Platelet activation and hypercoagulability following treatment with porcine factor VIII (HYATE:C).
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.
Freedman
J
J
Transfusion Medicine, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada. freedman@smh.toronto.on.ca
Mody
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Lazarus
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Dewar
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Song
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Blanchette
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Garvey
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Ofosu
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D000293:Adolescent; D000328:Adult; D000818:Animals; D001792:Blood Platelets / Q000276:immunology / Q000378:metabolism; D016022:Case-Control Studies; D002648:Child; D004340:Drug Contamination; D005169:Factor VIII / Q000008:administration & dosage / Q000494:pharmacology* / Q000592:standards; D006467:Hemophilia A / Q000097:blood / Q000150:complications / Q000188:drug therapy; D006487:Hemostasis / Q000187:drug effects; D006801:Humans; D016130:Immunophenotyping; D007700:Kinetics; D008875:Middle Aged; D015539:Platelet Activation / Q000187:drug effects*; D013552:Swine; D019851:Thrombophilia / Q000097:blood / Q000139:chemically induced*; D014841:von Willebrand Factor / Q000032:analysis / Q000494:pharmacology
D014841:von Willebrand Factor; D005169:Factor VIII