Platelets from Patients with Hereditary Dense-Granule Disorders Support Surface-Associated Factor XII Activation

Identifying the mechanisms underlying the contribution of coagulation factor XII (fXII) to arterial thrombosis is of particular clinical interest. The physiological importance of platelet dense granules-derived polyphosphates in fXII activation is a subject of intense discussion and controversy. Our previous study suggested that the potently activated platelet-surface plays the more essential role in fXII activation. We, therefore, assayed the plasma fXII activation by potently stimulated platelets from a variety of patients with inherited granule disorders to clarify the possible role of surfaceassociated denseor α-granule components. The assay was performed with A23187-stimulated platelets washed from secretions containing fXII(a) inhibitors. Platelets from two patients with dense granule defects and one patient with Wiskott-Aldrich syndrome supported surface-associated fXII activation significantly better than platelets from 52 healthy donors. The platelets from two patients with Hermansky-Pudlak syndrome demonstrated no significant difference compared with the donor group. In contrast, platelets from one patient with α,δ-storage pool deficiency as well as platelets from four patients with gray platelet syndrome of different genetic backgrounds did not support fXII activation. The results underscore the non-essential role of dense granule components in platelet surface-associated fXII activation.