Problems of Anticoagulant Control—II, Which Test?

"It is a sad reflection on the limitations of clinical trials that 20 years after the introduction of oral anti-coagulants their place in the long term management of coronary artery disease is still disputed". It is more of a reflection on the limitations of the tests used to control anticoagulants. For example, after the publication of the most recent M.R.C. report on the use of anticoagulants after cardiac infarction (10), it became apparent that three years work in eleven centres involving nearly 1500 patients was invalidated because the level of anticoagulant control ?although that originally advocated by the manufacturers of the thromboplastin used?had since been shown to result in homeopathic dosages well below the therapeutic range ("). The function of any test used for anticoagulant control is to ensure that enough of the drug is given to prevent thrombotic episodes, yet not enough to cause haemorrhagic complications. In practice no one has determined just how much is necessary to prevent thrombosis, and the usual procedure is to give the maximum dose compatible with safety (1). The test must therefore be able to predict bleeding. When blood escapes from a damaged vessel clotting is a relatively simple matter (Fig. 1); on the other hand clotting initiated within a vessel, because of stasis, or damage to the intima, is a rather more involved affair (Fig. 2). Oral anticoagulants act by depressing the levels of Factors VII, IX, X, and II in the blood in that order. Factor VII is more greatly affected than the others especially at the start of treatment, and is concerned only in the extrinsic clotting system. Factor IX is concerned only in the intrinsic system while the other two are involved in both. the one stage prothrombin time This is the most widely used test for anticoagulant control, and was introduced by Quick in 1935 (8). In this test a brain extract is used as a source of tissue activator, and is added to citrated plasma which is then recalcified. The time taken for the plasma to clot is then measured. The result is usually expressed as a ratio of the test time to that of a normal control. This test is therefore a measure of the effectiveness of the extrinsic clotting system (fig. 1), and in patients on oral anticoagulants is most affected by Factor VII levels (9). Unfortunately the ratio thus obtained varies with the type …