重症肺炎患者部分血栓前凝血及纤溶系统变化检测及临床意义

目的探讨重症肺炎患者部分血栓前凝血及纤溶系统变化。方法选择本院收治的重症肺炎患者60例为研究组,同期来院健康体检者60名为对照组,两组均抽外周静脉血,检测患者血细胞(PLT、WBC)、凝血指标(PT、APTT、Fg)、纤溶指标(D-D、FDP),并进行组间比较。结果研究组PLT低于对照组,WBC、PT、APTT、Fg明显高于对照组,D-D阳性率、FDP阳性率均高于对照组,两组间比较上述指标差异均有统计学意义(P<0.05);研究组不同程度血小板减少患者PT、APTT、Fg差异显著(P<0.05),血小板水平与PT、APTT、Fg呈明显负相关(r=-0.408、-0.517、-0.452,P<0.05);研究组不同程度WBC增多患者,PT、APTT、Fg差异显著(P<0.05),WBC水平与PT、APTT、Fg呈明显正相关(r=0.392、0.533、0.497,P<0.05)。结论重症肺炎患者存在一定程度的凝血及纤溶功能失调,临床应加强对该指标监测,在抗感染治疗的同时,调整凝血系统功能,对缓解重症病情有积极意义。     

番茄红素对实验性高甘油三酯血症大鼠血脂、血凝及纤溶的影响

目的研究番茄红素对实验性高甘油三酯血症大鼠血脂、血凝及纤溶的影响。方法建立大鼠高甘油三酯血症模型,同时给予番茄红素,测定大鼠空腹12~14 h血浆总胆固醇、甘油三酯、高密度脂蛋白胆固醇、凝血酶原时间、活化部分凝血活酶时间、组织型纤溶酶原激活物活性及纤溶酶原激活物抑制剂1活性,分析番茄红素对血脂、血凝及纤溶的影响。结果饲高糖高脂饲料后,大鼠血浆甘油三酯含量平均升高1.95倍,高密度脂蛋白胆固醇下降26%;与高糖高脂饲料组比较,饲高糖高脂饲料及番茄红素后大鼠血浆甘油三酯含量平均下降24%,高密度脂蛋白胆固醇含量平均增加32%,达正常水平。饲高糖高脂饲料后,大鼠血浆凝血酶原时间及活化部分凝血活酶时间均较对照组明显缩短(P<0.01),纤溶酶原激活物抑制剂1活性明显增加(P<0.01),组织型纤溶酶原激活物活性无显著变化。饲高糖高脂饲料及番茄红素后,大鼠血浆纤溶酶原激活物抑制剂1活性明显增加(P<0.01),组织型纤溶酶原激活物活性增加(P<0.01),凝血酶原时间及活化部分凝血活酶时间无明显变化。与高糖高脂饲料组比较,饲高糖高脂饲料及番茄红素后,大鼠血浆凝血酶原时间及活化部分凝血活酶时间均明显延长(P<0.01),纤溶酶原激活物抑制剂1活性明显降低(P<0.05),组织型纤溶酶原激活物活性增加(P<0.01)。结论番茄红素能降低血脂水平,使凝血系统活性降低,纤溶系统活性增加。     

Impaired fibrinolytic response to exercise in type II diabetes: effects of exercise and physical training

We studied the effects of exercise and physical training on coagulation parameters and fibrinolytic activity in 16 sedentary non-insulin-dependent diabetics and nine control subjects matched for prior physical activity. Parameters were measured at rest and after 30 minutes of bicycle exercise at 70% to 75% of maximal oxygen uptake before and after 6 weeks of thrice-weekly physical training. In the untrained state, fibrinolytic activity was impaired in diabetics compared with controls (1.26 +/- 0.19 v 2.20 +/- 0.34 U; P less than .03), and resting levels of plasma fibrinogen (329 +/- 21 v 266 +/- 17 mg/dL; P less than .01) and the prothrombin time (PT) maximal velocity (Vmax) (4.9 +/- 0.5 v 2.9 +/- 0.5; P less than .05) were increased. The activated partial thromboplastin time (APTT) Vmax was also increased but this did not reach statistical significance (3.6 +/- 0.2 v 2.3 +/- 0.5; P less than 0.10). Activation of fibrinolysis occurred following exercise in both groups but the peak activity and increment were less in diabetics. Physical training for 6 weeks had no effect on plasma fibrinogen levels but significantly improved the resting and postexercise APTT Vmax and resting fibrinolytic activity in diabetics. The exercise-induced increment in fibrinolytic activity following training remained depressed compared with normal controls. The changes in APTT Vmax correlated with changes in the indices of blood glucose control. The relevance of these findings to possible antiatherogenic effects of exercise and the mechanism by which exercise produces these effects remain to be established.     

