A functional clotting assay to monitor low molecular weight heparin dosage

Low molecular weight heparin (LMWH), an anticoagulant drug, has seen increased use in a variety of clinical situations. Mercuric ion (Hg/sup 2+/) has been shown to increase procoagulant activity via Tissue Factor (TF) stimulated production of Factor Xa, a pathway that has been linked to many thrombotic disorders. The effects of Hg/sup 2+/ on heparinized blood may provide valuable insight into the effectiveness of LMWH to counteract TF-induced hypercoagulability. We performed in vitro studies by spiking human citrated whole blood (CWB) with HgCl/sub 2/ and LMWH at final concentrations of 0.01 % HgCl/sub 2/, 0.5 U/mL LMWH, and a combination of these agents. The samples (n=19) were incubated at 37/spl deg/ for 10 minutes and recalcified with 0.1 M CaCl/sub 2/ to initiate clotting. The clotting or recalcification time (RT) was measured with a Sonoclot Coagulation Analyzer. The results indicate that HgC12 was able to significantly (p<0.0001) reduce the anticoagulant ability of LMWH. The data warrants a reassessment of current LMWH monitoring and therapeutic protocols.