Key Clinical Summary

• Direct oral anticoagulants (DOACs) demonstrate strong efficacy and safety for cancer-associated thrombosis (CAT), with growing evidence supporting their use in both primary prophylaxis and long-term treatment.
• Risk stratification models such as the Khorana Score help identify high-risk ambulatory patients, though gaps remain for hematologic malignancies and thrombocytopenic populations.
• Implementation barriers persist, including workflow limitations, knowledge gaps, and inconsistent adoption of guideline-recommended prophylaxis strategies.

At the 67th ASH Annual Meeting and Exposition, experts highlighted major advances and persistent gaps in anticoagulation for CAT. Speakers emphasized the growing CAT burden, evolving evidence for DOACs, and the need for better risk stratification and implementation strategies across oncology settings.

Session Highlights

Damon Houghton, MD, MS, Mayo Clinic Rochester, opened the session by reviewing CAT risk, prevention, and treatment challenges in hematologic malignancies. He emphasized the heterogeneity of venous thromboembolism (VTE) risk across leukemia, lymphoma, and myeloma, noting incidences ranging from 10% to 34% depending on disease and therapy—such as high thrombotic rates in patients with acute lymphoblastic leukemia (ALL) receiving asparaginase.

He detailed gaps in existing guidelines, such as ASH 2021 recommendations that broadly address cancer populations but lack hematologic-specific directives, particularly for those undergoing stem cell transplant or experiencing severe thrombocytopenia. Dr Houghton reviewed the limited representation of hematologic cancers in major randomized trials (3% to 14%), underscoring the need for individualized anticoagulation decisions and heightened awareness of drug–drug interactions and thrombocytopenia-related bleeding risks.

Marc Carrier, MD, MSc, The Ottawa Hospital, addressed persistent underuse of thromboprophylaxis in ambulatory oncology. He emphasized that patients with cancer face a 12-fold higher risk of VTE than the general population, increasing to 23-fold among those receiving systemic therapy. Long-term data demonstrate rising CAT incidence over 2 decades. Carrier highlighted randomized trials (CASSINI, AVERT, PROTECHT, SAVE-ONCO) showing ~50% relative risk reduction in symptomatic VTE with low–molecular-weight heparins or DOAC prophylaxis, without significant increases in major bleeding.

Carrier also presented evidence that only 10% of oncologists use structured VTE risk tools, despite guideline endorsement of the Khorana Score to identify high-risk patients (≥ 2 points = ~10% VTE risk; ≥3 = ~20% risk at six months). Implementation science interventions—such as embedding risk tools into electronic medical records (EMRs) and multidisciplinary workflows—have demonstrated increases in VTE education and prophylaxis adoption, along with reduced VTE events.

Michael Jaglal, MD, MS, Moffitt Cancer Center, provided a decade-in-review of DOACs in CAT management. He contrasted historical reliance on low–molecular-weight heparin with the growing preference for DOACs due to fixed dosing, fewer interactions, and improved adherence. Trial evidence shows DOACs are non-inferior for efficacy and offer practical advantages. He reviewed dosing parameters, renal considerations, gastrointestinal (GI) bleeding risks—especially in GI cancers—and recent data from the API-CAT trial, which demonstrated the safety and efficacy of reduced-dose apixaban (2.5 mg twice daily [BID]) beyond 6 months of treatment.

According to Dr Houghton, tailoring anticoagulation in hematologic malignancies requires “individualized thresholds” due to varying disease biology, treatment exposures, and thrombocytopenia patterns. He stressed that catheter-associated thrombosis, accounting for up to 50% of VTE in leukemia, demands heightened vigilance and guideline-concordant management.

Dr Carrier argued that the field has “all the data we need” to implement prophylaxis but continues to struggle with practical barriers. He emphasized that risk tools must be integrated into workflow, not used ad hoc. Surveys show that most clinicians underestimate VTE frequency and spend minimal time educating patients on symptoms or prevention, which are key contributors to guideline-practice gaps.

Dr Jaglal reinforced the importance of shared decision-making, especially in patients with renal impairment, prior bleeding, or GI tract alterations from surgery. He noted that DOAC absorption varies by drug and surgical anatomy, making apixaban preferable in many postoperative contexts.

Implications for Practice

These data support the expanded use of DOACs for CAT prevention and treatment, particularly in high-risk ambulatory cancer populations. Oncology practices should integrate EMR-embedded VTE risk tools, improve patient education, and standardize prophylaxis pathways. More disease-specific research—especially for hematologic cancers—is needed to refine risk models and bleeding-risk thresholds.

Conclusion

The session underscored a maturing evidence base supporting DOACs and structured risk assessment for CAT. Continued emphasis on implementation, individualized therapy, and multidisciplinary workflows will be essential to improving VTE outcomes across oncology settings.

Reference

Houghton D, Carrier M, Jaglal M. Between Clots and Complications: A new era of anticoagulation in cancer. Presented at: ASH 2025; December 6-9; Orlando, FL.