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Lionel P. Clyne, FIMLS (ENG), MS; Peter F. White, MD

Arch Intern Med. 1988;148(5):1060-1063.

Abstract
• Fifty-two patients (29 female and 23 male) with lupuslike anticoagulants were reviewed retrospectively to determine whether their inhibitors were time dependent (TD). In 21 cases (40%), a TD pattern emerged: when patient plasma was added to normal plasma and an activated partial thromboplastin time (APTT) test was performed on the mixture, the patient/control ratio after incubation for one hour at 37°C (60-minute ratio) exceeded significantly the respective preincubation ratio (zero-minute ratio). In four cases (8%), anticoagulant activity would have gone undetected if mixing studies had been restricted to the preincubation phase. The TD anticoagulants appeared to be more potent than their time-independent (TI) counterparts (mean APTT, 74.1 vs 58.5 s, respectively). An APTT greater than 63 s was 85% predictive of TD behavior. Greater overlap between the two groups was seen when zero-minute ratios were compared; an equivalent cutoff of 1.36 for the zero-minute ratio was only 65% predictive of TD behavior. The separation between the two groups was most striking when 60-minute ratios were compared. Nineteen TD patients (90%) had 60-minute ratios that exceeded the mean TI ratio of 1.33, while 30 TI patients (97%) had 60-minute ratios that were lower than the mean TD ratio of 1.89. Collectively, these findings indicate that many potent lupuslike anticoagulants require incubation to express maximal anticoagulant activity. Indeed, in some cases, anticoagulant activity might not be detected if mixing studies are restricted to the preincubation phase. The APTT can be helpful in predicting which anticoagulants will show TD behavior.

(Arch Intern Med 1988;148:1060-1063)

Author Affiliations
From the Department of Laboratory Medicine, Yale—New Haven (Conn) Hospital. Dr White is now with the Department of Pathology, Memorial Sloan Kettering Cancer Institute, New York.

Footnotes
Accepted for publication Dec 21, 1987.

Reprint requests to Department of Laboratory Medicine, Yale—New Haven Hospital, Room 438K CB, 20 York St, New Haven, CT 06504 (Mr Clyne).

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