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Neurological Complications Associated with Hereditary Bleeding Disorders

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Abstract

Purpose of Review

Hereditary bleeding disorders may have a wide variety of clinical presentations ranging from mild mucosal and joint bleeding to severe central nervous system (CNS) bleeding, of which intracranial hemorrhage (ICH) is the most dreaded complication. In this review, we will discuss the pathophysiology of specific hereditary bleeding disorders, namely, hemophilia A, hemophilia B, and von Willebrand disease (vWD); their clinical manifestations with a particular emphasis on neurological complications; a brief overview of management strategies pertaining to neurological complications; and a review of literature guiding treatment strategies.

Recent Findings

ICH is the most significant cause of morbidity and mortality in patients with hemophilia. Adequate control of bleeding with the administration of specific factors or blood products, identification of risk factors for bleeding, and maintaining optimal coagulant activity are essential for appropriately managing CNS bleeding complications in these patients. The administration of specific recombinant factors is tailored to a patient’s pharmacokinetics and steady-state levels. During acute bleeding episodes, initial factor activity should be maintained between 80 and 100%. Availability of monoclonal antibody Emicizumab has revolutionized prophylactic therapies in patients with hemophilia. Management of ICH in patients with vWD involves using plasma-derived factor concentrates, recombinant von Willebrand factor, and supportive antifibrinolytic agents individualized to the type and severity of vWD.

Summary

Hemophilia and vWD are the most common hereditary bleeding disorders that can predispose patients to life-threatening CNS complications—intracranial bleeds, intraspinal bleeding, and peripheral nerve syndromes. Early care coordination with a hematologist can help develop an effective prophylactic regimen to avoid life-threatening bleeding complications in these patients. Further research is needed to evaluate using emicizumab as an on-demand treatment option for acute bleeding episodes in patients with hemophilia.

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Authors and Affiliations

  1. Department of Neurology, University of Mississippi Medical Center, Jackson, MS, USA

    Muhammad Qasim Bhatti, Ezekiel Gonzalez-Fernandez & Kunal Bhatia

  2. Department of Neurology, University of New Mexico, Albuquerque, NM, USA

    Afshin A. Divani

  3. Neurological Service, SS Annunziata Hospital, Sulmona, L’Aquila, Italy

    Mario Di Napoli

  4. Department of Neurology, The Ohio State University Wexner Medical Center, Columbus, OH, USA

    Archana Hinduja

  5. Department of Medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota, Minneapolis, MN, USA

    Yvonne H. Datta

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Muhammad Qasim Bhatti, Ezekiel Gonzalez-Fernandez, Kunal Bhatia, Afshin A. Divani, Mario Di Napoli, Archana Hinduja, and Yvonne H. Datta each declare no potential conflicts of interest.

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Bhatti, M.Q., Gonzalez-Fernandez, E., Bhatia, K. et al. Neurological Complications Associated with Hereditary Bleeding Disorders. Curr Neurol Neurosci Rep 23, 751–767 (2023). https://doi.org/10.1007/s11910-023-01313-y

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