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Activated partial thromboplastin time (APTT) is the most widely used coagulation test for monitoring heparin therapy. This study quantitates the differences in heparin sensitivity of seven commercially available APTT reagents, using plasma samples obtained from 20 subjects. The reagents studied were Actin, Actin FS, Automated APTT, Cephotest, Coagachek KAPTT, Platelin plus activator, and Activated Thrombofax. The relationship between plasma heparin and APTT was established for all reagents in each subject. For each reagent studied there was a marked intersubject variability in heparin sensitivity. There was also a marked difference in heparin sensitivity among the different reagents. The average plasma heparin activities required to double baseline APTT values ranged from 0.19 +/- 0.04 (mean +/- SD) unit/mL for the most sensitive reagents (Platelin and Actin FS) to 0.43 +/- 0.12 unit/mL for the least sensitive reagent (Actin). It is concluded that reagent variability may significantly contribute to overdosage and under dosage of heparin in the individual patient. These results stress that a standard APTT reagent be developed.