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

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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)

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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)"

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