循环内皮细胞损伤标记物与抗中性粒细胞胞质抗体相关血管炎活动性的联系

目的:探讨外周血液中内皮细胞损伤标记物循环内皮细胞( CECs)数量、可溶性血栓调节蛋白( sTM)、血浆血管性假血友病因子(vWF)、E选择素(ES)和血管细胞黏附分子1(VCAM-1)水平与抗中性粒细胞胞质抗体(ANCA)相关血管炎(AAV)活动性的联系. 方法:84例AAV患者,根据伯明翰评分(BVAS)评估血管炎活动性将其分为活动组(n =56,男性23例,女性33例,平均年龄48.1 ±16.8岁,BVAS评分13.6±2.4分)和缓解组(n =28,男性9例,女性19例,平均年龄50.2±16.4岁,BVAS评分0分).性别、年龄相匹配健康志愿者20例为对照组.免疫磁珠分离方法检测CECs数量,ELISA法检测血浆sTM、vWF、ES和VCAM-1水平,并分别比较三组上述指标的差异. 结果:活动组CECs、sTM、vWF和ES水平均显著高于健康对照组(P＜0.01).缓解组血CECs、sTM、vWF和ES与健康对照组比较无显著差异,活动组和缓解组血浆VCAM-1水平与健康对照组比较均无显著差异.与缓解组比较,活动组CECs[ (30±12)个/ml vs (17:±5)个/ml,P＜0.01]与sTM[ (9.5±6.8)ng/ml vs (6.1±3.4) ng/ml,P＜0.01]水平显著升高,但经血清肌酐(SCr)校正后,两组间sTM水平无显著差异.两组间血浆vWF和ES也无显著差异(P＞0.05).活动组sTM水平与SCr和尿蛋白水平呈正相关性,CECs、vWF、ES和VCAM-1水平与SCr和尿蛋白无相关性. 结论:循环内皮细胞数量与血管炎活动性密切相关,可作为临床判断ANCA相关血管炎活动性的重要指标.     

骨髓间质干细胞对系统性红斑狼疮患者血管内皮细胞损伤模型修复作用的观察

目的 观察骨髓间质干细胞(MSCs)对系统性红斑狼疮(SLE)患者血清刺激后血管内皮细胞中血管假性血友病因子(vWF)和可溶性血栓调理蛋白(sTM)表达的影响,探讨MSCs对SLE血管内皮损伤后修复的可能作用.方法 人脐静脉内皮细胞株ECV-304和活动期SLE患者血清体外共培养12 h,诱导血管内皮细胞损伤,加入MSCs继续共培养3 d.采用酶联免疫吸附试验(ELISA)法检测上清液中vWF和sTM的表达.结果 SLE血清刺激ECV-304细胞后,上清液中vWF和sTM的表达显著高于未刺激组(P＜0.05)[(30.1±6.1)ng/ml vs(10.2±3.1)ng/ml;(2.41±0.16)vs(1.19±0.14)];加入MSCs后,能显著降低vWF的表达(P＜0.05)[(2.41±0.16)vs(2.19±0.14)],但是对sTM值无明显影响(P＞0.05)[(30.1±6.1)ng/ml vs(26.2±6.0)ng/ml].结论 活动期SLE患者血清可损伤血管内皮细胞,MSCs能降低血管内皮细胞中vWF表达,提示可能对SLE血管内皮损伤有一定的修复作用.     

