Cancer Patients and Blood Clots: How Can We Improve Prevention?
"Venous thromboembolism (VTE) is a serious risk for ambulatory cancer patients. Understand the current challenges and potential solutions for better prophylaxis."
Patients battling cancer face a significantly elevated risk of developing thromboembolic events, commonly known as blood clots. While often overlooked, these events can lead to severe complications that diminish a patient's overall quality of life. Although thromboprophylaxis, the prevention of blood clots, is a standard practice, its primary focus tends to be on patients admitted to hospitals for acute medical conditions or those undergoing major surgical procedures.
However, a considerable number of thrombotic events occur in ambulatory patients—those receiving outpatient care—where current guidelines typically do not recommend routine preventive measures. This gap in care underscores the need for a closer look at how we can better protect these vulnerable individuals.
This article explores the challenges and potential solutions for improving venous thromboembolism (VTE) prophylaxis in ambulatory cancer patients. It dives into recent research, risk assessment models, and innovative approaches aimed at reducing the incidence of blood clots without increasing the risk of bleeding.
A Persistent and Preventable Threat
Hospital-acquired thrombosis was identified in 6.1% (n = 6) of oncology inpatients, with prophylaxis adherence varying widely across services: 71.0% in medical oncology, 26.2% in surgical oncology, and 11.1% in myeloma pathways. A recently updated Cochrane review found that primary thromboprophylaxis with LMWH significantly reduced symptomatic VTE in ambulatory cancer patients receiving chemotherapy compared with no prophylaxis (risk reduction: 0.54; 95% CI: 0.38 to 0.75). The evidence base for prevention and treatment is substantial: ASCO's clinical practice guideline update reviewed 35 publications on VTE prophylaxis and treatment and 18 on VTE risk assessment, including two RCTs of direct oral anticoagulants (DOACs) for treating VTE in cancer patients. Together, these figures show both the ongoing burden of blood clots in this population and the measurable gains that adherence to prophylaxis can deliver.
The Standard Playbook and Where It Falls Short
The accepted approach centers on systematic VTE risk assessment paired with risk-appropriate prophylaxis, but implementation has clear gaps. Of an estimated 900,000 VTE diagnosed annually in the US, approximately 20% occur in patients with cancer. A retrospective audit of 99 oncology inpatients evaluated VTE risk-assessment completion and timing, prescription and appropriateness of pharmacological prophylaxis, 24-hour reassessment, and adherence to cancer-associated thrombosis treatment standards. For patients with active cancer and VTE receiving long-term anticoagulation for secondary prophylaxis, the ASH guideline panel suggests continuing indefinite anticoagulation over stopping after a definitive treatment period, a conditional recommendation based on very low certainty in the evidence. ASH notes that its guidelines are reviewed annually by expert work groups, reflecting how quickly this area is evolving, yet the audit data underline that risk assessment is still not reliably embedded in oncology workflows.
Building the Evidence Base Over Decades
Understanding of the link between cancer and venous thromboembolism (VTE) has developed over many decades of clinical observation and research. Early work recognized that patients with cancer carry an elevated risk of blood clots, a connection that later research tied to tumor burden, surgery, and systemic therapies. The arrival of structured risk-assessment tools and successive generations of anticoagulants, including low-molecular-weight heparins and direct oral anticoagulants, represented important milestones in prevention. Guidelines have gradually incorporated this knowledge, though a detailed account of specific landmark studies and dates lies beyond the scope of the available source material.
Why Are Cancer Patients at Higher Risk for Blood Clots?
Both venous and, to a lesser extent, arterial thrombosis are common complications in cancer patients, occurring during treatment and follow-up. Beyond patient-related factors and existing health issues, cancer itself and its treatments—including surgery and chemotherapy—significantly contribute to this increased risk.
- Deep vein thrombosis (DVT) can lead to post-thrombotic syndrome, characterized by painful swelling and recurrent ulcers.
- Pulmonary embolism (PE) is associated with substantial morbidity and mortality, with higher rates among cancer patients.
- Cancer patients who develop clots often require long-term anticoagulation, increasing their risk of bleeding complications and potentially disrupting chemotherapy schedules.
State of the Art in Risk Assessment and Prophylaxis
Recent reviews continue to sharpen the picture of how best to protect ambulatory cancer patients from thrombosis. A review published in January 2025 provides an overview of the state of the art in VTE risk assessment and thromboprophylaxis for ambulatory patients with cancer, focusing on existing risk-assessment models and the latest guideline recommendations. Internationally, the International Initiative on Thrombosis and Cancer (ITAC) Advisory Panel issued 2022 international clinical practice guidelines covering treatment and prophylaxis of VTE in patients with cancer, including patients with COVID-19. The ASCO guidance update from 2023 underscores why this work matters: VTE, which includes deep vein thrombosis and pulmonary embolism, is an important cause of morbidity and mortality among patients with cancer, who are significantly more likely to develop VTE than people without cancer and experience higher rates of VTE recurrence and bleeding.
