Email Alert | RSS

Journal of Peking University (Health Sciences) ›› 2023, Vol. 55 ›› Issue (6): 1033-1038. doi: 10.19723/j.issn.1671-167X.2023.06.012

Previous Articles     Next Articles

Predictive value of four items of new thrombus markers combined with conventional coagulation tests for thrombosis in antiphospholipid syndrome

Li-rong HONG1,2,Yu-jia CHEN2,Qing-lai JIANG2,Ru-lin JIA1,*(),Chun LI1,Liang-hua FENG2,*()   

  1. 1. Department of Rheumatology and immunology, Peking University People's Hospital, Beijing 100044, China
    2. Xiamen Fifth Hospital Rheumatology Department, Xiamen 361101, Fujian, China
  • Received:2023-08-20 Online:2023-12-18 Published:2023-12-11
  • Contact: Ru-lin JIA,Liang-hua FENG E-mail:1036013457@qq.com;flh9453@126.com
  • Supported by:
    Beijing Municipal Science and Technology Projects(Z191100006619110)

RICH HTML

 0   

PDF (PC)

151

Abstract:

Objective: To explore the predictive value of four items of new thrombus markers combined with conventional coagulation tests for thrombosis in antiphospholipid syndrome. Methods: A total of 121 antiphospholipid syndrome (APS) patients who hospitalized at Peking University People's Hospital from March 2022 to January 2023 were selected and divided into thrombus group (50 cases) and nonthrombus group (71 cases) according to whether thrombosis occurred. The differences of laboratory characteristics including antiphospholipid antibodies were compared between the thrombotic and non-thrombotic groups. Chemiluminescent immunoassay was used to detect thrombomodulin (TM), thrombin-antithrombin complex (TAT), Plasmin-α2 plasmin inhibitor complex (PIC), and tissue plasminogen activator inhibitor complex (t-PAIC) in plasma from venous. The independent risk factors of thrombosis in patients with APS were determined using binary Logistic regression. Receiver operating characteristic (ROC) curve analysis was applied to evaluate the efficacy of each index on the prediction of thrombosis. Results: Compared with the patients without thrombosis, the patients with thrombosis were older [49 (32, 64) years vs. 36 (32, 39) years, P < 0.05]. The percentages of male, smoking, hypertension, and global antiphospholipid syndrome score (GAPSS)≥10 in the patients with thrombosis were significantly higher than those in the patients without thrombosis (P < 0.05). The positive rates of anticardiolipin antibody (aCL) and lupus anticoagulant (LA) in the thrombotic group were significantly higher than those in the non-thrombotic group (P < 0.05), and the levels of prothrombin time, activated partial thromboplastin time, fibrinogen, fibrin degradation product in the thrombotic group were significantly higher than those in the non-thrombotic group (P < 0.05).Among the thrombosis group, venous thrombosis accounted for 19 (38.00%), including deep vein thrombosis (16, 84.21%) and pulmonary embolism accounted (5, 26.32%); Arterial thrombosis accounted for 35 (70.00%), including myocardial infarction (6, 17.14%) cerebral infarction (30, 85.71%). The patients in the thrombotic group had significantly greater TM levels than those in the non-thrombotic group (P < 0.05).There were no significant dif-ferences between the two groups in TAT (Z=-1.420, P=0.156), PIC (Z=-0.064, P=0.949), and t-PAIC (Z=-1.487, P=0.137). Univariate and binary Logistic regression analysis of relevant variables showed that advanced age [OR=1.126, P=0.002], elevated TM [OR=1.325, P=0.048], prolonged prothrombin time (PT) [OR=4.127, P=0.008] were independent risk factors for thrombosis in the patients with APS. ROC curve analysis of the above three independent risk factors showed that the combined detection of age, PT and TM had the highest Yoden index (0.727) and sensitivity (83.0%), with a specificity of 89.7%. Conclusion: TAT, PIC, TM, and t-PAIC may reflect thrombus formation from the coagulation system, fibrinolysis system, and endothelial system. The combined of age TM and PT is superior to the application of a single marker, which has diagnostic value for the early identification of APS thrombosis.

Key words: Thrombomodulin, Thrombin-antithrombin complex, Plasmin-α2 plasmin inhibitor complex, Tissue plasminogen activator inhibitor complex, Antiphospholipid syndrome

CLC Number: 

  • R593.2

Table 1

Clinical characteristics of the APS in the thrombotic and non-thrombotic group"

