Drugsthat Prevent Fibrinolysis

Antifibrinolytics are useful in a number of bleeding disorders.

Tranexamic acid competitively inhibits the binding of plasminogen and t-PA to fibrin and effectively blocks conversion of plasminogen to plasmin (which causes dissolution of fibrin); fibrinolysis is thus retarded. After an i.v. bolus injection it is excreted largely unchanged in the urine; the tx/2 is 1.5 h. It may also be administered orally or topically.

The principal indication for tranexamic acid is to prevent the hyperplasminaemic bleeding state that results from damage to certain tissues rich in plasminogen activator, e.g. after prostatic surgery, tonsillectomy, uterine cervical conisation, and menorrhagia, whether primary or induced by an intrauterine contraceptive device. Tranexamic acid may also reduce bleeding after ocular trauma and in haemophiliacs after dental extraction where it is normally used in combination with desmopressin. The drug benefits some patients with hereditary angioedema presumably by preventing the plasmin-induced uncontrolled activation of the complement system which characterises that condition. Tranexamic acid may be of value in thrombocytopenia (idiopathic or following cytotoxic chemotherapy) to reduce the risk of haemorrhage by inhibiting natural fibrinolytic déstabilisation of small platelet plugs; the requirement for platelet transfusion is thereby reduced. It may also be used for overdose with thrombolytic agents.

Adverse effects are rare but include nausea, diarrhoea and sometimes orthostatic hypotension. It is contraindicated in patients with haematuria as it will prevent clot lysis in the urinary tract and result in 'clot colic'.

Aprotinin is a naturally-occurring inhibitor of plasmin and other proteolytic enzymes which has been used to limit bleeding following open heart surgery with extracorporeal circulation, and for the treatment of life-threatening haemorrhage due to hyperplasminaemia complicating surgery of malignant tumours or thrombolytic therapy or in Jehovah's witnesses.19 It must be administered intravenously or topically.

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