from the initial episode, the relapse rate is high, and TTP remains a disease with substantial morbidity and mortality. Recent discovery of an association between decreased von Willebrand factorcleaving protease (vWCP) levels and disease activity together with the demonstration of an autoantibody directed at this protein in some patients, raise the possibility that additional immunomodulatory therapy may be of benefit. We propose a randomized study comparing plasma exchange to plasma exchange plus corticosteroids to test the hypothesis that corticosteroids will increase the rate of durable complete responses. We also propose to determine if removing the spleen will decrease the relapse rate in patients who have experienced a relapse of TTP. Studies correlating vWCP levels to disease activity and additional laboratory studies characterizing other possible disease correlates are planned. Study II: Preventing platelet alloimmunization and accompanying platelet transfusion refractoriness are not completely effective, particularly in individuals previously exposed to HLA and platelet antigens through transfusion of non-leukocyte reduced blood products or pregnancy. Selecting platelet products to avoid a refractory patient's alloantibody response is a mainstay of transfusion support for these patients but there is no consensus on which is most effective. We propose to compare the effectiveness of platelet crossmatching with HLA matching in providing platelet transfusion support to patients who are do not respond to random donor platelet transfusions. We will also find out how much factors unrelated to HLA or platelet-specific alloimmunization (non-immune factors, ABO incompatibility) influence platelet transfusion responses.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。[from CRISP网站（编辑）]研究I：血栓性血小板减少性紫癜（TTP）是一种原因不明的罕见疾病，由于微血栓闭塞小血管而导致多器官功能障碍。在过去的三十年中，等离子体疗法已经将死亡率从近100%降低到约20%。虽然大多数患者从初始发作中恢复，但复发率很高，TTP仍然是一种具有显著发病率和死亡率的疾病。最近发现血管性血友病因子裂解蛋白酶（vWCP）水平降低与疾病活动性之间存在相关性，并证明某些患者存在针对该蛋白的自身抗体，这提高了额外免疫调节治疗可能有益的可能性。我们建议进行一项比较血浆置换与血浆置换加皮质类固醇的随机研究，以检验皮质类固醇将增加持久完全缓解率的假设。我们还建议确定切除脾脏是否会降低TTP复发患者的复发率。计划将vWCP水平与疾病活动性相关的研究和表征其他可能的疾病相关性的额外实验室研究。研究II：预防血小板同种异体免疫和伴随的血小板输注无效并不完全有效，特别是在先前通过输注非白细胞减少的血液制品或妊娠暴露于HLA和血小板抗原的个体中。选择血小板产品以避免难治性患者的同种抗体反应是这些患者输血支持的主要支柱，但对于哪种最有效尚无共识。我们建议比较血小板交叉配型与HLA配型在为对随机供体血小板输注无反应的患者提供血小板输注支持方面的有效性。我们还将发现与HLA或血小板特异性同种异体免疫无关的因素（非免疫因素，ABO不相容性）影响血小板输注反应的程度。