Tarantino M D, Ross M P, Daniels T M, Nichols W L
Division of Pediatric Hematology-Oncology, University of Louisville School of Medicine, KY 40202, USA.
J Pediatr Hematol Oncol. 1997 May-Jun;19(3):226-31. doi: 10.1097/00043426-199705000-00009.
We report that treatment of an immune mediated postoperative Factor V (FV) deficiency with intravenous immune globulin (IVIg) resulted in serological and clinical disappearance of the inhibitor.
A 9-year-old girl was exposed to bovine thrombin during cardiovascular surgery and subsequently developed severe, refractory hemorrhage caused by acquired FV deficiency (FV activity < 5%). Despite blood product transfusions, hemorrhage continued, and the patient was given IVIg, 400 mg/kg daily, for 9 day.
Prolonged clotting times immediately trended toward normal, and the hemorrhage ceased by the fifth IVIg treatment day, concomitant with increasing plasma FV activity and disappearance of human FV inhibitor activity. The patient's plasma initially had a much higher inhibitor titer against bovine FV (122-215 Bethesda units) than against human FV (3-4 Bethesda units). Circulating antibodies (IgM and IgG) to bovine and human thrombin and FV were detected by enzyme-linked immunosorbent assay (ELISA). After completion of IVIg treatment, IgG antibodies to bovine FV and thrombin persisted, as did high-titer inhibition of bovine FV, whereas the subpopulation of IgG and IgM antibodies reactive with human FV were undetectable.
The inhibitor likely developed from a heterogenetic immune response to bovine FV contaminating the topical thrombin preparation used during surgery. To our knowledge, this is the first demonstration of immunological clearance of an acquired FV antibody associated with the use of IVIg. The data suggest an antiidiotypic mechanism of IVIg in modulating clearance of antihuman FV antibodies.
我们报告静脉注射免疫球蛋白（IVIg）治疗免疫介导的术后因子V（FV）缺乏症导致抑制剂的血清学和临床消失。
一名9岁女孩在心血管手术期间接触了牛凝血酶，随后因获得性FV缺乏症（FV活性<5%）出现严重难治性出血。尽管输注了血液制品，但出血仍持续，患者接受了IVIg治疗，每日400mg/kg，共9天。
延长的凝血时间立即趋于正常，出血在IVIg治疗的第5天停止，同时血浆FV活性增加，人FV抑制剂活性消失。患者血浆最初对牛FV的抑制剂滴度（122 - 215贝塞斯达单位）比对人FV的抑制剂滴度（3 - 4贝塞斯达单位）高得多。通过酶联免疫吸附测定（ELISA）检测到针对牛和人凝血酶及FV的循环抗体（IgM和IgG）。IVIg治疗完成后，针对牛FV和凝血酶的IgG抗体持续存在，对牛FV的高滴度抑制也持续存在，而与人类FV反应的IgG和IgM抗体亚群检测不到。
抑制剂可能源于对手术中使用的局部凝血酶制剂中污染的牛FV的异源免疫反应。据我们所知，这是首次证明与IVIg使用相关的获得性FV抗体的免疫清除。数据表明IVIg在调节抗人FV抗体清除方面具有抗独特型机制。
