抗磷脂综合征合并自身免疫性溶血性贫血37例临床特征及危险因素分析

Clinical characteristics of 37 antiphospholipid syndrome patients complicated by autoimmune hemolytic anemia

目的探讨抗磷脂综合征(APS)合并自身免疫性溶血性贫血(AIHA)的临床特点及危险因素。方法回顾性分析。选2017年5月至2021年5月北京协和医院风湿免疫科连续收治的315例APS患者,分析其临床特征,包括一般人口学资料、临床表型(起病首发症状,起病至确诊APS的时间,是否合并系统性红斑狼疮(SLE)、血栓事件、病理妊娠事件,是否合并APS标准外表现)、实验室检查结果[血常规、抗磷脂抗体(aPLs)、血脂、同型半胱氨酸、抗核抗体谱、免疫球蛋白水平、补体水平]。对临床特征及危险因素进行单因素及多因素logistic回归分析。结果315例APS患者中合并AIHA者37例(11.7%),未合并AIHA者278例,均以AIHA为首发表现或同时发病,其发病至确诊APS的中位时间12个月;APS合并AIHA者比未合并AIHA者出现SLE的比例高[62.2%(23/37)比19.4%(54/278),P<0.001];两者出现血栓及病理妊娠的比例差异无统计学意义(P>0.05)。合并AIHA者出现血小板减少的风险显著升高(OR=6.19,95%CI 2.81~13.65),且其出现低补体血症、狼疮抗凝物(LA)阳性、aPLs双抗体阳性[LA、aCL、抗β2糖蛋白Ⅰ(β2GPⅠ)抗体中任何2个抗体阳性]、aPLs三抗体阳性(LA、aCL、抗β2GPⅠ抗体均阳性)的比例显著升高(P<0.05)。多因素logistic回归分析显示,合并SLE(OR=3.46,95%CI 1.60~7.48)、血小板减少(OR=2.56,95%CI 1.15~5.67)、低补体血症(OR=4.29,95%CI 2.03~9.04)是APS合并AIHA的危险因素。对原发性APS合并AIHA的多因素logistic回归分析显示,网状青斑(OR=10.51,95%CI 1.06~103.78)、血小板减少(OR=3.77,95%CI 1.23~11.57)、低补体血症(OR=5.92,95%CI 1.95~17.95)是原发性APS合并AIHA的危险因素。结论AIHA在APS中并不少见。APS合并AIHA者更常见于SLE继发APS,且更易出现多种APS相关分类标准外的临床表现。对AIHA患者应及时检测抗磷脂抗体谱,同时警惕血栓事件的发生。

Objective We sought to investigate the clinical characteristics and risk factors of antiphospholipid syndrome(APS)complicated by autoimmune hemolytic anemia(AIHA).Methods Retrospective anaysis.Three hundred fifteen consecutive patients with APS were enrolled at the Department of Rheumatology of Peking Union Medical College Hospital between May 2017 to May 2021,and their clinical manifestations[including initial symptoms,time interval between APS onset and diagnosis,systemic lupus erythematosus(SLE),thrombotic events,obstetric morbidity,and extra-criteria manifestations]and laboratory test results[including blood routine,antiphospholipid antibodies(aPLs),blood lipid profile,homocysteine,anti-nuclear antibody profile,immunoglobulin levels,and complement levels]were collected.Then,univariate and multivariate logistic regression analyses were performed.Clinical features and risk factors were analyzed using univariable and multivariable logistic regression analysis.Results Among 315 APS patients,37 cases(11.7%)were complicated by AIHA,and AIHA was the first manifestation or co-occurrence.The median time interval between APS onset and diagnosis was 12 months.The proportion of SLE in APS patients combined with AIHA was higher than that in APS patients without AIHA[62.2%(23/37)vs.19.4%(54/278),P<0.001].There was no significant difference in the proportions of thrombosis and pregnancy morbidity between the two groups.In terms of extra-criteria manifestations,APS patients with AIHA had a significantly(P<0.05)greater risk of thrombocytopenia(OR=6.19,95%CI 2.81-13.65)and higher proportions of hypocomplementemia,a positive lupus anticoagulant(LA)result,double aPLs positivity[i.e.,any two of the following antibodies were positive:LA,anticardilolipin antibody(aCL),and anti-β2 glycoproteinⅠ(β2GPⅠ)],and triple aPLs positivity(i.e.,LA,aCL,and anti-β2GPⅠantibodies were all positive).Multivariate logistic regression analysis showed that SLE(OR=3.46,95%CI 1.60-7.48),thrombocytopenia(OR=2.56,95%CI 1.15-5.67),and hypocomplementemia(OR=4.29,95%CI 2.03-9.04)were independent risk factors for the complication of APS.In the primary APS subgroup,multivariate logistic regression analysis showed that livedo reticularis(OR=10.51,95%CI 1.06-103.78),thrombocytopenia(OR=3.77,95%CI 1.23-11.57),and hypocomplementemia(OR=5.92,95%CI 1.95-17.95)were independent risk factors for the complication of APS.Conclusions AIHA is not rare in APS patients;moreover,it occurs more frequently in APS secondary to SLE and is more likely to present with a variety of extra-criteria manifestations.Patients with AIHA should be promptly tested for antiphospholipid antibody profiles and alerted to the possibility of thrombotic events.