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

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.

Venous thromboembolism in a medical intensive care unit. The effect of implementing clinical practice guidelines.

OBJECTIVE: To determine the incidence of VTE in medical patients admitted to the intensive care unit (ICU) following the implementation of a standard deep venous thrombosis (DVT) prophylaxis protocol using unfractionated heparin (UFH), and to identify risk factors for DVT in these patients. METHODS: We prospectively studied 123 consecutive patients admitted to the Medical ICU of King Khalid University Hospital, Riyadh, Saudi Arabia. We excluded patients on anticoagulation or with contraindications for heparin. Patients who were negative for DVT by screening Doppler Ultrasound (U/S) were started on UFH twice a day. The Doppler U/S was repeated twice weekly for 6 weeks. RESULTS: One hundred and four critically ill medical patients were included. A DVT was diagnosed in 10 patients while receiving UFH, an incidence rate of 9.8%. The compliance rate was 98%. Sepsis (p=0.0167), limited mobility (p<0.0001), previous DVT (p=0.024), and nephrotic syndrome (p=0.008) were significantly more common in patients who developed DVT compared with others. However, by backward logistic regression, previous DVT was the only significant factor for the development of DVT (B=-0.439, AOR=5.01, p<0.0001). CONCLUSION: The implementation of clinical practice guidelines for VTE prophylaxis in critically ill medical patients using UFH twice daily resulted in a high compliance rate and low incidence of VTE. Previous DVT was a significant risk factor for development of VTE.