Acquired disorders of platelet function

Acquired disorders may affect platelet-vessel wall interaction and are among the most common causes of a haemorrhagic tendency. These conditions may be associated with a prolonged bleeding time, abnormal platelet aggregation studies and clinical bleeding or bruising.

Drugs that induce platelet dysfunction

• b-lactam antibiotics: penicillins and cephalosporins.

• 'Antiplatelet agents': prostacyclin, dipyridamole.

• Plasma expanders: dextran, hydroxyethyl starch.

• Other drugs: antihistamines, local anaesthetics, b-blockers.

Systemic conditions which affect platelet function

• Glycogen storage disorders types la and Ib.

Conditions causing platelet exhaustion

378 • Cardiopulmonary bypass surgery.

• Others: valvular heart disease, renal allograft rejection, cavernous hae-mangioma.

Dysproteinaemias and antiplatelet antibodies

• Multiple myeloma.

• Waldenstrom's macroglobulinaemia.

• Autoimmune disorders.

Haematological conditions with production of abnormal platelets

• Chronic myeloproliferative disorders.

• Myelodysplasia.


Wide range of drugs reported to impair platelet function (most commonly implicated drugs are listed).

Aspirin is commonest cause of clinically significant bleeding, due to irreversible acetylation and inhibition of cyclooxygenase which interferes with formation of thromboxane A2 in the platelet prostaglandin pathway. Effect on bleeding time occurs within 2h of ingestion of 75mg. Aspirin effect may last up to 10d after long term use. Greater effect on clinical bleeding seen in patients who already have bleeding tendency. Laboratory effects on a normal individual is usually mild and there is marked individual variation in the risk of bleeding.

Effects of aspirin

• Easy bruising, epistaxis, haematomas, haemorrhage after surgery especially in patients with a pre-existing bleeding tendency.

• Prolonged bleeding time/abnormal PFA-100.

• Inhibition of platelet release reaction and second wave of platelet aggregation to low concentrations of ADP and collagen.

NSAIDs cause reversible inhibition of cyclooxygenase. Effect on bleeding and platelet aggregation is brief (only as long as circulating drug present) and less likely to cause clinical bleeding in patients without a prior bleeding disorder. fi-lactam antibiotics affect platelet function by lipophilic attachment to cell membrane in dose-dependent manner. Do so only after sustained high dosage though effect may last 7—10d after discontinuation. Antiplatelet agents, prostacyclin and dipyridamole high cAMP concentration in platelets and inhibit platelet aggregation with little/no effect on bleeding time. A diet rich in fish oils (omega-3 fatty acids) can cause mild prolongation of bleeding time. Ethanol ingestion can impair in vitro platelet function.

Aspirin should be avoided in patients with bleeding tendency. A patient on aspirin should discontinue the drug at least a week prior to a surgical procedure. DDAVP or platelet transfusion should be administered to a patient with severe haemorrhage due to aspirin-induced platelet function defect. In cases with less severe bleeding, discontinuation of the suspected drug is usually effective.

Renal failure—clinical bleeding occurs in patients with uraemia due to chronic renal failure—the former correlates with the severity of the uraemia. Bleeding time does not predict risk of haemorrhage and is not indicated. PFA-100 requires evaluation as a predictor of risk of bleeding in this situation. Associated anaemia also contributes to prolongation of bleeding and correction of anaemia improves the abnormality. Abnormalities of platelet aggregation studies are seen frequently. If haemorrhage occurs in a patient with chronic renal failure, other causes should be excluded before it is attributed to uraemia. Dialysis is mainstay of treatment. DDAVP useful. Conjugated oestrogens improve platelet function.

Liver failure—chronic liver disease, most notably cirrhosis, may be associated with platelet function defects which may be due to abnormalities in the platelet membrane glycoproteins. Abnormalities in bleeding time and platelet aggregation studies may be improved by DDAVP. Haemorrhage in a patient with liver disease is usually multifactorial including decreased levels of coagulation factors, dysfibrinogenaemia, thrombocytopenia due to splenic pooling and DIC.

Conditions causing platelet exhaustion—a number of conditions have been associated with platelet exhaustion (acquired storage pool defect) in which there is laboratory evidence of in vivo platelet activation and decreased platelet aggregation in the pattern of a storage pool defect.

• Cardiopulmonary bypass surgery.

• Valvular heart disease.

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