Cancer-associated thrombosis (CAT) presents a unique and multifaceted challenge in clinical practice, particularly in patients who also suffer from thrombocytopenia. The management of anticoagulation in this setting requires a careful balance between preventing thromboembolic events and minimizing the risk of bleeding. During the ICTHIC webinar “Managing bleeding in cancer: from anticoagulants to artificial intelligence,” Dr. Mari Thomas provided a detailed and insightful overview of how to approach anticoagulation in cancer patients with thrombocytopenia. Her presentation covered current guidelines, clinical data, and the limitations in the evidence base, while also highlighting a pressing need for randomized clinical trials (RCTs) to better guide treatment decisions. You can also watch Mari Thomas’s lecture in the video below and the full webinar recording here.
Current Guidelines and Clinical Practices
Existing guidelines for the management of anticoagulation in thrombocytopenic cancer patients are largely based on expert consensus and limited-quality observational data. Both the International Society on Thrombosis and Haemostasis (ISTH) 2018 guidelines and the 2022 European Hematology Association (EHA) guidelines offer recommendations for platelet transfusion and dose adjustments of anticoagulants in these patients [1-2].
For high-risk patients—those with acute, proximal deep vein thrombosis (DVT) or symptomatic pulmonary embolism (PE)—the ISTH guidelines recommend maintaining platelet counts between 40-50×10⁹/L with platelet transfusion and administering therapeutic doses of low molecular weight heparin (LMWH) [1].
In patients with lower-risk CAT, such as those with distal or smaller clots, the guidelines suggest reducing the dose of LMWH or anticoagulants and holding treatment entirely if platelet counts fall below 25×10⁹/L [1].
Dr. Thomas noted that despite these guidelines, the quality of the evidence supporting them is often insufficient, as much of it is based on expert opinion rather than high-quality randomized trials. The 2022 EHA guidance further echoes these recommendations but expands the scope by covering additional conditions such as atrial fibrillation and mechanical heart valves in patients with cancer [2].
Dr. Thomas stated, “this lack of solid evidence leads to substantial variability in clinical practice, underscoring the need for well-designed RCTs to better define safe and effective treatment strategies for these high-risk patients”.
Case Study: A Real-World Challenge in CAT and Thrombocytopenia
To illustrate the clinical complexities of managing anticoagulation in cancer patients with thrombocytopenia, Dr. Thomas presented a real-world case from her own clinical practice. The patient, a 67-year-old male, was diagnosed with acute myeloid leukemia (AML) and bilateral pulmonary embolism with right heart strain, placing him at high risk of morbidity and mortality. His platelet count at diagnosis was critically low at 38×10⁹/L, a level that significantly increases the risk of bleeding complications if anticoagulation is not managed carefully.
The patient was initially treated with dose-adjusted LMWH, given his thrombocytopenia and high thrombotic risk. Despite this cautious approach, the patient’s clot burden progressed, and imaging revealed the development of a pulmonary infarction. At this point, platelet transfusions were initiated to maintain platelet counts above 50×10⁹/L, allowing for full-dose anticoagulation with LMWH during the first month of treatment. After stabilization, anticoagulation was gradually reduced to adjusted doses in subsequent months.
This case exemplifies the need for individualized treatment strategies, as well as the dynamic decision-making process required when managing patients with both CAT and thrombocytopenia.
Data from Cohort Studies: Variability in Practice and Outcomes
Dr. Thomas then discussed the results of several cohort studies that reflect the variability in clinical practice and outcomes in the management of CAT and thrombocytopenia. One of the key studies mentioned was the CAVEaT cohort study, which was conducted across 20 UK centers and included 105 patients with cancer-associated thrombosis and platelet counts below 50×10⁹/L. The study found a wide variation in platelet transfusion practices across centers, as well as significant differences in the management of anticoagulation, reflecting the uncertainty surrounding optimal treatment strategies in this population [3].
The outcomes in the CAVEaT study were also concerning, with 25% of patients experiencing clinically significant non-major bleeding events. Additionally, there was a high rate of thrombosis recurrence, highlighting the inadequacy of current treatment approaches for preventing thromboembolic events while minimizing bleeding risks [3].
