Cancer-associated thrombosis remains a leading cause of morbidity and mortality in oncology. At ASH 2025, Dr. Akshat Jain presented key advances shaping risk assessment, anticoagulation strategies, and individualized prevention for patients with cancer.

Dr. Akshat Jain is a hematologist-oncologist at Loma Linda University Health. At the Best of Hematology and Breast Cancer conference, Dr. Jain presented recent advances in cancer-associated thrombosis, a recognized yet commonly underemphasized complication in oncology.

His presentation focused on three key areas: establishing why cancer-associated thrombosis deserves clinical attention, reviewing top advances in basic science research, and discussing evidence-based decision-making guidelines for prevention and treatment.

The transcript below has not been reviewed by the speaker and may contain errors.

Epidemiology and Clinical Significance of Cancer-associated Thrombosis

The incidence of cancer-associated thrombosis is 12-fold higher in patients with diagnosed cancer, whether acute or recurrent, compared to the global population. This risk is particularly elevated in patients receiving active chemotherapy or other cancer therapies. Notably, venous thromboembolic-related deaths, including deep vein thrombosis, pulmonary embolism, and CNS thrombosis, represent the second leading cause of cancer-associated mortality.

The reported cumulative incidence of cancer-associated thrombosis has steadily increased in published literature, rising from approximately 1% in 1997 to 3.4% in newly diagnosed patients with malignancies in more recent studies.

ASH 2025 National Inpatient Analysis: Key Findings

A seminal retrospective analysis examined over 1.15 million patients diagnosed with cancer across North America. The study revealed several important findings about venous thromboembolic risk in cancer patients:

The highest venous thromboembolic risk was found in patients with gastrointestinal and lung-related cancers. Surprisingly, solid tumors demonstrated a higher incidence of venous thromboembolic events compared to hematological malignancies in this analysis. This finding was particularly notable, as hematological malignancies were logically expected to show higher rates due to disease-related coagulopathy and pathophysiologic mechanisms.

The study demonstrated that tumor biology functions as an independent risk factor for thrombogenicity, driving not only acute pulmonary embolism but also recurrent venous thromboembolic events. Additional well-recognized risk factors include chemotherapy, radiotherapy, surgery, central venous catheters, and blood transfusions, all of which contribute to increased occurrence of venous thromboembolic events in cancer patients.

The APICA Study: Reduced-Dose Anticoagulation

The landmark APICA study (Apixaban and Cancer) examined the use of direct oral anticoagulants in cancer patients. This randomized, double-blind, non-inferiority trial compared outcomes of venous thromboembolism recurrence and pulmonary embolism in patients receiving reduced-dose apixaban (2.5 mg) versus full-dose apixaban in the setting of acute venous thromboembolism.

The primary endpoint evaluated recurrent symptomatic venous thromboembolism, including incidental deep vein thrombosis and pulmonary embolism. The results were significant: the low-dose apixaban cohort demonstrated non-inferiority compared to the full-dose cohort during the maintenance phase in patients with underlying cancer.

Safety and Bleeding Outcomes

Secondary endpoints examined bleeding risks and hemorrhagic complications during DOAC therapy in the maintenance phase of anticoagulation. The reduced-dose regimen provided substantially lower rates of major bleeding and clinically relevant non-major bleeding compared to full-dose therapy. Importantly, no excess recurrent venous thromboembolic events were observed, confirming that safety was maintained without increased thrombotic risk when patients remained on low-dose anticoagulation therapy.

Analysis of all-cause mortality showed no significant differences between the two treatment cohorts.

Extended Duration Anticoagulation in Cancer-Associated Thrombosis

Another significant abstract addressed a critical clinical question faced when treating patients with cancer-associated thrombosis: how long should anticoagulation therapy continue for patients with a history of previous cancer-associated thrombosis?

The study specifically examined patients who developed acute venous thromboembolism, including deep vein thrombosis and pulmonary embolism, while excluding patients with central catheter-associated thrombosis. This design provided valuable data on true venous thromboembolism without the confounding variable of catheter-related events.

The results provided evidence that patients continuing apixaban as prophylaxis therapy demonstrated significant improvement when maintenance therapy was extended beyond six months in recipients of active cancer treatment.

