A B S T R A C T Since thrombin cleaves fibrinopeptides A (FPA)

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Drug-induced warfarin resistance may be mediated by the direct effect of a drug on warfarin's absorption, excretion, distribution, or metabolism. A 29-year-old man on long-term stable anticoagulation therapy with warfarin sodium developed resistance to warfarin while receiving nafcillin. His prothrombin time ranged between 14 and 17 s (control, 12 s) despite an increase in his warfarin dosage to 25 mg/d. Pharmacokinetic studies showed that the decreased hypoprothrombinemic effect of warfarin was most likely due to rapid metabolism of the anticoagulant induced by nafcillin. Warfarin's half-life was 11 hours when the patient was on nafcillin therapy and 44 hours when he was off nafcillin therapy. This interaction may be clinically important in patients requiring concomitant administration of nafcillin and warfarin.

Activated protein C is a potent, physiologic anticoagulant that inactivates the activated forms of factors V and VIII as well as facilitates in vivo fibrinolysis. We developed a competitive protein-binding enzyme-linked immunoadsorbent assay (ELISA) for protein C that was utilized to investigate if the hypercoagulability of the nephrotic syndrome is related to a deficiency of circulating plasma protein C. Protein C was measured in plasma of 11 patients with nephrotic syndrome (24 hr protein 8.4 +/- 1.6 g, SEM; serum creatinine 4.2 +/- .74 mg/dl, SEM). Ten azotemic nonnephrotic patients were employed as controls (serum creatinine 6.0 +/- 1.25 mg/dl, SEM). No significant reduction of protein C values was observed (mean 108%, range 65-200%) in nephrotic patients when compared with the controls (mean 127%, range 100-200%) even though protein C antigen was present in all nephrotic urine samples tested. Also, no correlation existed between blood levels of urea nitrogen, creatinine, albumin, total protein, or 24-hr urine protein excretion and the observed protein C values. These results suggest that in patients with the nephrotic syndrome, a hypercoagulable state may not be related to a deficiency of protein C and that the level of this zymogen in nephrotic syndrome reflects a dynamic balance between urinary losses and systemic production.

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