Hereditary intrinsic platelet disorders

[Tariq Zaki]

Hereditary intrinsic platelet disorders are rare and cause lifelong bleeding tendencies. Diagnosis is confirmed by platelet aggregation tests. Platelet transfusion is usually necessary to control serious bleeding.
(See also Overview of Platelet Disorders.)
Normal hemostasis requires platelet adhesion and activation.
Platelet adhesion (ie, of platelets to exposed vascular subendothelium) requires von Willebrand factor (VWF) and the platelet glycoprotein Ib/IX complex.
Platelet activation promotes platelet aggregation and fibrinogen binding and requires the platelet glycoprotein IIb/IIIa complex. Activation involves release of adenosine diphosphate (ADP) from platelet storage granules and conversion of arachidonic acid to thromboxane A2 via a cyclooxygenase-mediated reaction. The released ADP acts on the P2Y12 receptor on other platelets, thereby activating them and recruiting them to the site of injury. Additionally, ADP (and thromboxane A2) then promotes changes in the platelet glycoprotein IIb/IIIa complex, which in turn increases fibrinogen binding, thereby allowing platelets to aggregate.
Hereditary intrinsic platelet disorders can involve defects in any of these substrates and steps. These disorders are suspected in patients with lifelong bleeding disorders who have normal platelet counts and coagulation study results. Diagnosis usually is based on platelet aggregation tests; however, the results of platelet aggregation tests can be highly variable, and interpretation of results is often inconclusive (see Results of Aggregation Tests in Hereditary Disorders of Platelet Function). Platelet aggregation tests assess the ability of platelets to clump in response to the addition of various activators (eg, collagen, epinephrine , ADP, ristocetin).
Platelet aggregometry studies are unreliable when platelet counts are lt; 100,000/mcL.