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1.
β2-glycoprotein-I (β2GPI) is a phospholipid-binding plasma protein that consists of five homologous domains. Domain V is distinguished from others by bearing a positively charged lysine cluster and hydrophobic extra C-terminal loop. β2GPI has been known as a natural anticoagulant regulator. β2GPI exerts anticoagulant activity by inhibition of phospholipid-dependent coagulation reactions such as prothrombinase, tenase, and factor XII activation. It also binds factor XI and inhibits its activation. On the other hand, β2GPI inhibits anticoagulant activity of activated protein C. According to the data from knockout mice, β2GPI may contribute to thrombin generation in vivo. Phospholipid-bound β2GPI is one of the major target antigens for antiphospholipid antibodies present in patients with antiphospholipid syndrome (APS). Binding of pathogenic anti-β2GPI antibodies increases the affinity of β2GPI to the cell surface and disrupts the coagulation/fibrinolysis balance on the cell surface. These pathogenic antibodies activate endothelial cells via signal transduction events in the presence of β2GPI. Impaired fibrinolysis has been reported in patients with APS. Using a newly developed chromogenic assay, we demonstrated lower activity of intrinsic fibrinolysis in euglobulin fractions from APS patients. Addition of monoclonal anti-β2GPI antibodies with β2GPI also decreased fibrinolytic activity in this assay system. β2GPI is proteolytically cleaved by plasmin in domain V (nicked β2GPI) and becomes unable to bind to phospholipids, reducing antigenicity against antiphospholipid antibodies. This cleavage occurs in patients with increased fibrinolysis turnover. Nicked β2GPI binds to plasminogen and suppresses plasmin generation in the presence of fibrin, plasminogen, and tissue plasminogen activator (tPA). Thus, nicked β2GPI plays a role in the extrinsic fibrinolysis via a negative feedback pathway loop. 相似文献
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R. -M. Jolidon MD H. Knecht L. Humair A. de Torrente 《Journal of molecular medicine (Berlin, Germany)》1991,69(8):340-344
Summary A young man who had suffered several episodes of deep-vein thrombosis of the legs since the age of 20 had a myocardial infarction at the age of 33, at which time both a prolonged partial thromboplastin time (PTT), compatible with a lupus anticoagulant (LA), and decreased fibrinolytic capacity (FC) were found.His sister presented with deep-vein thrombosis of a leg and subsequent pulmonary embolism when she was 18 years old. She had a miscarriage three years later and developed a hemolytic-uremic syndrome at the age of 35. The PT and FC were normal. Laboratory investigations of the parents revealed positive antinuclear antibodies in the mother's serum but no anomaly in the father.This study suggests a familial tendency to develop autoimmune disorders associated with LA and thromboembolic complications related to decreased FC. 相似文献
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低分子肝素治疗不稳定型心绞痛33例疗效观察 总被引:1,自引:0,他引:1
目的:探讨低分子肝素治疗不稳定型心绞痛的疗效及安全性,方法:不稳定型心绞痛33例,经内科常规药物治疗疗效不佳,加用低分子肝素0.4ml,2次/d腹壁皮下注射,疗程10d。结果:低分子肝素治疗后总有效率93.9%,心绞痛发作次数,持续时间,硝酸甘油用量均显著减少(P<0.01),全血粘度,血浆粘度和纤维蛋白原均明显降低(P<0.05),无发生急性心肌梗塞和猝死,无出血不良反应,结论:低分子肝素治疗不稳定型心绞痛安全,有效。 相似文献
7.
