Skip to Main Content

Abnormalities of platelet function manifest themselves primarily as excessive hemorrhage at mucocutaneous sites, with ecchymoses, petechiae, epistaxis, gingival hemorrhage, and menorrhagia most common. Both quantitative and qualitative platelet abnormalities can produce these symptoms, so it is necessary to exclude thrombocytopenia (see Chap. 119) by performing a platelet count. A prolonged bleeding time in a patient with a normal platelet count is indicative of a qualitative platelet abnormality, von Willebrand disease (see Chap. 127), or afibrinogenemia (see Chap. 126). Chap. 122 discusses acquired qualitative platelet abnormalities, and this chapter discusses the hereditary qualitative platelet abnormalities.

The hereditary qualitative platelet disorders can be classified according to the major locus of the defect (Table 121–1; Fig. 121–1). Thus, abnormalities of platelet glycoproteins, platelet granules, and signal transduction and secretion can all result in hemorrhagic diatheses and prolonged bleeding times. Glanzmann thrombasthenia results from abnormalities in one of two integrin subunits, either αIIb (glycoprotein [GP] IIb) or β3 (GPIIIa), resulting in loss or dysfunction of the αIIbβ3 (GPIIb/IIIa) receptor. This results in a profound defect in platelet aggregation and secondary defects in platelet adhesion and platelet coagulant activity. Loss of the platelet GPIb/IX/V complex because of abnormalities in GPIbα, GPIbβ, or GPIX results in the Bernard-Soulier syndrome, which is characterized by giant platelets and modest thrombocytopenia. The major defect is in platelet adhesion because of a decrease in platelet interactions with von Willebrand factor, but abnormalities in αIIbβ3 activation and thrombin-induced aggregation are also present. A gain of function defect in GPIbα (platelet-type [pseudo-] von Willebrand disease) can also produce a hemorrhagic disorder via depletion of high-molecular-weight von Willebrand multimers. Inherited defects in agonist receptors or proteins involved in signal transduction may also produce hemorrhagic symptoms. Abnormalities of platelet coagulant activity, that is, the ability of platelets to facilitate thrombin generation (see Chap. 114), can also lead to a hemorrhagic diathesis, but this platelet defect is unique in not usually producing mucocutaneous hemorrhage or a prolonged bleeding time.

Table 121–1. Inherited Disorders of Platelet Function

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.