Dataset Information

Changes in Biomarkers of Coagulation, Fibrinolytic, and Endothelial Functions for Evaluating the Predisposition to Venous Thromboembolism in Patients With Hereditary Thrombophilia.

ABSTRACT: The changes in the coagulation, fibrinolytic, and endothelial functions are correlated with the pathophysiology of the thromboembolic diseases during acute illness. However, these changes in patients with hereditary thrombophilia who were not in the acute stage of venous thromboembolism (VTE) are unclear. A panel of 4 biomarkers, including thrombin-antithrombin complex (TAT), plasmin-?2-plasmin inhibitor complex (PIC), tissue-type plasminogen activator/plasminogen activator inhibitor-1 complex (t-PAIC), and soluble thrombomodulin (sTM), were assayed in 100 healthy controls and 100 patients with thrombophilia. Although significantly higher concentrations of TAT, PIC, t-PAIC, and sTM were observed in patients with thrombophilia than in healthy controls, 70 patients showed absolutely normal levels of the above 4 biomarkers. Among the other 30 patients who had at least 1 biomarker out of the corresponding reference interval, 26 of them presented elevated PIC with or without increased TAT. Except for sTM, other 3 biomarkers did not show significant differences in patients with previous VTE compared to those without. Patients with single episode of VTE had obviously lower t-PAIC than those with multiple episodes of VTE, whereas the levels of TAT, PIC, and sTM were unassociated with the number of thrombosis episodes. Most thrombophilia patients who were not in the acute stage of VTE showed normal coagulation, fibrinolytic, and endothelial functions. Thus, we were unable to show that the one-time response of this panel was clinically helpful in determining thrombosis risk in thrombophilia individuals. Future studies should focus on the dynamic monitoring during the chronic phase of VTE to offer special advantages for patients with thrombophilia.

SUBMITTER: Li L

PROVIDER: S-EPMC7479868 | biostudies-literature | 2020 Jan-Dec

REPOSITORIES: biostudies-literature

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Changes in Biomarkers of Coagulation, Fibrinolytic, and Endothelial Functions for Evaluating the Predisposition to Venous Thromboembolism in Patients With Hereditary Thrombophilia.

Li Lei L Gao Lixia L Wu Xi X Wu Wenman W Ding Qiulan Q Wang Xuefeng X

Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis 20200101

The changes in the coagulation, fibrinolytic, and endothelial functions are correlated with the pathophysiology of the thromboembolic diseases during acute illness. However, these changes in patients with hereditary thrombophilia who were not in the acute stage of venous thromboembolism (VTE) are unclear. A panel of 4 biomarkers, including thrombin-antithrombin complex (TAT), plasmin-α2-plasmin inhibitor complex (PIC), tissue-type plasminogen activator/plasminogen activator inhibitor-1 complex ( ...[more]

PMID: 32886527

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Project description:The clinical venous thromboembolism (VTE) pattern often shows wide heterogeneity within relatives of a VTE-affected family, although they carry the same thrombophilia defect. It is then mandatory to develop additional tools for assessing VTE risk in families with thrombophilia. This study aims to assess whether common environmental and genetic risk factors for VTE contribute to explain this heterogeneity. A total of 2,214 relatives from 651 families with known inherited thrombophilia were recruited at the referral center for thrombophilia in Marseilles, France, from 1986 to 2013. A thrombophilia screening was systematically performed in all included relatives. According to the severity of the thrombophilia defect, individuals were split into three groups: no familial defect, mild thrombophilia, and severe thrombophilia. In addition, common genetic factors (ABO blood group and 11 polymorphisms selected on the basis of their association with VTE in the general population) were genotyped. Furthermore, body mass index and smoking were collected. VTE incidence was 1.74, 3.64, and 6.40 per 1,000 person-years in individuals with no familial defect, mild thrombophilia, and severe thrombophilia, respectively. Five common risk factors were associated with VTE in this population: obesity, smoking, ABO blood group, and F11 _rs2036914 and FGG _rs2066865 polymorphisms. These common factors were then included into a three-level risk score. The score was highly efficient for assessing VTE risk in mild thrombophilia patients by identifying two groups with different VTE risk; individuals with low score had the same risk as individuals with no familial defect whereas individuals with high score had the same risk as individuals with severe thrombophilia. An overall score including the five items plus the thrombophilia status was built and displayed an area under the receiver operating characteristic curve of 0.702 for discriminating VTE and non-VTE relatives. In conclusion, integrating common environmental and genetic risk factors improved VTE risk assessment in relatives from families with thrombophilia.

Project description:In the phase 2b/3 DIVERSITY trial, 3 months treatment with dabigatran was noninferior to standard of care (SOC) for acute venous thromboembolism (VTE) in children. In a single-arm, phase 3, secondary VTE prevention study, up to 12 months dabigatran use was associated with favorable safety. Dabigatran is approved by the European Medicines Agency and US Food and Drug Administration for pediatric indications. We assessed primary composite efficacy (complete thrombus resolution and freedom from VTE recurrence/VTE-related death) in subgroups with thrombophilia vs those with negative/unknown thrombophilia status in the DIVERSITY trial and safety in both studies. Thrombophilia types were similar between the DIVERSITY trial (total population) and secondary prevention studies: factor V Leiden, 42% vs 33%; prothrombin mutation (G20210A), 19% vs 17%; antithrombin deficiency, 15% vs 20%; protein C/S deficiency, 23% vs 25%; and antiphospholipid antibodies, 18% vs 20% of patients, respectively. In DIVERSITY, 36% and 22% of thrombophilia subgroup patients treated with dabigatran and SOC, respectively, met the primary end point (Mantel-Haenszel-weighted rate difference, -0.135; 95% confidence interval, -0.36 to 0.08; noninferiority P = .0014); comparable to the total DIVERSITY trial population (46% vs 42%) showing dabigatran noninferiority to SOC. Within this subgroup, numerically fewer patients experienced VTE recurrence or progression of index thrombus in the dabigatran treatment group vs SOC. In the secondary prevention study, VTE recurrence at 12 months occurred in 2.8% of patients with thrombophilia vs 0% with negative/unknown thrombophilia. Safety profiles were consistent with those reported previously. Although they should be interpreted with caution, these exploratory findings suggest dabigatran could be an appropriate long-term anticoagulant for children with thrombophilia. These trials were registered at www.clinicaltrials.gov as #NCT01895777 and #NCT02197416.

Dataset Information

Changes in Biomarkers of Coagulation, Fibrinolytic, and Endothelial Functions for Evaluating the Predisposition to Venous Thromboembolism in Patients With Hereditary Thrombophilia.

Publications

Changes in Biomarkers of Coagulation, Fibrinolytic, and Endothelial Functions for Evaluating the Predisposition to Venous Thromboembolism in Patients With Hereditary Thrombophilia.

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