Aurélien Delluc

Patients with cancer have an increased risk of venous thromboembolism (VTE). This risk is further elevated in those with a central venous catheter (CVC). Previous studies have shown that prophylactic doses of direct oral anticoagulants (DOACs) reduce the risk of VTE in ambulatory cancer patients starting chemotherapy, which has led to recommendations from international clinical guidelines to use DOACs as primary thromboprophylaxis in this population. Primary thromboprophylaxis after CVC insertion is not recommended due to a lack of definitive evidence. As such, the TRIM-Line trial randomized 1,828 patients with active cancer and a newly inserted CVC to rivaroxaban 10 mg daily versus placebo. The primary efficacy outcome was the first objectively confirmed symptomatic or incidental major VTE (proximal upper or lower extremity deep vein thrombosis and/or pulmonary embolism) within 90 days of randomization. The primary safety outcome was major bleeding, as defined by the International Society on Thrombosis and Haemostasis criteria, within 90 days. The key secondary outcomes included clinically relevant non-major bleeding, arterial thrombosis, and overall mortality. The study provides high-quality evidence to address a key knowledge gap regarding the benefits and risks of thromboprophylaxis in patients with active cancer and an indwelling CVC (NCT05029063).

Prothrombin complex concentrates (PCC) are used off-label to treat direct factor Xa inhibitor (FXaI)-associated bleeding or before urgent surgery. GAUGE was a prospective observational cohort study of the effects of PCC on thrombin generation and hemostasis in FXaI-treated patients. FXaI-treated patients with major bleeding or needing urgent surgery received PCC (50 IU/kg). Platelet-poor plasma was collected pre-/post-PCC. TGA parameters (LT=lag time, TTP=time-to-peak, peak, ETP=endogenous thrombin potential, mVRI=mean velocity rate index) were measured using calibrated automated thrombography. Hemostatic efficacy, thromboembolism, and mortality were adjudicated in duplicate. Multivariable log-linear regression was used to evaluate PCC effects on FXaI levels. Unsupervised K-means clustering was used to identify patients with the largest ETP increment. GAUGE included 101 episodes of FXaI-associated PCC use (FXaI-associated bleeding = 71; urgent surgery = 30). Median PCC dosing was 48.0 IU/kg [42.0-50.0]. PCC did not affect FXaI levels (p>0.05). PCC increased ETP (Δ868.9±766.6 nM·min), peak (Δ85.7 nM±108.2), and the mVRI (Δ16.5 nM/min [4.4-45.0]). PCC did not affect the LT or TTP (p>0.05). Patients in Cluster 1 had significantly lower pre-PCC FXaI levels (79 ng/mL [55-93] vs 165 ng/mL [77-219]; p = 0.009) and a greater ΔETP increment (p < 0.0001) than patients in Cluster 2. Effective hemostasis occurred in 50.0% [95%CI 38.4-61.6] of major bleeds; procedural hemostasis was normal in 76.7% [95%CI 59.1-88.2]. The 30-day risks of thromboembolism and mortality were 6.9% [95%CI 3.4-13.6] and 12.9% [95%CI 7.7-20.8], respectively. PCC increased quantitative thrombin generation without shortening LT or TTP, supporting a prohemostatic effect rather than true FXaI reversal.

Patients with thrombotic antiphospholipid syndrome (APS) frequently require interruption of anticoagulation for invasive procedures; however, data to guide the perioperative management remain limited. We conducted a single-center, retrospective cohort study of adults with thrombotic APS who underwent planned periprocedural interruption of anticoagulation between 2016 and 2025. The primary outcomes were the 30-day risks for arterial thromboembolism (ATE), venous thromboembolism, and major bleeding; secondary outcomes included clinically relevant nonmajor bleeding (CRNMB), microvascular APS manifestations, and catastrophic APS (CAPS). Among 172 patients who underwent 282 interruptions, most (84.9%) received warfarin and 25% were triple-positive (anticardiolipin, anti–β2-glycoprotein I, and lupus anticoagulant). Bridging with low-molecular-weight heparin (LMWH) was used in 84.7% of warfarin interruptions. Therapeutic-dose bridging was more frequently used in patients with triple-positive APS (odds ratio [OR], 7.6; 95% confidence interval [CI], 3.2-18.2) and in those with a previous ATE (OR, 3.4; 95% CI, 1.5-7.8). The 30-day risk for ATE was 0.7% (95% CI, 0.2-2.6). Major bleeding occurred in 0.7% (95% CI, 0.2-2.6) of patients with both events following high bleed–risk procedures. One bleeding event was fatal, corresponding to a mortality risk of 0.4% (95% CI, 0.1-2.0). CRNMB occurred in 3.2% (95% CI, 1.7-6.0) of patients. A single case of probable CAPS occurred in a triple-positive patient who received postoperative prophylactic LMWH. Guideline-directed perioperative anticoagulation management tailored to individual thrombotic and procedural bleeding risks seems feasible and safe. Our findings support individualized, risk-adapted perioperative anticoagulation management in APS.

