The Changes of Peripheral Blood FⅫa-AT, TSP-1, LA Ratio in Patients with Systemic Lupus Erythematosus and the Clinical Value of Combined Diagnosis of Thrombotic Events / 中国实验血液学杂志

OBJECTIVE@#To explore the changes of Ⅻ antithrombin (FⅫa-AT), thrombospondin-1 (TSP-1), and lupus anticoagulant (LA) ratio in the peripheral blood factor of patients with systemic lupus erythematosus (SLE) and the clinical value of combined diagnosis of thrombotic events.@*METHODS@#A total of 133 SLE patients treated in Xingtai People's Hospital were selected and divided into simple SLE group (105 cases) and SLE complicated with thrombosis group (28 cases) according to whether thrombotic events occurred, and 102 cases of healthy people in the same period were selected as control. The clinical data of the 3 groups, the level of peripheral blood FⅫa-AT, TSP-1, and LA ratio were compared, the relationship between each peripheral blood index and SLE disease activity index (SLEDAI) score were analyzed. The influencing factors of thrombotic events in SLE patients were analyzed, and the value of each peripheral blood index in the diagnosis of SLE complicated with thrombotic events were evaluated.@*RESULTS@#The proportion of the patients with age ≥60 year, hypertension, and smoking history in SLE complicated with thrombosis group was higher than those in simple SLE group and control group (P＜0.05). The SLEDAI score, peripheral blood FⅫa-AT, TSP-1, LA ratio levels of the patients in SLE complicated with thrombosis group were significantly higher than those in simple SLE group and control group, and the simple SLE group was significantly higher than the control group (P＜0.05). FⅫa-AT, TSP-1, LA ratio in peripheral blood of SLE patients were positively correlated with SLEDAI score (r=0.663, 0.578 and 0.625). Age, blood pressure, smoking history, peripheral blood FⅫa-AT, TSP-1, LA ratio were the important influencing factors of thrombotic events in SLE patients (P＜0.05). The AUC diagnosed by the FⅫa-AT, TSP-1, and LA ratio in peripheral blood was 0.881, the 95% CI was 0.813-0.931, the sensitivity was 82.14%, and the specificity was 91.43%, which was superior to each index alone (P＜0.05).@*CONCLUSION@#Peripheral blood FⅫa-AT, TSP-1, LA ratio level changes in SLE patients are significantly related to disease activity, and the combined diagnosis of thrombotic events is more reliable.

Effect of tirofiban on perioperative thrombotic events in patients with unruptured intracranial aneurysms accepted stent-assisted coil embolization / 中华神经医学杂志

Objective:To investigate the safety of intraoperative prophylactic addition of tirofiban on the basis of preoperative oral administration of aspirin and clopidogrel in patients with unruptured intracranial aneurysms accepted stent-assisted coil embolization, and explore the effect of tirofiban on perioperative thrombotic events.Methods:The clinical data of 275 patients with unruptured intracranial aneurysms who underwent stent assisted coil embolization in our hospital from January 2016 to December 2019 were retrospectively collected. Among them, 110 patients admitted to our hospital from January 2016 to December 2017 only received preoperative oral administration of aspirin and clopidogrel combined with antiplatelet treatment (classic group), and 165 patients admitted to out hospital from January 2018 to December 2019 received intraoperative prophylactic addition of tirofiban on the basis of preoperative oral administration of aspirin and clopidogrel (improved group). The differences of perioperative safety and thrombotic events between the two groups were compared and analyzed.Results:The incidence of intraoperative visual thrombotic events in the classic group and the improved group were 6.4% (7/110) and 1.2% (2/165), respectively, with significant difference ( P<0.05); the incidence of postoperative thrombotic events was 4.5% (5/110) and 2.4% (4/165), respectively, without significant difference ( P>0.05); the incidence of urethrorrhagia was 9.1% (10/110) and 21.2% (35/165), respectively, with significant difference ( P<0.05); and the incidence of gingival hemorrhage was 13.6% (15/110) and 19.4% (32/165), respectively, without significant difference ( P>0.05). No acute gastrointestinal hemorrhage or cerebral hemorrhage occurred in both groups; urethrorrhagia and gingival hemorrhage were transient and relieved spontaneously. Conclusion:Intraoperative prophylactic addition of tirofiban on the basis of preoperative oral administration of aspirin and clopidogrel can reduce the incidence of intraoperative visual thrombotic events without increasing the risk of hemorrhage in stent-assisted coil embolization of unruptured intracranial aneurysms.

