卡托普利对动脉损伤后内膜增生时纤溶系统的影响

目的　通过兔颈总动脉球囊损伤模型 ,观察卡托普利 (开搏通 ,captopril)对动脉球囊损伤后内膜增生时纤溶系统的影响。方法　以兔右颈总动脉内膜剥脱为实验模型 ,36只兔随机分为假手术组 (对照组 )、单纯损伤组、损伤 +药物治疗组 (简称药物治疗组 ) ,每组各 12只。药物治疗组术前1d至术后 30d给予captopril2mg·kg 1 ·d 1 ,余二组不给药 ,用ELISA法检测各组术前、术后 1、3、7、14、30d的血浆组织纤溶酶原激活剂 (t PA)、纤溶酶原激活剂抑制物 1(PAI 1)的水平 ,并于术后 30d行病理形态学观察各组血管内膜厚度及管腔狭窄度。结果　动脉球囊损伤后 ,药物治疗组PAI 1水平、内膜的厚度及管腔狭窄度均明显低于单纯损伤组。结论　血管球囊损伤术后纤溶系统作用的减弱影响动脉壁损伤再修复过程 ,captopril可使纤溶系统保持平衡 ,预防血管成形术后再狭窄。     

中老年冠心病患者血浆t-PA、PAI活性变化的探讨

本文对55例各临床类型冠心病患者血浆t-PA、PAI活性进行了初步探索,并与正常对照组对比。结果表明:各组患者血浆t-PA活性均明显低于正常对照组,其中心绞痛和急性心肌梗塞(AMI)组降低更为显著、但此二组的血浆PAI活性明显高于正常对照组;各组患者血浆t-PA/PAI比值均明显低于正常对照组。与心绞痛 AMI组相比:心律失常、心衰、陈旧性心梗组的血浆t-PA活性及t-PA/PAI均明显增高,但血浆PAI活性均明显减低。心绞痛 AMI组的血浆t-PA活性及t-PA/PAI与年龄有明显负相关,提示血浆t-PA、PAI活性异常在冠心病、心绞痛和AMI的发生、发展中可能有重要的病理意义。     

Increased heparanase level and procoagulant activity in orthopedic surgery patients receiving prophylactic dose of enoxaparin

Background

Orthopedic hip and knee surgeries are followed by a hypercoagulable state. Heparanase is implicated in inflammation, coagulation activation and angiogenesis. Recently, heparanase was shown to directly interact with tissue factor (TF) and to enhance the generation of factor Xa (Nadir et al., Haematologica, 2010). In addition, an assay assessing heparanase procoagulant activity has been lately developed (Nadir et al., Thromb Res, 2011). In the present study heparanase level and procoagulant activity in patients undergoing orthopedic surgery were assessed.

Methods

The study group included 50 orthopedic patients. 31 patients underwent hip surgery and 19 had knee operation. 15 individuals suffered from traumatic hip fractures and 35 had osteoarthrosis of hip or knee joints. All patients received prophylactic dose of enoxaparin starting 6-8 hours post operation and lasting for 5 weeks. Plasma samples were drawn preoperatively and at 1 hour, 1 week and 1 month post operation. Samples were tested for heparanase levels by ELISA and TF/heparanase complex activity, TF activity, heparanase procoagulant activity, factor Xa and thrombin levels using chromogenic substrates.

Results

Heparanase levels were significantly higher 1 hour and 1 week post operatively compared to preoperative levels (p < 0.05, p < 0.005, respectively). The most dramatic changes were observed in heparanase procoagulant activity reaching a 2 fold increase 1 week postoperatively and 1.7 fold increase 1 month after surgery (p < 0.0001, p < 0.0001, respectively). Levels of factor Xa and thrombin did not significantly change.

Conclusions

Heparanase is involved in coagulation activation of orthopedic surgery patients. Heparanase procoagulant activity is highest 1 week postoperatively and remains high 1 month after operation. Considering extending prophylactic anticoagulant therapy or evaluating heparanase procoagulant activity may potentially prevent late thrombotic events.     

Efficacy and safety of clopidogrel in children with diarrhea associated hemolytic uremic syndrome

Introduction

Hemolytic uremic syndrome is a thrombotic microangiopathy. Clopidogrel, a recently developed platelet aggregation inhibitor, has not been previously reported as a treatment for this illness. Our study's objective was to explore the efficacy and safety of clopidogrel in children with diarrhea associated hemolytic uremic syndrome.

Materials and Methods

We performed a retrospective chart review of all children (≤ 18 years) hospitalized with diarrhea associated hemolytic uremic syndrome. Outcomes in clopidogrel treated children were described. In subgroup analysis, outcomes were compared to those untreated with platelet aggregation inhibitors.

Results

Of 72 children with diarrhea associated hemolytic uremic syndrome, 88% were treated with platelet aggregation inhibitors (clopidogrel 56%, sulfinpyrazone 19%, dipyridamole 13%). The median age of clopidogrel treated children was 5 years; 40% were male. Initial median hemoglobin, platelet count, and serum creatinine were 10.1 g/dL, 53 × 10³/μL, and 2.3 mg/dL respectively. Clopidogrel (median dose 1 mg/kg/d) was given for a median of 4 days (range 1-15). Other therapies included erythropoietin (98%), red blood cell transfusions (80%), diuretics (58%), anti-hypertensive agents (45%), and dialysis (33%). The median hospital length of stay was 9 days (range 3-26). Three children had bleeding complications (epistaxis/hematemesis). The risk of chronic kidney disease was 5% and death 2.5%. In subgroup analysis, median duration of dialysis was 11 days in thirteen clopidogrel treated children compared to 21 days in five untreated patients (P = 0.04).

Conclusions

Children with diarrhea associated hemolytic uremic syndrome treated with clopidogrel have outcomes comparable to untreated patients. Bleeding complications may occur.     

PAI-1 promotes the accumulation of exudate macrophages and worsens pulmonary fibrosis following type II alveolar epithelial cell injury

Fibrotic disorders of the lung are associated with perturbations in the plasminogen activation system. Specifically, plasminogen activator inhibitor‐1 (PAI‐1) expression is increased relative to the plasminogen activators. A direct role for this imbalance in modulating the severity of lung scarring following injury has been substantiated in the bleomycin model of pulmonary fibrosis. However, it remains unclear whether derangements in the plasminogen activation system contribute more generally to the pathogenesis of lung fibrosis beyond bleomycin injury. To answer this question, we employed an alternative model of lung scarring, in which type II alveolar epithelial cells (AECs) are specifically injured by administering diphtheria toxin (DT) to mice genetically engineered to express the human DT receptor (DTR) off the surfactant protein C promoter. This targeted AEC injury results in the diffuse accumulation of interstitial collagen. In the present study, we found that this targeted type II cell insult also increases PAI‐1 expression in the alveolar compartment. We identified AECs and lung macrophages to be sources of PAI‐1 production. To determine whether this elevated PAI‐1 concentration was directly related to the severity of fibrosis, DTR⁺ mice were crossed into a PAI‐1‐deficient background (DTR⁺: PAI‐1^?/?). DT administration to DTR⁺: PAI‐1^?/? animals caused significantly less fibrosis than was measured in DTR⁺ mice with intact PAI‐1 production. PAI‐1 deficiency also abrogated the accumulation of CD11b⁺ exudate macrophages that were found to express PAI‐1 and type‐1 collagen. These observations substantiate the critical function of PAI‐1 in pulmonary fibrosis pathogenesis and provide new insight into a potential mechanism by which this pro‐fibrotic molecule influences collagen accumulation. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.