Heilmann L, von Tempelhoff G F, Kuse S
Department of Obstetrics and Gynecology, City Hospital Ruesselsheim, Germany.
Clin Appl Thromb Hemost. 2001 Oct;7(4):281-5. doi: 10.1177/107602960100700405.
Several therapeutic regimens have been proposed for women with recurrent spontaneous abortion (RSA) and antiphospholipid antibodies (APA). Conflicting results have been reported about women with history of RSA, positive APA, and failure of standard therapy. To evaluate the use of intravenous immunoglobulin in RSA patients with APA and history of treatment failure, we initiated a study with standard therapy (aspirin and low-molecular-weight heparin) and intravenous immunoglobulin. We used an enzyme-linked immunosorbent assay (ELISA) test to screen IgG and IgM anticardiolipin antibodies, and a diluted Russel viper venom time assay for the lupus anticoagulant activity. Altogether, 66 pregnant women with positive APAs at the first visit could be included. Patients with hereditable thrombophilic factors were excluded. After confirmation of the pregnancy, women received a basis immunization of 0.3 g/kg immunoglobulin in a 4-week cycle until the 28th to 32nd week of gestation. All patients received 100 mg/d aspirin and 3,000 anti-Xa U/d certoparin. Among the 66 pregnant women, 17 were persistently autoantibody positive (25.8%), of whom 11 (16.7%) were ACA positive alone, 2 (3%) were lupus anticoagulant positive, and 4 (6.4%) had both antibody types. A total of 49 patients had positive APAs at the initial test, but were negative for ACA and lupus anticoagulant at the second test administered approximately 5 weeks after the start of therapy. We described this group in our following observation as "antibody negative." Sixteen of the 17 autoantibody-positive patients (94.1%) were delivered of live infants compared with 40 patients (81.6%) in the antibody-negative group (odds ratio [OR]: 1.2; 95% CI: 0.98 to 1.4). The overall miscarriage rate was 12.1% and the fetal loss rate was 15.2%. Four patients (25%) in the antibody-positive group developed symptoms of preeclampsia and fetal growth retardation compared with four patients (9.8%) in the antibody-negative group. In conclusion, we see a reduction of the fetal loss rate in patients with RSA and positive APA (5.8%) compared with APA-negative (18.4%) women with the same therapy (OR: 0.3; 95% CI: 0.04 to 2.3).
针对复发性自然流产（RSA）且伴有抗磷脂抗体（APA）的女性，已经提出了几种治疗方案。对于有RSA病史、APA阳性且标准治疗失败的女性，报道的结果相互矛盾。为了评估静脉注射免疫球蛋白在有APA且有治疗失败史的RSA患者中的应用，我们开展了一项采用标准治疗（阿司匹林和低分子量肝素）加静脉注射免疫球蛋白的研究。我们使用酶联免疫吸附测定（ELISA）试验来筛查IgG和IgM抗心磷脂抗体，并采用稀释的蝰蛇毒时间测定法检测狼疮抗凝活性。总共纳入了66例首次就诊时APA阳性的孕妇。排除有遗传性血栓形成倾向因素的患者。确认妊娠后，女性接受以0.3g/kg免疫球蛋白为基础的免疫治疗，每4周一个周期，直至妊娠第28至32周。所有患者均接受100mg/d阿司匹林和3000抗Xa单位/d的西曲肝素。在这66例孕妇中，17例持续自身抗体阳性（25.8%），其中11例（16.7%）仅ACA阳性，2例（3%）狼疮抗凝物阳性，4例（6.4%）两种抗体均阳性。共有49例患者在初始检测时APA阳性，但在治疗开始约5周后进行的第二次检测中ACA和狼疮抗凝物均为阴性。在我们接下来的观察中，将这组患者描述为“抗体阴性”。17例自身抗体阳性患者中有16例（94.1%）分娩活婴，而抗体阴性组为40例（81.6%）（优势比[OR]：1.2；95%置信区间：0.98至1.4）。总体流产率为12.1%，胎儿丢失率为15.2%。抗体阳性组有4例患者（25%）出现先兆子痫和胎儿生长受限症状，而抗体阴性组为4例患者（9.8%）。总之，我们发现与接受相同治疗的APA阴性（18.4%）女性相比，RSA且APA阳性的患者胎儿丢失率有所降低（5.8%）（OR：0.3；95%置信区间：0.04至2.3）。
