Heparin inhibition of von Willebrand factor-dependent platelet function in vitro and in vivo.
The intravenous administration of heparin to patients before open heart surgery reduced ristocetin cofactor activity by 58% (P less than 0.01, t test), and this impairment of von Willebrand factor-dependent platelet function was closely related to plasma heparin levels (r2 = 0.9), but not to plasma von Willebrand factor (vWF) levels. We hypothesized that heparin may inhibit vWF-dependent platelet hemostatic functions by directly binding vWF in solution and interfering with vWF-GpIb binding. Using the in vitro techniques of ristocetin-induced platelet agglutination, fluorescent flow cytometric measurement of vWF-platelet binding, and conventional radioligand binding assays we observed that heparin inhibited both vWF-dependent platelet function and vWF-platelet binding in a parallel and dose-dependent manner. Heparin also inhibited platelet agglutination induced by bovine vWF and inhibited the binding of human asialo-vWF to platelets in ristocetin-free systems. The inhibitory potency of heparin was not dependent upon its affinity for antithrombin III, but was molecular weight dependent: homogeneous preparations of lower molecular weight were less inhibitory. Heparin impairment of vWF function may explain why some hemorrhagic complications of heparin therapy are not predictable based on techniques for monitoring the conventional anticoagulant effects of heparin.
Sobel
M
M
Department of Surgery, Medical College of Virginia, Virginia Commonwealth University, Richmond.
McNeill
P M
PM
Carlson
P L
PL
Kermode
J C
JC
Adelman
B
B
Conroy
R
R
Marques
D
D
D000371:Agglutination; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D006493:Heparin / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D012310:Ristocetin / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014841:von Willebrand Factor / Q000032:analysis / Q000502:physiology*
D014841:von Willebrand Factor; D012310:Ristocetin; D006493:Heparin