3例自身免疫性血友病样凝血因子缺陷症患者ⅩⅢ诊断流程的初步建立及文献回顾

目的：对3例疑似自身免疫性血友病样凝血因子ⅩⅢ缺陷症（autoimmune haemorrhaphilia factor ⅩⅢ, AHⅩⅢ）患者进行检测, 明确其临床诊断、治疗及随访资料, 建立完整的AHⅩⅢ实验诊断流程。方法：收集3例AHⅩⅢ患者的临床信息, 通过氨释放法检测其凝血因子ⅩⅢ（factor ⅩⅢ, F ⅩⅢ）活性, 酶联免疫吸附试验（enzyme linked immunosorbent assay, ELISA）法检测F ⅩⅢ-A抗原（FⅩⅢ-A:Ag）、FⅩⅢ-B:Ag。抗FⅩⅢ抗体检测包括混合实验检测抗FⅩⅢ中和抗体的存在、Bethesda法测定抗FⅩⅢ抗体滴度、ELISA法检测抗FⅩⅢ-A亚基抗体等。结果：3例患者的尿素法FⅩⅢ定性试验均为阳性, FⅩⅢ活性<5%, FⅩⅢ-A:Ag<3%, FⅩⅢ-B:Ag分别为65.40%、116.28%、138.81%。3例患者混合实验均为阳性, Bethesda法测定抗FⅩⅢ中和抗体滴度分别为1.83 BU、1.67 BU、1.75 BU, 免疫法检测结果提示均存在抗FⅩⅢ-A亚基抗体。结论：建立了完整的ⅩⅢ的诊断流程, 并回顾了其诊断、治疗及预后相关文献。经诊断, 本研究3例患者均为低滴度抗FⅩⅢ-A亚基抗体导致的AHⅩⅢ。

Preliminary establishment of a flowchart for diagnosis,treatment of patients with autoimmune hemophilia-like coagulation factorⅩⅢ deficiency,review of literature

Objective: To test and diagnose definitely three patients with suspected autoimmune hemophilia-like coagulation factor ⅩⅢ (AH ⅩⅢ) deficiency and establish a flowchart for the laboratory diagnosis of AH ⅩⅢ deficiency. Methods: The clinical data of these 3 patients were recorded. FⅩⅢ: Act was detected by ammonia release assay. F ⅩⅢ-A: Ag and F ⅩⅢ-B: Ag were assayed by ELISA. Laboratory mixing tests and Bethesda method were used to detect anti-F ⅩⅢ neutralizing antibody, and ELISA was used to detect the autoantibodies against F ⅩⅢ-A. Results: For the 3 patients, positive results were shown by ammonia release assay. FⅩⅢ: Act <5%, F ⅩⅢ-A: Ag <3% and FⅩⅢ-B: Ag were 65.40%, 116.28% and 138.81%, respectively. Laboratory mixing tests were positive in all the 3 patients, and Bethesda method revealed that the neutralizing antibody were 1.83 BU, 1.67 BU and 1.75 BU, respectively. Autoantibodies against F ⅩⅢ-A were detected by immunological assay in all the 3 patients. Conclusions: A flowchart for laboratory diagnosis of AH ⅩⅢ deficiency is established. All the 3 patients were diagnosed as AH ⅩⅢ deficiency caused by low titer autoantibodies against F ⅩⅢ-A. Relevant literature about the diagnosis, treatment and prognosis of AH ⅩⅢ deficiency is reviewed.