单倍体造血干细胞移植治疗儿童急性淋巴细胞白血病后并发获得性血友病1例并文献复习

景沼贺; 王英洁; 买钰淼; 孙盼; 董芃芃; 刘健

doi:10.16766/j.cnki.issn.1674-4152.003530

单倍体造血干细胞移植治疗儿童急性淋巴细胞白血病后并发获得性血友病1例并文献复习

doi: 10.16766/j.cnki.issn.1674-4152.003530

郑州大学第一附属医院儿科，河南郑州 450052

基金项目:

郑州大学青年教师基础研究培育基金项目 JC21854036

详细信息

通讯作者:
刘健，E-mail：93624638@qq.com

中图分类号: R733.7 R554.1
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- 文章访问数: 150
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- 被引次数: 0
出版历程
- 收稿日期: 2023-04-19
- 网络出版日期: 2024-07-20

Acquired hemophilia following haploidentical hematopoietic stem cell transplantation for acute lymphoblastic leukemia in children: one case report and literature review

Department of Pediatrics, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China

摘要

摘要: 获得性血友病(AH)是由抗凝血因子的自身抗体引起的一种罕见疾病。本文报道1例急性淋巴细胞白血病(T系，高危)患儿，经单倍体造血干细胞移植(父供女，HLA 5/10)治疗后并发获得性血友病，同时结合文献进行复习。该患儿出现凝血因子Ⅸ、Ⅺ和Ⅻ活性降低，及Ⅸ因子抑制物滴度升高，临床较少见，经及时诊断并给予甲泼尼龙联合环孢素免疫抑制治疗后，患儿症状好转出院并继续规律服用甲泼尼龙及环孢素。患儿出院4个月后症状再发，予甲泼尼龙加量联合环孢素免疫抑制治疗后，患儿病情好转。随访至2023年3月患儿症状无再发。
- 获得性血友病 /
- 单倍体造血干细胞移植 /
- 儿童 /
- 凝血因子Ⅸ抗体
Abstract: Acquired hemophilia (AH) is a rare disease caused by autoantibodies against factors. We reported a case of acute lymphoblastic leukemia (T-lineage, high-risk) in a child who developed acquired hemophilia after haploidentical hematopoietic stem cell transplantation (paternal donor, HLA 5/10) and reviewed the relevant literature. Laboratory tests showed decreased coagulation factor Ⅸ activity (FⅨ: C), FⅪ: C, and FⅫ: C, and an elevated FⅨ inhibitor titer, which is rare the clinic. After diagnosis, the child was treated with methylprednisolone in combination with cyclosporine A. With improvement of symptoms, the patient was discharged and continued to take cyclosporine A and methylprednisolone regularly. Four months after discharge, symptoms recurred, and the treatment regimen was changed to double-dose methylprednisolone combined with cyclosporine A immunosuppressive therapy, and the child was discharged with improvement. There was no recurrence of symptoms until March 2023.
- Acquired hemophilia /
- Haploidentical hematopoietic stem cell transplantation /
- Children /
- Autoantibodies against factor Ⅸ

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表 1 患儿治疗过程中凝血功能检测结果

Table 1. Coagulation function test results during pediatric treatment

检测时间	APTT(s)	FⅨ：C(%)	FⅪ：C(%)	FⅫ：C(%)	凝血因子Ⅸ抑制物(BU/mL)
2021年9月15日治疗前	64.8	9.58	-	-	1.85
治疗后7 d	60.8	27.20	37.70	17.80	1.05
治疗后15 d	47.1	61.70	57.80	25.10	0.50
治疗后18 d	46.0	67.70	58.30	26.20	-
治疗后23 d	45.5	68.10	58.50	27.30	0.40
治疗后29 d	42.4	77.90	59.40	29.70	0.30
治疗后60 d	42.8	-	-	-	-
2022年2月8日AH反复	62.2	10.20	-	-	-
治疗后7 d	49.1	24.00	-	-	-
治疗后96 d	56.3	-	-	-	-
治疗后6月+	44.8	-	-	-	-
治疗后10月+	57.6	-	-	-	-
治疗后1年+	56.7	-	-	-	-
注：APTT为活化部分凝血活酶时间(参考值26~40 s)；FⅨ：C为凝血因子Ⅸ活性(参考值65%~150%)；FⅪ: C为凝血因子Ⅺ活性(参考值65%~150%)；FⅫ：C为凝血因子Ⅻ活性(参考值50%~150%)；“-”为未检测；凝血因子Ⅸ抑制物参考值为＜0.30 BU/mL。

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表 2 造血干细胞移植术后并发获得性血友病病例特点

Table 2. Characteristics of acquired hemophilia after hematopoietic stem cell transplantation

编号	性别/年龄(岁)	移植前疾病	抑制物特异性	抑制物滴度(BU/mL)	止血治疗	抑制物清除	AH结局	GVHD
1^[2]	男/41	多发性硬化症	FⅧ	-	rhFⅧ、FFP、rFⅦa	地塞米松、环磷酰胺、利妥昔单抗	出血持续	-
2^[3]	男/44	镰状细胞贫血	FⅧ	-	rhFⅧ、rFⅦa、rpFⅧ	强的松、利妥昔单抗	凝血正常	-
3^[4]	女/54	AML	FⅧ	2.80	未治疗	强的松、环磷酰胺、利妥昔单抗	凝血正常	慢性
4^[5]	女/28	系统性硬化症	FⅧ	最高达94.00	rFⅦa	甲基强的松、利妥昔单抗	凝血正常	-
5^[6]	女/10	ALL	FⅧ	10.20	rhFⅧ、rpFⅧ	类固醇、利妥昔单抗	凝血正常	慢性
6^[7]	男/11	AML	FⅧ	26.00	FFP、PCC	利妥昔单抗、环磷酰胺、泼尼松	凝血正常	急性
7^[8]	男/41	ALL	FⅧ	112.00	aPCC、rFⅦa	泼尼松、利妥昔单抗、环磷酰胺、艾米珠单抗	凝血正常	慢性
8	女/5	ALL	FⅨ	1.85	PCC	甲泼尼龙、环孢素	凝血正常	慢性
注：“-”代表未描述；rhFⅧ为重组人凝血因子Ⅷ；FFP为新鲜冷冻血浆；rFⅦa为重组活化凝血因子Ⅶ；rpFⅧ为重组猪Ⅷ；PCC为人凝血酶原复合物；GVHD为移植物抗宿主病。

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参考文献(16)

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