2263
document
Partial depletion of tissue factor pathway inhibitor during subcutaneous administration of unfractionated heparin , but not with two low molecular weight heparins . Tissue factor pathway inhibitor ( TFPI ) is released to circulating blood after intravenous ( i.v . ) and subcutaneous ( s.c. ) injections of heparins , and may thus contribute to the antithrombotic effect of heparins . We have recently shown that total TFPI activity , plasma free TFPI antigen , and heparin releasable TFPI were partially depleted during repeated and continuous i.v . infusion 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 doses of UFH was compared with s.c. administration of two LMWHs . 12 healthy male volunteers were treated for 3 d with UFH , 250 U/kg twice daily , dalteparin , 200 U/kg once daily , and enoxaparin , 1.5 mg/kg once daily . Six participants were also treated with UFH , 300 U/kg once daily . On day 5 a single dose of either drug was given . Peak levels of total TFPI activity and free TFPI antigen were detected 1 h after injection , whereas maximal prolongation of activated partial thromboplastin time ( APTT ) and peak levels of anti-factor Xa activity and anti-factor IIa activity were detected after 4 h. On UFH 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 5 respectively , compared with day 1 . Minimal depletion of TFPI was detected during treatment with LMWHs . The study demonstrates the different modes of action of LMWHs and UFH and may help to explain the superior antithrombotic efficacy of LMWHs .
2264
Intervention_Pharmacological
heparin
2265
Intervention_Pharmacological
unfractionated heparin
2266
Intervention_Pharmacological
UFH
2267
Intervention_Pharmacological
administration of two LMWHs
2268
Intervention_Pharmacological
UFH
2269
Intervention_Pharmacological
dalteparin , 200 U/kg once daily
2270
Intervention_Pharmacological
enoxaparin
2271
Intervention_Pharmacological
UFH
2272
Intervention_Pharmacological
UFH
2273
Intervention_Pharmacological
UFH
2274
Intervention_Pharmacological
LMWHs
2275
Intervention_Pharmacological
UFH
2276
Outcome_Physical
depletion of tissue factor pathway inhibitor
2277
Outcome_Physical
TFPI activity , plasma free TFPI antigen
2278
Outcome_Physical
heparin releasable TFPI
2279
Outcome_Physical
Peak levels of total TFPI activity and free TFPI antigen
2280
Outcome_Physical
maximal prolongation of activated partial thromboplastin time ( APTT ) and peak levels of anti-factor Xa activity and anti-factor IIa activity
2281
Outcome_Physical
free TFPI antigen
2282
Outcome_Physical
basal free TFPI antigen
2283
Outcome_Physical
Minimal depletion of TFPI
2284
Participant_Condition
12 healthy male volunteers