Low molecular weight heparin (bemiparin sodium) and the coagulation profile of patients with heart failure.
BACKGROUND
Congestive heart failure (CHF) is associated with a hypercoagulable state.


METHODS
A single-center, randomized, double-blind, placebo-controlled trial was performed to test the hypothesis that a prophylactic dose of low molecular weight heparin (bemiparin sodium 3500 IU/daily subcutaneously) will modify a hypercoagulable state in CHF. This study included 100 patients with CHF (New York Heart Association classification II to IV). All patients underwent 3 blood tests, at baseline (before randomization), 24 hours after randomization, and before hospital discharge or within 10 days from randomization.


RESULTS
In comparison of baseline bemiparin sodium 3500 IU/daily subcutaneously with after 24 hours, there was a significant decrease in plasma levels of D-dimer (-13.8 ng/mL; P =.01) and prothrombin fragments 1 and 2 (-0.11 nmol/L; P =.01), whereas protein C was significantly increased (+3.5%; P =.03). In comparison of baseline bemiparin sodium 3500 IU/daily subcutaneously with after 4 to 10 days of therapy, there were significantly decreased plasma levels for factor VII:c (-3.0%; P =.01), D-dimer (-44.0 ng/mL; P =.002), and thrombin-antithrombin complex (-0.7 microg/L; P =.0001), whereas protein C was significantly increased (+16.0%; P =.03). On the other hand, in the group of patients treated with placebo after 24 hours, a significant decrease was observed of protein C (-4.0%; P =.04). After 24 hours, the changes from baseline were significantly different for some of the hemostatic factors in comparison of bemiparin sodium 3500 IU/daily and placebo (factor VII:c: -1.7 versus 0.0%; P =.04; D-dimer: -14 versus +24.3 ng/mL; P =.009; prothrombin fragments 1 and 2: -0.11 versus +0.11 nmol/L; P =.01; protein C: +3.5 versus -4.0%; P =.01). Also at discharge, the changes from baseline were different for some of the markers in comparison of bemiparin sodium with placebo (D-dimer: -44 versus 3.8 ng/mL; P =.002; thrombin-antithrombin complex: -0.70 versus +0.14 microg/L; P =.002; protein C: +16.0 versus +0.5%; P =.02).


CONCLUSIONS
Our findings suggest that a hypercoagulable state in heart failure can be modified with bemiparin sodium therapy.
De Lorenzo
Ferruccio
F
Thrombosis Research Institute, Dept of Clinical Trials, London, UK. dlorenzo@tri-london.ac.uk
Newberry
Douglas
D
Scully
Mike
M
Kadziola
Zibgniew
Z
Dawson
Gloria
G
Ranlall
Nancy
N
Saba
Neelam
N
Noorani
Ali
A
Kashani
Shaharam
S
Williams
Rene'
R
Kakkar
Vijay Vir
VV
D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D001778:Blood Coagulation Disorders / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D005167:Factor VII / Q000032:analysis; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D006333:Heart Failure / Q000097:blood* / Q000150:complications; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage*; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D011486:Protein C / Q000032:analysis; D013917:Thrombin / Q000032:analysis
D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; D006495:Heparin, Low-Molecular-Weight; D011486:Protein C; C036309:fibrin fragment D; D005167:Factor VII; D013917:Thrombin; C411345:bemiparin