Yee Marianne E M, Josephson Cassandra D, Winkler Anne M, Webb Jennifer, Luban Naomi L C, Leong Traci, Stowell Sean R, Roback John D, Fasano Ross M
Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Department of Pediatrics and Hematology/Oncology, Emory University School of Medicine and the.
Center for Transfusion and Cellular Therapies, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia; the.
Transfusion. 2018 Jun;58(6):1363-1371. doi: 10.1111/trf.14610. Epub 2018 Apr 17.
Chronic transfusion therapy for sickle cell anemia reduces disease complications by diluting sickle-erythrocytes with hemoglobin A (HbA)-containing erythrocytes and suppressing erythropoiesis. Minor antigen mismatches may result in alloimmunization, but it is unknown if antigen mismatches or recipient characteristics influence HbA clearance posttransfusion.
Children with sickle cell anemia on chronic transfusion therapy were followed prospectively for 12 months. All patients received units serologically matched for C/c, E/e, and K; patients with prior red blood cell (RBC) antibodies had additional matching for Fy , Jk , and any previous alloantibodies. Patients' RBC antigen genotypes, determined by multiplexed molecular assays (PreciseType Human Erythrocyte Antigen, and RHCE and RHD BeadChip, Immucor) were compared to genotypes of transfused RBC units to assess for antigen mismatches. Decline in hbA (ΔHbA) from posttransfusion to the next transfusion was calculated for each transfusion episode.
Sixty patients received 789 transfusions, 740 with ΔHbA estimations, and 630 with donor Human Erythrocyte Antigen genotyping. In univariate mixed-model analysis, ΔHbA was higher in patients with past RBC antibodies or splenomegaly and lower in patients with splenectomy. RBC antigen mismatches were not associated with ΔHbA. In multivariate linear mixed-effects modeling, ΔHbA was associated with RBC antibodies (2.70 vs. 2.45 g/dL/28 d, p = 0.0028), splenomegaly (2.87 vs. 2.28 g/dL/28 d, p = 0.019), and negatively associated with splenectomy (2.46 vs. 2.70 g/dL/28 d, p = 0.011).
HbA decline was increased among patients with sickle cell anemia with prior immunologic response to RBC antigens and decreased among those with prior splenectomy, demonstrating that recipient immunologic characteristics influenced the clearance of transfused RBCs.
镰状细胞贫血的慢性输血治疗通过用含血红蛋白A（HbA）的红细胞稀释镰状红细胞并抑制红细胞生成来减少疾病并发症。次要抗原不匹配可能导致同种免疫，但尚不清楚抗原不匹配或受者特征是否会影响输血后HbA的清除。
对接受慢性输血治疗的镰状细胞贫血患儿进行了为期12个月的前瞻性随访。所有患者均接受了C/c、E/e和K血清学匹配的单位；既往有红细胞（RBC）抗体的患者对Fy、Jk及任何既往同种抗体进行了额外匹配。通过多重分子检测（PreciseType人类红细胞抗原、RHCE和RHD BeadChip，Immucor）确定患者的RBC抗原基因型，并与输注的RBC单位的基因型进行比较，以评估抗原不匹配情况。计算每次输血事件从输血后到下次输血时HbA的下降量（ΔHbA）。
60例患者接受了789次输血，其中740次有ΔHbA估计值，630次有供者人类红细胞抗原基因分型。在单变量混合模型分析中，既往有RBC抗体或脾肿大的患者ΔHbA较高，而脾切除患者的ΔHbA较低。RBC抗原不匹配与ΔHbA无关。在多变量线性混合效应模型中，ΔHbA与RBC抗体（2.70 vs. 2.45 g/dL/28天，p = 0.0028）、脾肿大（2.87 vs. 2.28 g/dL/28天，p = 0.019）相关，与脾切除呈负相关（2.46 vs. 2.70 g/dL/28天，p = 0.011）。
既往对RBC抗原有免疫反应的镰状细胞贫血患者HbA下降增加，而既往脾切除患者的HbA下降减少，这表明受者的免疫特征影响了输注RBC的清除。
