Molecular analysis of a patient with type I Glanzmann thrombasthenia and clinical impact of the presence of anti-αIIbβ3 alloantibodies
Molecular analysis of a patient with type I Glanzmann thrombasthenia and clinical impact of the presence of anti-αIIbβ3 alloantibodies
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DOI：
10.1007/s12185-010-0731-5
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发表时间：
2011-01-01
影响因子：
2.1
通讯作者：
Tomiyama, Yoshiaki
中科院分区：
文献类型：
--
作者：
Kashiwagi, Hirokazu;Kiyomizu, Kazunobu;Tomiyama, Yoshiaki
针对α IIb β 3的输血相关同种免疫的发生是Glanzmann血栓性贫血（GT）患者的一个主要问题。然而，关于抗α IIb β 3同种异体抗体的GT患者的分子缺陷以及这些抗体对血小板输注的临床影响的数据很少。在这里，我们报告一例患有抗hla和抗α IIb β 3同种异体抗体的I型GT患者，因胃癌接受腹腔镜全胃切除术。我们发现了一个新的β 3无义突变892C >t (Arg272X)，并且该患者是该突变的纯合子。连续输注hla匹配的浓缩血小板，每隔2 h大剂量注射重组VIIa因子，成功完成腹腔镜胃切除术。总出血370ml，无需红细胞输注。采用抗α IIb β 3单克隆抗体的流式细胞分析显示，术中输注血小板计数维持在20-30 × 10(9)/L左右，次日输注血小板计数维持在10 × 10(9)/L左右。流式细胞分析也显示输血小板对ADP刺激保持正常的反应性。这些结果表明，流式细胞术可用于评估抗α IIb β 3抗体GT患者输注血小板的生存和功能。
The occurrence of transfusion-related alloimmunization against alpha IIb beta 3 is a major concern in patients with Glanzmann thrombasthenia (GT). However, few data are available about molecular defects of GT patients with anti-alpha IIb beta 3 alloantibodies as well as clinical impact of these antibodies on platelet transfusion. Here, we report a case of type I GT with anti-HLA and anti-alpha IIb beta 3 alloantibodies, who underwent laparoscopic total gastrectomy due to gastric cancer. We found a novel beta 3 nonsense mutation, 892C > T (Arg272X), and the patient was homozygous for the mutation. Laparoscopic gastrectomy was successfully performed with continuous infusion of HLA-matched platelet concentrates and bolus injection of recombinant factor VIIa at 2 h intervals. Total bleeding was 370 mL and no red-cell transfusion was necessary. Flow cytometric analysis employing anti-alpha IIb beta 3 monoclonal antibody revealed that the transfused platelet count was maintained around 20-30 x 10(9)/L during the operation and 10 x 10(9)/L on the following day. Flow cytometric analysis also showed that transfused platelets retained normal reactivity to ADP stimulation. These results indicate that flow cytometry is useful to assess survival and function of transfused platelets in GT patients with anti-alpha IIb beta 3 antibodies.