Analysis of clinical characteristics and risk factors in primary antiphospholipid syndrome with thrombocytopenia
-
摘要:
目的 了解原发性抗磷脂综合征(APS)并发血小板减少症的主要临床特点，探讨APS发生血小板减少的危险因素。 方法 回顾性分析2016年1月—2024年2月就诊于蚌埠医科大学第一附属医院的69例APS患者，收集患者的临床资料及实验室检查结果。定义PLT＜100×109/L的患者为血小板减少，将患者分为APS并发血小板减少组(观察组，16例)和血小板计数正常组(对照组，53例)。比较2组临床表现、实验室检查及免疫学指标，采用多因素logistic逐步回归模型分析APS患者发生血小板减少的危险因素。 结果 69例APS患者中共有16例(23.2%)并发血小板减少。2组血栓形成、心脏瓣膜病、神经系统病变及肾脏病变等临床特点比较差异均无统计学意义(P＞0.05)。观察组低补体血症发生率较对照组显著升高[75.0%(12/16) vs. 43.4%(23/53), P＜0.05]。与对照组比较，观察组的纤维蛋白原(Fib)异常下降发生率升高[43.8%(7/16) vs.15.1%(8/53)，P＜0.05]。2组自身抗体阳性率比较差异无统计学意义。多因素分析显示，低补体血症(OR=0.198, P＜0.05)、Fib降低(OR=0.216, P＜0.05)均为APS并发血小板减少的独立危险因素。 结论 血小板减少症在APS患者中较常见，其中低补体血症及纤维蛋白原降低是APS并发血小板减少的独立危险因素。 Abstract:Objective To understand the main clinical characteristics of primary antiphospholipid syndrome (APS) complicated with thrombocytopenia and explore the risk factors for thrombocytopenia in APS. Methods A retrospective analysis was conducted on 69 APS patients who were enrolled from the First Affiliated Hospital of Bengbu Medical University from January 2016 to February 2024. Clinical data and laboratory test results were collected, and patients with platelet count (PLT) < 100×109/L were defined as cases of thrombocytopenia, and were divided into two groups: the observation group (n=16) with APS complicated thrombocytopenia and the control group (n=53) with normal platelet count clinical manifestations, laboratory tests, and immunological indicators were compared between the two groups. A multiple logistic stepwise regression model was used to analyze the risk factors for thrombocytopenia in APS patients. Results Out of 69 APS patients, a total of 16 (23.2%) developed thrombocytopenia. No statistically significant difference was observed between the observation and control groups in terms of clinical characteristics, including thrombosis, heart valve disease, neurological disorders, and renal disorders (P>0.05). The incidence of hypocomplementemia in the observation group was significantly higher than that in the control group [75.0% (12/16) vs. 43.4% (23/53), P < 0.05]. Compared with the control group, the incidence of abnormal decrease in fibrinogen in the observation group was also significantly higher [43.8% (7/16) vs. 15.1% (8/53), P < 0.05]. In addition, there was no statistically significant difference in the positive rate of autoantibodies between the two groups. Multivariate analysis showed that hypocomplementemia (OR=0.198, P < 0.05) and decreased Fib (OR=0.216, P < 0.05) were both independent risk factors for thrombocytopenia complicated with APS. Conclusion Thrombocytopenia is common in APS patients, with low complement levels and decreased fibrinogen being independent risk factors for APS complicated with thrombocytopenia. -
Key words:
- Primary antiphospholipid syndrome /
- Thrombocytopenia /
- Hypocomplementemia
-
表 1 2组APS患者一般资料及实验室检查指标比较
Table 1. Comparison of baseline characteristics and laboratory indicators between the two groups of APS patients
