摘要:

The interaction of the platelet surface with agonist or adhesive molecules can modify the platelet surface charge and thus its electrophoretic mobility. Electrophoretic quasi elastic light scattering (ELS) is a technique that permits the rapid and accurate determination of electrophoretic mobility of platelets. ELS was used to study changes in the platelet electrophoretic mobility induced by platelet activation and by fibrinogen binding. The platelet electrophoretic mobility decreases from - 2 (μ-cm)/(V-s) to - 0.5 (μ-cm)/(V-s) when the platelet is activated with either 1 μM ADP, 10 μM epinephrine or 0.5 NIH U/ml α-thrombin. Aspirin inhibits the ADP induced platelet activation and surface charge reduction. Thrombin overcomes the aspirin inhibition indication that the platelet surface charge reduction is associated with platelet activation. The magnitude of the decrease in the platelet electrophoretic mobility varies with the platelet donor and the extent of platelet activation. Platelet activation enhances the fibrinogen induced surface charge reduction, which is consistent with fibrinogen binding. Thus, ELS is shown to be a sensitive means to directly assess platelet activation and ligand binding.

ISSN:0957-5235    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Stimulation of monocytic cells by inflammatory agents such as bacterial lipopolysaccharide or tumour necrosis factor-alpha leads to the rapid and transient expression of tissue factor, the major cellular initiator of the extrinsic coagulation cascade in both haemostasis and tissue inflammation. In this study we investigated whether the synthetic anti-inflammatory glucocorticoid, dexamethasone, would inhibit agonist induction of tissue factor expression in both monocytes and endothelial cells. Surprisingly, dexamethasone significantly enhanced the induction of tissue factor expression by peripheral blood mononuclear cells and an established monocytic cell line, THP-1, in response to lipopolysaccharide or tumour necrosis factor-alpha. However, unlike monocytic cells, dexamethasone did not enhance agonist induction of tissue factor in endothelial cells. Synergistic enhancement of tissue factor expression by dexamethasone was also reflected in tissue factor mRNA levels in THP-1 cells, but was not the result of improved TF mRNA stability. Synergism between bacterial lipopolysaccharide and glucocorticoid in the induction of monocyte effector function is extremely unusual and may help to explain the variable outcome of glucocorticoid treatment of septic shock.

ISSN:0957-5235    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Increased plasma FVIII:C concentrations occur in several conditions, including diabetes, but whether this leads to clinically relevant hypercoagulability is uncertain. Accordingly, we investigated the effects of increasing FVIII:C levels on coagulationin vitrousing a computer-assisted measurement of thrombin activity. Defibrinated plasma was activated with kaolin, thrombin activity measured using the chromogenic substrate S2238 and time to generate 50% maximal thrombin activity (T50) recorded in seconds. Increasing FVIII:C levels from 100 to 350% significantly reduced T50 (mean ± SD) from 91 ± 3 to 64 ± 6.2 s (P< 0.001,n= 6), and T50 correlated inversely with FVIII:C(r= - 0.884,P< 0.001,n= 36). Increasing FV concentrations resulted in an additive effect with high FVIII:C levels on the rate of thrombin generation. The results showed that increasing plasma FVIII:C and FV concentrations accelerate rate of generation of thrombin activity independently, and in an additive manner.

ISSN:0957-5235    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Transmission of infectious diseases via the use of plasma concentrates has lent special significance to the manufacture of recombinant coagulation factor concentrates. At present, two factor VIII concentrates manufactured by recombinant DNA technology, produced by Baxter (RecombinateTM) and Bayer/Miles (KogenateTM), are undergoing clinical trials. At the haemophilia centres in Bonn and Frankfurt am Main a total of 4.1 million IU have been used by twelve patients for prophylaxis and treatment for bleeding between 1989 and 1990. The clinical efficacy, particularly in the treatment of bleeding episodes was good and corresponded with that of plasma-derived concentrates. There were no allergic reactions, development of inhibitors or other serious side effects. In laboratory investigations no adverse results were encountered.

ISSN:0957-5235    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

To explore the possibility of an interaction between platelets and antiphospholipid antibodies and its relationship with thromboembolic events, platelets from six patients with IgG anticardiolipin antibodies, lupus anticoagulant and thrombosis were isolated by gel filtration. Five patients had primary antiphospholipid syndrome and one had a form secondary to systemic lupus erythematosus. Two patients had mild thrombocytopenia. The six platelet membrane eluates contained less than 1.09 GPL units of anticardiolipin antibodies and displayed no lupus anticoagulant activity. Similarly, lysates of disrupted platelets did not show anticardiolipin or lupus anticoagulant activity. These results suggest that antiphospholipid antibodies do not interact with circulating platelets, at least in patients on oral anticoagulant treatment with no evidence of acute thrombosis.