血栓调节蛋白检测在狼疮性肾炎血管病变中的意义

目的：探讨狼疮性肾炎(LN)患者血浆可溶性血栓调节蛋白(sTM)水平和肾组织TM免疫组化染色特点，分析其与系统性红斑狼疮活动度(SLEDAI)、血管病变、肾功能、蛋白尿、肾组织病理类型之间的关系。方法：60例经肾穿刺活检明确诊断的LN患者，采用酶联免疫吸附法(ELISA)检测血浆sTM水平，免疫组化染色检测肾小球和间质血管TM的表达。结果：Ⅱ型LN患者血浆sTM水平与正常对照组相近，Ⅳ型LN患者血浆sTM水平显著高于Ⅱ型LN；而合并有血栓性微血管病变的LN患者血浆sTM水平显著高于Ⅳ型LN，血浆sTM水平与狼疮的病变活动度和血清肌酐水平呈正相关，与蛋白尿多少无关。肾组织TM免疫组化染色示Ⅳ型LN肾小球与血管TM染色强度强于Ⅱ型LN；合并血栓性微血管病变LN患者肾小球与血管TM的染色强度与Ⅳ型LN相似。结论：血浆sTM水平与SLEDAI、血管病变轻重、肾功能损害程度及肾组织病变类型有关。肾小球和肾间质血管的TM表达强度与LN病理类型有关，但不能反映血管病变的轻重。血浆sTM水平不仅反映SLE疾病活动性，而且与LN的血管病变严重程度有关。血浆sTM水平可作为LN血管病变程度的指标，为指导治疗、判断预后提供依据。     

局灶节段性肾小球硬化患者内皮细胞功能异常及临床意义

目的:前瞻性观察局灶节段性肾小球硬化(FSGS)患者的内皮细胞功能及其与疾病活动程度和并发症的关系。方法:63例经肾活检及临床确诊且蛋白尿≥3.5g/d的特发性FSGS患者进入本研究,选取年龄、性别相匹配的32例健康志愿者作对照。分析内皮细胞损伤指标循环内皮细胞计数(CECs)、血管性血友病因子(vWF)、可溶性血栓调节蛋白(sTM)、血管细胞粘附分子(VCAM)和E选择素(ES)的阳性率,观察起点内皮细胞损伤指标与其他临床指标及静脉血栓栓塞(VTE)并发症的关系,观察内皮细胞损伤指标的动态变化。结果:(1)FSGS患者的各项内皮细胞损伤指标均显著高于正常对照组。(2)无VTE的52例患者内皮细胞损伤指标的阳性率分别为CECs48.1%、vWF92.3%,sTM96.2%,VCAM67.3%,ES28.9%,其中VCAM阳性患者的血压水平、尿蛋白定量、血肌酐水平及肾小管损伤指标NAG酶、RBP均显著高于阴性者,CECs及ES阳性与阴性患者各项指标间无明显差异。相关性分析显示,sTM、VCAM与SCr显著正相关,VCAM、vWF与NAG、RBP均有正相关性。随访2月时15例达完全缓解(CR),13例部分缓解(PR),15例无效(NR),8例失随访,1例进入腹膜透析治疗退出本研究。CR组治疗后sTM、VCAM均明显下降,而vWF、ES水平变化不明显,PR组治疗前后相比sTM明显下降,余三项指标变化无统计学意义,NR组治疗前后各项内皮损伤指标均无明显变化。随访1年期间11例患者获得持续缓解,该组患者各观察点ES水平与正常对照组均无明显差异,sTM于随访2月时即降至正常,VCAM、vWF分别于随访2月、6月时开始下降,随访12月时仍高于正常对照。(3)合并VTE者CECs、vWF水平显著高于无VTE者。结论:FSGS患者存在明显内皮细胞功能异常,其中VCAM及CECs水平的异常升高分别与疾病的活动程度及血栓栓塞并发症的发生关系密切,随疾病的缓解内皮细胞功能得以不同程度的改善。内皮细胞损伤标志物的检测有助于对FSGS患者的病情及血栓栓塞并发症进行评估。     

血浆血管性血友病因子水平与冠状动脉病变的关系

目的:测定血浆血管性血友病因子(vWF)浓度,探讨血浆vWF水平与冠状动脉病变之间的关系。方法:根据冠状动脉造影结果选择冠心病患者78例,分为单支病变组、双支病变组、多支病变组,测定其血浆vWF水平,并与冠状动脉病变积分作相关分析。同时选非冠心病患者29例作为正常对照组。结果:冠心病组血浆vWF水平较正常对照组血浆vWF水平明显升高,(181.24±26.56)%∶(157.11±26.63)%,P<0.01;多支病变组较单支病变组、双支病变组的血浆vWF水平明显升高,(195.52±26.57)%∶(165.24±26.90)%、(180.54±18.58)%,P分别<0.01、<0.05;双支病变组较单支病变组的血浆vWF水平也明显升高(P<0.05),对照组与单支病变组的血浆vWF水平无差异。血浆vWF水平与冠状动脉病变积分呈正相关(r=0.702,P<0.01)。结论:血浆vWF水平可较好反映冠心病患者血管内皮功能损伤程度和冠状动脉病变范围。     

