Platelet activation induced by porcine factor VIII (Hyate:C).
We studied the effects of porcine factor VIII (P-FVIII; Hyate:C) and other coagulation products employed in the management of patients with hemophilia A, on platelet activation in vitro. Exposure of normal resting platelets to P-FVIII resulted in platelet activation, as manifested by increased expression of the platelet surface activation markers CD62, CD63, and activated-GPIIbIIIa, and by activation-induced modulation of expression of normal platelet membrane glycoproteins CD41, CD42, and CD36. In contrast, platelet activation was not observed after exposure of the platelets to human FVIII, FEIBA, recombinant FVIIa, or cryosupernatant plasma. As with thrombin, exposure of platelets to P-FVIII resulted in the generation of platelet microparticles, an effect not seen not with the other products. In contrast to the characteristic reduction in expression in the number of CD42 molecules detected on thrombin-activated platelets, P-FVIII-stimulated platelets showed a small increase in CD42 expression. In contrast to thrombin, P-FVIII did not cause platelet dense granule release. The results indicate that therapeutic P-FVIII activates platelets, likely in ways that are different from the platelet activation seen with thrombin. The observed platelet activation and microparticle generation may provide a "hypercoagulable" mechanism for hemostasis with P-FVIII therapy separate from, and additional to, that due to increased circulating FVIII levels.
Chang
H
H
St. Michael's Hospital University of Toronto, Ontario, Canada.
Mody
M
M
Lazarus
A H
AH
Ofosu
F
F
Garvey
M B
MB
Blanchette
V
V
Teitel
J
J
Freedman
J
J
D000818:Animals; D015703:Antigens, CD; D001792:Blood Platelets / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D019040:E-Selectin / Q000378:metabolism; D005169:Factor VIII / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D066298:In Vitro Techniques; D008830:Microbodies / Q000502:physiology; D015539:Platelet Activation / Q000187:drug effects*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D010980:Platelet Membrane Glycoproteins; D013552:Swine; D060149:Tetraspanin 30; D014841:von Willebrand Factor / Q000494:pharmacology
D015703:Antigens, CD; C554586:CD63 protein, human; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D010980:Platelet Membrane Glycoproteins; D060149:Tetraspanin 30; D014841:von Willebrand Factor; D005169:Factor VIII