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Walking a Tightrope: Approaches to Thrombosis in Patients With Bleeding, and Bleeding in Patients With Thrombosis

December 10, 2022
Juliana Perez Botero, MD

Dr. Juliana Perez Botero (@JuliPerezBot) was born in Bogota, Colombia, and graduated cum laude from the Universidad de los Andes Medical School and later completed training in internal medicine and hematology-oncology at the Mayo Clinic in Rochester, Minnesota. She is currently based at Versiti and Medical College of Wisconsin, specializing in nonmalignant hematologic disorders including inherited and acquired bleeding and clotting disorders. Her clinical interest and research focus is on phenotype-genotype correlation in inherited blood disorders (especially platelets) and novel diagnostic laboratory testing strategies. “I am fascinated by diagnostic mysteries and frequently describe my job as a ‘blood detective’ to patients,” she said, which calms their worries about meeting her at someplace called a “Cancer Center.”

Thrombosis and hemorrhage — not mutually exclusive processes, but ends of a dynamic spectrum that frequently leave clinicians walking on a tightrope. Patients with these disorders represent a small but complex subset that need our care and expertise the most. The task of maintaining balance is never simple, and limited data are available to inform decision-making, especially for a population that is typically not included in large, randomized trials. Are we leaning too much to one side? This question is particularly relevant beyond the acute presentation, when longer-term morbidity and mortality affect our patients the most. This year’s oral session abstracts include studies in classical hematology presenting real-world data in clinical scenarios in which specific risks of hemorrhage influence the treatment of thrombosis, and vice versa. Are we undertreating thrombosis in patients with thrombocytopenia? Are we causing iatrogenic thrombosis in those with bleeding disorders? What can we learn from our current practice as we look to the future?

Patients with immune thrombocytopenia (ITP) are not free of thrombotic complications, and it’s worthwhile to question how well we are managing arterial thrombosis in patients with ITP. In the session Disorders of Platelet Number or Function: Clinical and Epidemiological: Special Populations and Long-term Outcomes in ITP (Saturday, December 10, 10:15 a.m.), Dr. Lisa Wang will present on the prevalence and management of arterial thromboembolism in immune thrombocytopenia (session 311, abstract 22). Dr. Wang and her team found a rate of arterial thromboembolism of 14 percent in a cohort of patients with ITP and varying degrees of thrombocytopenia at the time of incident thrombosis. Many did not receive revascularization and/or antiplatelet and anticoagulant therapy due to the severity of their thrombocytopenia, and the mortality in those with arterial events approached 50 percent. With broader availability of ITP therapies boasting targeted mechanisms of action and faster onset of therapeutic effect, we must ask ourselves: Why are we undertreating our patients (and potentially affecting their survival)? While cardiovascular outcomes continue to improve for all comers, we are falling short for patients with ITP by not using all the tools available to us.

Recommending to not anticoagulate a patient with high thrombotic risk is sometimes harder than choosing to do so. The session titled Thrombosis and Anticoagulation: Clinical and Epidemiological: Controversies in Anticoagulation and Venous Thromboembolism (Saturday, December 10, 12:30 p.m.) includes Dr. Varun Iyengar’s data on bleeding risk in thrombocytopenic patients with atrial fibrillation (session 332, abstract 141). The bleeding risk was, as expected, shown to be higher in those with platelet counts less than 100,000/μL. However, the largest contribution of this study is its provision of cumulative incidence rates of bleeding that are useful when discussing risks of therapy, especially for patients with high risk of stroke, such as those with a CHA2DS2-VASc score greater than 4. While the increased safety of direct oral anticoagulants (DOACS) compared to warfarin has reduced risks of major bleeding in a large proportion of patients, we cannot lose sight of the fact that almost half of those with moderate to severe thrombocytopenia are still being treated with warfarin, mostly due to significant renal and/or hepatic disease.

In this clinical context, the pediatric population also deserves special attention. In the aforementioned session, Dr. Hope P. Wilson (Saturday, December 10, 1:00 p.m., abstract 143) will be reporting on alarmingly high rates of recurrent venous thromboembolism (VTE) in the setting of hospitalization in children with prior VTE. Importantly, their group noted that the proportion of patients receiving pharmacologic prophylaxis at the time of the venous thrombotic event was very low and driven largely by concerns of high bleeding risk. A mismatch in the perceived risk of bleeding and thrombosis, intensified by a paucity of safety data on anticoagulants in children, tips the balance in the decision-making process and could negatively affect outcomes. Perhaps a more consistent and systematic approach to VTE prophylaxis in high-risk children can steer us away from our cognitive bias.

Great challenges lead to great advances, and we have much to look forward to. Recent developments in the treatment of patients with severe inherited bleeding disorders, such as the bispecific monoclonal antibody emicizumab, have revolutionized clinical practice. Thrombosis, however, remains a concern with these medications, especially in situations requiring the use of additional hemostatic agents (see Dr. Francis Nissen’s talk during session 322, abstract 192). Dr. Vincent Muczynski (session 802, abstract 274) will bring us a promising new FVIII-mimetic antibody modified to self-regulate and inactivate the bispecific antibody when sufficient coagulation has occurred. This improvement provides hemostatic support that more closely resembles normal physiology and that will hopefully lead to effective hemostasis with fewer thrombotic complications. Talk about using technology to our advantage.

Get ready to add some extra outcomes data to your repertoire and enhance your practice with additional tools to tackle complex clinical scenarios in patients in whom bleeding and thrombosis compete.

Dr. Perez Botero indicated no relevant conflicts of interest.

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