The bleeding diathesis in human glycogen storage disease type I: [formula omitted] identification of a naturally occurring inhibitor of ristocetin-induced platelet aggregation

Abstract

Platelet aggregation in response to adenosine diphosphate (ADP), epinephrine and ristocetin was studied in six patients with glycogen storage disease type I (GSD-I), five of whom had Ivy bleeding times in excess of six minutes. As has been previously reported, these patients demonstrated impaired platelet aggregation in response to ADP and epinephrine. We now report impaired ristocetin dependent platelet aggregation in those patients having an abnormal bleeding time. The impaired platelet aggregation was not corrected by the addition of purified factor VIII/von Willebrand's factor to platelet rich plasma from these patients. Normal ristocetin-induced platelet aggregation was observed when GSD-I platelets were suspended in buffer and factor VIII/von Willebrand's factor was added. Moreover, in the presence of GSD-I serum, the response to ristocetin was normal. When washed platelets from normal subjects were suspended in GSD-I plasma, abnormal ristocetin-induced platelet aggregation was observed. These data indicate the presence of an inhibitor(s) in GSD-I plasma which may be responsible for impaired ristocetin-induced platelet aggregation in patients with glycogen storage disease type I. This conclusion.is further supported by the finding of a parallel inhibition in the binding of 125I-factor VIII/von Willebrand's factor to platelets by various fractions of GSD-I plasma separated by gel filtration. The elution position of the inhibitor and its absence from serum suggest that fibrinogen may be the inhibitor. Plasma from four patients with glycogen storage disease type III showed no evidence of a similar inhibitor(s).