The Case for Caution and the Reality of Underuse
Preventing cancer-associated thrombosis is not without controversy. Clinicians must weigh reduced clot risk against the bleeding risk that anticoagulation itself carries, and the balance of benefit and harm can shift with cancer type, treatment phase, and individual patient factors. In practice, prophylaxis is often underused, and compliance with recommended risk assessment is inconsistent across care settings, meaning many at-risk patients do not receive what evidence suggests they should. Questions about which patients truly derive net benefit from primary prophylaxis remain unsettled, and the debate is likely to continue as risk models and new agents mature.
Comparing Prevention Strategies and Their Trade-Offs
Pulmonary embolism and deep vein thrombosis, the two primary forms of venous thromboembolism (VTE), are well-documented complications in cancer patients that significantly reduce overall survival. The two conditions are likewise associated with significant morbidity and mortality in this population, which is why prophylaxis strategy comparisons matter. Recent investigations have shown that prolonged VTE prophylaxis of up to 28 days postoperatively in a gynecologic population was associated with fewer VTE events. Direct comparisons, such as the randomized clinical trial of apixaban versus enoxaparin for postoperative prophylaxis, aim to identify which agents and durations deliver the best balance of protection and safety across surgical and medical cancer populations.
Future Directions: Balancing Prevention and Risk
Despite considerable efforts to minimize thromboembolic events in cancer patients, VTE remains a concern, especially in ambulatory patients undergoing chemotherapy. A recent Cochrane review confirmed that VTE prophylaxis with LMWH significantly reduced symptomatic VTE in these patients. However, the potential for increased bleeding necessitates careful consideration before routine implementation.
When Evidence Meets Practice
Expert synthesis points to a toolkit that is ready but unevenly used. Evidence-based interventions have been developed to prevent VTE in ambulatory patients with cancer, including VTE-risk assessment for all patients and targeted primary thromboprophylaxis for high-risk patients. Yet despite supportive evidence and recommendations, oncologists rarely assess VTE risk or provide primary prophylaxis, and prior work has identified specific barriers driving that gap. On the data side, multiple randomized clinical trials have shown that low-molecular-weight heparins and direct oral anticoagulants such as rivaroxaban and apixaban are highly effective and relatively safe for primary prevention of VTE in people with cancer. The synthesis is clear: the science supports action, and the urgent task is translating the evidence into routine oncology care.
Extending Prevention Into Real-World Care
The next frontier is moving prophylaxis beyond the acute treatment window and proving it works in everyday practice. Cancer-associated venous thromboembolism is a common complication of cancer and its treatments, and the incidence of recurrent thrombosis, serious bleeding, and death is higher among affected patients, underscoring what is at stake. Real-world programs are now being tested: Dr. Holmes presented the Vermont Model at the International Society on Thrombosis and Haemostasis 2025 Congress, which demonstrated that a VTE prevention program using prescribed prophylactic anticoagulation lowered VTE rates and mortality over six months in a real-world cancer population at high risk for VTE. Such results suggest that structured, programmatic prevention can translate the trial evidence into measurable patient benefit.
System-Wide Obstacles to Better Prevention
Improving VTE prevention in cancer care depends on more than individual clinician decisions; it is shaped by systemic factors. Consistent clinician education, institutional protocols, adequate staffing, and reliable risk-assessment workflows all influence whether guidelines actually reach patients. Adherence and standardization vary across services and care settings, which limits the population-level impact of otherwise effective interventions. Sustained progress is therefore likely to require coordinated quality-improvement programs and institutional or policy support rather than guideline publication alone.
What a Blood Clot Means for a Patient
For a patient facing cancer, a blood clot can add a serious, life-shaping complication to an already difficult journey. Cancer-associated thrombosis is a significant concern among patients with malignant diseases, leading to increased mortality, and VTE remains a major cause of morbidity and mortality in high-risk cancer populations even though the risk can be mitigated with prophylactic anticoagulation. Despite multiple guideline recommendations, compliance with anticoagulant prophylaxis is poor, and primary thromboprophylaxis for medium-to-high-risk outpatients remains a controversial practice that needs better understanding. Closing the distance between guidelines and what actually happens at the bedside is ultimately what will protect the people this work is meant to serve.
Future research should focus on identifying targeted groups of cancer patients who would benefit most from thromboprophylaxis, considering their specific disease and treatment regimens. These studies should aim to improve the efficacy of anticoagulation while minimizing the risk of bleeding.
Ultimately, a more nuanced approach to VTE prophylaxis in ambulatory cancer patients is needed. By combining risk assessment models, targeted interventions, and ongoing research, healthcare professionals can better protect these vulnerable patients from the potentially devastating consequences of blood clots.