天麻素对心肺转流患者血管内皮细胞损伤的保护作用

目的探讨天麻素对心肺转流（CPB）全身性血管内皮细胞（VEC）急性损伤的保护作用。方法30例心血管择期手术患者随机分为两组,观察组CPB过程中给予天麻素,对照组CPB过程中给予生理盐水。动态监测两组患者血浆可溶性血栓调节蛋白（sTM）、血管性假血友病因子（vWF）、内皮素-1（ET-1）和NO的变化。结果两组患者血浆sTM、vWF和ET-1在CPB期间和术后1 d均显著增高,NO在CPB期间和术后1 d均显著下降,对照组较观察组变化明显,且观察组各指标于术后3 d恢复到术前水平,对照组未能恢复。结论天麻素可以减轻CPB导致的VEC损伤。     

不同分期2型糖尿病患者血浆vWF水平变化及与血液流变学指标的相关性

目的 探讨血浆血管性血友病因子(vWF)水平变化在2型糖尿病(T2DM)疾病进展中的作用.方法 对143例不同分期 T2DM患者(观察组)和30例健康查体者血浆vWF水平进行了测定,并分析其与血液流变学指标的相关性.结果 观察组各期血浆vWF水平及血液流变学指标均显著高于对照组,且随病程进展呈进行性升高;血浆vWF水平与血液流变学各指标均呈显著正相关.结论 血浆vWF水平升高可能在T2DM病情进展中起重要作用;监测血浆vWF水平和血液流变学指标对于T2DM慢性微血管病变、血管动脉粥样硬化的预防及早期诊治具有重要意义.     

系统性红斑狼疮患者血浆IL-17和IL-23的表达及意义

目的探讨IL-17和IL-23在系统性红斑狼疮(SLE)患者血浆中的表达水平及其临床意义。方法收集诊断明确的SLE患者33例,根据SLE疾病活动指数(SLEDAI)评分随机分为活动组和非活动组,根据肾脏受累与否分为肾炎组和非肾炎组,以性别和年龄相匹配的28例健康体检者作为对照组,采用ELISA法检测血浆中IL-17和IL-23的表达水平。结果活动组患者血浆IL-17和IL-23水平明显高于对照组(P均<0.01),亦高于非活动组(P<0.05或<0.01),但二者在SLE非活动组与对照组间及肾炎组与非肾炎组间差异无统计学意义;SLE患者血浆IL-17和IL-23水平与SLEDAI评分呈正相关(r分别为0.39、0.60,P<0.05或<0.01)。结论 IL-17和IL-23在活动期SLE患者血浆中表达明显增高,二者可能参与了SLE疾病的病理过程,且与疾病的活动性关系密切。     

