1. Evaluation of patients for inherited abnormalities in platelet number or function. The major and well-recognized entities are shown here. A reduced platelet count occurs in patients with purely quantitative platelet disorders (inherited or acquired) as well as in patients who have inherited qualitative platelet disorders. Chapter 117 discusses inherited thrombocytopenias. Notable among patients with thrombocytopenia and inherited platelet dysfunction is the Bernard-Soulier syndrome (BSS), which is characterized by giant platelets. Patients with the Gray platelet syndrome are characterized by thrombocytopenia and gray appearance of platelets on the blood smear due to paucity of granules. Platelet aggregation studies can provide clues regarding the nature of the underlying platelet abnormality. Decreased response to ristocetin alone with normal responses to other agonists is found in the BSS and von Willebrand disease (VWD; type I and type III). The response to ristocetin is enhanced in VWD type IIB and the platelet-type VWD. Impaired response to collagen or epinephrine alone may suggest a defect in their respective receptors. Patients with adenosine diphosphate (ADP) and thromboxane receptor defects have impaired responses to multiple agonists because of the feedback amplification provided by ADP and thromboxane A2 (TXA2) when activated by different agonists. Absence of both primary and secondary waves of aggregation in response to all physiologic agonists occurs in Glanzmann thrombasthenia (GT). A heterogeneous group of platelet defects are characterized by a decreased secondary wave of platelet aggregation in response to ADP and epinephrine, and diminished responses to low doses of collagen, TXA2 and thrombin. They can be broadly separated into granule defects (involving dense [δ] or both dense and α granules) and defects in the platelet secretion or release reaction associated with normal dense granule stores. The granule defects may occur in isolation or in association with other syndromes. Secretion abnormalities arise from defects in mechanisms that regulate the release of granule contents, and include defects at the level of platelet receptors (ADP, TXA2), signaling events involving guanosine triphosphate (GTP)–binding proteins that link surface receptors to intracellular enzymes, phospholipase C activation, and protein phosphorylation (protein kinase C [PKC]-θ). They may also arise from defects in TXA2 synthesis because of deficiencies of phospholipase A2 (PLA2), cyclooxygenase, or thromboxane synthase. Patients with the Scott syndrome are characterized by a normal bleeding time, normal responses in aggregation studies, and a shortened prothrombin time, which reflects the defect in the platelet–coagulant protein interactions. Additional details on the various entities are described in the section “General Approach to Patients with Mucocutaneous Bleeding Symptoms for Abnormalities in Platelet Number or Function.” GP, glycoprotein; PLA2, phospholipase A2; PLC, phospholipase C; SPD, storage pool deficiency; u-PA, urokinase plasminogen activator; VWF, von Willebrand factor.
Source: Hereditary Qualitative Platelet Disorders, Williams Hematology, 9e
Citation: Kaushansky K, Lichtman MA, Prchal JT, Levi MM, Press OW, Burns LJ, Caligiuri M. Williams Hematology, 9e; 2015 Available at: Accessed: March 08, 2018
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