1. A heterogeneous group of platelet defects can result in an abnormal secondary wave of platelet aggregation in response to ADP and epinephrine, and diminished responses to low doses of collagen and thrombin. They can be broadly separated into granule defects and defects in the platelet secretion or release reaction. Operationally, these two groups can be separated on the basis of their release of dense granule contents in response to high doses of thrombin. Thrombin activation can overcome most or all of the release reaction abnormalities, so platelets from patients with these disorders will release normal amounts of granule contents; in contrast, patients with reduced granule contents have abnormal release responses even when using high doses of thrombin. α-Granule contents and dense body contents can be measured immunologically and biochemically; electron microscopy can confirm the diagnosis of granule defects. Analysis of the genes or proteins implicated in the different granule defect abnormalities (Wiskott-Aldrich syndrome [WASP], Hermansky-Pudlak syndrome [HPS], Chédiak-Higashi syndrome [LYST], Paris-Trousseau/Jacobson syndrome [FLI1], and inherited platelet disorder with predisposition to leukemia [RUNX1]) can establish the diagnosis. The Quebec platelet disorder is characterized by increased urokinase plasminogen activator (uPA) in α granules and degradation of several α-granule proteins. The diagnosis can be established by immunoblot analysis or analysis of uPA activity. Secretion abnormalities arise due to defects in mechanisms that regulate the release of granule contents, and include abnormalities at the level of guanosine triphosphate (GTP)-binding proteins that link surface receptors to intracellular enzymes, phospholipase C activation, and protein phosphorylation (protein kinase C [PKC]-θ). They also arise from defects in thromboxane A2 synthesis because of deficiencies of phospholipase A2 (PLA2), cyclooxygenase, or thromboxane synthase. Specific studies on signal transduction mechanisms, phosphoinositide metabolism, Ca2+ mobilization, protein phosphorylation, and thromboxane production are needed to define these defects.
Source: Chapter 121. Hereditary Qualitative Platelet Disorders, Williams Hematology, 8e
Citation: Lichtman MA, Kipps TJ, Seligsohn U, Kaushansky K, Prchal JT. Williams Hematology, 8e; 2010 Available at: Accessed: October 13, 2017
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