Platelet activation and hypercoagulability following treatment with porcine factor VIII (HYATE:C) Journal Articles uri icon

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abstract

  • AbstractActivation 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. Am. J. Hematol. 69:192–199, 2002. © 2002 Wiley‐Liss, Inc.

authors

  • Freedman, J
  • Mody, M
  • Lazarus, AH
  • Dewar, L
  • Song, S
  • Blanchette, VS
  • Garvey, MB
  • Ofosu, Frederick A

publication date

  • March 2002