靶向“失功能性”高密度脂蛋白的研究进展

高密度脂蛋白(HDL)是血浆中携运胆固醇的一类主要脂蛋白,正常情况下,HDL具有介导胆固醇逆向转运(RCT)、抗氧化及抗炎、抑血栓形成、促内皮修复等调节血管功能的作用,是机体重要的动脉粥样硬化(As)防御因素。但HDL是在起源、大小、组成及功能上表现极不均一性的脂蛋白颗粒,同时炎症、氧化应激、血脂紊乱、高糖等环境下可引起HDL结构及组分的     

Vitamin E and alpha-lipoic acid supplementation increase bleeding tendency via an intrinsic coagulation pathway.

Vitamin E and alpha-lipoic acid are potent nutritional antioxidants, and when used together, their antioxidant capabilities are improved as alpha-lipoic acid recycles vitamin E. Supplementation of vitamin E has been shown to prolong platelet aggregation but the effects of vitamin E and alpha-lipoic acid supplementation on bleeding tendency have yet to be reported. Young, male rats consumed either control diet (n=5) or vitamin E and alpha-lipoic acid-supplemented diet (n=5) for 14 weeks. Activated partial thromboplastin time (APTT) and prothrombin time (PT) were measured as markers of intrinsic and extrinsic coagulation pathways respectively in addition to lipid peroxidation (malondialdehyde). Supplementation significantly prolonged APTT (23.8+/-1.5 vs 31.4+/-1.2s, p<0.05) compared to the control diet; however, there was no significant difference in PT (27.8+/-1.5 vs 26.6+/-0.9s, p>0.05). While vitamin E was increased (p<0.05), there was no significant difference in plasma levels of malondialdehyde (p>0.05). Dietary supplementation of vitamin E and alpha-lipoic acid increases bleeding tendency via inhibition of the intrinsic coagulation pathway with no change in markers of lipid peroxidation. Such supplementation could benefit patients with cardiovascular disease who exhibit elevated levels of coagulation and oxidative stress.     

Global assays of fibrinolysis

Fibrinolysis is an important and integral part of the hemostatic system. Acting as a balance to blood coagulation, the fibrinolytic system protects the body from unwanted thrombus formation and occlusion of blood vessels. As long as blood coagulation and fibrinolysis remain in equilibrium, response to injury, such as vessel damage, is appropriately regulated. However, alterations in this balance may lead to thrombosis or bleeding. A variety of methods have been proposed to assess fibrinolytic activity in blood or its components, but due to the complexity of the system, the design of a “gold standard” assay that reflects overall fibrinolysis has remained an elusive goal. In this review, we describe the most commonly used methods that have been described, such as thromboelastography (TEG and ROTEM), global fibrinolytic capacity in plasma and whole blood, plasma turbidity methods, simultaneous thrombin and plasmin generation assays, euglobulin clot lysis time and fibrin plate methods. All of these assays have strengths and limitations. We suggest that some methods may be preferable for detecting hypofibrinolytic conditions, whereas others may be better for detecting hyperfibrinolytic states.     

