Diagnostic methodologies for circulating anticoagulants.

Various types of circulating anticoagulant are encountered in coagulation testing laboratories. Those associated with bleeding often cause problems in diagnosis. The most common type of acquired coagulation inhibitor not associated with bleeding is the so-called lupus anticoagulant (LA). Differing from SLE which occurs predominantly in women, primary LA occurs both in females and males. LA are now frequently sought in patients with recurrent foetal losses and acquired thrombotic problems as a causative factor, whereas in the past they were regarded as a laboratory nuisance. Due to the complicating effect of inhibitors on clotting tests, diagnosis of various coagulation inhibitors remains difficult. There may also be significant overlap between different types of inhibitors. With the recent interest shown in LA, almost all non-specific inhibitors tend to be classed as LA. LA are defined as phospholipid-interfering antibodies. Current criteria have recently been confirmed and include screening with phospholipid-responsive tests, abnormal mixing studies and correction with phospholipids. However it is becoming clear that even LA as defined may be heterogeneous. Most LA are not directed at negatively-charged phospholipids alone as originally suggested, but rather at complexes of either beta-2-glycoprotein 1 or prothrombin with such phospholipids. There may also be other lipid-associated antigens involved. Although earlier work suggested that all LA functioned through a similar mechanism, there is now some preliminary evidence suggesting that various subclasses of LA may account for discrepant results sometimes obtained with different clotting tests. A variety of improvements to the basic screening tests for LA (APTT, KCT, DTTI and DRVVT) have recently been suggested.(ABSTRACT TRUNCATED AT 250 WORDS)