A novel recombinant tissue factor assay for measuring the anti-Xa effect of Low-Molecular-Weight Heparin (LMWH): implications for interventional coronary procedures

Abstract number: P1895

Laduca^* F., Lee† T., El Rouby† S., Zucker† M., Cohen‡ M.

^*International Technidyne Corporation, USA; †ITC, USA; ‡Newark-Beth Israel, USA

Intensive LMWH therapy for unstable angina, which may lead to interventional coronary procedures, creates anti-coagulation management problems, particularly in patients with renal compensation. Consequently, an increasing need for monitoring of LMWH has been cited in the literature to optimize therapy. We have developed a fast, convenient, economical, point of care (POC) assay for measuring the anti-Xa effect of LMWH, using a proprietary mixture of recombinant rabbit brain tissue factor (RBTF, Pel-Freez Corp.), synthetic phospholipids to lipidate the RBTF and a formulation buffer. This whole blood, single-step assay performed using the Hemochron Jr. Signature+ system (International Technidyne Corp) provides appropriate sensitivity within the therapeutic LMWH concentration range of 0.6–1.0 anti-Xa U mL^-1. Using fresh blood samples from normal donors (n = 10) known amounts of enoxaparin (Lovenox, Aventis Corp.) were added and the clotting times shown in the table were determined.

A significant variation was observed amongst the donors indicating that such a monitoring assay would be useful to establish safe anti-coagulation during coronary interventions. Preliminary clinical feasibility demonstrated a proportional increase of the LMWH assay clotting time to the anti-Xa level, suggesting that appropriate safe target times could be identified. Studies of other LMWH preparations (dalteparin, Fragmin, Pharmacia Upjohn Corp. and tinzaparin, Innohep Bristol Meyers Squibb – DuPont Corp.) demonstrated that the LMWH dose–response clotting time was specific for each agent and reflective of the anti-coagulant effect of each agent.

Conclusion  

A novel precise and sensitive POC assay which measures the anti-Xa effect of LMWH has been developed which provides the opportunity to deliver individualized patient LMWH therapy during interventional coronary procedures, such that the risks associated with ineffective anti-thrombotic prophylaxis, particularly undesirable clotting and bleeding, are avoided.