遗传性凝血因子缺乏和血管出血性疾病,与各种严重程度的出血有关,通常被归类为罕见出血性疾病(RBD)。这些包括遗传性纤维蛋白原紊乱,遗传性血小板功能障碍(IPFD)和遗传性出血性毛细血管扩张症(HHT)。在过去的几十年里,关于流行病学的知识有了很大的增加,遗传学,病理生理学,临床特征,和RBD的诊断,但是管理方面的改进更加有限,仍然具有挑战性。RBD的治疗主体仅基于替换一些可用的凝血因子浓缩物或冷沉淀物。对增强RBD中的凝血或抑制抗凝血途径的治疗剂越来越感兴趣。在严重的IPFD中,最佳血小板输注策略尚未确定.此外,有关去氨加压素和/或抗纤溶药物通常用于轻度IPFD治疗的有效性和安全性的数据很少.最佳纤维蛋白原替代策略(预防与根据需求)的纤维蛋白原血症仍在争论中。同样,治疗急性出血的最佳纤维蛋白原目标水平,以及妊娠期间纤维蛋白原替代在轻度低纤维蛋白原血症和异常纤维蛋白原血症中的作用,没有得到适当的评估。HHT的治疗资源库包括抗纤维蛋白溶解剂和一系列抗血管生成剂,其潜在功效已在小型研究中测试或正在研究用于治疗出血。然而,需要解决几个问题,包括最佳给药策略,长期使用的潜在紧急毒性,全身抗血管生成治疗对内脏动静脉畸形的影响。
Inherited factor coagulation deficiencies and vascular bleeding disorders, associated with bleeding of various severity, are often classified as rare bleeding disorders (RBDs). These include inherited fibrinogen disorders, inherited platelet function disorders (IPFD) and hereditary haemorrhagic telangiectasia (HHT). In the last decades, there have been large increases in knowledge on the epidemiology, genetics, physiopathology, clinical features, and diagnosis of RBDs, but improvements in management have been more limited and remain challenging. The treatment mainstay of RBDs is based only on replacement of a few available coagulation factor concentrates or cryoprecipitates. There is growing interest in therapeutic agents that enhance coagulation or inhibiting anticoagulant pathways in RBDs. In severe IPFD, the optimal platelet transfusion strategy is not yet established. Moreover, data is scarce on the effectiveness and safety of desmopressin and/or antifibrinolytic drugs often used for milder IPFD treatment. The best fibrinogen replacement strategy (prophylaxis vs. on demand) in afibrinogenemia is still debated. Similarly, the optimal trough fibrinogen target level for treatment of acute bleeding, and the role of fibrinogen replacement during pregnancy in mild hypofibrinogenemia and dysfibrinogenemia, have not been properly evaluated. The therapeutic arsenal in HHT includes antifibrinolytics and a series of antiangiogenic agents whose potential efficacy has been tested in small studies or are under investigation for treatment of bleeding. However, there is need to address several issues, including the optimal dosing strategies, the potential emergent toxicity of longer-term use, and the impact of systemic antiangiogenic treatment on visceral arteriovenous malformations.