Conference Coverage

Aspirin Use Linked to Higher Bleeding, Thrombotic Risks in Patients with Antiphospholipid Syndrome and Arterial Thrombosis

Edited by:
Anthony Calabro, MA

Key Highlights

  • Adding aspirin to warfarin increased gastrointestinal bleeding, intracranial hemorrhage, and transfusion risk.
  • Ischemic stroke and acute myocardial infarction rates were higher in the aspirin group despite matched baseline characteristics.
  • No difference in all-cause mortality was observed between treatment strategies.

Adding low-dose aspirin to warfarin for adults with antiphospholipid syndrome (APS) and arterial thrombosis was associated with higher risks of both bleeding and arterial thrombotic events without a mortality benefit, according to a real-world analysis presented at the 67th ASH Annual Meeting and Exposition in Orlando, FL.

Although aspirin is often added to anticoagulation for secondary prevention, evidence supporting this approach has been limited. To fill this gap, Fayaz Khan, chief hospice and palliative care fellow at Roswell Park Comprehensive Cancer Center, and colleagues evaluated the clinical impact of combining low-dose aspirin with warfarin in adults with APS and arterial thrombosis.

The study investigators used the TriNetX Network to identify adults aged ≥18 years with APS (ICD-10 D68.61) and documented arterial thrombotic events, including cerebral infarction, myocardial infarction, and arterial embolism. The study patients were required to have an International Normalized Ratio between 2.0 and 3.0.

Two cohorts were defined: those receiving warfarin plus 81-mg aspirin and those receiving warfarin alone. Individuals using other antiplatelet therapy or direct oral anticoagulants were excluded. Propensity score matching (1:1) balanced demographics and comorbidities across groups. Outcomes assessed over a 4-year follow-up included thrombotic events, bleeding complications, mortality, and healthcare utilization. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated.

Study Findings

A total of 2144 patients were included in each matched cohort, with mean follow-up durations of 1479 days for the aspirin group and 1,589 days for the non-aspirin group. Aspirin use was associated with significantly increased hazards for multiple bleeding events: gastrointestinal bleeding (hazard ratio [HR], 1.44; 95% CI, 1.14–1.81; P = .002), hemoperitoneum (HR, 3.20; 95% CI, 1.44–7.13; P = .003), iron deficiency anemia (HR, 1.35; 95% CI, 1.12–1.63; P = .001), and transfusion requirement (HR, 1.34; 95% CI, 1.02–1.77; P = .037). Intracranial hemorrhage risk was also elevated (HR, 1.40; 95% CI, 1.01–1.93; P = .041).

Arterial thrombotic events were also higher in the aspirin group. The HR for ischemic stroke was 1.52 (95% CI, 1.10–2.08; P = .009), and for acute myocardial infarction, 2.10 (95% CI, 1.47–3.00; P < .001). Peripheral arterial events did not significantly differ. Healthcare utilization was higher with aspirin, including hospitalizations (HR, 1.75; P < .001), outpatient visits (HR, 1.84; P = .001), and emergency department visits (HR, 1.31; P = .001). No difference in all-cause mortality was observed (HR, 1.02; P = .779).

Clinical Implications

According to the study authors, these findings suggest that adding low-dose aspirin to warfarin in patients with APS and arterial thrombosis may increase the risk of both bleeding and arterial thrombotic events without improving survival. The authors also noted that, despite careful propensity matching, the higher event rates may reflect residual confounding by indication, particularly if clinicians selected combination therapy for patients perceived to be at higher thrombotic risk.

Expert Commentary

“Despite careful propensity score matching, unmeasured differences in disease severity and clinical decision-making may have contributed to these findings,” the researchers concluded. “These findings raise important questions about routinely combining aspirin with warfarin in APS patients with arterial thrombosis, as it appears to increase bleeding risk without improving survival.”

Reference
Khan F, Chandra MB, Alam Z. Impact of aspirin use on clinical outcomes in antiphospholipid syndrome patients with arterial thrombosis: A real-world cohort study. Presented at: 67th ASH Annual Meeting and Exposition; December 8, 2025; Orlando, FL. https://submit.hematology.org/program/presentation/673789