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Hereditary Intrinsic Platelet Disorders


David J. Kuter

, MD, DPhil, Harvard Medical School

Reviewed/Revised Jun 2022 | Modified Sep 2022
Topic Resources

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.

  • Platelet adhesion

  • Platelet 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 Results of Aggregation Tests in Hereditary Disorders of Platelet Function 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). Diagnosis of these disorders usually requires the assistance of physicians expert in such coagulation disorders.

Platelet aggregometry studies are unreliable when platelet counts are < 100,000/mcL (< 100 × 109/L).


Disorders of platelet adhesion

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 platelet activation

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.

Drugs Mentioned In This Article

Drug Name Select Trade
DDAVP, Minirin, Nocdurna, Noctiva, Stimate
Anacin Adult Low Strength, Aspergum, Aspir-Low, Aspirtab , Aspir-Trin , Bayer Advanced Aspirin, Bayer Aspirin, Bayer Aspirin Extra Strength, Bayer Aspirin Plus, Bayer Aspirin Regimen, Bayer Children's Aspirin, Bayer Extra Strength, Bayer Extra Strength Plus, Bayer Genuine Aspirin, Bayer Low Dose Aspirin Regimen, Bayer Womens Aspirin , BeneHealth Aspirin, Bufferin, Bufferin Extra Strength, Bufferin Low Dose, DURLAZA, Easprin , Ecotrin, Ecotrin Low Strength, Genacote, Halfprin, MiniPrin, St. Joseph Adult Low Strength, St. Joseph Aspirin, VAZALORE, Zero Order Release Aspirin, ZORprin
NOTE: This is the Professional Version. CONSUMERS: View Consumer Version
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