异基因造血干细胞移植后并发自身免疫性溶血性贫血患者产生类抗体血清学检测方法及输血策略

doi:10.3877/cma.j.issn.1674-0785.2022.05.015

目的

探讨异基因造血干细胞移植（AHSCT）后免疫介导的自身免疫性溶血性贫血（AIHA）患者交叉配血不合的原因，血浆中不规则抗体筛选试验阳性时，不规则抗体鉴定的血清学检测方法的选择，处理措施及输血策略。

方法

一例AHSCT后的3岁男性患儿因重度贫血为改善贫血症状需输注红细胞入住四川省人民医院。通过盐水试管法确定了患儿ABO、Rh血型后进行交叉配血试验发现患儿与多个同型供者血液不相合，考虑到患儿贫血严重，于是采用直接抗球蛋白试验来判断红细胞是否被致敏；通过盐水介质试管法、微柱抗球蛋白法和聚凝胺法进行ABO血型系统以外的不规则抗体筛选试验以确定血浆中有无不规则抗体；根据不规则抗体筛选试验结果选择聚凝胺法来确定抗体的特异性；通过盐水介质试管法、经典抗球蛋白法和聚凝胺法进行交叉配血实验，结合抗体鉴定的结果，综合分析选择合适的供者红细胞输注。

结果

本例患儿ABO血型为AB型，Rh分型为CCDee，ABO血型已转变为供者血型。直接抗球蛋白试验强阳性，红细胞被抗体致敏。血浆中检出了不规则抗体，红细胞上放散下来的致敏抗体与血清中检出的不规则抗体均为类抗-Ce自身抗体。选择了避开类抗-Ce抗体的Ce抗原阴性的AB型红细胞输注后血色素升高，3 d后复查血常规Hb为79 g/L，输血有效。

结论

任何类型的AHSCT后都有可能发展成AIHA，也就是血浆中可能存在某种自身抗体（类抗体）而破坏自身红细胞，若能够明确患者血清中存在的类抗体，即可避开这种抗体而筛选红细胞无相应抗原的供者，也就避免发生溶血性输血反应以安全输血。

关键词: 异基因造血干细胞移植, 自身免疫性溶血性贫血, 自身抗体, 同种抗体, 类抗体, 安全输血

Objective

To investigate the causes of cross-matching incompatibility in patients with autoimmune hemolytic anemia (AIHA) following allogeneic hematopoietic stem cell transplantation (AHSCT), and the selection of serological detection methods for irregular antibody identification, treatment measures, and blood transfusion strategies when the irregular antibody screening test in plasma is positive.

Methods

A child aged 3 years with severe anemia following AHSCT was hospitalized at Sichuan Provincial People's Hospital for red blood cell (RBC) transfusion in order to alleviate the symptoms of anemia. The ABO and Rh blood groups of the child were determined through the brine test method, and then the cross-matching test was carried out. It was found that the blood of the child was inconsistent with that of multiple homogeneous donors. Considering the serious anemia of the child, the direct antiglobulin test was performed to judge whether the RBC was sensitized; irregular antibody screening tests outside the ABO blood group system were carried out using the brine test tube method, and microcolumn antiglobulin method and polybrene method were used to determine whether there were irregular antibodies in plasma. According to the results of the irregular antibody screening test, the polybrene method was selected to determine the specificity of antibody; the cross-matching experiment was carried out by the brine test tube method, classical antiglobulin method, and polybrene method. Combined with the results of antibody identification, the appropriate donor RBC infusion was comprehensively analyzed and selected.

Results

The ABO blood group in the child was AB, RH was CCDee, and the ABO blood group had changed to the donor blood group. The direct antiglobulin test was strongly positive, and the red blood cells were sensitized by antibodies. Irregular antibodies were detected in plasma, and sensitizing antibodies released from RBCs and irregular antibodies detected in plasma were anti-Ce mimicking antibodies. Type AB RBCs with negative Ce antigen avoiding anti-Ce mimicking antibodies were selected. Three days after transfusion, the hemoglobin increased to 79 g/L, and the blood transfusion was effective.