项目 观察组(n=16) 对照组(n=53) 统计量 P值 性别(女性/男性，例) 13/3 32/21 2.360a 0.124 年龄[M(P25, P75), 岁] 49(43, 71) 56(44, 69) -0.683b 0.495 红细胞计数(x±s, ×109/L) 3.50±0.89 3.53±0.91 0.110c 0.913 血红蛋白(x±s, g/L) 101.30±20.31 106.60±25.49 0.736c 0.064 白细胞计数[M(P25, P75), ×109/L] 4.50(4.00, 6.75) 4.00(3.60, 6.00) -0.380b 0.704 ALT[M(P25, P75), U/L] 17(13, 53) 17(12, 33) -1.567b 0.117 AST[M(P25, P75), U/L] 50(37, 54) 55(34, 57) -1.432b 0.117 低蛋白血症[例(%)] 7(43.8) 10(18.9) 4.098a 0.043 肌酐[M(P25, P75), μmol/L] 77.0(48.0, 97.0) 64.0(47.0, 76.5) -2.178b 0.209 尿素氮[M(P25, P75), mmol/L] 5.43(4.06, 7.68) 4.33(2.86, 6.29) -1.694b 0.090 PT延长[例(%)] 4(25.0) 8(15.1) 0.839a 0.360 APTT延长[例(%)] 2(12.5) 13(24.5) 0.458a 0.499 Fib降低[例(%)] 7(43.8) 8(15.1) 5.932a 0.015 D-Dimer升高[例(%)] 7(43.8) 32(60.4) 1.383a 0.240 注：a为χ2值，b为Z值，c为t值。 
下载: 导出CSV
表 2 2组APS患者合并症及系统病变情况比较[例(%)]
Table 2. Comparison of systemic lesion and immunological indicators between the two groups of APS patients [cases(%)]
组别 例数 糖尿病 高脂血症 消化道出血 肾脏病变 心肌梗死 心脏瓣膜病 脑梗死 认知障碍及癫痫 静脉血栓 观察组 16 3(18.8) 1(6.2) 1(6.2) 7(43.8) 4(25.0) 7(43.8) 6(37.5) 1(6.2) 2(12.5) 对照组 53 12(22.6) 5(9.4) 4(7.5) 11(20.8) 9(17.0) 13(24.5) 19(35.8) 2(3.8) 3(5.7) χ2值 ＜0.001 0.012 0.140 2.283 0.125 1.371 0.014 0.140 P值 0.988 0.912 0.708 0.131 0.723 0.242 0.904 0.553a 0.708 注：a为使用Fisher精确检验。
下载: 导出CSV
表 3 2组APS患者免疫学指标比较
Table 3. Comparison of immunological laboratory indexes between the two groups of APS patients
组别 例数 补体C3 (x±s, g/L) 补体C4 (x±s, g/L) IgG [M(P25, P75), g/L] IgM [M(P25, P75), g/L] 低补体血症[例(%)] aCLIgA阳性[例(%)] aCLIgG阳性[例(%)] aCLIgM阳性[例(%)] 抗β2GPI-IgG阳性[例(%)] 观察组 16 0.718±0.135 0.165±0.048 11.60(8.90, 18.22) 1.295(0.990, 1.528) 12(75.0) 14(87.5) 9(56.2) 8(50.0) 9(56.2) 对照组 53 0.818±0.160 0.187±0.064 11.30(9.62, 16.50) 0.960(0.770, 1.300) 23(43.4) 41(77.4) 22(41.5) 37(69.8) 22(41.5) t值 2.272a 1.197a -0.014b -2.688b 4.911c 0.280c 1.079c 2.216c 1.079c P值 0.026 0.236 0.989 0.007 0.027 0.597 0.299 0.145 0.299 注：a为t值，b为Z值，c为χ2值。
下载: 导出CSV
表 4 APS并发血小板减少影响因素的多因素logistic回归分析
Table 4. Multivariate logistic regression analysis of factors associated with thrombocytopenia in APS patients
变量 B SE Waldχ2 P值 OR(95% CI) IgM水平 1.016 0.666 2.332 0.127 2.763(0.750~10.185) 低补体血症 1.480 0.749 3.907 0.048 4.395(1.013~19.074) 低蛋白血症 1.302 0.708 3.382 0.066 3.677(0.918~14.731) Fib降低 1.820 0.749 5.907 0.015 6.174(1.422~26.795)
下载: 导出CSV
-
[1] MIYAKIS S, LOCKSHIN M D, ATSUMI T, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS)[J]. J Thromb Haemost, 2006, 4(2): 295-306. doi: 10.1111/j.1538-7836.2006.01753.x [2] 白伊娜, 孟菁菁, 赵久良, 等. 抗磷脂综合征中非标准抗磷脂抗体的诊断价值和风险预测[J]. 中华临床免疫和变态反应杂志, 2023, 17(5): 395-406.BAI Y N, MENG J J, ZHAO J L, et al. Diagnostic value and risk prediction of non-criteria antiphospholipid antibodies in antiphospholipid syndrome[J]. Chinese Journal of Allergy & Clinical Immunology, 2023, 17(5): 395-406. [3] PARDOS-GEA J, MARQUES-SOARES J R, BUJÁN S, et al. Persistent thrombocytopenia predicts poor long-term survival in patients with antiphospholipid syndrome: a 38-year follow-up study[J]. Rheumatology(Oxford), 2022, 61(3): 1053-1061. doi: 10.1093/rheumatology/keab475 [4] NEUNERT C, LIM W, CROWTHER M, et al. The American society of hematology 2011 evidence-based practice guideline for immune thrombocytopenia[J]. Blood, 2011, 117(16): 4190-4207. doi: 10.1182/blood-2010-08-302984 [5] MITITELU A, ONISÂI M C, ROŞCA A, et al. Current understanding of immune thrombocytopenia: a review of pathogenesis and treatment options[J]. Int J Mol Sci, 2024, 25(4): 2163. DOI: 10.3390/ijms25042163. [6] PATSOURAS M, TSIKI E, KARAGIANNI P, et al. The role of thrombospondin-1 in the pathogenesis of antiphospholipid syndrome[J]. J Autoimmun, 2020, 115: 102527. DOI: 10.1016/j.jaut.2020.102527. [7] TANG Z, SHI H, CHEN C, et al. Activation of platelet mTORC2/Akt pathway by anti-β2GP1 antibody promotes thrombosis