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.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.

Evaluation of COVID‐19 coagulopathy; laboratory characterization using thrombin generation and nonconventional haemostasis assays

“…However, it is a marker for endothelial dysfunction, which would fit with a localized endothelial effect of COVID‐19 20 . TFPI was also significantly increased in COVID‐19 critical vs noncritical patients; TFPI usually is found on the endothelial surface and release could be triggered by sepsis though data are conflicting 21,22 . The elevated tPA may explain part of the component of increased D‐dimer seen within the patients, due to dysfunctional fibrinolysis, and can also be seen as marker of endothelial dysfunction 23 .…”

Burn-Induced Coagulopathies: a Comprehensive Review

“…TFPI activity levels were decreased in animals subjected to either burn injury or sepsis alone, with even lower activity when combinatory insults occurred, this decrease was most pronounced at 24 h with a rebound to near normal TFPI activity at 72 h ( 76 ). In humans, TFPI levels are found to be increased in several disease states, including sepsis ( 98 , 99 ). However, interpretation of TFPI levels as a biomarker of coagulopathy can be misleading, given its various isoforms and distribution within the body, and varied methods of measurement ( 100 ).…”

Tissue Factor Pathway Inhibitor Levels During Veno-Arterial Extracorporeal Membrane Oxygenation in Adults

“…This finding is consistent with a prior study, where TFPI levels increases during sepsis. 28 An important clinical implication from our study is that when vascular injury occurs in an ECMO patient, thrombin generation may be delayed and protamine administration may not immediately reverse this abnormality. Donahue et al previously demonstrated a similar phenomenon in CPB patients where free TFPI levels and TFPI activity remained elevated after protamine administration and did not return to normal until 24 hours after heparin was given.…”