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Laboratory biomarkers for venous thromboembolism risk in patients with hematologic malignancies: A review.

ABSTRACT: INTRODUCTION:Despite high rates of venous thromboembolism (VTE) among patients with hematologic malignancies, few tools exist to assist providers in identifying those patients at highest risk for this potentially fatal complication. Laboratory biomarkers, such as d-dimer, have demonstrated utility in some clinical settings to distinguish patients at increased risk. MATERIALS AND METHODS:We performed a systematic review of the literature utilizing search terms including "biomarker", "venous thromboembolism", "hematologic malignancy", "lymphoma", "myeloma" and "leukemia" in the Medline database. A total of 25 studies investigating laboratory biomarkers of increased thrombotic risk in the setting of hematologic malignancy were identified and included in this review. RESULTS AND CONCLUSIONS:The most studied biomarkers, d-dimer and fibrinogen, demonstrated some degree of efficacy in identifying high-risk patients at levels >4.0?mg/L or <1.0?g/L respectively. Additional markers which demonstrated promise included thrombin generation, mean platelet volume, soluble VEGF, soluble P-selectin and extracellular vesicles. Other biomarkers reviewed, which did not consistently demonstrate significant associations with VTE included prothrombin fragments F1?+?2, factor VIII, protein C, protein S, von Willebrand antigen and activity, antithrombin, thrombin antithrombin complex, antiphospholopid antibody, plasminogen activator inhibitor, tissue factor pathway inhibitor and several variants associated with known hypercoagulable states (factor V Leiden, prothrombin gene variant, methylenetetrahydrofolate reductase variant). Data to support any of the biomarkers discussed here in routine clinical decision-making are currently lacking, but additional investigation in clinical studies, ideally in combination with clinical factors known to be associated with increased thrombotic risk, is warranted.

SUBMITTER: Samuelson Bannow BT

PROVIDER: S-EPMC5879008 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Laboratory biomarkers for venous thromboembolism risk in patients with hematologic malignancies: A review.

Samuelson Bannow B T BT Konkle B A BA

Thrombosis research 20180131

<h4>Introduction</h4>Despite high rates of venous thromboembolism (VTE) among patients with hematologic malignancies, few tools exist to assist providers in identifying those patients at highest risk for this potentially fatal complication. Laboratory biomarkers, such as d-dimer, have demonstrated utility in some clinical settings to distinguish patients at increased risk.<h4>Materials and methods</h4>We performed a systematic review of the literature utilizing search terms including "biomarker" ...[more]

PMID: 29407626

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Project description:Importance:Although malignancy is an established risk factor for venous thromboembolism (VTE), the risk of VTE specifically in patients with keratinocyte carcinoma (KC) has not been previously studied. Objective:To determine the risk of VTE in patients with KC compared with patients not diagnosed with cancer and with patients diagnosed with common malignant neoplasms associated with VTE. Design, Setting, and Participants:Population-based retrospective analysis of patient insurance claims made between January 1, 2007, and December 31, 2014, from the Truven MarketScan Commercial and Medicare Supplemental Databases. Patients treated across the United States were divided into 3 cohorts: patients with KC, patients with pancreatic cancer or acute myelogenous leukemia who are thus at high risk for VTE, and patients without a history of common malignant neoplasms. Patients were excluded from the KC cohort if they had a history of another type of cancer. Data were analyzed between April 1, 2017, and January 15, 2018. Main Outcomes and Measures:Diagnosis of VTE within 1 year following the index date (for the KC and high-risk cohorts, the date of the initial diagnosis of cancer; for the control cohort, the date following 365 days of continuous insurance enrollment). Logistic regression was used to assess the risk of VTE in the KC cohort compared with the high-risk and control cohorts before and after matching across patient characteristics and known risk factors for VTE. Results:Of 5 753 613 potentially eligible patients, the final sample consisted of 740 246 patients (12.8%) across 3 cohorts. Of the 740 246 study participants, 417 839 were in the KC cohort (223 986 [53.6%] men, mean [SD] age, 64.2 [13.6] years); 314 736 were in the control cohort (135 203 [43.0%] men, 42.9 [15.2] years); and 7671 were in the high-risk cohort (3502 [45.7%] men, 59.4 [14.4] years) The risk of VTE in the KC cohort was lower compared with the high-risk cohort in univariable analysis (odds ratio [OR], 0.22; 95% CI, 0.20-0.23; P < .001), multivariable analysis (OR, 0.29; 95% CI, 0.26-0.32; P < .001), and after matching across patient characteristics and known risk factors (OR, 0.52; 95% CI, 0.35-0.78; P = .001). The risk of VTE in the KC cohort was higher in the univariable analysis (OR, 2.31; 95% CI, 2.23-2.41; P < .001), lower in the multivariable analysis (OR, 0.85; 95% CI, 0.80-0.90; P < .001), and not different after matching of patient characteristics and risk factors (OR, 0.95; 95% CI, 0.89-1.01; P = .08) than that of the control cohort. Conclusions and Relevance:The results of this study provided no evidence supporting the increased risk of VTE in the KC cohort compared with the control cohort. Given the inherent risks of chemoprophylaxis, the need for prophylactic anticoagulation in patients with KC who are scheduled for surgery should be carefully considered. Level of Evidence:NA.

