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Original Paper
Pathophysiol Haemost Thromb 2005;34:263–268
DOI: 10.1159/000093105
Combinations of Low Doses of Unfractionated
Heparin and of Low-Molecular-Weight Heparin
Prevent Experimental Venous Thrombosis
Guareide Carelli Francisco H.A. Maffei Luci Mattar Iracema C. Ferrari
Izolete A. Thomazini-Santos Lídia R. de Carvalho
Faculdade de Medicina and Instituto de Biociências de Botucatu, UNESP, Botucatu, Brazil
tion. Thrombus developed in 90.9% of control animals,
20% of the H
350
group, 22.2% of the E
2
group, 10% of the
H
175
+ E
1
group, and 30% of the H
100
+ E
0.5
group; there
was a difference between group C and the other groups.
Only in the H
350
and H
175
+ E
1
groups were TT and acti-
vated partial thromboplastin time prolonged in relation
to control at the end of the experiment. Forty minutes
after injection, TT was prolonged in the H
350
and H
175
+ E
1
groups. In conclusion, combinations of low doses of low-
molecular-weight heparin and low doses of UH were as
effective as high doses of each one used alone in prevent-
ing thrombus development in rat vena cava.
Copyright © 2005 S. Karger AG, Basel
Introduction
The standard drug for prevention and treatment of
thromboembolism is unfractionated heparin (UH); it has
a heterogeneous structure, molecular weight, anticoagu-
lant activity and chromatographic affinity. Moreover, it
presents pharmacokinetic limitations such as binding to
plasmatic proteins, endothelial cells, and leucocytes, re-
sulting in a complex clearance mechanism, variability of
anticoagulant response, and resistance to heparin [1, 2] .
Low-molecular-weight heparins (LMWHs) produce
an antithrombotic response with a better dose/effect re-
Key Words
Low-molecular-weight heparin Experimental
thrombosis Rat vena cava
Abstract
Synergism between low-molecular-weight heparin and
low doses of unfractionated heparin (UH) enhancing
anti-factor Xa activity and the release of tissue factor
pathway inhibitor was observed. The aim of this study
was to verify whether this association is effective in pre-
venting experimental venous thrombosis. Seventy rats
were allocated into 7 groups: the control group treated
with distilled water, the H
350
group treated with UH
350 IU/kg, the E
2
group treated with enoxaparin 2 mg/kg,
the H
175
group treated with UH 175 IU/kg, the E
1
group
treated with enoxaparin 1 mg/kg, the H
175
+ E
1
group
treated with UH 175 IU/kg plus enoxaparin 1 mg/kg, and
the H
100
+ E
0.5
group treated with UH 100 IU/kg plus
enoxaparin 0.5 mg/kg. Forty minutes after subcutaneous
injection, thrombosis was induced in vena cava. Three
hours later, if present, thrombi were withdrawn and
weighed. Bleeding time, activated partial thromboplastin
time, thrombin time (TT), and anti-factor Xa were mea-
sured at the beginning and end of the experiment. Forty-
eight other animals were treated, but without inducing
thrombus, and tests were performed 40 min after injec-
Received: April 27, 2005
Accepted after revision: August 29, 2005
Francisco H.A. Maffei
Depto. Cirurgia e Ortopedia
Faculdade de Medicina de Botucatu, UNESP
Botucatu, SP (Brazil)
Tel. +55 14 3811 6269, Fax +55 14 3815 7428, E-Mail fmaffei@fmb.unesp.br
© 2005 S. Karger AG, Basel
1424–8832/05/0346–0263$22.00/0
Accessible online at:
www.karger.com/pht