Enhanced fibrinolytic activity during cardiopulmonary bypass in open-heart surgery in man is caused by extrinsic (tissue-type) plasminogen activator

The nature of the enhanced blood fibrinolytic activity which is known to occur during cardiopulmonary bypass is not understood. We show here that the cause is an increase in extrinsic (tissue-type) plasminogen activator. In six patients, the nature of the enhanced blood fibrinolytic activity that evolved during cardiopulmonary bypass was characterized by differential inhibition using the fibrin plate method and was shown to be C1-inactivator-resistant (extrinsic-activator activity). The C1-inactivator-resistant-activator activity was completely quenched by an antibody against extrinsic (tissue-type) plasminogen activator but not by antiurokinase, proving that the activity was due to the presence of extrinsic (tissue-type) plasminogen activator. The concentration of extrinsic (tissue-type) plasminogen activator increased during cardiopulmonary bypass and disappeared rapidly thereafter. Fibrinogen, plasminogen and alpha 2-antiplasmin were not consumed during cardiopulmonary bypass, while no increase or occasionally a moderate one in fibrinogen degradation products occurred. This is in accord with the property of extrinsic (tissue-type) plasminogen activator which activates plasminogen predominantly at sites where fibrin is present and not in the free circulation.     

Predictive Value of Inflammatory and Coagulation Parameters in the Course of Severe Ulcerative Colitis

Alterations in markers of coagulation have been found in patients with inflammatory bowel disease. Our aim was to study the predictive value of coagulation and inflammatory parameters in the course of severe ulcerative colitis. Twenty-seven patients were included. The disease course was followed for one year. Sensitivity, specificity, negative predictive value, positive predictive value, and likelihood ratio, as well as the clinical predictive value of laboratory variables were calculated. Inflammatory variables, such as ESR, CRP, and leukocyte and platelet count showed poor diagnostic accuracy. Several coagulation parameters, such as fibrinogen and fibrin(ogen) degradation products, were increased in patients with active ulcerative colitis, whereas coagulation factor XIII was decreased. No significant relationship between clinical course and coagulation parameters was demonstrated, though both inflammatory and coagulation parameters were useful in the assessment of disease activity in patients with active ulcerative colitis.     

TAFI polymorphisms at amino acids 147 and 325 are not risk factors for cerebral infarction

Thrombin-activatable fibrinolysis inhibitor (TAFI) was reported as an anaphylatoxin-inactivating enzyme generated by proteolytic cleavage of its zymogen, and is the same enzyme as that first designated by our group as procarboxypeptidase R (proCPR). Its level in plasma appears to influence vascular disease. In addition, TAFI activity is strongly influenced by genetic polymorphism, especially at amino acids 147 and 325. We investigated whether these TAFI polymorphisms would act as a risk factor for cerebral infarction (CI) by examining 253 samples in which the diagnosis was cliniconeuropathologically confirmed. We found little that was statistically significant in terms of these polymorphisms among patients with no vascular problems or in a population-based control group. In the present study of an elderly Japanese group, our samples revealed a lower percentage of the Ile allele at Thr/Ile-325 compared with western counterparts. Although patients with severe infarcts had a lower percentage of the Ile allele (10%) at amino acid position 325 compared with the slightly and moderately affected patients and the population-based control group (15-18%), no statistical significance was found. None of our results showed any statistical correlation between TAFI polymorphisms and CI.     

清肺活血方对AECOPD患者凝血、纤溶活性影响

目的观察慢性阻塞性肺病急性加重期(AECOPD)患者应用清肺活血方对其凝血和纤溶活性的干预作用。方法将48例AECOPD患者随机分成治疗组和对照组,两组均给予常规治疗,治疗组(24例)在常规治疗基础上加用清肺活血中药,治疗10 d,治疗前后均检测凝血和纤溶活性指标。结果对照组治疗前后凝血功能指标略有改善,但无显著性差异(P0.05),显示常规治疗虽能使患者病情得到改善,但无法有效改善患者血液的高粘、高凝状态;治疗组治疗前后凝血和纤溶活性改善明显(P0.01或P0.05),显示其可有效改善患者血液的高粘、高凝状态。结论对AECOPD患者常规治疗同时配合清肺活血治疗,效果肯定,防止血栓形成起着重要的作用。     

Introduction: Stockholm stroke symposium – from genes to acute care

Abstract. Wester P (Umeå University, Sweden). Introduction: Stockholm stroke symposium – from genes to acute care. J Intern Med 2010; 267: 136–138. The acute stroke research field is dynamic and exciting with several clinical breakthroughs, which give reason for optimism. There is gradually a broader understanding of the genetic linkage with different aspects of stroke. As a majority of stroke cases are caused by thrombo‐embolism with blocking of one or more of the cerebral arteries, the obvious acute treatment strategy is to remove the occluded vessel and thereby restore the aerobic metabolism provided that neuroimaging analyses reveal the presence of rescuable ischaemic tissue. On January 28–29, 2009, the Journal of Internal Medicine arranged a 2‐day symposium entitled Stockholm stroke symposium – from genes to acute care. In this issue of JIM, five comprehensive reviews from this symposium are presented. These include the genetic factors in the aetiology and treatment of ischaemic stroke, the interplay between microvessels, neurons and glia (i.e., the microvascular unit) in the setting of acute stroke, a critical review of various neuroimaging techniques to visualize ischaemic tissue that is still viable (the ischaemic penumbra), recanalization strategies by means of intravenous thrombolysis as well as future recanalization techniques by, for example, intra‐arterial or mechanical thrombolysis and sonothrombolysis by a transcranial approach.     

