What provokes thrombocytopathies?

Acquired thrombocytopathy. Impaired functional properties of thrombocytes are observed in many severe infectious and somatic diseases, but this is rarely accompanied by the development of hemorrhagic syndrome. The development of hemorrhagic syndrome in these diseases is often provoked by the prescription of physiotherapeutic procedures (UHF, UFO) or drugs that have side effects in the form of inhibition of the functional activity of thrombocytes (drug, iatrogenic thrombocytopathy).

In acquired drug thrombocytopathy, hemorrhagic syndrome is often provoked by the simultaneous administration of several thrombocytoactive drugs. Among thrombocytoactive drugs, acetylsalicylic acid occupies a special place, which in small doses (2.0-3.5 mg/kg) inhibits platelet aggregation, provoking the development of hemorrhagic syndrome, but in large doses (10 mg/kg) inhibits the synthesis of prostacyclin, an inhibitor of adhesion and aggregation of platelets to the damaged vascular wall, thereby promoting thrombus formation.

Acquired thrombocytopathy also occurs in hemoblastoses, B12-deficiency anemia, renal and hepatic failure, DIC syndrome, scurvy and endocrinopathies.

In case of acquired thrombocytopathy, it is necessary to analyze the patient's pedigree, conduct a functional assessment of platelets in parents and close relatives to exclude unrecognized hereditary forms of thrombocytopathy. Some hereditary diseases of amino acid, carbohydrate, lipid and connective tissue metabolism are also accompanied by secondary thrombocytopathy (Marfan, Ehlers-Danlos syndromes, glycogenoses).

Hereditary thrombocytopathies are a group of genetically determined biochemical or structural platelet abnormalities that are accompanied by a disruption of their hemostatic functions. Hereditary thrombocytopathies are the most common genetically determined hemostatic defect, found in 60-80% of patients with recurrent vascular-platelet bleeding and, presumably, in 5-10% of the population.

Depending on the type of molecular and functional disorders, the following types of hereditary thrombocytopathy are distinguished:

1. pathology of membrane proteins - receptors (glycoproteins) to endothelial collagen, von Willebrand factor, thrombin or fibrinogen - manifested by a violation of adhesion and/or aggregation of platelets
2. platelet activation defects (gray platelet syndrome), due to deficiency of alpha and beta granules with substances involved in platelet activation, coagulation and platelet thrombus formation. The defect is manifested by impaired platelet activation and aggregation, slow coagulation, retraction and platelet thrombus formation
3. arachidonic acid metabolism disorder - manifested by a disorder in the synthesis of thromboxane A2 _and platelet aggregation
4. ^{disruption of Ca 2+} ion mobilization - accompanied by disruption of all types of platelet aggregation
5. Deficiency of the 3rd platelet factor - manifests itself as a disruption of the interaction between platelets and blood clotting factors in the retraction of the blood clot.

The defect in the functional activity of platelets in thrombasthenia (described in 1918 by the Swiss pediatrician Glanzmann) is based on the absence of the glycoprotein (GP) IIb/IIIa complex on their membrane, and hence the inability to bind fibrinogen, aggregate with each other, and cause retraction of the blood clot. The IIb/IIIa combination is a receptor specific for platelets and megakaryocytes integrin - a complex that mediates extracellular signals to the cytoskeleton of platelets, which is the initiator of their activation due to the release of mediators of vascular-platelet hemostasis.

Hereditary membrane defects are the reason for the inability of platelets to aggregate in athrombia, and to bind von Willebrand factor and adhere to collagen in Bernard-Soulier anomaly. In various variants of hereditary thrombocytopathy with a defect in the release reaction, deficiencies of cyclooxygenase, thromboxane synthetase, etc. have been identified, which leads to impaired release of hemostatic mediators. In some hereditary thrombocytopathy, a deficiency of dense granules (Herzmansky-Pudlak disease, Landolt syndrome), a deficiency of protein granules (gray platelet syndrome) or their components, and lysosomes have been found. In the genesis of increased bleeding in all variants of thrombocytopathy, the primary significance is given to impaired interaction of platelets with each other, with the plasma link of hemostasis, and the formation of a primary hemostatic plug.

Functional properties of platelets in the most common hereditary thrombocytopathies

Thrombocytopathies	Nature of the functional defect (diagnostic criteria)
Primary
Thrombasthenia	Absence or decrease in platelet aggregation induced by ADP, collagen and adrenaline, absence or sharp decrease in blood clot retraction
Athrombia	Reduction of platelet aggregation induced by ADP, collagen and adrenaline during normal blood clot retraction
Thrombocytopathy with impaired release reaction	A sharp decrease in platelet aggregation: normal primary aggregation, but absence or sharp decrease of the 2nd wave of aggregation
Bernard-Soulier disease	Decreased platelet aggregation induced by ristocetin, bovine fibrinogen with normal aggregation with ADP, collagen, adrenaline
Secondary
Von Willebrand disease	Normal platelet aggregation with ADP, collagen, adrenaline, reduced with ristomycin (the defect is corrected with donor plasma). Decreased level of VIII. Decreased adhesive capacity of platelets
Afibrinogenemia	Sharply reduced fibrinogen levels in the blood in combination with reduced platelet aggregation