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D-Dimer Combined with Fibrinogen Predicts the Risk of Venous Thrombosis in Fracture Patients.

ABSTRACT: Objective:While D-dimer can successfully diagnose venous thrombosis due to its excellent negative predictive value (NPV), it cannot be used to detect venous thromboembolism (VTE) because of its low positive predictive value (PPV). This study aims to investigate if a combination of using D-dimer and fibrinogen can improve PPV in the VTE diagnosis. Methods:We retrospectively analyzed various data including D-dimer, fibrinogen, C-reactive protein, ultrasound, and others collected from 10775 traumatic fracture patients and categorized them into two groups of VTE and non-VTE. By comparing the difference between the two groups, we employ multiple logistic regression to find risk factors that are useful to detect VTE. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic yield of using fibrinogen, D-dimer, and their combination, respectively. Also, these data were classified into quartiles by patient age. We perform the same analysis on the quartiles and find if the patient's age has an impact on diagnosing VTE. Results:The univariate analysis demonstrated that five factors of age, D-dimer, fibrinogen, C-reactive protein, and high-density lipoprotein cholesterol were significant to predict VTE. ROC showed that D-dimer was more useful than fibrinogen for the diagnosis of VTE, while the area under the curve (AUC) was 0.7296 for D-dimer and 0.5209 for fibrinogen. The cutoff point of D-dimer and fibrinogen was 424.89?ng/ml and 3.543?g/L, respectively. The specificity of fibrinogen was 0.777 which was better than D-dimer, while the sensitivity of fibrinogen was lower than that of D-dimer. Both PPV and NPV were similar in D-dimer and fibrinogen. The PPV of combining D-dimer and fibrinogen in ages Q3 (60??70) was better than using either D-dimer or fibrinogen. Conclusions:Fibrinogen is a promising strategy for the diagnosis of subclinical VTE and postoperative VTE. In particular, a combination of D-dimer and fibrinogen can improve the PPV to successfully diagnose VTE in traumatic fracture patients who are more than 60 years old. Levels of Evidence. This assay is a diagnostic test at level II.

SUBMITTER: Lin C

PROVIDER: S-EPMC7530481 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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D-Dimer Combined with Fibrinogen Predicts the Risk of Venous Thrombosis in Fracture Patients.

Lin Chaohui C Chen Yifan Y Chen Bin B Zheng Ke K Luo Xiongbiao X Lin Fengfei F

Emergency medicine international 20200923

<h4>Objective</h4>While D-dimer can successfully diagnose venous thrombosis due to its excellent negative predictive value (NPV), it cannot be used to detect venous thromboembolism (VTE) because of its low positive predictive value (PPV). This study aims to investigate if a combination of using D-dimer and fibrinogen can improve PPV in the VTE diagnosis.<h4>Methods</h4>We retrospectively analyzed various data including D-dimer, fibrinogen, C-reactive protein, ultrasound, and others collected fro ...[more]

PMID: 33029403

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Project description:BackgroundVenous thromboembolism (VTE) is a complex multifactorial disease influenced by genetic and environmental risk factors. An example for the latter is the regular use of combined oral contraceptives (CC), which increases the risk to develop VTE by 3 to 7 fold, depending on estrogen dosage and the type of progestin present in the pill. One out of 1'000 women using CC develops thrombosis, often with life-long consequences; a risk assessment is therefore necessary prior to such treatment. Currently known clinical risk factors associated with VTE development in general are routinely checked by medical doctors, however they are far from being sufficient for risk prediction, even when combined with genetic tests for Factor V Leiden and Factor II G20210A variants. Thus, clinical and notably genetic risk factors specific to the development of thrombosis associated with the use of CC in particular should be identified.Methods and findingsStep-wise (logistic) model selection was applied to a population of 1622 women using CC, half of whom (794) had developed a thromboembolic event while using contraceptives. 46 polymorphisms and clinical parameters were tested in the model selection and a specific combination of 4 clinical risk factors and 9 polymorphisms were identified. Among the 9 polymorphisms, there are two novel genetic polymorphisms (rs1799853 and rs4379368) that had not been previously associated with the development of thromboembolic event. This new prediction model outperforms (AUC 0.71, 95% CI 0.69-0.74) previously published models for general thromboembolic events in a cross-validation setting. Further validation in independent populations should be envisaged.ConclusionWe identified two new genetic variants associated to VTE development, as well as a robust prediction model to assess the risk of thrombosis for women using combined oral contraceptives. This model outperforms current medical practice as well as previously published models and is the first model specific to CC use.

Project description:Serious vaccine-associated side effects are very rare. Major complications of vaccines are thrombocytopenia and thrombosis in which pathogenetic mechanism is consistent with endotheliopathy characterized by "attenuated" sepsis-like syndrome, leading to the activation of inflammatory and microthrombotic pathway. In the COVID-19 pandemic, acute respiratory distress syndrome caused by microthrombosis has been the major clinical phenotype from the viral sepsis in association with endotheliopathy-associated vascular microthrombotic disease (EA-VMTD), sometimes presenting with thrombotic thrombocytopenic purpura (TTP)-like syndrome. Often, venous thromboembolism has coexisted due to additional vascular injury. In contrast, clinical phenotypes of vaccine complication have included "silent" immune thrombocytopenic purpura (ITP-like syndrome), multiorgan inflammatory syndrome, and deep venous thrombosis (DVT), cerebral venous sinus thrombosis (CVST) in particular. These findings are consistent with venous (v) EA-VMTD. In vEA-VMTD promoted by activated complement system following vaccination, "consumptive" thrombocytopenia develops as ITP-like syndrome due to activated unusually large von Willebrand factor (ULVWF) path of hemostasis via microthrombogenesis. Thus, the pathologic phenotype of ITP-like syndrome is venous microthrombosis. Myocarditis/pericarditis and other rare cases of inflammatory organ syndrome are promoted by inflammatory cytokines released from activated inflammatory pathway, leading to various organ endotheliitis. Vaccine-associated CVST is a form of venous combined "micro-macrothrombosis" composed of binary components of "microthrombi strings" from vEA-VMTD and "fibrin meshes" from vaccine-unrelated incidental vascular injury perhaps such as unreported head trauma. This mechanism is identified based on "two-path unifying theory" of in vivo hemostasis. Venous combined micro-macrothrombosis due to vaccine is much more serious thrombosis than isolated distal DVT made of macrothrombus. This paradigm changing novel concept of combined micro-macrothrombosis implies the need of combined therapy of a complement inhibitor and anticoagulant for CVST and other complex forms of DVT.

Dataset Information

D-Dimer Combined with Fibrinogen Predicts the Risk of Venous Thrombosis in Fracture Patients.

Publications

D-Dimer Combined with Fibrinogen Predicts the Risk of Venous Thrombosis in Fracture Patients.

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