Anticoagulant and Thrombolytic Drugs1 II

Abstract

Since platelets have a dominant role in the early stages of thrombosis, interference with fibrin formation by anticoagulant drugs can have only a limited place in the prevention or treatment of thrombosis. The precise indications for the use of anticoagulant drugs are not yet defined: there is evidence for their value in the prophylaxis and treatment of deep venous thrombosis and pulmonary embolism, in transient cerebral ischaemic attacks, to prevent emboli in rheumatic heart disease, and in ischaemic heart disease. Sensitivity reactions to the indanedione derivatives are relatively frequent: coumarin derivatives are therefore preferred for oral anticoagulant therapy. Heparin is valuable for the rapid induction of an anticoagulant effect. The place of ancrod is not established, but it holds promise as an agent in the management of thrombotic disease. Most surgical procedures can be carried out in patients under treatment with coumarinindanedione drugs, but heparin must be neutralised if surgery becomes necessary. In pregnancy coumarin-indanedione drugs should probably be avoided and heparin used if anticoagulant therapy is indicated. Breast-feeding should be stopped if oral anticoagulants are required in the post-partum period. Thrombolytic therapy has been used in a wide variety of thrombo-embolic disorders, but adequate evaluation in specific conditions is largely lacking. Disseminated intravascular coagulation presents a wide spectrum of clinical severity: treatment must take account of both the cause and the effects of the process and includes the elimination of the source of coagulant material and, where appropriate, the use of heparin, the replacement of depleted coagulation factors and treatment of the underlying disease. Difficulty in the maintenance of a stable therapeutic level of anticoagulant effect with the coumarin-indanedione derivatives may be due to erratic ingestion of the tablets, intercurrent illness, or the concurrent therapy with drugs which potentiate or decrease the anticoagulant effect of the coumarin drugs. The side-effects of the oral anticoagulant drugs fall into two groups: (i) haemorrhagic side-effects due to over-dosage and (ii) non-haemorrhagic side-effects. Non-haemorrhagic side-effects are rare with coumarin derivatives, but sensitivity reactions to indanedione derivatives are not uncommon and may be severe. Anticoagulant therapy is contra-indicated, unless reliable control can be maintained; in patients who have lesions of the gastrointestinal or renal tracts which are liable to bleed; in patients in whom there is danger of bleeding into the central nervous system (severe hypertension, previous cerebrovascular accident or recent surgery or trauma); and in patients with chronic renal failure.