Correlation of contact system activation with occurrence of thrombotic events in patients with systemic lupus erythematosus / 中华危重病急救医学

Objective To explore the role of contact system activation in the mechanism of systemic lupus erythematosus (SLE) patients with thrombotic events.Methods A simple sample drawing study was conducted.Sixty-nine patients with SLE admitted to Department of Rheumatism in Tianjin Hospital from June 2014 to February 2016 were enrolled.The patients were divided into simple SLE group (n =38) and SLE + vascular diseases (VD) group (n =31) according to whether the patients complicated with VD or not.The VD patients were subdivided into three subgroups including SLE complicated with myocardial infarction (SLE + MI,n =10),SLE complicated with deep vein thrombosis (SLE + DVT,n =13),and SLE complicated with arterial thrombosis (SLE + AT,n =8).Sixty-eight healthy age and gender-matched volunteers without history of VD were served as controls.Enzyme-linked immunosorbent assay (ELISA) was used to detect the content of FⅫa-C1 inhibitor (FⅫa-C1INH) and FⅫa-antithrombin (FⅫa-AT) in plasma.Flow cytometry was used to analyze the contents of platelets associated factors.The correlation between platelet associated factor and FⅫA-C1INH and FⅫa-AT was analyzed by Spearman correlation analysis.Receiver operating characteristic curve (ROC) was plotted to analyze the predictive value of FⅫA-C1INH and FⅫa-AT for SLE thrombotic events.Results Compared with health control group,the expression of FⅫa-C1INH in plasma in SLE group was significantly decreased [nmol/L:0.00 (0.00,0.07) vs.0.08 (0.03,0.13),P ＜ 0.01],the expression of FⅫa-AT was significantly up-regulated [nmol/L:0.18 (0.07,0.38) vs.0.16 (0.12,0.26),P ＜ 0.05].Compared with the simple SLE group,the expression of FⅫa-C1INH in SLE + DVT and SLE + AT groups was significantly decreased [nmol/L:0.03 (0.02,0.07),0.02 (0.01,0.04) vs.0.07 (0.02,0.11),both P ＜ 0.05],and the expression of FⅫa-AT in plasma in SLE + AT group was significantly increased [nmol/L:0.34 (0.21,0.53) vs.0.17 (0.06,0.30),P ＜ 0.01].It was shown by correlation analysis that FⅫa-C1INH was negatively related with FⅫa-AT in patients with SLE (r =-0.24,P =0.041 6).Activated platelet associated factors such as the production of interferon mediated by transmembrane protein 1 (IFTMI1) and interferon induced by double stranded RNA dependent activation agent (PRKRA) were positively related with up-regulation of FⅫa-AT and down-regulation of FⅫa-C1INH (IFITM1 and FⅫa-AT:r =0.39,P =0.001 2;IFITM1 and FⅫa-C1INH:r =-0.30,P =0.0146;PRKRA and FⅫa-AT:r =0.29,P =0.017 6;PRKRA and FⅫa-C1INH:r =-0.36,P =0.0029).The thrombospondin-1 (TSP-1) and platelet P-selectin were positively related with up-regulation of FⅫa-AT (r1 =0.72,P1 ＜ 0.0001;r2 =0.34,P2 =0.003 8).It was shown by ROC curve analysis that the area under the ROC curve (AUC) for FⅫa-C1INH on evaluating the risk of SLE thrombotic events was 0.998,the sensitivity was 100％,and specificity was 97.4％ when cut-off ＜ 0.01 nmol/L;AUC for FⅫa-AT for evaluating the risk of SLE thrombotic events was 0.954,the sensitivity was 95.0％,and specificity was 84.2％ when cut-off ＞ 0.40 nmol/L;predicted probability of two markers for predicting diagnosis was 0.5,the sensitivity and specificity were both 100％.Conclusions Contact system is activated in patients with SLE.FⅫA-C1INH and FⅫa-AT levels are closely related with platelet associated factors IFITM1 and PRKRA.FⅫA-C1INH and FⅫa-AT can be served as a promising potential biomarker for evaluation of the risk of thrombotic events in SLE.

Prevalence of thrombophilia and thrombotic events in patients with Fabry disease in a reference center for lysosomal disorders in Southern Brazil

Introduction: Venous thromboembolism (VTE) is a multifactorial genetic disorder that occurs in approximately one in a thousand adults per year. Because there is no laboratory test or clinical marker useful for predicting which patients with Fabry disease may develop thrombotic events, this study aimed to determine whether there is a hereditary predisposition to hypercoagulation in these patients. Methods: The prevalence of p.R506Q mutation in the factor V gene and of c.G20210A mutation in Factor II (prothrombin) gene was evaluated in 39 patients with Fabry disease from Southern Brazil and correlated with clinical findings. The DNA analysis was performed by real-time polymerase chain reaction on genomic DNA using TaqMan probes. Results: In this group of patients, the frequency of mutation in the prothrombin gene was 1.28%, whereas no patient showed mutation in the factor V gene; additionally, there was no correlation between these mutations and the incidence of thrombotic events. Conclusion: Hereditary thrombophilia due to mutations in factor V and prothrombin genes does not seem to be related to thrombotic events in Fabry patients in our cohort, although studies in larger cohorts and the inclusion of additional factors may be required to determine if a correlation exists.