Impact of anticoagulation on recurrent thrombosis and bleeding after hematopoietic cell transplantation.

History of venous thromboembolism (VTE) is prevalent among patients undergoing hematopoietic cell transplantation (HCT). Management of anticoagulation is particularly challenging as most patients will have chemotherapy-induced thrombocytopenia while awaiting engraftment post-HCT. We conducted a retrospective study of autologous and allogeneic HCT recipients with prior VTE from 2006-2015 to 1) compare anticoagulant strategies on short-term VTE recurrence and bleeding and 2) assess predictors for VTE recurrence beyond 30 days. Patients with VTE were allocated to two cohorts based on anticoagulant strategy at thrombocytopenia onset and underwent inverse probability weighting to assess primary outcomes of VTE recurrence and bleeding within 30 days post-HCT. Subsequently, multivariable logistic regression model was used to assess the association of 100-day VTE recurrence by the HIGH-2-LOW VTE risk assessment score and whether patients resumed anticoagulation at platelet recovery. Thirteen percent of recipients had VTE prior to HCT; of those meeting inclusion criteria, 227 continued anticoagulation and 113 temporarily discontinued it. Anticoagulant strategy was not significantly associated with decreased risk of VTE recurrence within 30 days (3% vs 4%, p = 0.61); however, risk of overall bleeding was non-significantly higher in those who continued vs discontinued anticoagulation (41% vs 31%, p = 0.08). In a subgroup of 250 allogeneic HCT patients, every one-point increase of HIGH-2-LOW score was significantly associated with VTE recurrence at 100 days (OR 1.57 [95% CI 1.10-2.23]), while anticoagulation resumption upon platelet engraftment was associated with lower recurrent risk (OR 0.48 [0.20-1.14]). Temporarily withholding anticoagulation during thrombocytopenia may optimize risk-benefit tradeoffs, though additional strategies are essential to prevent VTE recurrence after hematopoietic recovery.

HIGH-2-LOW risk model to predict venous thromboembolism in allogeneic transplant patients after platelet engraftment.

Venous thromboembolism (VTE) after allogeneic hematopoietic cell transplantation (HCT) is a significant treatment-associated complication, although optimal timing of thromboprophylaxis remains uncertain when weighing concurrent risks of bleeding. We aimed to derive and internally validate a risk assessment model (RAM) using patients who underwent first allogeneic HCT from 2006 through 2015 (n = 1703). Index date was defined as the 30th day after transplant, at which point we estimated >75% of patients would have achieved platelet engraftment >50 × 109/L. Stepwise logistic regression modeling was used for model development, and internal validation was achieved by fitting a logistic regression model with 1000 bootstrapped resamples to estimate the optimism-corrected c-statistic. The final RAM, "HIGH-2-LOW," included 7 predictors obtained at 30 days after transplant: History of catheter-related deep venous thrombosis (DVT), Inpatient at day 30, Graft-versus-host disease grade 3 to 4, History of pulmonary embolism or lower-extremity DVT, Lymphoma diagnosis, Obesity with body mass index ≥35 kg/m2, and White blood cell count ≥11 × 109/L. Approximately 16% of patients were stratified as high risk, with incident VTE rate of 10.3% at 100 days compared with 1.5% for those at low risk. VTE odds ratios at 100 days were 5.87 (95% confidence interval [CI], 2.98-11.57) and 2.71 (95% CI, 1.38-5.35) in the high- and intermediate-risk vs low-risk groups, respectively. HIGH-2-LOW model serves as a novel and potentially clinically meaningful tool to identify high-risk allogeneic HCT patients who may benefit from early thromboprophylaxis after platelet engraftment.

Management of venous thromboembolism during thrombocytopenia after autologous hematopoietic cell transplantation.

Management of venous thromboembolism (VTE) remains challenging in patients with hematologic malignancy who undergo hematopoietic cell transplantation (HCT) due to prolonged thrombocytopenia. This study aims to (1) determine the incidence of VTE recurrence and bleeding during autologous HCT, (2) assess the impact of continuing vs temporarily withholding anticoagulation during thrombocytopenia, and (3) explore the impact of platelet threshold among other variables on the risk of bleeding. We performed this observational study in adults with lymphoma and myeloma who underwent autologous HCT between 2006 and 2015. We selected patients with index VTE prior to HCT and assigned them to different cohorts based on antithrombotic management at the onset of thrombocytopenia. Primary outcomes included VTE recurrence and major bleeding by 30 days after HCT. Secondary outcomes included platelet and red blood cell transfusions, time to engraftment, and overall survival. Of the 1631 patients who underwent autologous HCT, 204 patients (12.5%) had preceding index VTE events, and among them, 132 patients continued and 72 patients temporarily withheld anticoagulation during thrombocytopenia. There were no significant differences in VTE recurrence (1.5% vs 1.4%) or major bleeding (3.8% vs 4.2%) between 2 groups by 30 days. The number of platelet transfusions was significantly higher in the first group. Baseline elevated bilirubin, creatinine, and prothrombin time were independently associated with increased risk in major bleeding, whereas neither platelet threshold nor average platelet count was predictive. Our findings suggest that for many patients undergoing autologous HCT, temporarily withholding anticoagulation during thrombocytopenia may offer the best risk-benefit tradeoff among available options.