ISSN:0957-5235    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

We have measured various fibrinolytic and coagulation parameters (t-PA antigen, PAI, fibrinogen, plasminogen and factor VII) before and after 10 min of venous occlusion in 20 hypertryglyceridaemic subjects (twelve males and eight females, age 38 ± 4 years, body mass index 23 ± 1.5) and 20 healthy normal subjects, matched for sex (twelve males and eight females), age (37 ± 3.5 years) and body mass index (22.8 ± 1.4). At rest, t-PA:Ag, PAI, fibrinogen, plasminogen and factor VII were significantly (P< 0.005) higher in hypertriglyceridaemic subjects than in normal controls. After venous occlusion, the increase in all parameters except t-PA:Ag was more marked in the patient group than in the controls. Only the percentage increase in t-PA:Ag was higher in normal controls (358.8%) than in hypertriglyceridaemic subjects (91.9%). There was a positive correlation between serum triglycerides levels and PAI at rest (r= 0.72,P< 0.01) and a negative correlation between serum triglycerides levels and t-PA antigen after venous occlusion (r= −0.45,P< 0.05) suggesting an impairment of fibrinolysis in hypertriglyceridaemia.

ISSN:0957-5235    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

To assess the degree of haemos tatic System activation, plasma levels of prothrombin fragment 1 + 2 (F1+2), a direct indicator for thrombin generationin vivo, were measured in 49 patients with thrombotic disease undergoing long-term warfarin therapy (Thrombotest± values ≤ 40%). In these patients, vitamin K dependent coagulation factors (factors II, VII, IX and X) were decreased together with the anticoagulant proteins C and S, but the mean plasma concentration of F1+2was significantly decreased compared with 48 healthy subjects. In warfarin-treated patients, F1+2was positively correlated with the Thrombotest value, factors II, VII, IX and X. When analysed according to the intensity of anticoagulation, patients with Thrombotest values less than 30% showed a significant decrease in F1+2, but the mean F1+2level was normal in patients with Thrombotests higher than 30%. These findings indicate that long-term oral anticoagulant therapy suppresses thrombin generation approximately in parallel to the decrease in coagulation factors, and levels of F1+2lower than healthy subjects are observed when Thrombotest values are less than 30%.

ISSN:0957-5235    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

The cysteine proteinase, cancer procoagulant (CP;EC 3.4.22.26) was isolated from human amnion-chorion and purified by precipitation with polyethylene glycol and either ion exchange or immunoaffinity chromatography. A new, sensitive, three-stage chromogenic assay was developed for determination of CP factor X-activating activity. Using this assay some properties induding dose–response, effect of calcium, phospholipid and pH on the activation of factor ± by CP were determined. There was an excellent linear correlation (r2= 0.99) between concentration and the enzymatic activity of CP. The activation of factor X by purified CP was calcium dependent with an optimum calcium concentration of 7 mM. CP was not phospholipid dependent. There was a rather broad pH optimum between pH 6.9 and 7.25 for the activation of factor X by CP.

ISSN:0957-5235    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Paramagnetic particles coated with a monoclonal antibody to D-dimer (mAb S4) were used to isolate and concentrate D-dimer and D-dimer-containing complexes in plasma and serum. Antibody-captured material was eluted with SDS-urea buffer and examined by either SDS-polyacrylamide or submerged SDS-agarose gel electrophoresis followed by Western blotting. The protein pattern was visualized by either polyclonal antibodies to human fibrinogen or monoclonal antibodies specific for fibrinogen derivatives containing fibrinopeptide A (FpA; mAb Y18), the N-terminus of the β-chain in fibrin (mAb 59D8) or the γ-chains (mAb J88B). The results obtained show that paramagnetic particles coated with mAb S4 catch intact D-dimer as well as a variety of cross-linked fibrin molecules of highmolecular-weight (HMW) in plasma. The existence of HMW derivatives in fibrinaemic serum indicates that some of the HMW fibrin related material in such plasma is not dottable. Fibrinogen/fibrin monomers and some of the fibrinogen/fibrin related derivatives found in the eluates were probably non-covalently bound to the complexes caught by mAb S4 coated particles. The present technique combines the selective concentrating power of immunoparticles and the sensitivity of immunovisualization and allows rapid and direct identification of minute amounts of circulating immunoreactive fibrinogen/fibrin derivatives.

ISSN:0957-5235    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Plasma thrombomodulin (TM) concentrations were studied in a population sample of 175 subjects aged 35–65 years. There was no age variation in males (mean value 65 ± 15 μg/l) but females aged 35–45 years had lower values than women aged 55–65 years, suggesting an effect of the menopause. The TM levels were unrelated to body build measurements (body mass index, waist/hip ratio) and blood pressure, and also to lipid levels (triglycerides, total cholesterol) and insulin before and during an oral glucose tolerance test. There was no difference in mean TM levels in subjects with and without electrocardiographic signs of ischaemic heart disease. Tobacco smokers had 15% lower mean levels of plasma TM than non-smokers.

ISSN:0957-5235    

出版商:OVID    

年代:1993

数据来源: OVID