水蛭地龙提取液对抗大心肌缺血作用的实验研究

目的观察水蛭地龙提取液的抗心肌缺血作用，为该药治疗心绞痛、心肌梗死等缺血性心脏病提供实验依据。方法采用结扎冠状动脉制作心肌梗死模型，将60只大鼠分为模型对照组（模型组）、假手术组、水蛭地龙提取液治疗组（治疗组），观察各组大鼠治疗后凝血酶时间（TT）、凝血酶原时间（PT）、部分凝血酶原时间（APTT）、D-二聚体（DD）及组织纤溶酶原激活物（t—PA）含量的变化。测定各组大鼠血清中磷酸肌酸激酶（CPK）、乳酸脱氢酶（LDH）、丙二醛（MDA）含量和超氧化物歧化酶（SOD）的活性，并测定心肌梗死范围。结果与假手术组与模型对照组比较，治疗组TT、PT、APTT、明显延长（P〈0．05或P〈0．01），血清CPK、LDH、MDA含量降低（P〈0．05或P〈0．01），且可提高SOD活性，显著减少心肌梗死范围。结论水蛭地龙提取液有抗心肌缺血作用，这一作用与其抗凝促纤溶、心肌保护、改善心肌血液循环有关。     

Thrombin activatable fibrinolysis inhibitor (TAFI) and its importance in the regulation of fibrinolysis

Thrombin activatable fibrinolysis inhibitor (TAFI) also named procarboxypeptidase U (CPU), procarboxypeptidase R (CPR) and plasma procarboxypeptidase B (CPB) provides an important link between fibrinolysis and coagulation cascade. Activated TAFI (TAFIa) reduces a generation of plasmin because it cleaves off the carboxy-terminal lysine residues from partially degraded fibrin and thereby abrogates the fibrin cofactor function in the tPA-mediated catalysis of plasminogen to plasmin. TAFI is activated by thrombin-thrombomodulin complex. TAFI transformation to the activated TAFI (TAFIa) induced by thrombin supports the important role of coagulation cascade in regulation of fibrinolysis. This can be proved by a fact that the patients with a factor XI (FXI) deficiency are prone to bleeding from tissues with a high local fibrinolytic activity (urinary tract, nose, oral cavity, tonsils) that can be explained by a decreased thrombin-mediated TAFI activation. On the other hand the prothrombotic mutation of factor V (FV Leiden) associated with a resistance to activated protein C (APC-resistance) possess both mechanisms-an increased thrombin generation in coagulation cascade and a down regulation of fibrinolysis by a way of the thrombin-induced TAFI activation. For the future an inhibition of TAFI (e.g. by FXI inhibitors) offers the therapeutic possibilities to improve the decreased fibrinolysis and increase the efficiency of fibrinolytic therapy in thrombotic disorders. In bleeding disorders (hemophilia A, B) the drugs with a higher efficiency of TAFI for down regulation of an increased fibrinolysis could be used.     

Effect of high-dose progestogen on hemostatic properties of blood in patients with endometrial cancer

Fifteen cases of endometrial cancer were administered daily doses of 600 mg of MPA after surgery to prevent the recurrence of cancer. The initiation times of coagulation (time necessary for fibrin network formation) were measured with a highly sensitive damped oscillation rheometer and compared with those of 15 control patients who were not administered MPA. Biochemical studies of blood coagulation and fibrinolysis were also done. The initiation times of coagulation were 19.0+/-1.8 minutes (min mean +/- standard deviation) after 3-6 months and 16.0+/-2.0 min after 9-12 months of MPA administration, both times being significantly shorter compared with the controls (24.0+/-2.5 min). Hematocrit values, platelet counts and fibrinogen levels were similar between the two groups. Activated partial thromboplastin time (APTT) was significantly decreased and antithrombin III activity (AT III), thrombin-antithrombin complex (TAT), plasminogen level, plasmin-alpha(2) plasmin inhibitor complex level (PIC) and the fibrin degradation product level (FDP) were significantly increased in the MPA group compared with the control group. Accelerated coagulation of blood was definitely induced by high-dose MPA but antithrombin and fibrinolytic activities were also induced, and, thus, thromboembolic complications were prevented.     