Conclusion

Any type of AHSCT may result in AIHA, that is, there may be some autoantibodies (mimicking antibodies) in plasma which can break the ring of autologous RBCs. If the mimicking antibodies can be identified in a patient's plasma, and a donor without corresponding antigen on RBCs can be screened, the hemolytic transfusion reaction can be avoided to ensure safe and effective blood transfusion.

Key words: Allogeneic hematopoietic stem cell transplantation, Autoimmune hemolytic anemia, Autoantibody, Alloantibody, Mimicking antibody, Safe blood transfusion

表1 本例重度贫血患儿血清与筛查细胞反应格局表

序号	Rh					Kidd		MNS				Duffy		Lewis		P	患儿血清凝集强度
序号	D	C	E	c	e	Jka	Jkb	M	N	S	s	Fya	Fyb	Lea	Leb	P1	Brine多次离心	Gel	Poly
1	+	0	+	+	0	+	0	+	+	0	+	+	0	0	0	0	0	3+	2+
2	+	+	0	0	+	+	+	+	+	+	+	+	+	0	+	0	0	3+	4+
3	+	+	+	+	+	+	+	+	+	0	+	+	0	+	0	+	0	3+	4+

表1 本例重度贫血患儿血清与筛查细胞反应格局表

序号	Rh					Kidd		MNS				Duffy		Lewis		P	患儿血清凝集强度
序号	D	C	E	c	e	Jka	Jkb	M	N	S	s	Fya	Fyb	Lea	Leb	P1	Brine多次离心	Gel	Poly
1	+	0	+	+	0	+	0	+	+	0	+	+	0	0	0	0	0	3+	2+
2	+	+	0	0	+	+	+	+	+	+	+	+	+	0	+	0	0	3+	4+
3	+	+	+	+	+	+	+	+	+	0	+	+	0	+	0	+	0	3+	4+

表2 本例重度贫血患儿血清、酸放散液与谱细胞反应格局

序号	Rh					Kell		Duffy		Kidd		Lewis		P	MNS				血清凝集强度		酸放散液凝集强度
序号	C	D	E	c	e	K	k	Fya	Fyb	JKa	JKb	Lea	Leb	P₁	M	N	S	s	Gel	Poly	Poly（稀释16倍）
1	+	+	0	0	+	0	+	+	0	+	0	0	+	+	+	+	+	0	3+	4+	3+
2	+	+	0	0	+	+	+	0	+	+	+	0	+	+	0	+	0	+	3+	4+	3+
3	0	+	+	+	0	0	+	+	0	+	0	+	0	+	0	+	0	+	3+	2+^w	±
4	0	+	0	+	+	0	+	0	0	+	0	0	0	+	0	+	0	+	3+	2+^s	1+
5	+	0	0	0	+	0	+	+	+	+	+	0	+	+	+	0	+	+	3+	4+	3+
6	0	0	+	+	0	0	+	0	+	+	0	0	+	+	+	+	0	+	3+^s	2+^w	±
7	0	0	0	+	+	+	0	0	+	+	+	0	+	0	+	0	+	0	3+^s	2+^s	1+
8	0	0	0	+	+	0	+	0	+	0	+	+	0	+	+	+	0	+	3+	2+^s	1+
9	0	0	0	+	+	+	+	+	0	+	0	+	0	+	0	+	0	+	3+^s	2+^s	1+
10	0	0	0	+	+	0	+	+	0	+	0	+	0	+	+	0	+	+	3+	2+^s	1+
11	+	+	+	0	+	+	+	+	+	0	+	0	+	0	+	+	+	+	3+^s	4+	3+
12	w	+	+	+	0	0	+	+	0	+	+	0	+	+	+	+	+	+	3+^s	2+	±
13	0	0	+	+	+	0	+	0	+	+	+	0	+	+	0	+	0	+	3+	2+^s	1+
14	+	+	+	+	+	0	+	+	0	0	+	+	0	+	+	+	0	+	3+^s	4+	3+
15	+	0	0	+	+	0	+	0	+	+	0	+	0	+	+	0	+	+	3+^s	4+	3+
16	+	0	0	+	+	0	+	+	+	+	0	0	+	0	+	0	+	+	3+^s	4+	3+

