Aspirin responsive platelet thrombophilia in essential thrombocythemia and polycythemia vera

Figure 6 JAK2^V617F or MPL⁵¹⁵ constitutively activated (hypersensitive) platelets in thrombocythemia spontaneously aggregate and secrete products (platelet derived growth factor et) at high shear stress in the end-arterial cerebral, ocular, coronary and peripheral circulation. This is associated with a broad spectrum of microvascular ischemic circulation disturbances (B) caused by transient von Willebrand factor (vWF)-rich platelet agregates or occlusive vWF-rich platelet thrombi on histological investigation (Figure 1). Circulating activated platelets express increase of platelet membrane surface markers, e.g., CD62p, and circulating platelet aggregates induce endothelial cell activation with increased thrombomoduline (TM) and soluble vascular adhesion molecule (sVCAM) plasma levels (right). Increase of platelet counts from below to far above 1000 × 10⁹/L is associated with platelet-induced proteolysis of large vWF multimers with clinical features of hemorrhagic thrombocythemia (HT, A) due to an acquired von Willebrand disease type 2A [prolonged PFA-110 closure times (CT) and bleeding times]. TIA: Transient cerebral ischemic attack; E: Erythromelalgia.