Research Appraisals
Evidence-based critical appraisals of the latest medical research, systematically evaluated using Oxford CEBM methodology.
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European heart journal
Venous thromboembolism and bleeding in cancer patients: role of inflammatory and cardiac biomarkers.
BACKGROUND AND AIMS: Patients with cancer have increased risk of venous thromboembolism (VTE) and bleeding. Inflammatory and cardiac biomarkers may predict these complications, but their role remains unclear. This study examined associations between two inflammatory-related markers (C-reactive protein and growth differentiation factor-15) and two cardiac markers [N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T (hs-TnT)] with VTE and clinically relevant bleeding in cancer patients. METHODS: A post hoc analysis of the AVERT trial, which evaluated apixaban for VTE prevention in ambulatory cancer patients with a Khorana score of ≥2, was performed. Biomarkers were measured at baseline and 1 month, with C-reactive protein also at 3 months. Fine and Gray regression, accounting for competing risk of death and adjusted for age and advanced cancer, estimated subdistribution hazard ratios (SHRs) for VTE and clinically relevant bleeding. RESULTS: Of 574 patients, 514 provided baseline samples. One- and 3-month samples were available from 454 and 447, and 378 and 364, patients without prior VTE and bleeding events, respectively. Elevated baseline growth differentiation factor-15 was associated with increased VTE risk [SHR 1.36, 95% confidence interval (CI) 1.01-1.84]. N-terminal pro-B-type natriuretic peptide (SHR 1.44, 95% CI 1.08-1.92) and C-reactive protein (SHR 1.38, 95% CI 1.07-1.76) were linked to bleeding risk. Increasing high-sensitivity troponin T from baseline to 1 month was associated with higher VTE risk (SHR 1.89, 95% CI 1.14-3.16). Nomograms were developed to estimate VTE and clinically relevant bleeding risks. CONCLUSIONS: Select inflammatory-related and cardiac markers were associated with VTE and bleeding risks in cancer patients, which can be determined using developed nomograms. Prospective research is needed to confirm these findings.
23 Apr 2026
Read appraisal →Blood advances
How to determine the optimal duration of anticoagulation for VTE: an evidence-based decision-analytical approach
When advising patients on the optimal duration of anticoagulation for venous thromboembolism (VTE), current management often relies on the intuition of treating physicians and guideline panels, an approach that remains opaque to outside observers. We present a decision-analytical framework adopted in our practice. This approach formalizes the intuition of physicians and guideline panels, providing an explicit and transparent integration of the best available evidence on benefits and harms. It also incorporates a systematic method for eliciting patient values and preferences to determine the optimal duration of anticoagulation. To demonstrate the practical utility of the decision-analytical approach, we apply it to 3 clinical scenarios: unprovoked VTE, VTE related to long-haul travel, and portal vein thrombosis in cirrhosis. By transparently synthesizing evidence and patient values, this method supports individualized, evidence-based, patient-centered recommendations for the duration of anticoagulation, and it is applicable to solving similar clinical problems in hematology and medicine.
14 Apr 2026
Read appraisal →Journal of the American Heart Association
Ex Vivo Effect of Apixaban on Hemostatic Biomarkers in Children With Heart Disease: A SAXOPHONE Trial Substudy
BACKGROUND: The SAXOPHONE (Safety of Apixaban on Pediatric Heart Disease on the Prevention of Embolism) trial demonstrated the safety of apixaban for thromboprophylaxis in children with heart disease. Included a priori in the trial design was an exploratory biomarker substudy to evaluate the effects of apixaban on surrogate biomarkers of efficacy, thrombin generation capacity, and hemostatic proteins. The study assessed changes in d-dimer, thrombin generation assay parameters, factor VIII, fibrinogen, protein C, and protein S in children receiving apixaban compared with standard-of-care vitamin K antagonists (VKAs) or low-molecular-weight heparin. METHODS: SAXOPHONE participants aged >1 year (n=182) had blood samples for biomarkers collected at baseline, week 2, or month 6. Participants were randomized to apixaban (n=123) or standard of care (VKA or low-molecular-weight heparin; n=59). Subgroup analyses accounted for prior VKA exposure. RESULTS: d-dimer levels decreased at month 6 in all treatment groups and remained stable during VKA-to-apixaban bridging. Apixaban significantly prolonged thrombin generation assay lag time and time to peak compared with VKAs and decreased peak thrombin similarly to VKAs in anticoagulant-naïve participants. Apixaban was associated with decreased fibrinogen and factor VIII at month 6, with no effect on protein C or S. Prior VKA exposure produced carryover effects, suppressing baseline d-dimer, thrombin generation assay parameters, and proteins C and S. CONCLUSIONS: Apixaban reduced hypercoagulability, as shown by decreased d-dimer levels and prolonged lag time, and preserved endogenous thrombin potential in thrombin generation assay, changes consistent with adult data. These findings align with SAXOPHONE's primary outcomes, supporting apixaban's favorable risk-benefit profile as a thromboprophylaxis option in children with heart disease.
8 Apr 2026
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