果糖二磷酸钠片联合脑蛋白水解物对老年急性脑梗死病人血管内皮损伤和神经功能恢复的影响

目的探讨果糖二磷酸钠片联合脑蛋白水解物对老年急性脑梗死病人血管内皮损伤和神经功能恢复的影响。方法选择2015年2月—2017年2月我院接诊的96例老年急性脑梗死病人,通过随机数字表法分为观察组(n=48)和对照组(n=48);在常规治疗基础上,对照组使用脑蛋白水解物治疗,观察组联合使用果糖二磷酸钠片,两组均连续治疗14 d。比较治疗前后血液流变学、血清血管性血友病因子(vWF)、血栓调节蛋白(sTM)、美国国立卫生研究院卒中量表(NIHSS)的变化,并比较临床疗效。结果治疗后,两组血细胞比容、纤维蛋白原、全血黏度、血浆黏度较治疗前均显著降低(P0.05),观察组血红细胞比容、纤维蛋白原、全血黏度、血浆黏度明显比对照组低(P0.05);治疗后,两组血清vWF、sTM较治疗前比较均显著降低(P0.05),观察组血清vWF、sTM明显比对照组低[(110.23±15.64)%与(136.84±17.45)%,(23.72±2.63)μg/L与(31.88±3.09)μg/L,P0.05)];治疗后,两组NIHSS评分较治疗前比较均显著降低(P0.05),观察组NIHSS评分明显比对照组低[(9.83±1.02)分与(12.14±1.27)分,P0.05];观察组临床疗效总有效率明显比对照组高(85.42%与62.50%,P0.05)。结论老年急性脑梗死病人应用果糖二磷酸钠片联合脑蛋白水解物效果显著,可有效缓解血管内皮损伤,促进神经功能恢复,临床应用价值高。     

系统性红斑狼疮患者血浆血管假性血友病因子和内皮素水平

系统性红斑狼疮（SLE）是一种以免疫复合物介导的血管炎为基本病理改变的系统性自身免疫病，其病因和发病机制尚未阐明。本研究通过检测SLE患者血浆血管假性血友病因子（vWF）和内皮素（ET）水平，分析二者与SLE疾病活动程度的关系。     

Persistent increase in plasma thrombomodulin in patients with a history of lupus nephritis: endothelial cell activation markers

OBJECTIVE: To investigate the presence of continuing endothelial cell activation in patients with systemic lupus erythematosus (SLE) and its relationship with lupus nephritis. METHODS: We measured plasma concentrations of soluble thrombomodulin (sTM), vascular cellular adhesion molecule-1 (sVCAM-1), von Willebrand factor (vWf), sP-selectin, and ED1-fibronectin in 75 SLE patients with a median SLE disease activity index (SLEDAI) of 4. Forty patients with a history of lupus nephritis, confirmed by renal biopsy in 33, were compared with 35 patients without lupus nephritis and 25 controls. For subgroup analysis in patients with clinically stable remission we excluded patients with a SLEDAI > 6 or with evidence of renal disease activity. RESULTS: In the total SLE patient group sTM, sVCAM-1, vWf, and sP-selectin were significantly elevated compared with controls. In patients with a history of lupus nephritis plasma levels of sTM and vWf were significantly increased compared with SLE patients without nephritis. After adjustment for significantly associated variables, especially creatinine clearance and age, in a multivariate linear regression analysis, sTM remained significantly elevated in patients with a history of lupus nephritis (difference 28.9 ng/ml, 95% CI 11.5-46.4). In the subgroup analysis of 57 patients, the results remained unchanged. CONCLUSION: The increase of sVCAM-1, sP-selectin, sTM, and vWf reflects a state of persistent endothelial cell activation. Multivariate regression analysis shows that the elevated sTM levels are strongly associated with a history of lupus nephritis, independent of creatinine clearance or disease activity, suggesting endothelial cell activation specifically localized in the kidneys.     

Elevated plasma concentrations of nitric oxide,soluble thrombomodulin and soluble vascular cell adhesion molecule-1 in patients with systemic lupus erythematosus

OBJECTIVE: To investigate the correlations among plasma concentrations of nitric oxide (NO), soluble thrombomodulin (sTM) and vascular cell adhesion molecule (sVCAM-1), and whether these three molecules are associated with renal involvement in patients with systemic lupus erythematosus (SLE). METHODS: Plasma NO concentrations of 73 SLE patients (35 with renal disease, RSLE patients; 38 without renal disease, SLE patients) and 28 age- and sex-matched healthy control subjects were measured by the non-enzymatic Griess assay, and sTM and sVCAM-1 by enzyme-linked immunosorbent assay. RESULTS: In RSLE patients, plasma nitrite concentrations were significantly higher than in control subjects (P=0.009) and correlated positively with plasma sTM, plasma creatinine and urea (all P<0.05). Plasma sTM and sVCAM-1 concentrations were significantly elevated in RSLE and SLE patients (both P<0.0001) compared with controls. Plasma sTM was significantly correlated with plasma sVCAM-1, and both were correlated with plasma creatinine and urea and the SLE Disease Activity Index (all P<0.05). CONCLUSION: Elevated plasma NO, sTM, and sVCAM-1 concentrations have significant intercorrelations and are strongly associated with renal involvement in SLE.     

