Heparin-induced increase in the international normalized ratio. Responses of 10 commercial thromboplastin reagents.

A clinician's concern about an erratic response to oral anticoagulation in a patient treated concurrently with heparin and warfarin led the authors to investigate the effect of heparin on INR values obtained with various commercial thromboplastin reagents. Studies conducted with pooled normal plasma and with pooled plasma from patients treated long-term with oral anticoagulants demonstrated a wide range of sensitivities to heparin of these reagents as characterized by prolongation of INR values. Innovin was unaffected by concentrations of heparin as high as 1 U/mL. In contrast, Ortho thromboplastin showed the greatest increase in INR values over the range of heparin concentrations studied. Three other thromboplastins including Neoplastine CI, Dade thromboplastin, and Simplastin A demonstrated only limited sensitivity to heparin. Prolongation of the INR by heparin was reversed by protamine in a dose-related manner and also by preincubation of the plasma with heparinase. Some patients treated with warfarin while on the authors' institutional protocol for heparin had plasma concentrations greater than 0.8 U/mL. When thromboplastin reagents sensitive to heparin were used with such specimens, the INR values obtained were falsely elevated. The authors suggest that reagents insensitive to heparin be employed to avoid this difficulty.