Items thrombotic group (n=50) Non-thrombotic group (n=71) X2/Z P
Age/years, M(P25, P75) 49 (32, 64) 36 (32, 39) -3.735 0.000
Female, n(%) 28 (56.00) 68 (95.77) 28.315 0.000
Hypertension, n(%) 22 (44.00) 9 (12.68) 4.858 0.028
Hyperlipemia, n(%) 10 (20.00) 3 (4.23) 2.767 0.096
Diabetes, n(%) 6 (12.00) 4 (5.63) 0.001 0.976
Smoking history, n(%) 11 (22.00) 1 (1.41) 4.505 0.034
GAPSS≥10, n(%) 17 (34.00) 9 (12.67) 7.908 0.005
aCL (+), n(%) 20 (40.00) 14 (19.72) 5.973 0.015
anti-β2GPⅠ(+), n(%) 31 (62.00) 39 (54.93) 0.602 0.438
LA (+), n(%) 32 (64.00) 19 (26.76) 16.686 0.000
double aPL positivity, n(%) 17 (34.00) 9 (12.68) 7.908 0.005
triple aPL positivity, n(%) 10 (20.00) 7 (9.86) 2.499 0.114
PT/s, M(P25, P75) 15.67 (11.20, 17.20) 11.24 (10.68, 11.70) -4.131 0.000
FIB/(mg/L), M(P25, P75) 307.34 (249.00, 348.00) 316.88 (278.25, 350.00) -1.067 0.286
APTT/s, M(P25, P75) 42.56 (31.80, 48.60) 32.39 (28.65, 35.08) -3.667 0.000
FDP/(mg/L), M(P25, P75) 2.07 (0.50, 1.60) 1.62 (0.50, 1.00) -2.009 0.045
D-dimer/(μg/L), M(P25, P75) 283.51 (41.00, 239.00) 255.55 (54.75, 153.75) -0.303 0.762

Figure 1

Plasma concentrations of TAT, PIC, t-PAIC, and TM in the thrombotic and non-thrombotic groups TAT, thrombin-antithrombin complex; PIC, plasmin-α2 plasmin inhibitor complex; t-PAIC, tissue plasminogen activator inhibitor complex; TM, thrombomodulin. # P<0.001."

Table 2

The independent risk factors of thrombosis in patients with APS were determined using binary Logistic regression"

Risk factors B SE Wald P OR(95%CI)
Age 0.119 0.039 9.166 0.002 1.126 (1.043, 1.216)
Female -1.661 1.045 2.525 0.112 0.190 (0.024, 1.474)
Hypertension -0.023 1.017 0.000 0.982 0.978 (0.133, 7.175)
Smoking history 1.358 1.411 0.926 0.336 3.889 (0.245, 61.785)
GAPSS≥10 -0.283 1.271 0.050 0.824 0.753 (0.062, 9.096)
aCL(+) 0.435 1.055 0.170 0.680 1.545 (0.195, 12.228)
LA(+) 1.072 0.774 1.918 0.166 2.921 (0.641, 13.316)
TM/(IU/mL) 0.282 0.142 3.912 0.048 1.325 (1.003, 1.752)
PT/s 1.418 0.537 6.969 0.008 4.127 (1.441, 11.823)
APTT/s 0.029 0.057 0.256 0.613 1.029 (0.920, 1.152)
FDP/(mg/L) 0.069 0.053 1.705 0.192 1.071 (0.966, 1.187)

Figure 2

ROC curves of the predictive value of age, prothrombin time (PT), and thrombomodulin (TM) for thrombosis diagnosis in patients with antiphospholipid syndrome (APS)"

