Читать книгу Pathy's Principles and Practice of Geriatric Medicine - Группа авторов - Страница 580

By far the most frequent platelet functional defects (Table 24.2) are those acquired following treatment with aspirin or clopidogrel medication. Aspirin works by irreversibly acetylating the platelet enzyme prostaglandin synthase and thereby decreases platelet reactivity and aggregation for the platelet’s entire lifespan. Aspirin also prolongs the skin bleeding time. In recent years, aspirin has become established in treating acute arterial thrombotic events, such as unstable angina and myocardial infarction, and in the secondary prophylaxis of myocardial infarction and transient ischaemic attack and stroke. There is a trend toward decreasing the dose of aspirin, which not only decreases gastrointestinal toxicity but also results in the platelet being irreversibly acetylated by aspirin in the portal circulation; with low total dose, aspirin is then deacetylated within the liver, resulting in no systemic bioavailability of aspirin and thus in no inhibition of the beneficial effects of endothelial cell prostacyclin production. Clopidogrel is another orally active antiplatelet agent that acts by irreversible inhibition of the platelet ADP receptor. Prasugrel and Ticagrelor work by inhibiting irreversibly the same target. Other drugs that affect platelet function include non‐steroidal anti‐inflammatory drugs (NSAIDs), high doses of penicillin and cephalosporins, and some antidepressants and anaesthetics. Abnormal platelet function can occur in any of the myeloproliferative disorders – primary proliferative polycythaemia, essential thrombocythaemia, chronic myeloid leukaemia, and myelofibrosis – leading to both bleeding and thrombosis. Bleeding is paradoxically more common with raised platelet counts, especially when greater than 1000 × 10⁹/l.

Table 24.2 Causes of acquired platelet functional defects other than due to drugs, especially aspirin or clopidogrel.

Myeloproliferative syndromes

Myelodysplasia

Uraemia

Cardiopulmonary bypass

Similarly, in myelodysplastic syndromes, in addition to frequent thrombocytopenia, abnormal platelet function is common, and bleeding can cause severe morbidity requiring platelet transfusion; bleeding and infection are the most common causes of death. Abnormalities of platelet function leading to a prolonged bleeding time frequently occur in uraemia. This improves with dialysis and can be specifically treated, if necessary, with desmopressin (DDAVP). Due primarily to proteolytic degradation of platelet surface glycoproteins by plasma, an acquired platelet function defect occurs during extracorporeal circulation in cardiopulmonary bypass. It can be ameliorated by using the fibrinolytic inhibitor aprotinin but may also require platelet transfusion. Congenital functional platelet defects are extremely rare, with an incidence of less than one per million of the population. Deficiency of the platelet‐specific glycoprotein Ib, which allows interaction with the von Willebrand factor, occurs in Bernard–Soulier syndrome; and deficiency of the platelet surface glycoprotein IIb/IIIa occurs in Glanzmann’s thrombasthenia. Deficiency of platelet alpha and dense granules, which are usually released upon platelet aggregation and are involved in the recruitment of large numbers of platelets into the platelet plug, are deficient in storage pool disease.⁶