The Impact of Anticoagulant Activity of Tissue Factor Pathway Inhibitor Measured by a Novel Functional Assay for Predicting Deep Venous Thrombosis in Trauma Patients: A Prospective Nested Case-Control Study

Abstract

Objective Deep venous thrombosis (DVT) is a common complication in patients with traumatic injury. Tissue factor pathway inhibitor (TFPI) is a natural anticoagulant protein in the extrinsic coagulation pathway. However, the relationship between DVT after trauma and the anticoagulant activity of TFPI remains unclear. In this prospective study, we investigated the role of TFPI in trauma patients with DVT to evaluate whether the anticoagulant activity of TFPI measured by a new functional assay can be used to help predict the risk of DVT. Patients and methods: This prospective nested case-control study enrolled trauma patients and healthy volunteers. Forty-eight trauma patients diagnosed with DVT and forty-eight matched trauma patients without DVT were included in the study. 120 healthy volunteers were also included as controls. Blood samples and case information were collected at admission. Patients accepted angiography before surgery to diagnose DVT. The parameters examined included TFPI anticoagulant activity, free-TFPI antigen, blood cell counts, and routine clinical coagulation tests. Results: For the parameters of TFPI anticoagulant activity, three were markedly increased in the DVT group compared to the non-DVT group (TFPI initial anticoagulant time ratio, P = .022; TFPI whole anticoagulant time ratio, P = .048; and TFPI anticoagulant rate, P = .034). The free-TFPI antigen concentration also showed a significant increasing trend in trauma patients with DVT compared with trauma patients without DVT (P = .035). Multivariate logistic regression analysis identified four independent factors for the development of DVT (TFPI initial anticoagulant time ratio, free-TFPI antigen, prothrombin time, and red blood cell count). We calculated the TFPI correlation coefficient and found that the area under the receiver operating characteristic curve was .821. Conclusions: A novel functional assay was developed to measure the anticoagulant activity of TFPI. The anticoagulant activity of TFPI can be used as a potential biomarker for diagnosing DVT in trauma patients.

Reversal of apixaban and rivaroxaban with andexanet alfa prior to invasive or surgical procedures

“… 24 , 25 This along with the upregulation of tissue factor incurred in surgical endothelial manipulation and the observed thrombotic rate suggests needed balance when weighing andexanet alfa use and anticoagulation reinitiation. 29 , 30 Despite the high rate of thromboischemic events, obtained postreversal TEG parameters did not detect or suggest hypercoagulability in the current study. It may also be worth noting that two of the six patients presenting without active bleeding who received andexanet alfa as an off‐label indication developed a thromboischemic complication.…”

“…Andexanet alfa has been suggested to induce hypercoagulability through inhibition of TFPI, the main regulator of the tissue factor pathway 24,25 . This along with the upregulation of tissue factor incurred in surgical endothelial manipulation and the observed thrombotic rate suggests needed balance when weighing andexanet alfa use and anticoagulation reinitiation 29–30 . Despite the high rate of thromboischemic events, obtained postreversal TEG parameters did not detect or suggest hypercoagulability in the current study.…”

“…24,25 This along with the upregulation of tissue factor incurred in surgical endothelial manipulation and the observed thrombotic rate suggests needed balance when weighing andexanet alfa use and anticoagulation reinitiation. [29][30] Despite the high rate of thromboischemic events, obtained postre- This study is the first to describe real-world application of these assays by comparing baseline and follow-up coagulation assays in patients undergoing FXa-I reversal. We observed a significant decrease in PT and anti-Xa concentrations pre-versus postandexanet alfa administration suggesting an intended pharmacodynamic effect from reversal to normalize coagulation hemostasis.…”

Hepatocyte-derived Microparticles as Novel Biomarkers for the Diagnosis of Deep Venous Thrombosis in Trauma Patients

“… 46 In previous studies, our team observed significantly increased levels of thrombomodulin and tissue factor pathway inhibitor in trauma patients with DVT. 47 In addition, the content of endothelial tissue factor MPs was increased significantly (results not published), which indicated endothelial dysfunction in trauma patients with DVT. Overall, the uptake of vesicles by endothelial cells with the concomitant occurrence of endothelial dysfunction and the role they play in DVT in trauma patients deserve further exploration.…”

Establishment and validation of a nomogram predicting the risk of deep vein thrombosis before total knee arthroplasty

“…Cao et al compared clinical data between people who developed DVT after fracture with those who did not develop DVT after fracture and with healthy controls. They observed that the level of PT was significantly increased in the DVT group, and they noted that the optimal threshold for PT to diagnose DVT was 12.05s, with a sensitivity of 72.92% and specificity of 47.92% (AUC = 0.617, 95% CI 0.505-0.730, p = 0.048) [39]. Above all, the predictors included in our prediction model in this study were all inflammatory in previous studies, proving the validity of our study.…”