逐痰通络汤对局灶性脑缺血大鼠凝血纤溶系统的影响

目的：观察逐痰通络汤对局灶性脑缺血大鼠凝血纤溶系统的影响。方法：清洁级雄性SD大鼠18只,随机分为假手术组（K组）、模型组（C组）和逐痰通络汤组（Z组）,每组各6只。应用线栓法建立大脑中动脉栓塞（MCAO）模型。造模后第7天观察各组大鼠神经功能缺损并评分,脑组织TTC染色并测定梗死体积,以发色底物法测定血浆组织型纤溶酶原激活物（t-PA）、组织型纤溶酶原激活抑制物（PAI）、纤溶酶原（PLG）活性,ELISA法测定血浆D-二聚体（DD）活性。结果：C组、Z组均出现不同程度神经功能缺损和梗死灶。与C组相比,Z组神经功能缺损较轻、梗死体积较小（P〈0.05）。C组、Z组PLG、PAI、DD活性显著高于K组,t-PA活性显著低于K组（P〈0.01）。Z组PLG、PAI、DD活性低于C组（P〈0.05,P〈0.01）,t-PA活性高于C组（P〈0.05）。结论：增强血浆纤溶活性,纠正凝血纤溶系统失衡,可能是逐痰通络汤治疗脑缺血的机制。     

连续性血液净化对合并ARF的MODS患者炎性因子和凝血功能的改变

目的探讨连续性静脉-静脉血液滤过(CVVH)技术对合并急性肾功能衰竭(ARF)的多器官功能障碍综合征(MODS)患者体内炎性因子的清除作用及对凝血纤溶的影响,同时观察连续性血液净化(CBP)对患者肾功能、血流动力学的影响和预后的影响。方法选择合并ARF行CVVH治疗的MODS患者106例,CVVH治疗前及治疗后6h、12h、24h,分别检测TNF-α、IL-6、IL-10、血浆纤溶酶原活性抑制物-1(PAI-1)浓度;血液电解质及肾功能;血气分析、pH值、动脉血氧分压、动脉血二氧化碳分压;体温、心率、呼吸、平均动脉压、中心静脉压。结果 106例患者CBP治疗后TNF-α水平显著低于治疗前(P<0.05);血清IL-6,IL-10水平在CBP治疗后均下降,但较治疗前差异无统计学意义(P>0.05);MODS组血清PAI-1、CRP浓度明显高于健康人(P<0.05);随着CBP时间的延长下降逐渐减小,与CBP前比较差异无统计学意义(P>0.05);CVVH前后BUN、Scr、血清K+和HR比较,差异有统计学意义(P<0.05);血清Na+、Cl-、Glu、pH值、PaCO2,差异无统计学意义(P>0.05)。结论 CBP能清除合并ARF的MODS患者血清中多种炎性因子,对凝血纤溶紊乱有改善。CBP过程中血流动力学平稳,对患者有良好的治疗作用。     

Perioperative use of modified thrombelastography in factor XI deficiency: a helpful method to assess drug effects

Factor XI deficiency is a rare, hereditary bleeding disorder associated with a trauma-related bleeding tendency, caused by insufficient generation of the thrombin activatable fibrinolysis inhibitor (TAFI) evoking increased fibrinolysis. We present the case of a five year old girl with homozygote, severe factor XI deficiency presenting for surgery on two occasions. Modified thrombelastography (ROTEM) was used to assess effects of factor XI deficiency on coagulation, endogenous fibrinolysis, and potential effects of tranexamic acid, aprotinin and recombinant, activated Factor VII in an in vitro model of hyperfibrinolysis. According to our data and in consideration of the mechanisms of factor XI deficiency we decided on prophylactic use of tranexamic acid.     

Fibrinolytic responses of human peritoneal fluid in laparoscopic cholecystectomy: a prospective clinical study

Background The reduction in peritoneal fibrinolysis is believed to be the pathogenetic mechanism of adhesion formation. The general conclusion based on previous clinical and experimental studies is that laparoscopic procedures produce less adhesion formation. The association between this beneficial effect of laparoscopic cholecystectomy and peritoneal fibrinolytic changes is not clear. Therefore, the authors aimed to compare the effects of open and laparoscopic cholecystectomy on peritoneal fibrinolysis. For this purpose, fibrinolytic parameters in peritoneal fluid were investigated 24 h after laparoscopic and open cholecystectomies. Methods In a prospective clinical study, peritoneal fluid was sampled via a drain 24 h after laparoscopic (n = 10) and open (n = 9) cholecystectomies. Activities and concentrations of tissue plasminogen activator (tPA), plasminogen activator inhibitor type 1 (PAI-1), and tPA/PAI-1 complex were determined by enzyme-linked immunosorbent assay (ELISA) kits. Results In peritoneal fluids, tPA and tPA/PAI-1 complex concentrations were higher in the open cholecystectomy group (p = 0.009 and p < 0.001, respectively), but tPA activity and PAI-1 concentrations did not differ between the groups (p = 0.514 and p = 0.716, respectively). Conclusions Fibrinolytic changes in peritoneal fluid have several similarities in open and laparoscopic cholecystectomies with regard to tPA activity and PAI-1 levels. However, higher tPA levels after the open procedure probably are secondary to more intense tissue handling leading to mesothelial release of tPA.