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Dynamic assessment of venous thromboembolism risk in patients with cancer by longitudinal D-Dimer analysis: A prospective study.

ABSTRACT: BACKGROUND:Venous thromboembolism (VTE) is a frequent complication of cancer. Elevated D-dimer is associated with an increased risk of cancer-associated VTE. Whether changes in D-dimer over time harbor additional prognostic information that may be exploited clinically for dynamic prediction of VTE is unclear. OBJECTIVES:To explore the potential role of longitudinal D-dimer trajectories for personalized prediction of cancer-associated VTE. PATIENTS/METHODS:A total of 167 patients with active malignancy were prospectively enrolled (gastrointestinal: n = 59 [35%], lung: n = 56 [34%], brain: n = 50 [30%], others: n = 2 [1%]; metastatic disease: n = 74 [44%]). D-dimer (median = 0.8 µg/mL [25th-75th percentile: 0.4-2.0]) was measured at baseline and during 602 monthly follow-up visits. Joint models of longitudinal and time-to-event data were implemented to quantify the association between D-dimer trajectories and prospective risk of VTE. RESULTS:VTE occurred in 20 patients (250-day VTE risk = 12.1%, 95% confidence interval [CI], 7.8-18.5). D-dimer increased by 34%/month (0.47 µg/mL/month, 95% CI, 0.22-0.72, P < .0001) in patients who developed VTE, but remained constant in patients who did not develop VTE (change/month = -0.06 µg/mL, 95% CI, -0.15 to 0.02, P = .121). In joint modeling, a doubling of the D-dimer trajectory was associated with a 2.8-fold increase in the risk of VTE (hazard ratio = 2.78, 95% CI, 1.69-4.58, P < .0001). This finding was independent of established VTE risk factors. Highly personalized, dynamic predictions of VTE conditional on individual patients' D-dimer trajectories could be obtained. CONCLUSIONS:D-dimer increases before the onset of cancer-associated VTE, but remains constant over time in patients without VTE. This study represents proof-of-concept that longitudinal trajectories of D-Dimer may advance the personalized assessment of VTE risk in the oncologic setting.

SUBMITTER: Posch F

PROVIDER: S-EPMC7317804 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Dynamic assessment of venous thromboembolism risk in patients with cancer by longitudinal D-Dimer analysis: A prospective study.

Posch Florian F Riedl Julia J Reitter Eva-Maria EM Crowther Michael J MJ Grilz Ella E Quehenberger Peter P Jilma Bernd B Pabinger Ingrid I Ay Cihan C

Journal of thrombosis and haemostasis : JTH 20200415 6

<h4>Background</h4>Venous thromboembolism (VTE) is a frequent complication of cancer. Elevated D-dimer is associated with an increased risk of cancer-associated VTE. Whether changes in D-dimer over time harbor additional prognostic information that may be exploited clinically for dynamic prediction of VTE is unclear.<h4>Objectives</h4>To explore the potential role of longitudinal D-dimer trajectories for personalized prediction of cancer-associated VTE.<h4>Patients/methods</h4>A total of 167 pat ...[more]

PMID: 32073229

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Project description:ImportancePatients hospitalized with COVID-19 have higher rates of venous thromboembolism (VTE), but the risk and predictors of VTE among individuals with less severe COVID-19 managed in outpatient settings are less well understood.ObjectivesTo assess the risk of VTE among outpatients with COVID-19 and identify independent predictors of VTE.Design, setting, and participantsA retrospective cohort study was conducted at 2 integrated health care delivery systems in Northern and Southern California. Data for this study were obtained from the Kaiser Permanente Virtual Data Warehouse and electronic health records. Participants included nonhospitalized adults aged 18 years or older with COVID-19 diagnosed between January 1, 2020, and January 31, 2021, with follow-up through February 28, 2021.ExposuresPatient demographic and clinical characteristics identified from integrated electronic health records.Main outcomes and measuresThe primary outcome was the rate per 100 person-years of diagnosed VTE, which was identified using an algorithm based on encounter diagnosis codes and natural language processing. Multivariable regression using a Fine-Gray subdistribution hazard model was used to identify variables independently associated with VTE risk. Multiple imputation was used to address missing data.ResultsA total of 398 530 outpatients with COVID-19 were identified. The mean (SD) age was 43.8 (15.8) years, 53.7% were women, and 54.3% were of self-reported Hispanic ethnicity. There were 292 (0.1%) VTE events identified over the follow-up period, for an overall rate of 0.26 (95% CI, 0.24-0.30) per 100 person-years. The sharpest increase in VTE risk was observed during the first 30 days after COVID-19 diagnosis (unadjusted rate, 0.58; 95% CI, 0.51-0.67 per 100 person-years vs 0.09; 95% CI, 0.08-0.11 per 100 person-years after 30 days). In multivariable models, the following variables were associated with a higher risk for VTE in the setting of nonhospitalized COVID-19: age 55 to 64 years (HR 1.85 [95% CI, 1.26-2.72]), 65 to 74 years (3.43 [95% CI, 2.18-5.39]), 75 to 84 years (5.46 [95% CI, 3.20-9.34]), greater than or equal to 85 years (6.51 [95% CI, 3.05-13.86]), male gender (1.49 [95% CI, 1.15-1.96]), prior VTE (7.49 [95% CI, 4.29-13.07]), thrombophilia (2.52 [95% CI, 1.04-6.14]), inflammatory bowel disease (2.43 [95% CI, 1.02-5.80]), body mass index 30.0-39.9 (1.57 [95% CI, 1.06-2.34]), and body mass index greater than or equal to 40.0 (3.07 [1.95-4.83]).Conclusions and relevanceIn this cohort study of outpatients with COVID-19, the absolute risk of VTE was low. Several patient-level factors were associated with higher VTE risk; these findings may help identify subsets of patients with COVID-19 who may benefit from more intensive surveillance or VTE preventive strategies.

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.

Dataset Information

Dynamic assessment of venous thromboembolism risk in patients with cancer by longitudinal D-Dimer analysis: A prospective study.

Publications

Dynamic assessment of venous thromboembolism risk in patients with cancer by longitudinal D-Dimer analysis: A prospective study.

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