Freedman J, Mody M, Lazarus A H, Dewar L, Song S, Blanchette V S, Garvey M B, Ofosu F A
Transfusion Medicine, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.
Am J Hematol. 2002 Mar;69(3):192-9. doi: 10.1002/ajh.10057.
Activation of platelets and coagulation in vivo was studied in nine patients with hemophilia A and inhibitors to human Factor VIII, prior to and following treatment with porcine Factor VIII (PFVIII; HYATE:C). In addition, six hemophiliac patients were similarly studied after treatment with recombinant Factor VIII (rFVIII). Platelet activation was also examined in vitro using porcine von Willebrand factor (PvWF)-enriched and PvWF-depleted fractions obtained by fractionation of PFVIII. Coagulation was assessed by measuring the concentrations of plasma prothrombin fragment 1+2 concentrations (prothrombinase generation) and Factor Xa-ATIII. Patients treated with PFVIII had significantly increased numbers of circulating platelets expressing CD62 and CD63 (markers of platelet activation) and annexin V (marker of platelet procoagulant activity) compared to patients treated with rFVIII; the former patients also demonstrated an increase in plasma coagulability after therapy. In in vitro experiments it was observed that the platelet-activating and procoagulant capacity of PFVIII resided in the PvWF-enriched fraction, and the same was true for the plasma hypercoagulability following exposure of platelets to PFVIII. These results support the hypothesis that PFVIII-induced platelet activation provides a mechanism for enhancing hemostasis, separate from, and additional to, that due to increased circulating Factor VIII, and it is due to residual PvWF in the PFVIII preparation.
在9例甲型血友病且体内存在人凝血因子VIII抑制剂的患者中，研究了猪凝血因子VIII（PFVIII；HYATE:C）治疗前后体内血小板的激活及凝血情况。此外，对6例血友病患者使用重组凝血因子VIII（rFVIII）治疗后进行了类似研究。还使用通过PFVIII分级分离得到的富含猪血管性血友病因子（PvWF）和去除PvWF的组分在体外检测血小板激活情况。通过测量血浆凝血酶原片段1+2浓度（凝血酶原酶生成）和因子Xa-抗凝血酶III（ATIII）评估凝血情况。与接受rFVIII治疗的患者相比，接受PFVIII治疗的患者循环中表达CD62和CD63（血小板激活标志物）以及膜联蛋白V（血小板促凝活性标志物）的血小板数量显著增加；前者患者治疗后血浆凝固性也有所增加。在体外实验中观察到，PFVIII的血小板激活和促凝能力存在于富含PvWF的组分中，血小板暴露于PFVIII后血浆高凝性情况也是如此。这些结果支持以下假说：PFVIII诱导的血小板激活提供了一种增强止血的机制，这一机制与循环中凝血因子VIII增加所致的机制不同且额外存在，并且这是由于PFVIII制剂中残留的PvWF所致。