低氘白酒对实验性高脂血症大鼠凝血及纤溶系统的影响

目的研究低氘水和白酒对高脂血症大鼠血脂、凝血及纤溶的影响。方法设正常对照组,建立大鼠的高脂血症模型,同时对高脂血症大鼠连续白酒[0.01 L/(kg.d)]灌胃或/和自由饮用低氘水,测定如下指标:大鼠血浆甘油三酯、总胆固醇、高密度脂蛋白、低密度脂蛋白、凝血酶原时间、活化部分凝血活酶时间、组织型纤溶酶原激活物及活性纤溶酶原激活物抑制剂1活性。组织标本经苏木精-伊红染色法后观察各组大鼠的胸主动脉及肝脏的病理学变化。结果与高脂模型组相比,低氘水组大鼠高密度脂蛋白及组织型纤溶酶原激活物显著升高(P<0.05),活性纤溶酶原激活物抑制剂1显著降低(P<0.05);低剂量白酒组大鼠低密度脂蛋白及活性纤溶酶原激活物抑制剂1显著降低(P<0.05),凝血酶原时间、组织型纤溶酶原激活物显著升高(P<0.05);高剂量白酒组大鼠总胆固醇、高密度脂蛋白、凝血酶原时间及组织型纤溶酶原激活物均显著升高(P<0.05);低氘白酒高剂量组大鼠总胆固醇、高密度脂蛋白、低密度脂蛋白、凝血酶原时间及组织型纤溶酶原激活物均显著升高(P<0.05),甘油三酯、活性纤溶酶原激活物抑制剂1显著降低(P<0.05);低氘白酒低剂量组大鼠总胆固醇、甘油三酯...     

Coagulation disorders in patients with severe leptospirosis are associated with severe bleeding and mortality

Objective To determine the involvement of coagulation in bleeding and poor outcome in patients with severe leptospirosis. Methods In a prospective study, parameters of the coagulation system were measured on admission and during follow‐up in 52 consecutive patients with severe leptospirosis. Results All patients showed coagulation disorders, such as prolonged prothrombin time (PT) and activated partial thromboplastin time, marked procoagulant activity [thrombin–antithrombin (TAT) complexes, prothrombin fragment 1+2, D‐dimer], reduced levels of anticoagulant markers (protein C, antithrombin) and increased (anti‐) fibrinolytic activity [plasmin–antiplasmin (PAP) complexes, plasminogen activator inhibitor‐1]. These disorders were more pronounced in patients who died eventually. PT prolongation was associated with mortality (OR 1.4, 95% CI: 1.0–1.8, P = 0.04). Bleeding occurred in 31 subjects (60%). Of these, 24 had mild bleeding and seven had severe haemorrhages. Thrombocytopenia (platelets ≤100 × 10⁹/l) was significantly associated with clinical bleeding (OR 4.6, 95% CI: 1.3–16). A subanalysis of patients with and without severe bleeding revealed a more pronounced imbalance of the coagulation system in patients with severe bleeding, as reflected by a significant association with PT (OR 1.4, 95% CI: 1.0–1.8, P = 0.05) and the TAT/PAP ratio (OR 1.3, 95% CI: 1.0–1.6, P = 0.05), which is an indicator of the balance between coagulation and fibrinolysis. Overt disseminated intravascular coagulation (DIC) was found in 10 (22%) of the 46 patients for whom the score could be calculated. There was no significant association between DIC scores, bleeding diathesis or poor outcome. Conclusion The coagulation system was strongly activated in patients with leptospirosis. This was more pronounced in the deceased and in patients with severe bleeding than in than the survivors and in those without severe bleeding.     

Activation and inhibition of fibrinolysis in septic patients in an internal intensive care unit

Disseminated thrombotic processes in the microcirculation are considered to be an important cause of multiple organ failure in septic patients. Fibrinolysis is one endogenous mechanism protecting the circulation from overwhelming thrombosis. Therefore, we looked for alterations of fibrinolytic parameters (tissue plasminogen activator (t-PA), tissue plasminogen activator inhibitor (PAI), D-dimer, euglobulin-clot-lysis-time (ECLT), plasminogen, alpha 2-antiplasmin) and of some coagulation parameters (prothrombin time, fibrinogen, platelets, antithrombin III, protein C, factor XII) in clearly defined septic patients and for the relations of these values to the severity of the disease (APACHE II-score). An increase in D-dimer and t-PA-antigen was registered in all patients, while factor XII and plasminogen were decreased, indicating an activated fibrinolysis. In contrast the systemic fibrinolytic capacity of the blood was strongly inhibited: t-PA-activity was not detectable, PAI-function was elevated, the ECLT was prolonged and alpha 2-antiplasmin was normal. Coagulation was moderately activated: the platelets, antithrombin III and protein C were decreased, the prothrombin time was prolonged and fibrinogen was normal. The changes in t-PA-antigen, PAI-function, factor XII, prothrombin time and antithrombin III were significantly related to the APACHE II-score of the patients. We conclude that the activation of coagulation is accompanied by an activation of fibrinolysis in the microcirculation, but that systemically the increased inhibitors of fibrinolysis (PAI, alpha 2-antiplasmin) induce a decrease of the fibrinolytic capacity of the blood. The severity of the disease determines the extent of the alterations.     