表2 本例重度贫血患儿血清、酸放散液与谱细胞反应格局

序号	Rh					Kell		Duffy		Kidd		Lewis		P	MNS				血清凝集强度		酸放散液凝集强度
序号	C	D	E	c	e	K	k	Fya	Fyb	JKa	JKb	Lea	Leb	P₁	M	N	S	s	Gel	Poly	Poly（稀释16倍）
1	+	+	0	0	+	0	+	+	0	+	0	0	+	+	+	+	+	0	3+	4+	3+
2	+	+	0	0	+	+	+	0	+	+	+	0	+	+	0	+	0	+	3+	4+	3+
3	0	+	+	+	0	0	+	+	0	+	0	+	0	+	0	+	0	+	3+	2+^w	±
4	0	+	0	+	+	0	+	0	0	+	0	0	0	+	0	+	0	+	3+	2+^s	1+
5	+	0	0	0	+	0	+	+	+	+	+	0	+	+	+	0	+	+	3+	4+	3+
6	0	0	+	+	0	0	+	0	+	+	0	0	+	+	+	+	0	+	3+^s	2+^w	±
7	0	0	0	+	+	+	0	0	+	+	+	0	+	0	+	0	+	0	3+^s	2+^s	1+
8	0	0	0	+	+	0	+	0	+	0	+	+	0	+	+	+	0	+	3+	2+^s	1+
9	0	0	0	+	+	+	+	+	0	+	0	+	0	+	0	+	0	+	3+^s	2+^s	1+
10	0	0	0	+	+	0	+	+	0	+	0	+	0	+	+	0	+	+	3+	2+^s	1+
11	+	+	+	0	+	+	+	+	+	0	+	0	+	0	+	+	+	+	3+^s	4+	3+
12	w	+	+	+	0	0	+	+	0	+	+	0	+	+	+	+	+	+	3+^s	2+	±
13	0	0	+	+	+	0	+	0	+	+	+	0	+	+	0	+	0	+	3+	2+^s	1+
14	+	+	+	+	+	0	+	+	0	0	+	+	0	+	+	+	0	+	3+^s	4+	3+
15	+	0	0	+	+	0	+	0	+	+	0	+	0	+	+	0	+	+	3+^s	4+	3+
16	+	0	0	+	+	0	+	+	+	+	0	0	+	0	+	0	+	+	3+^s	4+	3+

表3 血液供者交叉配血试验记录

供者	供者抗原							主侧试验方法
供者	-A	-B	-D	-C	-c	-E	-e	Brine	Gel	Poly
1	+	+	+	+	+	+	+	-	3+^s	4+
2	+	+	+	+	-	-	+	-	3+	3+^s
3	+	+	+	-	+	+	-	-	3+^s	2+^w

表3 血液供者交叉配血试验记录

供者	供者抗原							主侧试验方法
供者	-A	-B	-D	-C	-c	-E	-e	Brine	Gel	Poly
1	+	+	+	+	+	+	+	-	3+^s	4+
2	+	+	+	+	-	-	+	-	3+	3+^s
3	+	+	+	-	+	+	-	-	3+^s	2+^w

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Autoimmune hemolytic anemia following allogeneic hematopoietic stem cell transplantation in a patient: serological detection methods for mimicking antibodies and blood transfusion strategy

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Autoimmune hemolytic anemia following allogeneic hematopoietic stem cell transplantation in a patient: serological detection methods for mimicking antibodies and blood transfusion strategy