Sawecka Jadwiga, Skulimowska Joanna, Windyga Jerzy, Lopaciuk Stanisław, Kościelak Jerzy
Department of Biochemistry, Institute of Hematology and Blood Transfusion, Warsaw, Poland.
Arch Immunol Ther Exp (Warsz). 2005 Jul-Aug;53(4):352-6.
Patients with severe hemophilia A often develop inhibitors (antibodies) against transfused factor VIII.
MATERIAL/METHODS: One hundred thirteen Polish patients with severe hemophilia A, who had been treated on demand with cryoprecipitate until 1992 and exclusively with factor VIII concentrates after 1995, were examined for intron 22 inversion by Southern blotting and the presence and magnitude of inhibitor activity in blood as determined by the Bethesda assay. The patients' ages ranged 4--67 years (mean: 33.7+/-12.4 years, median: 32 years).
The number of patients with the inversion amounted to 57, while in 56 patients the mutation types were unknown; 47 patients had a distal and 10 patients a proximal type of inversion. Thirteen patients with inversions (22.8%) were found to have inhibitor in their blood. Most patients (14 out of 15) who developed inhibitors in the course of cryoprecipitate therapy were high responders. Conversely, 4 of 5 patients treated between 1992 and 1995 with both cryoprecipitate and intermediate-purity factor VIII concentrates were low responders. One multitransfused patient who had remained inhibitor-free on cryoprecipitate therapy developed inhibitor after receiving a large dose of factor VIII concentrate during surgery. None of these 5 patients developed inhibitors during their 12--40 years of treatment with cryoprecipitate, suggesting that it was less immunogenic than factor VIII concentrates.
The prevalence of the intron 22 inversion mutation of the factor VIII gene in Polish hemophiliacs is similar to that in other European countries. Treatment regimens with either cryoprecipitate or virus-inactivated plasma-derived factor VIII concentrates may affect inhibitor formation in hemophilia A patients.
重度甲型血友病患者常产生针对输注的凝血因子VIII的抑制物（抗体）。
材料/方法：对113例重度甲型血友病波兰患者进行研究，这些患者在1992年之前按需接受冷沉淀治疗，1995年之后仅接受凝血因子VIII浓缩物治疗。通过Southern印迹法检测第22内含子倒位情况，并采用贝塞斯达试验测定血液中抑制物活性的存在及水平。患者年龄范围为4至67岁（平均：33.7±12.4岁，中位数：32岁）。
倒位患者有57例，56例患者的突变类型未知；47例患者为远端倒位类型，10例为近端倒位类型。13例倒位患者（22.8%）血液中存在抑制物。在冷沉淀治疗过程中产生抑制物的大多数患者（15例中的14例）为高反应者。相反，1992年至1995年期间同时接受冷沉淀和中纯度凝血因子VIII浓缩物治疗的5例患者中有4例为低反应者。1例多次输血患者在冷沉淀治疗期间未产生抑制物，但在手术中接受大剂量凝血因子VIII浓缩物后产生了抑制物。这5例患者在接受冷沉淀治疗的12至40年中均未产生抑制物，表明冷沉淀的免疫原性低于凝血因子VIII浓缩物。
波兰血友病患者中凝血因子VIII基因第22内含子倒位突变的发生率与其他欧洲国家相似。冷沉淀或病毒灭活的血浆源性凝血因子VIII浓缩物的治疗方案可能会影响甲型血友病患者抑制物的形成。
