Hereditary intracellular disturbances of platelets: causes, symptoms, diagnosis, treatment

Hereditary intracellular disturbances of platelets are rare diseases and lead to the manifestation of bleeding throughout life. The diagnosis is confirmed by the study of platelet aggregation. In the presence of severe manifestations of bleeding, transfusion of platelets is necessary.

For normal hemostasis, adhesion and aggregation of platelets are necessary. For platelet adhesion, von Willebrand factor and platelet glycoprotein complex Ib-IX are necessary. Activation of platelets causes their aggregation, which is mediated by the platelet glycoprotein complex llb-llla and the fibrinogen molecule. When platelets are activated from platelet storage granules, adenosine diphosphate (ADP) is released, and arachidonic acid converts to thromboxane A2, in which cyclooxygenase participates. Hereditary intracellular platelet abnormalities can include defects at any of the stages listed. These abnormalities are suspected in patients with hemorrhagic diseases, manifesting from childhood, having a normal number of platelets and normal tests of secondary hemostasis. The diagnosis is usually based on the study of platelet aggregation.

Violation of platelet aggregation is the most common hereditary intracellular platelet disorder, which causes mild bleeding. The defect can be the result of a decrease in the content of ADP in platelets (a storage pool deficit), a violation of thromboxane A generation from arachidonic acid, a violation of platelet aggregation in response to thromboxane A ₂. Platelet aggregation tests reveal a decrease in platelet aggregation after exposure to collagen, adrenaline and small doses of ADP and normal aggregation in response to high doses of ADP. Similar abnormalities may be the result of exposure to non-steroidal anti-inflammatory drugs or aspirin, the effect of which manifests itself within a few days. Therefore, the study of platelet aggregation should not be performed in patients who have recently used these drugs.

Results of aggregation studies with hereditary platelet function abnormalities

Disease	Collagen adrenaline small doses	High doses	Ristocetin
Impaired amplification of platelet activation	Weakened	Norm	Norm
Thrombosis	Absent	Absent	Normal or weak
Bernard-Soulier Syndrome	Norm	Norm	Weakened

ADP - adenosine diphosphate.

Thrombostenia (Glanzman's disease) is a rare autosomal recessive disease with an abnormality of the platelet glycoprotein IIb-IIIa complex, in which platelet aggregation is impossible. Patients may exhibit severe bleeding of the mucous membranes (eg, nosebleeds, stopping only after tamponade of the nose or transfusion of thromboconcentrate). The diagnosis can be suspected when studying the smear of peripheral blood obtained after a finger puncture, and the absence of aggregated platelets. This fact is confirmed by the violation of platelet aggregation with adrenaline, collagen and even high doses of ADP, but the presence of aggregation with ristocetin.

The Bernard-Soulier Syndrome is another rare autosomal recessive disease in which platelet adhesion is reduced due to the anomaly of the Ib-IX glycoprotein complex. Bleeding can be pronounced. Thrombocytes are unusually large. They do not aggregate with ristocetin, but normally aggregate with ADP, collagen and adrenaline.

Large platelets are associated with the Meya-Heglin anomaly, thrombocytopenic disease with abnormal leukocytes and Chediak-Higashi syndrome.

[1], [2], [3], [4], [5], [6], [7]