Effect of disease activity and corticosteroids on serum levels of soluble endothelial cell protein C receptor in patients with systemic lupus erythematosus

To assess the effects of disease activity of systemic lupus erythematosus (SLE) and high-dose corticosteroids on endothelial injuries, the significance of soluble endothelial cell protein C receptor (sEPCR) and soluble thrombomodulin (sTM) was analyzed. Serum levels of sEPCR and sTM were measured by enzyme-linked immunosorbent assay (ELISA) cross-sectionally in 97 SLE patients, 49 patients with other rheumatic diseases and 22 normal subjects. The changes in these levels upon corticosteroid treatment were also analyzed in 41 patients. The levels of sEPCR and sTM were both higher in SLE and other rheumatic disease patients than in normal subjects. When low-dose corticosteroids were used, both the level of sEPCR and the ratio of positive tests for sEPCR were significantly higher in active SLE patients than in inactive patients [median 2.30 ng/ml (range 0.00–147.10 ng/ml) vs 0.00 ng/ml (0.00–58.90 ng/ml) and 53.5 vs 13.0%, respectively] (P < 0.005). Moreover, the ratio of positive tests for sEPCR was higher after corticosteroid treatment in 9 of 19 (47.3%) SLE patients compared to other rheumatic diseases (3/22; 13.6%). Although the mean level of sTM was significantly higher in active SLE patients than in inactive patients, the ratio of positive tests for sTM was not affected by disease activity or corticosteroids. In conclusion, the positive test for sEPCR is a more sensitive biomarker than that for sTM in reflecting endothelial injuries caused by active disease and often by corticosteroids in SLE.     

A cross-sectional and diurnal study of thrombogenesis among patients with chronic atrial fibrillation

OBJECTIVES

First, we sought to determine whether there is diurnal variation in hemostatic factors related to thrombogenesis and hypercoagulability among patients with chronic atrial fibrillation (AF). Second, we sought to determine whether levels of soluble thrombomodulin (sTM), a marker of endothelial function, or soluble P-selectin (sP-sel), an index of platelet activation, are altered in patients with AF as compared with subjects in sinus rhythm.

BACKGROUND

Atrial fibrillation is associated with an increased risk of stroke and thromboembolism and is known to confer a hypercoagulable state, with abnormalities of thrombosis, platelet activation and endothelial cell function. Many cardiovascular events, such as acute myocardial infarction, have thrombosis as an underlying process, and they undergo diurnal variation.

METHODS

Fifty-two patients (45 men, mean [±SD] age 66 ± 6 years) with chronic AF, none of whom received antithrombotic therapy, were studied. Baseline levels of fibrinogen, sP-sel, sTM and von Willebrand factor (vWF) were compared to those levels in matched healthy control subjects in sinus rhythm. In a subgroup of 20 patients, five venous blood samples were collected through an indwelling cannula at 6-h intervals from 12 to 12 the following day and were analyzed for the same markers.

RESULTS

Patients with chronic AF had higher plasma sP-sel, sTM, vWF and fibrinogen levels as compared with control subjects in sinus rhythm. Significant correlations were found between fibrinogen and sP-sel in patients with AF (r = 0.567 [Spearman], p < 0.001) and in control subjects (r = 0.334, p = 0.016). There was no significant diurnal variation in plasma levels of sP-sel, sTM, vWF or fibrinogen over the 24-h study period (repeated measures analysis of variance, p = NS).

