Department of Interdisciplinary of Medicine, University of Bari 'Aldo Moro', Bari, 70029, Italy.
Ital J Pediatr. 2024 Nov 28;50(1):253. doi: 10.1186/s13052-024-01819-2.
Hemophilia B is a rare bleeding disorder in males, characterized by a deficiency in coagulation factor IX (FIX). Replacement of FIX with a recombinant FIX (rFIX) fusion protein, to sustain therapeutic plasma levels, is recommended as both treatment and prophylaxis to prevent bleeding episodes, particularly intracranial hemorrhage (ICH).
This case report outlines the management of ICH in a 7-month-old infant with severe hemophilia B, following an accidental trauma-related event, resulting in a thin compound fracture of the left occiput. FIX levels were extremely low (˂1.0%) and large deletions of the coagulation F9 gene (including exons 1-6) were identified. Intensive treatment with a rFIX fusion protein conjugated to the immunoglobulin Fc fragment (rFIXFc) continued for 18 days before hospital discharge. A continuous regimen of weekly rFIXFc infusions was implemented. Thirty days after initiating rFIXFc therapy, neutralizing antibodies or FIX inhibitors (common in patients with large F9 gene deletions) were observed, causing a diffuse skin rash. Such allergic reactions typically indicate progression to potentially serious nephrotic syndrome. A unique immunotolerance regimen of oral oxatomide and intravenous hydrocortisone was started to proactively prevent allergic reactions in this patient during rFIXFc prophylaxis. Even though low titers of the inhibitor (0.6-1.0 Bethesda units) were observed occasionally during subsequent follow-up, there were no signs of further allergies or development of nephrotic syndrome.
This is an uncommon case in which rFIXFc was continued despite the appearance of an allergic reaction and the development of FIX inhibitors. Subsequent allergic reactions were prevented with a combination of oral oxatomide and intravenous hydrocortisone given prior to prophylactic rFIXFc. Further studies are recommended to determine the usefulness of this combination with rFIX therapy.
血友病 B 是一种罕见的男性遗传性出血性疾病，其特征是凝血因子 IX（FIX）缺乏。建议使用重组 FIX（rFIX）融合蛋白替代 FIX，以维持治疗性血浆水平，作为治疗和预防措施，以防止出血发作，特别是颅内出血（ICH）。
本病例报告概述了一名 7 个月大的重度血友病 B 婴儿在意外创伤相关事件后 ICH 的管理，导致左枕骨薄复合性骨折。FIX 水平极低（<1.0%），凝血因子 F9 基因大片段缺失（包括外显子 1-6）。在出院前，使用与免疫球蛋白 Fc 片段缀合的 rFIX 融合蛋白（rFIXFc）进行了 18 天的强化治疗。实施了每周 rFIXFc 输注的连续方案。在开始 rFIXFc 治疗后 30 天，观察到中和抗体或 FIX 抑制剂（在大 F9 基因缺失患者中常见），导致弥漫性皮疹。这种过敏反应通常表明进展为潜在严重的肾病综合征。开始了一种独特的免疫耐受方案，即口服奥沙米特和静脉内氢化可的松，以在该患者接受 rFIXFc 预防时主动预防过敏反应。尽管在随后的随访中偶尔观察到抑制剂的低滴度（0.6-1.0 贝塞斯达单位），但没有进一步过敏或肾病综合征发展的迹象。
这是一个罕见的病例，尽管出现过敏反应和 FIX 抑制剂的发展，但仍继续使用 rFIXFc。在预防性 rFIXFc 之前给予口服奥沙米特和静脉内氢化可的松联合使用可预防随后的过敏反应。建议进一步研究以确定这种组合与 rFIX 治疗的有用性。
