Abstract 17226: Heparin Antagonist PMX-60056 Rapidly Reverses Anti-Xa and aPTT Effects of Tinzaparin in Man
Background: PMX-60056 is a small compound designed to quickly reverse the anticoagulant effects of heparin and low molecular weight heparins (LMWH).
Methods: Six normal male subjects entered this IRB-approved GCP double-blind placebo-controlled crossover trial. On 2 occasions separated by a 2-day washout period, each received the standard prophylactic dose (175 IU/kg) of tinzaparin subcutaneously. Five hours later (at the time of the expected maximum anticoagulation) each received either 0.3 mg/kg PMX-60056 or placebo as a 10-minute intravenous infusion. Three hours later, the same dose of test drug was infused again. Coagulation was assessed by anti-Xa activity, ACT, and aPTT.
Results: The anti-Xa results, bedside ACT, and aPTT were all concordant. The effect was complete before the end of each infusion. The peak anti-Xa effect of tinzaparin ranged from 0.4 to 1.0 IU/mL in these subjects, while the degree of reversal was relatively constant at 0.4 anti-Xa units/mL. Despite the resumption of anticoagulation presumably from the subcutaneous tinzaparin store, after the second reversal dose the anti-Xa level usually remained low. The aPTT was reversed to normal by the end of each infusion, and remained low thereafter. Mean systolic/diastolic blood-pressure reductions of 21/17 mmHg were seen; longer low-rate infusions are expected to avoid them in future. No important side effects were associated with this study.
Conclusions: PMX-60056 rapidly and safely reversed the effects of prophylactic doses of tinzaparin in healthy male subjects. It may find important utility in bleeding emergencies for patients on thromboprophylaxis with LMWH, and may also permit the expanded use of LMWH in thrombogenic medical or surgical procedures that require rapid reversal of anticoagulation afterward.
- © 2010 by American Heart Association, Inc.