CONCLUSIONS

There is no circadian or diurnal variation in the hypercoagulable state seen in AF, as assessed by plasma fibrinogen and markers of platelet (sP-sel) and endothelial function (vWF and sTM). The persistent hypercoagulable state, together with the loss of diurnal variation in various hemostatic markers, in chronic AF may contribute to the high risk of stroke and thromboembolic complications in these patients.     

Clinical significance of selected endothelial activation markers in patients with systemic lupus erythematosus

OBJECTIVE: Systemic lupus erythematosus (SLE) is an autoimmune disease in which immunologically mediated vascular endothelial cell activation is regarded as a potential pathophysiological mechanism of systemic organ damage. We investigated selected endothelial cell activation markers in serum of patients with SLE and their relationships with systemic organ manifestations and disease activity. METHODS: Serum levels of endothelin-1 (ET-1), soluble E-selectin, and thrombomodulin (sTM) were determined by ELISA in 76 SLE patients and in 34 healthy controls. RESULTS: Higher serum concentrations of ET-1, sE-selectin (p < 0.05), and sTM (p < 0.001) were observed in SLE patients in comparison with controls. Significant differences of ET-1, (p < 0.01), sTM (p < 0.001), and sE-selectin serum concentrations (p < 0.01) were found between SLE patients with systemic involvement and controls. Patients with organ manifestations (n = 34) showed significantly higher serum levels of ET-1 than patients without systemic involvement (n = 42) (p < 0.05). Comparison between patients with active and inactive SLE according to SLE Disease Activity Index (SLEDAI) score showed significantly higher concentration of ET-1 in the sera of patients with active SLE compared with inactive patients and the controls (p < 0.001). CONCLUSION: Our findings suggest that the elevated serum concentrations of ET-1, sTM, and sE-selectin reflect persisting endothelial cell activation in SLE, and point to an important role of ET-1 in the pathogenesis of internal organ involvement. Moreover, elevated ET-1 concentrations are related to disease activity, suggesting a key role of endothelial cell activation in systemic manifestations in SLE patients.     

Effects of hyperinsulinemia on plasma levels of circulating adhesion molecules

Plasma levels of circulating intercellular adhesion molecule-1 (cICAM-1), a potential cardiovascular risk factor, are increased in diabetics. Among other factors, hyperinsulinemia has been proposed to enhance its release into the circulation. Thus, we directly examined the effects of insulin infusion on plasma levels of circulating adhesion molecules, and two other endothelial markers, i.e. von Willebrand factor (vWF) and soluble thrombomodulin (sTM). The study design was balanced, randomized, placebo-controlled, double blind, and cross-over. Twelve healthy male subjects received, on separate study days, a euglycemic hyperinsulinemic clamp (3 mU/kg x min) or placebo over 6 h. Plasma levels of cICAM-1, vascular cell adhesion molecule-1, circulating E-selectin, and sTM were measured by enzyme immunoassay; vWF-Ag was measured using a STA clot analyzer. Plasma levels of these adhesion molecules and endothelial cell activation markers were not affected despite a 30-fold increase in insulin levels. Hyperinsulinemia has no adverse effect on circulating ICAM-1, vascular cell adhesion molecule-1, E-selectin, vWF, or sTM and therefore does not directly induce endothelial activation.     

Soluble E-selectin, von Willebrand factor, soluble thrombomodulin, and total body nitrate/nitrite product as indices of endothelial damage/dysfunction in paroxysmal, persistent, and permanent atrial fibrillation

