The Levels of Tissue Factor Pathway Inhibitor in Sepsis Patients Receiving Prophylactic Enoxaparin

Journal Article

A.H.abdelrazik, Hadil A Al Otair, Abdel Galil M Abdel Gader, Syed M Khurshid, Abdulaziz H. Alzeer, Abdulkareem Almomen, Mashael Alshaikh, Farja Al Gahtani, Zohair A. Alaseri, Hossam . 2016

• نوع عمل المنشور: article
• رابط المنشور على الويب: DOI: 10.4274/tjh.2014.0312
• المجلة \ الصحيفة: Turk J Hematol
• رقم الإصدار السنوي: 33:
• الصفحات: 112-118

مستخلص المنشور

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.
Materials and 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.
Conclusion:  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