Thrombin Generation in a patient with Triple Positive Antiphospholipid Syndrome Treated with Three Different Anticoagulants

IntroductionVenous and arterial thrombosis is one of the hallmarks of Antiphospholipid Antibody Syndrome (APS). The traditional treatment for individuals with APS and venous thrombosis has been vitamin K antagonists. However, with the widespread use of direct oral anticoagulants (DOACs) there has been conflicting evidence regarding their safety and failure rate as alternatives to warfarin. Reasons for this failure remain elusive. We utilized the thrombin generation assay (TGA) to investigate the anticoagulation efficacy of three different agents in a patient with triple-positive APS to acquire a better understanding of the pathophysiology of APS.MethodsBlood samples were obtained from a single patient with APS at five distinct time points while on three different anticoagulants: rivaroxaban, warfarin, and enoxaparin. The effects of these anticoagulants on TG potential were evaluated using the TGA.ResultsIn the presence of thrombomodulin, rivaroxaban had the highest endogenous thrombin potential, thrombin peak, velocity index, and thrombin inactivation velocity (821.9 nMmin, 121.5 nM, 36.44 nM/min, 7.19 nM/min) when compared to warfarin (121-367 nMmin, 13.85-121.5 nM, 3.02-3.85 nM/min, 0.64-4.55 nM/min) and enoxaparin (242-378.8 nM min, 21.33-23.78 nM, 2.87-3.85 nM/min, 0.747-0.784 nM/min). This trend was also observed in the absence of thrombomodulin.ConclusionsThese results suggest that patients with APS treated with rivaroxaban may be at greater risk for thrombosis compared to warfarin or enoxaparin. The findings may provide insight into the recent studies in patients with triple positive APS randomized to different anticoagulants demonstrating high rates of thrombosis with rivaroxaban. Further studies are necessary to elucidate the clinical significance.     

Nafamostat mesilate improves function recovery after stroke by inhibiting neuroinflammation in rats

Inflammation plays an important role in stroke pathology, making it a promising target for stroke intervention. Nafamostat mesilate (NM), a wide-spectrum serine protease inhibitor, is commonly used for treating inflammatory diseases, such as pancreatitis. However, its effect on neuroinflammation after stroke was unknown. Hence, the effects of NM on the inflammatory response post stroke were characterized. After transient middle cerebral artery occlusion (tMCAO) in rats, NM reduced the infarct size, improved behavioral functions, decreased the expression of proinflammatory mediators (TNF-α, IL-1β, iNOS and COX-2) in a time-dependent manner and promoted the expression of different anti-inflammatory factors (CD206, TGF-β, IL-10 and IL-4) at different time points. Furthermore, NM could inhibit the expression of proinflammatory mediators and promote anti-inflammatory mediators expression in rat primary microglia following exposure to thrombin combined with oxygen–glucose deprivation (OGD). The immune-modulatory effect of NM might be partly due to its inhibition of the NF-κB signaling pathway and inflammasome activation after tMCAO. In addition, NM significantly inhibited the infiltration of macrophage, neutrophil and T lymphocytes, which was partly mediated by the inhibition of monocyte chemotactic protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Taken together, our results indicated that NM can provide long-term protection of the brain against tMCAO by modulating a broad components of the inflammatory response.     

早期凝血酶原活动度对预测慢性乙型肝炎慢加急性肝衰竭预后的价值

目的探讨早期凝血酶原活动度（ PTA）对预测慢性乙型肝炎（ CHB）慢加急性肝衰竭患者预后的价值。方法分析156例CHB相关慢加急性肝衰竭患者3个月的预后,根据临床结局分为生存组和死亡组,分析两组患者在基线、1周及2周时的 PTA 及终末期肝病模型（ MELD）评分的差异,应用受试者工作特征曲线（ ROC曲线）评估基线、1周及2周时的PTA、MELD评分对预后判断的价值。结果在156例患者中有58例死亡,病死率为37.18％。生存组与死亡组患者的PTA （％）比较,在基线、1周及2周时分别为：31.49±7.22 vs 25.44±8.10、37.56±11.72 vs 24.22±11.22及49.28±20.82 vs 23.08±7.43,差异均有统计学意义（ P均＜0.05）;生存组与死亡组患者的MELD评分比较,在基线、1周及2周时分别为：25.53±4.61 vs 28.56±6.39、24.21±4.64 vs 31.07±6.03及20.06±5.06 vs 31.77±6.33,差异均有统计学意义（P均＜0.05）。在基线、1周及2周时PTA、MELD评分的ROC曲线下面积（AUC）比较中,2周时PTA的AUC最大（0.957）,其次为2周时MELD评分的AUC（0.938）,但两者比较差异无统计学意义（P＝0.405）;2周时PTA的最佳临界值为35.55％,敏感度为96.60％,特异度为80.40％。2周时,PTA＜20％的3个月病死率为100％;20％≤PTA＜35％为70.81％;35％≤PTA＜50％为4.17％;PTA≥50％的均存活。 PTA越低,病死率越高,线性趋势检验χ2＝85.70,P＜0.001。结论慢性乙型肝炎慢加急性肝衰竭患者治疗2周时的PTA可作为其3个月预后的早期预测指标。     

Improved Stability of Proline-Derived Direct Thrombin Inhibitors through Hydroxyl to Heterocycle Replacement

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Impact of an autologous oxygenating matrix culture system on rat islet transplantation outcome

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两种不同试剂对SD大鼠血凝四项检测结果的比对

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Current Clinical Practice DIC 2002: A Review of Disseminated Intravascular Coagulation

The turn of the millennium has seen clear advances in the understanding and management of Disseminated Intravascular Coagulation (DIC). The recognition that its pathogenesis stems from sustained thrombin generation in fuelling the cycle between inflammation and coagulation has seen the first successful treatment in severe sepsis through targeting this activity. An advance in treatment brings heightened relevance to laboratory testing, which now emphasises earlier detection and better monitoring to facilitate improved risk-identification and assessment of therapeutic efficacy. This review article also provides insights into future strategies that might build on the foundation of improving prognosis for the patient with DIC.     

急性冠脉综合征患者pentraxin-3与凝血酶活化的纤溶抑制物的变化

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