The effect of heparin on platelet aggregation by common inductors and by ristocetin in congenital bleeding disorders due to factor VIII or fibrinogen defects

Abstract

Platelet aggregation by various inductors was studied in citrated and heparinized plasma of the following groups of subjects: Normal, hemophilia A, combined factor V and factor VIII deficiency, v. Willeprand's disease and congenital afibrinognemia. The results may be summarized as follows: A-platelet aggregation in citrated plasm 1) platelet aggregation by common inductors ADP, adrenalin and collagen was normal in all groups of subjects but for the patients with congential afibrinogenemia in whom adrenalin induced aggregation was absent or markedly refuced whereas ADP and collagen gave slightly reduced or near normal aggregation curves. 2) platelet aggregation by ristocetin was normal in all groups of subjects but for v. Willebrand's disease in which it was absent. B-platelet aggregation in heparized plasma. 1) platelet aggregation by common inductors resulted to be normal in all groups of subjects except in congenital afibrinogenemia. In this latter case the pattern was still mildly defective but here was an increased aggregation as compared to citrated plasma. These findings have been interpretemmon inductors. 2) platelet aggregation by ristocetin resulted to be absent in all groups of subjects investigated. The possible mechanism of action of the inhibitory effect exercised py heparin with regard to restocetin is discussed.

The Effect of Heparin on the Interaction of Factor VIII and Human Platelets <i>in vitro</i>

“…In 1975, data presented by Howard and by us [7,8] showed that high concentrations of heparin inhibited ristocetin-induced platelet aggregation; similar results were reported later by Pekcelen and Inceman [14].…”

“…High concentrations of heparin were reported to inhibit RIPA in citrated PRP; a similar inhibitory effect was also noted in heparinized PRP [7,8,14]. In contrast to our results, Howard [8] found that smaller amounts of heparin were needed to inhibit RIPA in washed platelets.…”

“…Material and methods have been described in detail elsewhere [6,7]. Only new data will be given herein.…”

“…Most of the results reported seem to indicate that heparin has a potentiating effect on platelet aggregation induced by ADP, adrenalin and collagen or at least a potentiating effect on primary aggregation induced by these agents [7,12,13,15,17,22]. It has never been 1 This study was supported in part by a grant from the CNR, Rome (grant CT 75.00902.04) and by a grant from the Anna Villa Rusconi Foundation, Varese, Italy. found that heparin exercises an inhibitory effect on platelet aggregation to common inducers, like to that observed in the ristocetin-induced platelet aggregation system.…”

Heparin inhibition of von Willebrand factor-dependent platelet function in vitro and in vivo.

“…) platelet function may be contributory (1,4). Clinical and laboratory investigations have shown that therapeutic doses ofheparin can prolong the bleeding time (5,6), and several investigators have noted that heparin in vitro could inhibit ristocetinmediated platelet agglutination (7)(8)(9). These findings raise the possibility that heparin's interference with platelet function may involve von Willebrand factor (vWF).'…”