Obesity is a known risk factor for venous thromboembolism (VTE), but the long‐term effect of weight‐loss interventions such as bariatric surgery on VTE risk is uncertain. We conducted a population‐based matched cohort study using administrative health data from Ontario, Canada. Adults who underwent bariatric surgery between 2010 and 2016 were matched 1:1 to controls on age, sex, body mass index (BMI), and diabetes status. The primary outcome was incident VTE (deep vein thrombosis or pulmonary embolism), measured after a 3‐month landmark period. Hazard ratios (HRs) were estimated using Cox models adjusted for confounders, including time‐varying VTE risk factors. We included 13 502 patients who underwent bariatric surgery and 13 502 matched controls. The mean age was 45.0 years (SD 11.1), and 81.4% were women. Median follow‐up was 8.4 years. VTE incidence was 0.24 per 100 person‐years in the surgical group and 0.26 in the control group. Bariatric surgery was associated with a 21% reduced risk of VTE (HR 0.79; 95% CI 0.66–0.96). Risk reduction was more pronounced in men (HR 0.59; 95% CI 0.36–0.96) and in patients with BMI < 50 kg/m ² . No benefit was observed in patients with BMI ≥ 50 kg/m ² or those who had sleeve gastrectomy. Bariatric surgery is associated with a long‐term reduction in VTE risk, particularly among men and individuals with moderate obesity. These findings support the reversibility of obesity‐related thrombosis risk and inform long‐term VTE prevention strategies.

Patients with cancer‐associated thrombosis (CAT) are commonly treated with low‐molecular‐weight heparin (LMWH), but whether dose capping is needed in patients over 90 kg is unclear. We conducted the WAVe study, a multicenter prospective cohort study in adult patients (≥ 18 years) with acute CAT and a weight of over 90 kg starting anticoagulation. Patients received weight‐adjusted dalteparin at 200 IU/kg per day (up to 33 000 IU) for 30 (± 4) days, after which anticoagulation was continued per clinician discretion and followed for 6 months. The primary outcome was major bleeding (MB) at 30 days. Secondary outcomes included objectively confirmed recurrent venous thromboembolism (VTE) at 30 days and trough anti‐Xa levels. The cumulative incidences of outcomes were estimated by time‐to‐event analysis, with death as a competing risk. The study stopped early due to recruitment challenges after 91 patients. Median weight and daily dose of dalteparin were 107.5 kg and 22 500 IU, respectively. Three patients had a MB episode for a cumulative incidence of 5.3% (95% CI 1.1%–14.8%) at 30 days. One patient had recurrent VTE for a cumulative incidence of 1.2% (95% CI 0.1%–5.7%) at 30 days. No significant bioaccumulation noted up to Day 30 based on trough anti‐Xa levels. The median Day 7 trough anti‐Xa levels were higher in those with bleeding events within 30 days compared to those without (0.6 vs. 0.2 IU/mL, p = 0.01). Our results suggest that weight‐adjusted dosing of dalteparin in patients over 90 kg is associated with acceptable rates of bleeding and thrombosis. Trial Registration: NCT03297359

Animal studies show ovarian follicle damage and mutagenesis after ionizing radiation exposure. Computed tomography (CT) imaging is commonly done outside pregnancy, but risks to future pregnancy are unknown. To evaluate the risk for spontaneous pregnancy loss and congenital anomalies in offspring of women exposed to CT ionizing radiation before conception. Population-based observational study. Ontario, Canada. 5 142 339 recognized pregnancies and 3 451 968 live births identified between 1992 and 2023. The exposure was the cumulative number of CT scans up to 4 weeks before conception. Outcomes were spontaneous pregnancy loss (miscarriage, ectopic pregnancy, or stillbirth) among recognized pregnancies and congenital anomalies diagnosed within the first year of life among live births. Mean maternal age was 29 years. Diabetes, hypertension, obesity, and smoking were more common in those exposed to CT imaging. Among recognized pregnancies, rates of spontaneous pregnancy loss were 101, 117, 130, and 142 per 1000 pregnancies with 0, 1, 2, and 3 or more preconception CT scans, respectively, and adjusted hazard ratios (aHRs) were 1.08 (95% CI, 1.07 to 1.08) for 1 CT scan, 1.14 (CI, 1.12 to 1.16) for 2 CT scans, and 1.19 (CI, 1.16 to 1.21) for 3 or more CT scans. Among live births, rates of congenital anomalies were 62, 84, 96, and 105 per 1000 births in those with 0, 1, 2, and 3 or more CT scans, and aHRs were 1.06 (CI, 1.05 to 1.08) for 1 CT scan, 1.11 (CI, 1.09 to 1.14) for 2 CT scans, and 1.15 (CI, 1.11 to 1.18) for 3 or more CT scans. The risk observed with head CT was not consistently lower than with CT of the abdomen, pelvis, or lower spine. Incomplete ascertainment of CT exposure and underlying indication may have contributed to residual confounding. Exposure to preconception CT imaging may be associated with higher risks for spontaneous pregnancy loss and congenital anomalies, but causal mechanisms remain to be elucidated. Alternative imaging methods should be considered when appropriate. Canadian Institutes of Health Research.