in antiphospholipid syndrome[J]. Arterioscler Thromb Vasc Biol, 2023, 43(10): 1818-1832. doi: 10.1161/ATVBAHA.123.318978 [8] TOHIDI-ESFAHANI I, MITTAL P, ISENBERG D, et al. Platelets and thrombotic antiphospholipid syndrome[J]. J Clin Med, 2024, 13(3): 741. DOI: 10.3390/jcm13030741. [9] CERVERA R, TEKTONIDOU M G, ESPINOSA G, et al. Task force on catastrophic antiphospholipid syndrome (APS) and non-criteria APS manifestations (Ⅱ): thrombocytopenia and skin manifestations[J]. Lupus, 2011, 20(2): 174-181. doi: 10.1177/0961203310395052 [10] YELNIK C M, NGUYEN Y, LE GUERN V, et al. Thrombocytopenia in primary antiphospholipid syndrome, a marker of high-risk patients?[J]. Eur J Intern Med, 2020, 74: 106-107. doi: 10.1016/j.ejim.2020.01.017 [11] BARBHAIYA M, ZUILY S, NADEN R, et al. The 2023 ACR/EULAR antiphospholipid syndrome classification criteria[J]. Arthritis Rheumatol, 2023, 75(10): 1687-1702. doi: 10.1002/art.42624 [12] KRAUSE I, BLANK M, FRASER A, et al. The association of thrombocytopenia with systemic manifestations in the antiphospholipid syndrome[J]. Immunobiology, 2005, 210(10): 749-754. doi: 10.1016/j.imbio.2005.10.005 [13] DEMETRIO PABLO R, MUÑOZ P, LÓPEZ-HOYOS M, et al. Thrombocytopenia as a thrombotic risk factor in patients with antiphospholipid antibodies without disease criteria[J]. Med Clin(Barc), 2017, 148(9): 394-400. [14] SHI Y, ZHAO J, JIANG H, et al. Thrombocytopenia in primary antiphospholipid syndrome: association with prognosis and clinical implications[J]. Rheumatology(Oxford), 2022, 62(1): 256-263. doi: 10.1093/rheumatology/keac264 [15] PABLO R D, CACHO P M, LÓPEZ-HOYOS M, et al. Risk factors for the development of the disease in antiphospholipid antibodies carriers: a long-term follow-up study[J]. Clin Rev Allergy Immunol, 2022, 62(2): 354-362. doi: 10.1007/s12016-021-08862-5 [16] PROULLE V, FURIE R A, MERRILL-SKOLOFF G, et al. Platelets are required for enhanced activation of the endothelium and fibrinogen in a mouse thrombosis model of APS[J]. Blood, 2014, 124(4): 611-622. doi: 10.1182/blood-2014-02-554980 [17] TABACCO S, GIANNINI A, GARUFI C, et al. Complementemia in pregnancies with antiphospholipid syndrome[J]. Lupus, 2019, 28(13): 1503-1509. doi: 10.1177/0961203319882507 [18] SALET D M, BEKKERING S, MIDDELDORP S, et al. Targeting thromboinflammation in antiphospholipid syndrome[J]. J Thromb Haemost, 2023, 21(4): 744-757. doi: 10.1016/j.jtha.2022.12.002 [19] COLE M A, GERBER G F, CHATURVEDI S. Complement biomarkers in the antiphospholipid syndrome: approaches to quantification and implications for clinical management[J]. Clin Immunol, 2023, 257: 109828. DOI: 10.1016/j.clim.2023.109828. [20] SAUTER R J, SAUTER M, REIS E S, et al. Functional relevance of the anaphylatoxin receptor C3aR for platelet function and arterial thrombus formation marks an intersection point between innate immunity and thrombosis[J]. Circulation, 2018, 138(16): 1720-1735. doi: 10.1161/CIRCULATIONAHA.118.034600 [21] MEZGER M, NORDING H, SAUTER R, et al. Platelets and immune responses during thromboinflammation[J]. Front Immunol, 2019, 10: 1731. DOI: 10.3389/fimmu.2019.01731. [22] SUBRAMANIAM S, JURK K, HOBOHM L, et al. Distinct contributions of complement factors to platelet activation and fibrin formation in venous thrombus development[J]. Blood, 2017, 129(16): 2291-2302. doi: 10.1182/blood-2016-11-749879 -
点击查看大图
表(4)
计量
- 文章访问数: 6
- HTML全文浏览量: 2
- PDF下载量: 0
- 被引次数: 0
