Partial depletion of tissue factor pathway inhibitor during subcutaneous administration of unfractionated heparin, but not with two low molecular weight heparins
B. Bendz et al., Partial depletion of tissue factor pathway inhibitor during subcutaneous administration of unfractionated heparin, but not with two low molecular weight heparins, BR J HAEM, 107(4), 1999, pp. 756-762
Tissue factor pathway inhibitor (TFPI) is released to circulating blood aft
er intravenous (i.v.) and subcutaneous (s.c.) injections of heparins, and m
ay thus contribute to the antithrombotic effect of heparins. We have recent
ly shown that total TFPI activity, plasma free TFPI antigen, and heparin re
leasable TFPI were partially depleted during repeated and continuous i.v. i
nfusion of unfractionated heparin (UFH), but not during s.c, treatment with
a low molecular weight heparin (LMWH). The difference may be attributed to
a different mode of action or the different mode of administration. In the
present randomized cross-over study, s.c, administration of therapeutic do
ses of UFH was compared with s.c. administration of two LMWHs. 12 healthy m
ale volunteers were treated for 3 d with UFH, 250 U/kg twice daily, daltepa
rin, 200 U/kg once daily, and enoxaparin, 1.5 mg/kg once daily. Six partici
pants were also treated with UFH, 300 U/kg once daily. On day 5 a single do
se of either drug was given. Peak levels of total TFPI activity and free TF
PI antigen were detected 1 h after injection, whereas maximal prolongation
of activated partial thromboplastin time (APTT) and peak levels of anti-fac
tor Xa activity and anti-factor IIa activity were detected after 4 h. On UF
H administered twice daily free TFPI antigen decreased by 44% from baseline
level before the first injection on day 1 to pre-injection level on day 5,
On UFH administered once daily, basal free TFPI antigen decreased by 50%,
56% and 27% on day 2, 3 and respectively, compared with day 1. Minimal depl
etion of TFPI was detected during treatment with LMWHs. The study demonstra
tes the different modes of action of LMWHs and UFH and may help to explain
the superior antithrombotic efficacy of LMWHs.