PMID- 10604885
OWN - NLM
STAT- MEDLINE
DCOM- 20000113
LR  - 20220330
IS  - 0009-7322 (Print)
IS  - 0009-7322 (Linking)
VI  - 100
IP  - 25
DP  - 1999 Dec 21-28
TI  - Heparin blunts endotoxin-induced coagulation activation.
PG  - 2485-90
AB  - BACKGROUND: Lipopolysaccharide (LPS) is a major trigger of sepsis-induced 
      disseminated intravascular coagulation (DIC) via the tissue factor (TF)/factor 
      VIIa-dependent pathway of coagulation. Experimental endotoxemia has been used 
      repeatedly to explore this complex pathophysiology, but little is known about the 
      effects of clinically used anticoagulants in this setting. Therefore, we compared 
      with placebo the effects of unfractionated heparin (UFH) and low-molecular-weight 
      heparin (LMWH) on LPS-induced coagulation. METHODS AND RESULTS: In a randomized, 
      double-blind, placebo-controlled trial, 30 healthy male volunteers received LPS 2 
      ng/kg IV followed by a bolus-primed continuous infusion of UFH, LMWH, or placebo. 
      In the placebo group, activation of coagulation caused marked increases in plasma 
      levels of prothrombin fragment F(1+2) (P<0.01) and polymerized soluble fibrin, 
      termed thrombus precursor protein (TpP; P<0.01); TF-positive monocytes doubled in 
      response to LPS, whereas levels of activated factor VII slightly decreased and 
      levels of TF pathway inhibitor remained unchanged. UFH and LMWH markedly 
      decreased activation of coagulation caused by LPS, as F(1+2) and TpP levels only 
      slightly increased; TF expression on monocytes was also markedly reduced by UFH. 
      TF pathway inhibitor values increased after either heparin infusion (P<0.01). 
      Concomitantly, factor VIIa levels dropped by >50% at 50 minutes after initiation 
      of either heparin infusion (P<0.01). CONCLUSIONS: This experimental model proved 
      the anticoagulatory potency of UFH and LMWH in the initial phase of experimental 
      LPS-induced coagulation. Successful inhibition of thrombin generation also 
      translates into blunted activation of coagulation factors upstream and downstream 
      of thrombin.
FAU - Pernerstorfer, T
AU  - Pernerstorfer T
AD  - Department of Clinical Pharmacology-The Adhesion Research Group Elaborating 
      Therapeutics (TARGET), University of Tromso, Norway. 
      thomas.pernerstorfer@univie.ac.at
FAU - Hollenstein, U
AU  - Hollenstein U
FAU - Hansen, J
AU  - Hansen J
FAU - Knechtelsdorfer, M
AU  - Knechtelsdorfer M
FAU - Stohlawetz, P
AU  - Stohlawetz P
FAU - Graninger, W
AU  - Graninger W
FAU - Eichler, H G
AU  - Eichler HG
FAU - Speiser, W
AU  - Speiser W
FAU - Jilma, B
AU  - Jilma B
LA  - eng
PT  - Clinical Trial
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Circulation
JT  - Circulation
JID - 0147763
RN  - 0 (Anticoagulants)
RN  - 0 (Antigens)
RN  - 0 (Endotoxins)
RN  - 0 (Factor Xa Inhibitors)
RN  - 0 (Fibrin Fibrinogen Degradation Products)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Lipoproteins)
RN  - 0 (Peptide Fragments)
RN  - 0 (Plasminogen Activator Inhibitor 1)
RN  - 0 (factor VII clotting antigen)
RN  - 0 (fibrin fragment D)
RN  - 0 (lipoprotein-associated coagulation inhibitor)
RN  - 0 (prothrombin fragment 1.2)
RN  - 9000-94-6 (Antithrombin III)
RN  - 9001-25-6 (Factor VII)
RN  - 9001-26-7 (Prothrombin)
RN  - 9001-31-4 (Fibrin)
RN  - 9005-49-6 (Heparin)
RN  - 9035-58-9 (Thromboplastin)
RN  - EC 3.4.21.21 (Factor VIIa)
RN  - S79O08V79F (Dalteparin)
SB  - IM
MH  - Adult
MH  - Anticoagulants/*pharmacology
MH  - Antigens/analysis
MH  - Antithrombin III/analysis
MH  - Blood Coagulation/*drug effects
MH  - Dalteparin/*pharmacology
MH  - Double-Blind Method
MH  - Endotoxins/*antagonists & inhibitors
MH  - Factor VII/analysis
MH  - Factor VIIa/analysis
MH  - Factor Xa Inhibitors
MH  - Fibrin/analysis
MH  - Fibrin Fibrinogen Degradation Products/analysis
MH  - Heparin/*pharmacology
MH  - Humans
MH  - Leukocyte Count/drug effects
MH  - Lipopolysaccharides/*pharmacology
MH  - Lipoproteins/analysis
MH  - Male
MH  - Monocytes/drug effects
MH  - Peptide Fragments/analysis
MH  - Plasminogen Activator Inhibitor 1/analysis
MH  - Prothrombin/analysis
MH  - Thromboplastin/biosynthesis
EDAT- 1999/12/22 00:00
MHDA- 1999/12/22 00:01
CRDT- 1999/12/22 00:00
PHST- 1999/12/22 00:00 [pubmed]
PHST- 1999/12/22 00:01 [medline]
PHST- 1999/12/22 00:00 [entrez]
AID - 10.1161/01.cir.100.25.2485 [doi]
PST - ppublish
SO  - Circulation. 1999 Dec 21-28;100(25):2485-90. doi: 10.1161/01.cir.100.25.2485.