Pathophysiology: Understanding Thrombogenicity in Cancer

Multiple abstracts and oral presentations explored what drives thrombogenicity in cancer patients. Research has demonstrated the important role of tissue factors, specifically cancer-derived microparticles, in activating the extrinsic coagulation pathway.

Mouse model studies showed this pathway of thrombogenesis leads to platelet activation, initiation of cytokine cascades, and release of tumor necrosis factor alpha, interleukins, and other inflammatory cytokines. These processes result in inflammatory endotheliopathy, which serves as the underlying mechanism of tumor thrombosis-related venous thromboembolism.

Translating Research to Clinical Practice

The ASH educational curriculum highlighted several practical applications for this emerging knowledge. Identifiable and easily testable tumor-related laboratory markers, such as D-dimer and P-selectin, can help prognosticate which patients at diagnosis may show early warning signs of thrombotic risk. This is especially relevant for patients receiving active therapy in inpatient settings.

Coagulation studies, specifically evaluating coagulopathy and thrombin generation when available, can help guide decisions regarding full-dose versus half-dose anticoagulation, or thromboprophylaxis with enoxaparin for primary prevention of venous thromboembolism in newly diagnosed patients.

Prophylaxis Strategies for High-Risk Populations

Identifying cancer patients at high risk for thrombosis remains a priority. Several factors distinguish high-risk from standard-risk cohorts:

Active chemotherapy treatment, hematologic malignancies, and inpatient hospitalization emerged as independent high-risk factors for venous thromboembolic development. Patients receiving active chemotherapy while hospitalized face a particularly elevated risk.

Mechanical and Systemic Prevention

For patients with contraindications to systemic anticoagulation, mechanical interventions such as compression stockings provide a preventative benefit. Patients with bleeding contraindications, those already receiving prophylactic anticoagulation for atrial fibrillation or other conditions, would be ideal candidates for IVC filter placement. Early consultation with radiology teams and strategic planning for patients expected to remain hospitalized for extended periods can facilitate timely intervention.

Supportive care measures, including hydration, early mobilization, and [unclear] interventions, also reduce venous thromboembolic risk.

Disease-Specific Risk Stratification

Additional guidance from ASH presentations identified specific malignancies associated with particularly high thrombotic risk based on the CAT clinical trial data. Patients with lung, gastrointestinal, and pancreatic cancers demonstrated the highest risk profiles.

Treatment Guidelines and Practical Recommendations

Despite the increasing adoption of direct oral anticoagulants, low molecular weight heparin remains commonly used for cancer-associated thrombosis. Direct oral anticoagulants, including rivaroxaban and apixaban, offer advantages for many patients, though low molecular weight heparin may be preferred in patients with renal dysfunction and other contraindications.

Individualized treatment decisions should consider patient adherence and education. Clinical experience demonstrates that requiring patients to maintain subcutaneous injections once or twice daily after discharge often leads to non-compliance due to the additional burden. Direct oral anticoagulants provide a more convenient option. With data from the APICA trial, low-dose apixaban (2.5 mg) appears as efficacious as, if not superior to, low molecular weight heparin when bleeding risk is factored in for prevention of secondary pulmonary embolism after acute venous thromboembolic events.

Risk Factors and Therapeutic Markers

ASH educational materials highlighted cancer-associated thrombosis risk drivers, including novel therapeutic markers shown to correlate highly with hematological malignancies and pulmonary embolism risk. Patient-related factors, including gender, age, type of malignancy, and central venous catheters, contribute to both primary venous thromboembolism and the risk of recurrent thrombosis within six months.

Emerging Frontiers in Cancer-Associated Thrombosis

Several key principles emerged for individualizing care in venous thromboembolism prevention:

Avoiding a one-size-fits-all strategy for anticoagulation prophylaxis is essential. Solid tumors carry different venous thromboembolic risks compared to hematological malignancies. High-risk solid tumors, particularly lung and colon carcinoma, demonstrate the highest pulmonary embolism risk and should be considered for early initiation of prophylactic anticoagulation.

Utilization of D-dimer and comprehensive coagulation panels at the time of cancer diagnosis, along with consideration of direct oral anticoagulants when appropriate, represents an evolving standard of care. These emerging frontiers in cancer thrombosis management emphasize the importance of individualized, risk-stratified approaches to prevention and treatment.