Poon Man-Chiu, Di Minno Giovanni, d'Oiron Roseline, Zotz Rainer
University of Calgary Foothills Hospital, Southern Alberta Rare Blood and Bleeding Disorders Comprehensive Care Program, Calgary, Canada.
Department of Clinical Medicine and Surgery, Regional Reference Center for Coagulation Disorders, Federico II University, Naples, Italy.
Transfus Med Rev. 2016 Apr;30(2):92-9. doi: 10.1016/j.tmrv.2016.01.001. Epub 2016 Jan 30.
Glanzmann thrombasthenia (GT) is a rare inherited autosomal recessive bleeding disorder of platelet function caused by a quantitative or qualitative defect of platelet membrane glycoprotein IIb/IIIa (integrin αIIbβ3), a fibrinogen receptor required for platelet aggregation. Bleeds in GT are variable and may be severe and unpredictable. Bleeding not responsive to local and adjunctive measures, as well as surgical procedures, is treated with platelets, recombinant activated factor VII (rFVIIa), or antifibrinolytics, alone or in combination. Although platelets are the standard treatment for GT, their use is associated with the risk of blood-borne infection transmission and may also cause the development of platelet antibodies (to human leukocyte antigens and/or αIIbβ3), potentially resulting in platelet refractoriness. Currently, where rFVIIa is approved for use in GT, this is mostly for patients with platelet antibodies and/or a history of platelet refractoriness. However, data from the prospective Glanzmann's Thrombasthenia Registry (829 bleeds and 206 procedures in 218 GT patients) show that rFVIIa was frequently used in nonsurgical and surgical bleeds, with high efficacy rates, irrespective of platelet antibodies/refractoriness status. The mechanisms underpinning rFVIIa effectiveness in GT have been studied. At therapeutic concentrations, rFVIIa binds to activated platelets and directly activates FX to FXa, resulting in a burst of thrombin generation. Thrombin converts fibrinogen to fibrin and also enhances GT platelet adhesion and aggregation mediated by the newly converted (polymeric) fibrin, leading to primary hemostasis at the wound site. In addition, thrombin improves the final clot structure and activates thrombin-activatable fibrinolysis inhibitor to decrease clot lysis.
Glanzmann血小板无力症（GT）是一种罕见的遗传性常染色体隐性血小板功能出血性疾病，由血小板膜糖蛋白IIb/IIIa（整合素αIIbβ3）的数量或质量缺陷引起，整合素αIIbβ3是血小板聚集所需的纤维蛋白原受体。GT患者的出血情况各不相同，可能严重且不可预测。对局部和辅助措施以及外科手术无反应的出血，可单独或联合使用血小板、重组活化因子VII（rFVIIa）或抗纤维蛋白溶解剂进行治疗。虽然血小板是GT的标准治疗方法，但其使用与血源性感染传播风险相关，还可能导致血小板抗体（针对人类白细胞抗原和/或αIIbβ3）的产生，从而可能导致血小板不应性。目前，在rFVIIa被批准用于GT的地区，主要用于有血小板抗体和/或有血小板不应性病史的患者。然而，来自前瞻性Glanzmann血小板无力症登记处（218例GT患者中的829次出血和206次手术）的数据显示，rFVIIa经常用于非手术和手术出血，无论血小板抗体/不应性状态如何，疗效都很高。已经对rFVIIa在GT中有效性的机制进行了研究。在治疗浓度下，rFVIIa与活化的血小板结合并直接将FX激活为FXa，导致凝血酶大量生成。凝血酶将纤维蛋白原转化为纤维蛋白，还增强了由新转化的（聚合的）纤维蛋白介导的GT血小板黏附和聚集，从而在伤口部位实现初级止血。此外，凝血酶改善最终的血凝块结构并激活凝血酶可激活的纤维蛋白溶解抑制剂以减少血凝块溶解。
