Patients with congenital factor V deficiency have decreased factor Xa binding sites on their platelets.
Human platelets have binding sites for plasma coagulation Factor X(a) that are available only after the platelet release reaction. Platelets from 15 normal donors bound 216+/-52 (SD) molecules of Factor X(a) per platelet. The association of Factor X(a) with its platelet surface receptor results in a 300,000-fold increase in the catalytic activity of Factor X(a) in forming thrombin from prothrombin. The turnover number for platelet-bound Factor X(a) was 1,850+/-460 mol thrombin/ml per min per mol Factor X(a) in experiments with platelets from 15 normal donors. Platelets from five patients with varying degrees of Factor V deficiency were investigated to determine whether or not coagulation Factor V participates in either aspect of the Factor X(a)-platelet interaction. The binding of Factor X(a) to platelets and the accompanying increase in rate of thrombin formation were either reduced in parallel or absent in each case with values ranging from 0 to 45% of control values. The apparent affinity of Factor X(a) from Factor V-deficient patients was normal when platelet binding was detected. The supernate from thrombin-treated control platelets, which contains Factor V activity, corrected the Factor X(a) binding deficiency of the platelets from three patients tested. Immunoreactive Factor V determined with an homologous antibody corresponded to the functional Factor V activity of platelets from one patient with Factor V deficiency, suggesting that the patient's platelets have a decreased amount of normal Factor V. The ability of platelets from the patients to bind Factor X(a) and increase the rate of thrombin formation correlated with the severity of each patient's bleeding disorder better than the plasma level of Factor V. The results indicate that Factor V is required for the Factor X(a)-platelet interaction and that thrombin formation at the platelet surface is important in normal hemostasis.
D000328:Adult; D001665:Binding Sites; D001792:Blood Platelets / Q000378:metabolism*; D005165:Factor V / Q000032:analysis / Q000378:metabolism; D005166:Factor V Deficiency / Q000097:blood* / Q000151:congenital; D005170:Factor X / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008722:Methods; D008875:Middle Aged; D011485:Protein Binding; D012701:Serotonin / Q000097:blood; D013917:Thrombin / Q000378:metabolism
D012701:Serotonin; D005165:Factor V; D005170:Factor X; D013917:Thrombin