1 Miyakis S , Lockshin MD , 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 Galli M , Luciani D , Bertolini G , et al. Anti-β2-glycoprotein Ⅰ, antiprothrombin antibodies, and the risk of thrombosis in the antiphospholipid syndrome[J]. Blood, 2003, 102 (8): 2717- 2723.
doi: 10.1182/blood-2002-11-3334
3 Cervera R , Serrano R , Pons-Estel GJ , et al. Morbidity and mortality in the antiphospholipid syndrome during a 10-year period: A multicentre prospective study of 1 000 patients[J]. Ann Rheum Dis, 2015, 74 (6): 1011- 1018.
doi: 10.1136/annrheumdis-2013-204838
4 徐文龙, 沙宇. 血栓分子标志物联合Caprini评分预测创伤性下肢骨折后深静脉血栓形成风险研究[J]. 中国卫生检验杂志, 2023, 33 (2): 245-248, 257.
5 Zhao X , Yang S , Lei R , et al. Clinical study on the feasibility of new thrombus markers in predicting massive cerebral infarction[J]. Front Neurol, 2022, 13, 942887.
6 Tonello M , Mattia E , Favaro M , et al. IgG phosphatidylserine/prothrombin antibodies as a risk factor of thrombosis in antiphospholipid antibody carriers[J]. Thromb Res, 2019, 177, 157- 160.
doi: 10.1016/j.thromres.2019.03.006
7 Schaller J , Gerber SS . The plasmin-antiplasmin system: structural and functional aspects[J]. Cell Mol Life Sci, 2011, 68 (5): 785- 801.
doi: 10.1007/s00018-010-0566-5
8 Salet DM , 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
9 Zhou K , Zhang J , Zheng ZR , et al. Diagnostic and prognostic value of TAT, PIC, TM, and t-PAIC in malignant tumor patients with venous thrombosis[J]. Clin Appl Thromb Hemost, 2020, 26, 1- 10.
10 Wang L , Zhong J , Xiao D , et al. Thrombomodulin (TM), thrombin-antithrombin complex (TAT), plasmin-α2-plasmininhibitor complex (PIC), and tissue plasminogen activator-inhibitor complex (t-PAIC) assessment of fibrinolytic activity in postpartum hemorrhage: A retrospective comparative cohort study[J]. Ann Transl Med, 2022, 10 (23): 1273.
doi: 10.21037/atm-22-5221
11 Loghmani H , Conway EM . Exploring traditional and nontraditional roles for thrombomodulin[J]. Blood, 2018, 132 (2): 148- 158.
doi: 10.1182/blood-2017-12-768994
12 Pletsch-Borba L , Grafetstatter M , Husing A , et al. Vascular injury biomarkers and stroke risk: A population-based study[J]. Neurology, 2020, 94 (22): e2337- e2345.
13 Kamtchum-Tatuene J , Mwangalika Kachingwe G , Mwandumba HC , et al. Endothelial dysfunction and carotid atherosclerosis in Malawian adults: A cross-sectional study[J]. eNeurologicalSci, 2020, 20, 100252.
doi: 10.1016/j.ensci.2020.100252
14 Gosselin RC . An acute need inspiration: Autoneutralization of lupus anticoagulants in affected prothrombin times (PT) and activated partial thromboplastin times (APTT)[J]. Methods Mol Biol, 2023, 2663, 289- 295.
15 Fei Y , Tang N , Zhang H , et al. Significantly prolonged prothrombin time and activated partial thromboplastin time with no bleeding tendency: A patient with lupus anticoagulant-hypoprothrombinemia syndrome positive for immunoglobulin M anti-phosphatidylserine/prothrombin complex antibodies[J]. Semin Thromb Hemost, 2020, 46 (4): 507- 511.
16 Erzen B , Sabovic M . In young post-myocardial infarction male patients elevated plasminogen activator inhibitor-1 correlates with insulin resistance and endothelial dysfunction[J]. Heart Vessels, 2013, 28 (5): 570- 577.
17 Nordenhem A , Leander K , Hallqvist J , et al. The complex between tPA and PAI-1: Risk factor for myocardial infarction as studied in the SHEEP project[J]. Thromb Res, 2005, 116 (3): 223- 232.
18 Winter MP , Kleber ME , Koller L , et al. Prognostic significance of tPA/PAI-1 complex in patients with heart failure and preserved ejection fraction[J]. Thromb Haemost, 2017, 117 (3): 471- 478.
19 Lundbech M , Krag AE , Christensen TD , et al. Thrombin generation, thrombin-antithrombin complex, and prothrombin fragment F1+2 as biomarkers for hypercoagulability in cancer patients[J]. Thromb Res, 2020, 186, 80- 85.
20 Tao J , Guo X , Li D , et al. Increased level of thrombomodulin is associated with endothelial injury in patients with sepsis-induced disseminated intravascular coagulation[J]. Clin Lab, 2021, 67 (8): 1863- 1870.
21 Asanuma K , Nakamura T , Okamoto T , et al. Do coagulation or fibrinolysis reflect the disease condition in patients with soft tissue sarcoma[J]. BMC cancer, 2022, 22 (1): 1075.
22 Guo X , Tao H , Li D , et al. The α2-plasmin inhibitor-plasmin complex is a potential biomarker of venous thromboembolism in orthopedic trauma patients[J]. Clin Lab, 2021, 67 (4): 1065- 1072.
[1] Yu-ke HOU,Qing-meng CAI,Xiang-jun LIU,Ze-lin YUN,Chun LI,Xue-wu ZHANG. Clinical significance of oxidized low-density lipoprotein antibody in antiphospholipid syndrome [J]. Journal of Peking University (Health Sciences), 2022, 54(6): 1117-1122.
[2] Yu-hua WANG,Guo-hua ZHANG,Ling-ling ZHANG,Jun-li LUO,Lan GAO. Adrenal hemorrhage in a patient with systemic lupus erythematosus [J]. Journal of Peking University(Health Sciences), 2019, 51(6): 1178-1181.
[3] Ji LI,Li ZHENG,Lian-jie SHI,Jing XU,Jian-long SHU,Xue-wu ZHANG. Increased serum soluble-endoglin level and its clinical significance in antiphospholipid syndrome [J]. Journal of Peking University(Health Sciences), 2018, 50(6): 1027-1032.
[4] Jie-yu GU,Cui LU,Hui SHI,Cheng-de YANG. Case series and clinical analysis of 14 cases of catastrophic antiphospholipid syndrome [J]. Journal of Peking University(Health Sciences), 2018, 50(6): 1033-1038.
[5] ZHENG Xiao-Juan, DENG Xiao-Li, LIU Xiang-Yuan. Pregnancy outcome in 54 patients with antiphospholipid syndrome：a retrospective clinical study [J]. Journal of Peking University(Health Sciences), 2014, 46(2): 323-328.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!
Copyright © Journal of Peking University (Health Sciences), All Rights Reserved.
Powered by Beijing Magtech Co. Ltd