Project description:ImportanceThe size of the risk of recurrent venous thromboembolism (VTE) after surgery in patients with a history of VTE is not well known.ObjectivesTo estimate the risk of and to identify the factors associated with recurrent VTE in patients undergoing surgery who have a history of VTE.Design, setting, and participantsThis population-based, follow-up cohort study includes patients with VTE who participated in the Multiple Environment and Genetic Assessment (MEGA) study. Original data were collected from March 1999 to April 2010. Data analysis began in June 1999 and ended in April 2010.ExposuresSurgery following a first VTE.Main outcomes and measurementsKaplan-Meier analyses were used to estimate cumulative incidences of recurrent VTE. Cox regression with a time-dependent covariate (surgery) was used to calculate the hazard ratio (HR) for developing recurrent VTE after surgery compared with no surgery.ResultsOverall, 3741 patients (mean [SD] age, 48.4 [12.8] years; 2020 [54.0%] women) with a history of VTE were included in the analysis, amounting to 18 899 person-years, with a median (interquartile range) follow-up of 5.7 (3.0-7.2) years. Of the 3741 patients, 580 (15.5%) underwent surgery and 601 (16.1%) developed a recurrent thrombotic event. The 1-month cumulative incidence of recurrent VTE for all surgery types was 2.1% (95% CI, 1.2%-3.6%), which increased to 3.3% (95% CI, 2.1%-5.1%) at 3 months and 4.6% (95% CI, 3.1%-6.6%) at 6 months. At 6 months, risk of recurrent VTE ranged from 2.3% to 9.3%, depending on surgery type. In addition to surgery type, factor V Leiden mutation (HR, 3.4; 95% CI, 1.6-7.4) and male sex (HR, 2.7; 95% CI, 1.3-5.8) were associated with increased risk of recurrent VTE.Conclusions and relevanceSurgery was associated with an increased risk of recurrent VTE in patients with a history of VTE; risk remained high for up to 6 months after the procedure. This study suggests that high-risk individuals may be identified based on surgery type, sex, and the presence of factor V Leiden mutation. These findings stress the need for revision of the current thromboprophylactic approach to prevent recurrence in these patients.

Project description:IntroductionHospital-acquired thrombosis accounts for a large proportion of all venous thromboembolism (VTE), with significant morbidity and mortality. This subset of VTE can be reduced through accurate risk assessment and tailored pharmacological thromboprophylaxis. This systematic review aimed to determine the comparative accuracy of risk assessment models (RAMs) for predicting VTE in patients admitted to hospital.MethodsA systematic search was performed across five electronic databases (including MEDLINE, EMBASE and the Cochrane Library) from inception to February 2021. All primary validation studies were eligible if they examined the accuracy of a multivariable RAM (or scoring system) for predicting the risk of developing VTE in hospitalised inpatients. Two or more reviewers independently undertook study selection, data extraction and risk of bias assessments using the PROBAST (Prediction model Risk Of Bias ASsessment Tool) tool. We used narrative synthesis to summarise the findings.ResultsAmong 6355 records, we included 51 studies, comprising 24 unique validated RAMs. The majority of studies included hospital inpatients who required medical care (21 studies), were undergoing surgery (15 studies) or receiving care for trauma (4 studies). The most widely evaluated RAMs were the Caprini RAM (22 studies), Padua prediction score (16 studies), IMPROVE models (8 studies), the Geneva risk score (4 studies) and the Kucher score (4 studies). C-statistics varied markedly between studies and between models, with no one RAM performing obviously better than other models. Across all models, C-statistics were often weak (<0.7), sometimes good (0.7-0.8) and a few were excellent (>0.8). Similarly, estimates for sensitivity and specificity were highly variable. Sensitivity estimates ranged from 12.0% to 100% and specificity estimates ranged from 7.2% to 100%.ConclusionAvailable data suggest that RAMs have generally weak predictive accuracy for VTE. There is insufficient evidence and too much heterogeneity to recommend the use of any particular RAM.Prospero registration numberSteve Goodacre, Abdullah Pandor, Katie Sworn, Daniel Horner, Mark Clowes. A systematic review of venous thromboembolism RAMs for hospital inpatients. PROSPERO 2020 CRD42020165778. Available from https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=165778https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=165778.

Project description:BackgroundVenous thromboembolism (VTE) increases the risk of death or adverse outcomes in patients with lung cancer. Therefore, early identification and treatment of high-risk groups of VTE have been the research focus. In this systematic review, the risk assessment tools of VTE in patients with lung cancer were systematically analyzed and evaluated to provide a reference for VTE management.MethodsRelevant studies were retrieved from major English databases (The Cochrane Library, Embase, Web of Science, PubMed, Scopus, Medline) and Chinese databases (China National Knowledge Infrastructure [CNKI] and WanFang Data) until July 2023 and extracted by two researchers. This systematic review was registered at PROSPERO (no. CRD42023409748).ResultsFinally, two prospective cohort studies and four retrospective cohort studies were included from 2019. There was a high risk of bias in all included studies according to the Prediction Model Risk of Bias Assessment tool (PROBAST). In the included studies, Cox and logistic regression were used to construct models. The area under the receiver operating characteristic curve (AUC) of the model ranged from 0.670 to 0.904, and the number of predictors ranged from 4 to 11. The D-dimer index was included in five studies, but significant differences existed in optimal cutoff values from 0.0005 mg/L to 2.06 mg/L. Then, three studies validated the model externally, two studies only validated the model internally, and only one study validated the model using a combination of internal and external validation.ConclusionVTE risk prediction models for patients with lung cancer have received attention for no more than 5 years. The included model shows a good predictive effect and may help identify the risk population of VTE at an early stage. In the future, it is necessary to improve data modeling and statistical analysis methods, develop predictive models with good performance and low risk of bias, and focus on external validation and recalibration of models.

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Laboratory biomarkers for venous thromboembolism risk in patients with hematologic malignancies: A review.

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Laboratory biomarkers for venous thromboembolism risk in patients with hematologic malignancies: A review.

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