Bleeding in anticoagulated patients: A study using the australasian reference thromboplastin

Abstract

Thirty-five patients, all receiving long term warfarin therapy, most of them from the Anticoagulant Clinic at the Royal North Shore Hospital, were studied over a 12mth period. There were 21 patients bleeding to various degrees, and 14 patients who were non-bleeders. Severity of bleeding was graded as O—non-bleeders, I—minor bleeders, II—serious bleeding, and III—major bleeding. There were 14 group O, 13 group I, and 8 in groups II and III. Each patient had a prothrombin time test using the Australasian Reference Thromboplastin (ART), Simplastin (S), and Thrombotest (T). In addition, patients had an activated partial thromboplastin time test using kaolin and Thrombofax (TFX), a thrombin time test using Fibrindex, platelet count employing a Technicon automated platelet counter, skin bleeding time (Ivy), and assays for factors II, VII, IX and X (one stage assays). All of the group II and III patients were outside the accepted therapeutic range for T, all but one were outside the range for ART, but all except one patient were <i>within</i> the accepted therapeutic range for S, in most cases well within the range. Most of the minor bleeders displayed no particular pattern when considering the APTT, but 11 of the 13 non-bleeders had an APTT of less than 80 sec, whereas 7 of the 8 serious and major bleeders had an APTT of greater than 80 sec. The results indicate that factor II levels are of major importance in the genesis of bleeding, with factors IX and X being of lesser importance: factor VII levels appeared to be significant only when considered in conjunction with the other 3 factors. A series of factor II deficient plasmas (factor II deficient plasma + fresh pooled normal plasma) demonstrated the greater sensitivity of ART to factor II deficiency compared to S. The APTT was also sensitive to factor II deficiency <i>in vitro</i>. Factor II levels, as assessed by the one stage assay, are probably a useful independent indicator of the intensity of oral anticoagulation. In view of the results obtained with the APTT, this simple laboratory procedure may be a guide to the probable factor II levels in patients, and hence to the prospect of serious bleeding occurring, without the need for an immediate factor II assay.