Hereditary Intrinsic Platelet Disorders

Bernard-Soulier syndrome is a rare autosomal recessive disorder. It impairs platelet adhesion via a defect in the glycoprotein Ib/IX complex that binds endothelial VWF. Bleeding may be severe. Platelets are unusually large. They do not aggregate with ristocetin but aggregate normally with ADP, collagen, and epinephrine.

Large platelets associated with functional abnormalities also occur in the May-Hegglin anomaly, a thrombocytopenic disorder with abnormal white blood cell inclusions, and in the Chédiak-Higashi syndrome Chédiak-Higashi Syndrome Chédiak-Higashi syndrome is a rare, autosomal recessive immunodeficiency disorder characterized by impaired lysis of phagocytized bacteria, resulting in recurrent bacterial respiratory and other... read more .

Platelet transfusion is necessary to control serious bleeding in all of these disorders.

Von Willebrand disease Von Willebrand Disease Von Willebrand disease (VWD) is a hereditary quantitative deficiency or functional abnormality of von Willebrand factor (VWF), which causes platelet dysfunction. Bleeding tendency is usually... read more is due to a deficiency or defect in the von Willebrand factor (VWF) that is needed to permit platelet adhesion. It is often treated with desmopressin or VWF replacement with virally inactivated intermediate-purity factor VIII concentrate or the newer recombinant VWF products.

Disorders of amplification of platelet activation are the most common hereditary intrinsic platelet disorders and produce mild bleeding. They may result from decreased ADP in the platelet granules (storage pool deficiency), from an inability to generate thromboxane A2 from arachidonic acid, or from an inability of platelets to aggregate in response to thromboxane A2.

Platelet aggregation tests reveal impaired aggregation after exposure to collagen, epinephrine, and low levels of ADP and normal aggregation after exposure to ristocetin and high levels of adenosine diphosphate (ADP). The same pattern can result from use of nonsteroidal anti-inflammatory drugs (NSAIDs) or aspirin, the effect of which can persist for several days. Therefore, platelet aggregation tests should not be done in patients who have recently taken these drugs.

Thrombasthenia (Glanzmann disease) is a rare autosomal recessive disorder causing a defect in the platelet glycoprotein IIb/IIIa receptor; platelets cannot aggregate. Patients may have severe mucosal bleeding (eg, nosebleeds that stop only after nasal packing and transfusions of platelet concentrates). The diagnosis is confirmed by the finding that platelets fail to aggregate after exposure to epinephrine, collagen, or even high levels of ADP but do aggregate transiently after exposure to ristocetin. Platelet transfusion is necessary to control serious bleeding.