Hereditary intracellular platelet disorders: causes, symptoms, diagnosis, treatment

Hereditary intracellular platelet disorders are rare diseases and result in lifelong bleeding. Diagnosis is confirmed by platelet aggregation testing. If bleeding is severe, platelet transfusions are necessary.

Platelet adhesion and aggregation are essential for normal hemostasis. Platelet adhesion requires von Willebrand factor and platelet glycoprotein complex Ib-IX. Platelet activation causes platelet aggregation, which is mediated by platelet glycoprotein complex llb-llla and the fibrinogen molecule. Upon platelet activation, adenosine diphosphate (ADP) is released from platelet storage granules and a reaction occurs that converts arachidonic acid to thromboxane A2, which involves cyclooxygenase. Inherited intracellular platelet disorders may involve defects in any of these steps. These abnormalities are suspected in patients with a history of hemorrhagic disease since childhood, normal platelet counts, and normal tests of secondary hemostasis. The diagnosis is usually based on platelet aggregation studies.

Platelet aggregation defect is the most common inherited intracellular platelet disorder that causes easy bleeding. The defect may result from decreased ADP content of platelet granules (storage pool deficiency), defective generation of thromboxane A2 from arachidonic acid, or defective platelet aggregation in response to thromboxane A2 _. Platelet aggregation tests reveal impaired platelet aggregation after exposure to collagen, epinephrine, and low doses of ADP and normal aggregation in response to high doses of ADP. Similar abnormalities may result from exposure to nonsteroidal anti-inflammatory drugs or aspirin, the effects of which occur within a few days. Therefore, platelet aggregation studies should not be performed in patients with recent use of these drugs.

Results of aggregation studies in hereditary platelet function disorders

Disease	Collagen adrenaline small doses	High doses	Ristocetin
Platelet Activation Amplification Disorder	Weakened	Norm	Norm
Thrombasthenia	Absent	Absent	Normal or weakened
Bernard-Soulier syndrome	Norm	Norm	Weakened

ADP - adenosine diphosphate.

Thrombasthenia (Glanzmann disease) is a rare autosomal recessive disorder with an abnormality of the platelet glycoprotein IIb-IIIa complex, in which platelet aggregation is impossible. Patients may have severe mucosal bleeding (eg, nosebleeds that stop only after nasal packing or platelet concentrate transfusion). The diagnosis can be suspected by examining a peripheral blood smear obtained after a finger prick and finding the absence of aggregated platelets. This fact is confirmed by the impairment of platelet aggregation with adrenaline, collagen, and even high doses of ADP, but the presence of aggregation with ristocetin.

Bernard-Soulier syndrome is another rare autosomal recessive disorder in which there is a weakening of platelet adhesion caused by an abnormality of the glycoprotein complex Ib-IX. Bleeding may be severe. Platelets are unusually large. They do not aggregate with ristocetin, but aggregate normally with ADP, collagen, and epinephrine.

Large platelets are associated with May-Hegglin anomaly, thrombocytopenic disorder with abnormal white blood cells, and Chediak-Higashi syndrome.

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