A new life-long hemorrhagic disorder due to excess plasminogen activator

A life-long bleeding disorder is described, characterized by hemorrhage occurring after surgery, injury, or dental extraction, and finally by spontaneous intracerebral bleeding. No abnormality of platelet function or plasma coagulation was demonstrable, but grossly enhanced overall fibrinolytic activity was present. The patient had, additionally, a hyperlipidemia with gross arterial atheroma and a family history of myocardial infarction but not of any hemorrhagic disorder. Laboratory studies led to the conclusion that the enhanced fibrinolysis was due to consistently greatly raised levels of a plasma plasminogen activator physically and immunologically related to that in human tissues and blood vessel endothelium. No deficiency of any known inhibitor of fibrinolysis was detected. Free plasmin was not detectable in functional assays but continuous intravascular plasmin generation clearly occurred as evidenced by presence of plasmin-alpha 2- antiplasmin complexes and of fibrin/fibrinogen-related antigens. Excessive production of plasminogen activator appeared to have occurred throughout life and to be independent of the hyperlipidemia. The pathologically increased fibrinolytic activity may have accounted for the complete absence of detectable thrombotic vascular occlusion at autopsy despite extensive arterial disease with severe narrowing of coronary and cerebral arteries.     

健康急进高原者纤溶系统变化的研究

目的：探讨健康急进高原者纤溶系统的变化。方法：总共50名青年男性入选本试验，均为从四川省（海拔400m）招募的新兵。在乘飞机从四川进入拉萨（海拔3658m）之前及之后3d，测定血凝血酶原时间（PT）、凝血酶时间（TT）、活化部分凝血活酶时间（APTT）、纤维蛋白原（Fg）、纤溶酶原（Plg）、纤溶酶抑制物、D-二聚体（DD）含量。结果：进入高原后，PT、TT、APTT、DD比在平原时增高，FIB、Plg、纤溶酶抑制物降低（P〈0．05）。结论：健康人急进高原后纤溶系统变化显著。     

老年肺心病急性发作期凝血功能检测的临床意义

目的探讨凝血功能和血液流变学检测对老年肺心病患者的临床意义。方法检测30例老年肺心病急性加重期患者凝血功能(PT,APTT,TT,FBG),D-二聚体以及血液流变学指标,包括红细胞压积、全血粘度、血浆粘度(高切、低切),并同肺心病缓解期和正常健康老人相比较。结果慢性肺心病急性发作期与其缓解期以及对照组相比,PT,APTT,TT缩短,FBG,D-二聚体上升,且差异有显著性;红细胞压积、血浆粘度、全血粘度升高,且差异有显著性。结论血浆D-二聚体,FBG,血液流变学,凝血功能监测对评估疾病程度及其预后以及疗效观察提供有力的依据。     

老年前列腺癌患者去势后性激素水平变化及对凝血和纤溶系统的影响

目的探讨老年前列腺癌患者去势后性激素水平变化及对血液凝血和纤溶系统活性的影响。方法27例早期前列腺癌经手术去势的患者作为研究组,39例非前列腺癌老年患者作为正常对照组。分别测定黄体生成素(LH)、卵泡刺激素(FSH)、总睾酮(TT)、游离睾酮(FT)、雌激素(E2)、部分凝血酶原时间(PT)、活化部分凝血酶时间(APTT)、纤维蛋白原(Fib)、凝血酶原活动度(PA)、纤溶酶原(PLG)活性、α2-抗纤溶酶(α2-PI)活性、抗凝血酶-Ⅲ(AT-Ⅲ)活性、二磷酸腺苷(ADP)活性、D-二聚体(DD)含量、血小板聚集率和黏附率、组织型纤溶酶原激活剂(t-PA)及组织型纤溶酶原激活剂抑制物(PAI-1)抗原浓度。结果研究组中患者TT、FT、E2水平显著降低,E2降低幅度小于TT,LH、FSH、FT/TT、E2/TT显著升高;PT、APTT显著缩短,Fib及DD含量显著增加,血小板聚集率、黏附率及ADP活性均显著升高,PLG、α2-PI活性显著增强,t-PA抗原含量及t-PA/PAI-1显著下降,PAI-1含量显著增加。AT-Ⅲ活性无显著变化。结论前列腺癌患者去势后性激素比例严重失调;血小板活性及血液凝血活性显著增强,纤溶活性显著抑制,提示去势患者存在发生动脉硬化的高度危险性。     

