Low-molecular-weight and unfractionated heparins are frequently used to treat
venous thromboembolism, but it is not known whether they are equally effective in inhibiting in vivo generation of
thrombin. In this multicenter trial, 1048 patients were randomized to intravenous
unfractionated heparin (group A), twice daily
low-molecular-weight heparin (
reviparin) for 1 week (group B), or once daily
reviparin for 4 weeks (group C). All patients received
vitamin K antagonists. Blood samples withdrawn at the baseline and at weeks 1 and 3 were analyzed using markers of in vivo
thrombin generation and other coagulation parameters. During the first 3 weeks symptomatic recurrent
deep vein thrombosis-
pulmonary embolism (DVT/PE) occurred in 17 (4.5%) of 375 patients in group A compared with 4 (1.0%) of 388 patients in group B, and 9 (2.4%) of 374 patients in group C. Forty percent of patients in group A, 53.4% in group B, and 53.5% in group C showed 30% or greater reduction in
thrombus size assessed by venography. Patients in group B had significantly greater reduction in
D-dimer,
prothrombin fragments 1 and 2 (F1 + 2), endogenous
thrombin potential (ETP), and
thrombin-
antithrombin (TAT) complexes compared to groups A and C. Greater release of
tissue factor pathway inhibitor (
TFPI) and reduction in levels of
thrombin activatable fibrinolysis inhibitor (TAFI) and
fibrinogen were significantly more pronounced in group C patients.
Reviparin administered twice daily plus
vitamin K antagonist is more effective in inhibiting in vivo
thrombin generation compared to intravenous
unfractionated heparin plus
vitamin K antagonist, and
reviparin once daily produced significantly higher
TFPI release and greater reduction in TAFI and
fibrinogen levels.