BACKGROUND: Atrial fibrillation (AF) is associated with a prothrombotic state, which is related to endothelial damage/dysfunction. Plasma levels of soluble E-selectin (sE-sel), von Willebrand factor (vWf), and soluble thrombomodulin (sTM) have been used as indexes of endothelial activation, damage/dysfunction, and endothelial damage, respectively. Nitric oxide is also made by a healthy endothelium, and a total body nitrate/nitrite product (NOx) is used as a measure of endothelial nitric oxide production. We hypothesized that the levels of these markers of endothelial function would be abnormal in patients with paroxysmal, persistent, and permanent AF. METHODS: We studied 145 AF patients (paroxysmal AF, 35 patients; permanent AF, 50 patients; persistent AF, 60 patients) and 35 patients with "lone" AF. Plasma levels of sE-sel, vWf, and sTM (measured by enzyme-linked immunosorbent assay) and NOx (measured by a colorimetric assay based on the Griess reaction) were compared to 40 age-matched healthy control subjects in sinus rhythm. RESULTS: Patients with AF had significantly higher plasma levels of vWf (p < 0.001) and sE-sel (p = 0.005) compared with control subjects, but sTM and NOx levels were not significantly different. Levels did not differ significantly among the clinical subgroups of patients with paroxysmal, persistent, and permanent AF. Patients with lone AF had significantly higher vWF levels (p = 0.003) and significantly lower sTM levels (p = 0.0361) compared to control subjects, but sE-sel and NOx levels were not significantly different. There were no significant differences in the AF study population in vWF, sE-sel or sTM levels after 4 weeks of warfarin treatment. CONCLUSION: Endothelial perturbation exists in all clinical subgroups of patients with AF, including those with lone AF, which may contribute to the prothrombotic state seen in these patients.     

Clinical significance of von Willebrand factor in patients with adult dermatomyositis

Because the clinical significance of von Willebrand factor (vWF), a marker of endothelial injury, has not been well studied in adult patients with dermatomyositis (DM), we evaluated whether plasma vWF levels are useful as an index of disease activity in these patients. We measured plasma vWF antigen levels in 11 patients with active adult DM, 13 patients with inactive DM, and 18 healthy subjects using an enzyme-linked immunosorbent assay. The association of vWF level with clinical condition and muscle-derived enzyme leakage among DM patients was examined using analysis of covariance and logistic regression analysis. Furthermore, we studied the effects of treatment on the vWF antigen level. The mean vWF antigen level was significantly higher in active DM patients than in inactive DM patients and healthy subjects. Higher vWF levels were associated with clinical symptoms, such as general fatigue, fever, and muscle weakness. They were also associated with the levels of aspartate aminotransferase, alanine aminotransferase, and aldolase, but not with those of lactate dehydrogenase and creatine kinase (CK). vWF antigen was correlated with muscle enzymes except for CK. The plasma vWF levels in six patients with active DM significantly decreased after successful corticosteroid treatment. Plasma vWF level may be considered a useful marker of disease activity in adult DM patients.     

Clinical significance of hemostatic markers and thrombomodulin in systemic lupus erythematosus: evidence for a prothrombotic state

Systemic lupus erythematosus (SLE) is a systemic autoimmune disorder with overwhelming thrombotic states. The precise pathogenetic mechanisms underlying the prethrombotic state in SLE is not fully understood, but interactions between the antiphospholipid antibodies and antigen targets on the coagulation components have been incriminated to play fundamental roles. To evaluate this issue, 34 women with antiphospholipid antibody negative SLE were investigated for molecular markers of blood coagulation and fibrinolytic activity: prothrombin fragment1+2 (PF1+2), thrombin-antithrombin complex (TAT), plasmin-alpha2-antiplasmin inhibitor complex (PAP), and tissue factor pathway inhibitor (TFPI). We also analysed plasma soluble thrombomodulin (sTM) levels. SLE disease activity was determined using the SLE Disease Activity Index (SLEDAI). Concentrations of TAT, PAP, PF1+2 and sTM were significantly elevated (P<0.0001, P=0.0002, P<0.0001, and P<0.0001, respectively), while TFPI antigen levels were found to be reduced (P<0.0001) in patients with SLE compared to the control group. In patients with active SLE, anti-ds DNA levels were correlated positively with plasma TAT (P<0.05), PF1+2 (P<0.05), and sTM (P<0.01) concentrations and negatively with plasma TFPI levels (P<0.05). SLEDAI scores were correlated positively with plasma TAT (P<0.01), PF1+2 (<0.01), and sTM (P<0.01) levels. This study illustrates that both a prethrombotic state and a compensatory fibrinolytic process secondary to subclinical intravascular coagulation might coexist in SLE with elevated sTM levels, indicating impaired endothelial functions.