D. Oberladstätter W. Voelckel C. Schlimp J. Zipperle B. Ziegler O. Grottke H. Schöchl 《Anaesthesia》2021,76(3):373-380
In urgent clinical situations, such as trauma, urgent surgery or before thrombolysis, rapid quantification of direct oral anticoagulant plasma drug levels is warranted. Using the ClotPro® analyser, we assessed two novel viscoelastic tests for detection of clinically-relevant plasma drug levels in trauma patients. The ecarin clotting time was used to assess the plasma concentration of dabigatran and Russell´s viper venom clotting time to determine the plasma concentration of direct factor Xa inhibitors. In parallel, plasma concentrations were analysed using plasma-based chromogenic assays. A total of 203 simultaneous measurements were performed. Strong to very strong linear correlations were detected between ecarin clotting time and plasma concentration of dabigatran (r = 0.9693), and between Russell´s viper venom clotting time and plasma concentrations of apixaban (r = 0.7391), edoxaban (r = 0.9251) and rivaroxaban (r = 0.8792), all p < 0.001. An ecarin clotting time ≥ 189 seconds provided 100% sensitivity and 90% specificity for detecting plasma dabigatran concentrations ≥ 50 ng.ml-1. Corresponding Russell´s viper venom clotting time cut-off values were ≥ 136 seconds for apixaban (80% sensitivity, 88% specificity), ≥ 168 seconds for edoxaban (100% sensitivity, 100% specificity) and ≥ 177 seconds for rivaroxaban (90% sensitivity, 100% specificity). Detection of drug levels ≥ 100 ng.ml-1 was also investigated: for dabigatran, an ecarin clotting time ≥ 315 seconds yielded 92% sensitivity and 100% specificity; while Russell´s viper venom clotting time cut-offs of 191, 188 and 196 seconds were calculated for apixaban (67% sensitivity, 88% specificity), edoxaban (100% sensitivity, 75% specificity) and rivaroxaban (100% sensitivity, 91% specificity), respectively. We have demonstrated strong positive correlations between plasma drug levels and clotting time values in the specific ClotPro assays. Cut-off values for detecting clinically-relevant drug levels showed high levels of sensitivity and specificity. 相似文献
8.
Anticoagulation therapy for pulmonary embolism involving a myxoma mimicking,giant type C thrombus: A case report 下载免费PDF全文
Right heart thrombus (RHTh) with concurrent acute pulmonary embolism (PE) is rare and can seriously destabilize hemodynamics, leading to an emergency situation with high mortality. Diagnosis and treatment of RHTh with acute PE are not yet standardized. There are few reports of acute PE concurrent with RHTh and even less is known about patients with a right heart mural thrombus. For physicians, the diagnostic choice and treatment of these patients are particularly difficult due to the lack of knowledge. Here, we report a rare case of partial mural RHTh (type C RHTh) with acute PE. The mural mass in the right heart was initially diagnosed as atrial myxoma according to transthoracic echocardiography (TTE), and both pulmonary embolus and the mural mass were completely absorbed after administering Rivaroxiban. This case suggests that TTE alone is insufficient to identify and diagnoses a right heart mural mass such as this. However, novel oral anticoagulants may be effective at alleviating PE with type C RHTh. 相似文献
9.
The interaction of phenylbutazone with the enantiomers and racemic [
3
H]phenprocoumon was studied in male inbred Wistar-Lewis rats following a single i.v. dose of the three forms of phenprocoumon and chronic oral treatment with phenylbutazone (average plasma concentration of about 60 g/ml). Phenylbutazone augmented the anticoagulant effect of R(+), S(–), and R, S (±) phenprocoumon to a similar extent. The free fraction of drug in the plasma of the enantiomers and racemic phenprocoumon increased in the presence of phenylbutazone. However, the rate of elimination of total drug from plasma and liver and the distribution between liver and plasma of all three forms of phenprocoumon remained nearly unaffected by phenylbutazone. Thus there is no evidence for a stereoselective drug interaction between phenprocoumon and phenyl-butazone. For racemic [
3
H]phenprocoumon it was possible to follow the kinetics of free drug in plasma and liver along with the time course of anticoagulant activity. In these studies, free drug concentrations in plasma and liver increased during treatment with phenylbutazone, but the elimination rate constant of free racemic phenprocoumon in plasma and liver remained essentially unchanged. Phenylbutazone markedly decreased the volume of distribution referenced to free drug and the clearance of free phenprocoumon (i.e., intrinsic metabolic clearance). Whereas the total (bound and unbound) drug concentration-effect relationship in plasma and liver was shifted to the left in rats treated with phenylbutazone, such shift was not seen in the free drug concentration-response relationship. In conclusion, the increase in the free concentration of phenprocoumon in plasma and liver and the concomitant decrease in the clearance of free drug are the mechanisms responsible for the marked and sustained enhancement of the anticoagulant effect which follows treatment with phenbutazone.This work was supported by the Deutsche Forschungsgemeinschaft. 相似文献
10.
抗凝药物的临床应用及安全性评价 总被引:1,自引:0,他引:1
目的 :评价抗凝药物肝素和维生素K拮抗剂的临床应用及安全性。方法 :查阅国内外近期相关文献进行综述。结果与结论 :临床上多种血栓栓塞、缺血性疾病中应用肝素、维生素K拮抗剂等抗凝药物时 ,应注意根据患者个体情况 ,掌握剂量 ,防治各种可能发生的不良反应 相似文献