These findings are consistent with international studies such as the TROVE cohort, which evaluated 121 patients from North America with cancer-associated thrombosis and thrombocytopenia. The TROVE study reported major bleeding rates of 12.8% at 60 days in patients receiving full-dose anticoagulation, with a recurrence rate of 5.6% for thrombotic events. Even in patients receiving modified-dose anticoagulation, bleeding rates remained high, at 6.6% [4].
Revisiting Assumptions on Platelet Transfusion and Anticoagulation
One of the central themes of Dr. Thomas’s presentation was the need to critically reassess the assumptions that currently guide platelet transfusion practices. She emphasized that thrombocytopenia alone may not be a reliable predictor of bleeding risk. In fact, data from a landmark study published in the New England Journal of Medicine in 2010 suggested that increasing the dose of platelet transfusions in patients with hematological malignancies does not necessarily reduce the risk of bleeding. Patients in this study who received higher doses of prophylactic platelets did not show a significant reduction in bleeding events compared to those who received lower doses [5].
Additionally, Dr. Thomas highlighted data from the UK’s SHOT (Serious Hazards of Transfusion) hemovigilance program, which tracks adverse reactions to blood transfusions. She stated, “according to SHOT, platelets are the blood component most likely to cause transfusion reactions, including allergic responses and febrile reactions, which can further complicate the management of these patients”.
Another important study, the PATCH trial, which looked at the use of platelet transfusions in patients with spontaneous cerebral hemorrhage, found that platelet transfusions were associated with worse neurological outcomes compared to standard care alone. This finding suggests that platelet transfusions may not always be as safe or effective as previously believed, particularly in certain high-risk groups [6].
Conclusions and Future Directions
In her concluding remarks, Dr. Thomas stressed that the management of anticoagulation in cancer patients with thrombocytopenia remains an area fraught with uncertainty. Current guidelines, while helpful, are largely based on low-quality evidence, leading to significant variability in clinical practice and often suboptimal patient outcomes. The high rates of bleeding and recurrent thrombosis observed in cohort studies like CAVEaT and TROVE underscore the urgent need for randomized controlled trials to better guide clinical decision-making in this challenging patient population.
Looking forward, Dr. Thomas introduced the ongoing START trial (NCT05255003), a pilot study being conducted in both the UK and Canada to explore alternative anticoagulation strategies in patients with cancer-associated thrombosis and thrombocytopenia. The START trial aims to determine whether modified-dose anticoagulation, combined with selective platelet transfusion, can provide a safer and more effective approach to managing these patients. However, as Dr. Thomas emphasized, large-scale international collaboration will be crucial to generate the high-quality evidence needed to inform future clinical guidelines. Until such data are available, clinicians will need to rely on careful clinical judgment and individualized treatment plans to optimize outcomes for patients with both cancer and thrombocytopenia.
Watch Thomas’s lecture:
References
- Samuelson Bannow BT et al. Management of cancer-associated thrombosis in patients with thrombocytopenia: guidance from the SSC of the ISTH. J Thromb Haemost. 2018; 16(6):1246-1249
- Falanga A et al. EHA Guidelines on Management of Antithrombotic Treatments in Thrombocytopenic Patients With Cancer. Hemasphere. 2022; 6(8):e750
- Booth S et al. Platelet transfusion and anticoagulation in hematological cancer-associated thrombosis and thrombocytopenia: The CAVEaT multicenter prospective cohort. J Thromb Haemost. 2022; 20(8):1830-1838
- Carney BJ et al. Anticoagulation in cancer-associated thromboembolism with thrombocytopenia: a prospective, multicenter cohort study. Blood Adv. 2021; 5(24):5546-5553
- Slichter SJ et al. Dose of prophylactic platelet transfusions and prevention of hemorrhage. N Engl J Med. 2010; 362(7):600-13
- Baharoglu MI et al. Platelet transfusion versus standard care after acute stroke due to spontaneous cerebral haemorrhage associated with antiplatelet therapy (PATCH): a randomised, open-label, phase 3 trial. Lancet. 2016; 387(10038):2605-2613