A dyspnea patient with abnormal prolonged prothrombin time and activated partial thromboplstin time, but without bleeding symptoms

A patient with erythrocytosis secondary to chronic obstructive pulmonary disease (COPD) was admitted to hospital because of dyspnea. The coagulation tests revealed abnormal prolonged prothrombin time (PT) and activated partial thromboplstin time (APTT), however, it could not be explained by the patient's medical history or physical signs of coagulation disorder. High hematocrit (Hct), which leads to reduced plasma-to-anticoagulant rate and increased final plasma anticoagulant concentration, was identified as the reason for false prolongation of PT and APTT.     

Plasmin-a2-antiplasmin complexes in bleeding disorders characterized by primary or secondary fibrinolysis

A two-dimensional immunoelectrophoresis (2DIEP) method detects plasmin complexed to its major inhibitor, alpha 2-antiplasmin, in plasma in the blood of patients during (a) thrombolytic therapy with urokinase, (b) episodes of disseminated intravascular coagulation (DIC) with active fibrinolysis, and (c) episodes of fibrinolytic haemorrhage without evidence of DIC. Clearance of the complexes from the blood is rapid and their detection thus implies active plasmin generation at the time of blood sampling or within the preceding 24 h. Abolition of the complexes using tranexamic acid therapy allowed surgery without bleeding in two previously grossly haemorrhagic patients in group (c). Antithrombin III complexed with activated procoagulants was detected using a similar 2DIEP method in only two of four patients with DIC. Abnormalities of alpha 2-macroglobulin were detected on 2DIEP of plasma in the patients studied with proteolytic disorders; these did not appear to reflect complex formation.     

Long-term administration of highly purified eicosapentaenoic acid ethyl ester prevents diabetes and abnormalities of blood coagulation in male WBN/Kob rats

We investigated the effect of long-term administration of highly purified eicosapentaenoic acid ethyl ester (EPA-E), an n-3 polyunsaturated fatty acid, on the development of diabetes, insulin resistance, and abnormalities of blood coagulation in male WBN/Kob rats, a model of spontaneous diabetes mellitus. After 8-month oral EPA-E treatment, the incidence of diabetes at a dose of 0.1, 0.3, and 1.0 g/kg was 92%, 50%, and 17%, respectively. Its incidence was suppressed significantly and dose-dependently at a dose of 0.3 g/kg or higher compared with the rate (100%) for the vehicle control. Additionally, EPA-E significantly and dose-dependently decreased the elevation of plasma glucose after an oral glucose load and increased the glucose infusion rate (GIR) during the euglycemic insulin-glucose clamp test at a dose of 0.1 g/kg or higher compared with the vehicle control. Furthermore, EPA-E significantly and dose-dependently ameliorated coagulation-related parameters, including the prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen level, and factor II, V, VII, VIII, IX, X, XI, and XII and antithrombin III (AT III) activities, and fibrinolysis-related parameters, including plasminogen, tissue-type plasminogen activator (t-PA), alpha2-plasmin inhibitor (alpha2-PI), and plasminogen activator inhibitor (PAI), and also suppressed ADP- or collagen-induced platelet aggregation and the cholesterol to phospholipid (C/P) molar ratio in platelet membranes at a dose of 0.1 g/kg or higher. These data demonstrate multiple actions of the product in these laboratory animals. These include changes in platelet function, coagulation/fibrinolysis factors, plasma immunoreactive insulin secretion, and plasma glucose/insulin resistance.