妊娠合并再生障碍性贫血患者存在抗-HLA引起血小板输注无效的诊疗

Treatment of platelet transfusion refractory caused by anti-HLA in pregnancy complicated with aplastic anemia

目的为存在抗-HLA的妊娠合并再生障碍性贫血(简称再障)而血小板输注无效患者,从血小板供者库中寻找相匹配的血小板输注并追踪输注效果,确保患者顺利生产以及后续的治疗。方法对1名再障孕妇用ELISA方法检测血小板抗体、用Luminex方法检测抗-HLA特异性;提取患者及血小板供者(库)523名DNA做高分辨HLA基因分型检测;利用自行设计的"血小板输注无效风险评估"软件在血小板供者库中查找出与患者ABO血型相、HLA基因型与患者相容且不含患者特异性HLA Eplets(表位)及其抗体的供者,招募其来做单克隆抗体固相血小板抗体试验(MASPAT)配型后捐献1 U血小板输注给患者,并追踪输注24 h效果。结果血小板抗体检测:患者仅含抗-HLAⅠ类抗体;抗体特异性鉴定:针对Eplets为65QIA,相应的抗-HLA为HLA-B^(*)27∶08、B^(*)27∶05、B^(*)07∶02、B^(*)55∶01、B^(*)67∶01、B^(*)54∶01;抗-HLA-Ⅱ类阴性。高分辨HLA基因分型:患者与供者HLA基因型均为HLA-A^(*)02∶07、A^(*)11∶01,B^(*)46∶01、B^(*)46∶01,C^(*)01∶02、01∶03,DRB1^(*)04∶05、DRB1^(*)0901,DQB1^(*)03∶03、DQB1^(*)04∶01;MASPAT配型:阴性。患者输注该供者的配型血小板1 U后24 h血小板计数(Plt)(×10^(9)/L)由输注前1上升至33。4周后患者剖宫产1男婴,术后血小板低下,有出血倾向,再次招募该献血者,输注1 U血小板后24 h Plt(×10^(9)/L)由输注前5上升至37。追踪产后2 d母婴生命体征均正常。结论妊娠合并再障患者抗-HLA导致的血小板输注无效,可通过建立血小板供者库,及时筛选输注HLA基因型相容且不含患者特异性HLA表位供者的血小板,而得到有效治疗。

Objective To find the HLA-matched platelets from platelet donor registry and track the transfusion effect for aplastic anemia patients in pregnancy with platelet transfusion refractory(PTR)caused by anti-HLA,so as to support the childbirth and follow-up treatment of the patients.Methods Antibodies to HPA and HLA were detected by ELISA kit and Luminex,respectively.DNA of the patient and 523 platelet donors from the donor registry were extracted for high-resolution HLA genotyping.The Risk Factors Evaluation Software of PTR was used to select the ABO-compatible and HLA-matched donors,without HLA Eplets specific to the patient.After MASPAT cross matching,the patient was transfused with 1 U of platelets,and the 24 h post-transfusion effect was recorded.Results Only anti-HLAⅠantibody was found in the patient serum,and the specificity Eplet was 65 QIA,including HLA-B^(*)27∶08,B^(*)27∶05,B^(*)07∶02,B^(*)55∶01,B^(*)67∶01 and B^(*)54∶01;anti-HLAⅡantibody was negative.The HLA genotypes of both the patient and donor were HLA-A^(*)02∶07,A^(*)11∶01,B^(*)46∶01,B^(*)46∶01,C^(*)01∶02,01∶03,DRB1^(*)04∶05,DRB1^(*)0901,DQB1^(*)03∶03 and DQB1^(*)04∶01.The results of MASPAT matching were negative.HLA-matched platelets transfusion provided a satisfactory posttransfusion platelet responses in patients(1 before vs 33×10^(9)/L after).A baby boy was delivered by cesarean section 4 weeks later,and the same donor was recruited due to the mother′s low Plt and bleeding trend.The 24 h posttransfusion Plt(×10^(9)/L)rose from 5 to 37 after the secondary transfusion of 1 U platelet.The vital signs of the mother and her baby were normal during the two-day follow up.Conclusion The establishment of blood donor registry and screening of HLA-matched donors is an effective approach to treat PTR caused by HLA antibodies in pregnancy complicated with aplastic anemia.