Department of Neurology, University of Mississippi Medical Center, Jackson, MS, USA.
Department of Neurology, University of New Mexico, Albuquerque, NM, USA.
Curr Neurol Neurosci Rep. 2023 Nov;23(11):751-767. doi: 10.1007/s11910-023-01313-y. Epub 2023 Oct 21.
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.
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. 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.
遗传性出血性疾病的临床表现多种多样，从轻微的黏膜和关节出血到严重的中枢神经系统（CNS）出血，其中颅内出血（ICH）是最可怕的并发症。在这篇综述中，我们将讨论特定遗传性出血性疾病的病理生理学，即血友病 A、血友病 B 和血管性血友病（vWD）；其临床表现，特别强调神经并发症；简要概述与神经并发症管理策略相关的内容；并回顾指导治疗策略的文献。
ICH 是血友病患者发病率和死亡率的主要原因。通过给予特定的因子或血液制品来充分控制出血、识别出血的危险因素以及维持最佳凝血活性，对于恰当地管理这些患者的 CNS 出血并发症至关重要。特定重组因子的给药取决于患者的药代动力学和稳态水平。在急性出血发作期间，初始因子活性应维持在 80%至 100%之间。单克隆抗体 Emicizumab 的出现彻底改变了血友病患者的预防性治疗策略。vWD 患者 ICH 的管理涉及使用血浆衍生的因子浓缩物、重组血管性血友病因子和个体化的抗纤维蛋白溶解剂，具体取决于 vWD 的类型和严重程度。血友病和 vWD 是最常见的遗传性出血性疾病，可使患者易患危及生命的 CNS 并发症-颅内出血、脊髓内出血和周围神经综合征。与血液科医生进行早期的护理协调有助于制定有效的预防方案，以避免这些患者发生危及生命的出血并发症。需要进一步研究以评估 Emicizumab 作为血友病患者急性出血发作按需治疗选择的效果。
