Differential effects of low molecular weight heparin and unfractionated heparin on circulating levels of antithrombin and tissue factor pathway inhibitor (TFPI): a possible mechanism for difference in therapeutic efficacy.
There is growing evidence on the superior efficacy and safety of low molecular weight heparins (LMWHs) over unfractionated heparin (UFH) for the treatment of both venous and arterial thromboembolism. Heparin exerts its function by potentiating antithrombin and by mobilizing tissue factor pathway inhibitor (TFPI) into the circulation. The present study was conducted to compare the effect of subcutaneous LMWH and infusion of UFH on these two anticoagulants in plasma. Eighteen healthy male volunteers were randomly allocated to therapy with continuous intravenous (iv) UFH (n=6) (initial infusion rate 450 IU/kg/day) or low molecular weight heparin (LMWH) (enoxaparin, 1.5 mg/kg/day) subcutaneously (sc) once daily for 72 hours. Free TFPI antigen, measured by a solid-phase two-site enzyme immunoassay, and antithrombin and protein C activities, measured by chromogenic assays, were assessed in plasma samples before, during, and after anticoagulant treatment. Infusion of UFH, but not subcutaneous LMWH, was found to attenuate the antithrombotic defense by a selective decrease of both circulating antithrombin (-21+/-7%, p<0.0001) and of free and endothelial-bound TFPI. The changes in antithrombin and TFPI by LMWH and UFH were statistically different between groups (p<0.001). The differential effect of UFH and LMWH on antithrombin and TFPI may explain the superior efficacy of subcutaneous LMWH compared with conventional intravenous UFH for treatment of both arterial and venous thrombosis.
Hansen
J B
JB
Department of Medicine, Institute of Clinical Medicine, University of Tromsø, Norway. johnbh@fagmed.uit.no
Sandset
P M
PM
D000279:Administration, Cutaneous; D000328:Adult; D000925:Anticoagulants / Q000008:administration & dosage*; D000991:Antithrombins / Q000378:metabolism*; D006493:Heparin / Q000008:administration & dosage*; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage*; D006801:Humans; D007262:Infusions, Intravenous; D008074:Lipoproteins / Q000097:blood*; D008297:Male; D011486:Protein C / Q000378:metabolism
D000925:Anticoagulants; D000991:Antithrombins; D006495:Heparin, Low-Molecular-Weight; D008074:Lipoproteins; D011486:Protein C; C051928:lipoprotein-associated coagulation inhibitor; D006493:Heparin