title: The Levels of Tissue Factor Pathway Inhibitor in Sepsis Patients Receiving Prophylactic Enoxaparin.
abstract: OBJECTIVE
  Sepsis syndrome is usually accompanied by activation of blood coagulation mechanisms. Earlier studies found deficiencies of the 3 main natural anticoagulants, antithrombin, protein C, and protein S. However, none of these inhibitors block tissue factor, the prime trigger of coagulation during sepsis that is controlled specifically by the tissue factor pathway inhibitor (TFPI). The aim of this study was to characterize the fluctuations in the levels of natural anticoagulants, particularly TFPI, in the course of sepsis and to find out their association with the anticoagulant action of the low-molecular-weight heparin enoxaparin.
  
  
  METHODS
  We studied 51 consecutive patients with sepsis. Blood samples were collected from patients at baseline (0 h) and at 4, 12, and 24 h after enoxaparin administration. The following assays were undertaken using commercial kits: activated partial thromboplastin time, prothrombin time, thrombin time, total and free TFPI, protein C and protein S, antithrombin, fibrinogen, and anti-factor Xa.
  
  
  RESULTS
  Before enoxaparin administration, there was significant prolongation of the prothrombin time and activated partial thromboplastin time, and this remained the case in the 3 subsequent samples. There was marked reduction in the levels of antithrombin, protein C, and total and free protein S to below control values throughout the study. In contrast, plasma levels of both total and free TFPI were markedly elevated and increased after enoxaparin therapy. Anti-factor Xa levels were within the therapeutic range throughout. There was no difference in TFPI levels between those patients who died and those who survived.
  
  
  CONCLUSIONS
  Sepsis triggered marked release of TFPI from endothelial cells. This persisted and was increased further following the administration of enoxaparin. In contrast, there was marked consumption of the natural coagulation inhibitors antithrombin, protein C, and protein S. These results go some way towards explaining why the therapeutic use of recombinant TFPI fails to correct sepsis-associated coagulopathy.
authors.affiliation: King Saud University College of Medicine, King Khalid University Hospital, Department of Critical Care, Riyadh, Saudi Arabia, Phone : +96611-4692253, E-mail : hadil.alotair@live.com.
authors.forename: Hadil A
authors.initials: HA
authors.lastname: Al Otair
authors.forename: Abdel Galil M
authors.initials: AG
authors.lastname: Abdel Gader
authors.forename: Syed M
authors.initials: SM
authors.lastname: Khurshid
authors.forename: Abdulaziz H
authors.initials: AH
authors.lastname: Alzeer
authors.forename: Abdul Kareem
authors.initials: AK
authors.lastname: Al Momen
authors.forename: Mashael
authors.initials: M
authors.lastname: Al Shaikh
authors.forename: Farja
authors.initials: F
authors.lastname: Al Gahtani
authors.forename: Zohair A
authors.initials: ZA
authors.lastname: Al Aseri
authors.forename: Hossam A H
authors.initials: HA
authors.lastname: Abdelrazik
mesh_terms: D018806:APACHE; D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage / Q000627:therapeutic use*; D015415:Biomarkers; D001777:Blood Coagulation; D001780:Blood Coagulation Tests; D016022:Case-Control Studies; D015897:Comorbidity; D017984:Enoxaparin / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008074:Lipoproteins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011292:Premedication; D018805:Sepsis / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000925:Anticoagulants; D015415:Biomarkers; D017984:Enoxaparin; D008074:Lipoproteins; C051928:lipoprotein-associated coagulation inhibitor