Dr. Manoharan asks about the Thrombotest, which was described by Owren in 1959 as an alternative to Quick's thromboplastin time (prothrombin time) for monitoring oral anticoagulant therapy [1]. The Thrombotest was designed to be sensitive to decreases in levels of all four vitamin K-dependent procoagulant factors (factors II, VII, IX, and X), whereas Quick's test was sensitive to decreases in levels of factors II, VII, and X only. The original Thrombotest reagent consisted of an active cephalin and a low-activity thromboplastin to activate both intrinsic and extrinsic pathways. In addition, the sample was diluted into adsorbed bovine plasma that was essentially free of bovine factors II, VII, IX, and X [1].

Owren hypothesized that the sensitivity of the Thrombotest to decreases in levels of the four vitamin K-dependent factors would make it a better method for monitoring oral anticoagulant therapy [1]. However, Sise and coworkers [2] reported that thrombotic and hemorrhagic complications were more closely related to factor II levels than to factor VII levels or prothrombin times. In addition, Zivelin and coworkers [3], using an animal model, showed that decreases in factors X and II but not factors VII or IX were important for the antithrombotic effect of warfarin. The ability of the original Thrombotest to measure decreases in factor IX, therefore, would not necessarily make it superior to the prothrombin-proconvertin assay or the chromogenic factor X assay for monitoring oral anticoagulant therapy.

The Thrombotest reagent (Nycomed AS, Oslo, Norway) currently in use contains thromboplastin, bovine fibrinogen, and factor V but no cephalin, making it insensitive to decreased factor IX levels. This reagent is therefore similar to the Simplastin A (Organon Teknika Corp., Durham, North Carolina) used in the prothrombin-proconvertin time assay, which also incorporates adsorbed bovine plasma [4]. We investigated the prothrombin-proconvertin time assay because it had been previously investigated in patients with lupus anticoagulants, we studied the factor II level because of the above reports, and we investigated the chromogenic factor X assay because it is phospholipid independent. The original Thrombotest was never systematically studied in patients with lupus anticoagulants, and combined prothrombin time and activated partial thromboplastin time reagents would not necessarily result in an assay that was completely insensitive to the presence of a lupus anticoagulant. Although the current Thrombotest may be a reasonable alternative for monitoring warfarin therapy in certain patients with lupus anticoagulants, we agree with Dr. D'Angelo and coworkers and would recommend that it be compared with the prothrombin-proconvertin time or chromogenic factor X before use in individual patients.