摘要:

There are few well-controlled studies of the clinical efficacy of fibrin sealant, defined by lives saved or reduced need for blood transfusions. Evaluation of fibrin sealant in trauma situations, e.g. liver laceration, has been difficult to perform. Only recently has fibrin sealant been actively promoted by US manufacturers as a commercially valuable alternative to the relatively inexpensive crude bovine thrombin and cryoprecipitate that are in current use. Regulatory agencies and manufacturers are aware that patients in the USA are receiving a suboptimal form of fibrin glue since cryoprecipitate is not virally inactivated and has a variable fibrinogen concentration. In addition, bovine thrombin is not regulated with respect to factor V content or any other impurities. During the past year regulatory agencies, together with manufacturers and clinicians, have begun to define clinically valid endpoints for efficacy of a commercially prepared fibrin sealant. These may include improvement in hemostasis compared with a placebo or agents considered to be 'standard of care'. Thus, the regulatory agencies may be willing to consider studies in animals that demonstrate efficacy as well as surrogate endpoints, such as reduced factor concentrate requirements in patients with severe hemophilia requiring dental extraction. As fibrin sealant becomes available in a liquid and potentially in a bandage form, it may also become an essential matrix for recombinant factors that can affect endothelial function.

ISSN:0957-5235    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

The effects of polymers, dextran and polyvinylpyrrolidone (PVP) and of albumin on the permeability of thrombin-induced fibrin networks developed in plasma were examined. Both PVP and dextran increased the network permeability and turbidity and increased the fibrin fibre thickness. The effect was molecular weight dependent. Derivation of the dimensionless permeability (permeability/fibre radius2) indicated that the increase in network permeability was mainly from altered arrangement of fibres and not from increased fibre thickness. The effects of albumin on network structure were similar to those of the polymers. Scanning electron microscopy of networks developed in plasma under the influence of dextran and poloxamer 188 showed fibres with increased thickness and a coarse nodular appearance. There was an increased tendency for fibres to be aggregated into clumps. It is suggested that during polymerization fibrin fibres and fibrin polymerization intermediaries behave as colloidal particles. Attractive forces between the particles are generated by soluble macromolecules such as plasma proteins or polymers. Attractive forces increase the thickness of fibrin fibres and induce a more permeable arrangement of the fibres in the network. The most likely colloidal mechanism is depletion flocculation. This would account for (1) the molecular weight dependence and concentration dependence of the effects of macromolecules, (2) the effects of macromolecules which do not bind to fibrin, (3) the effects of the surfactant poloxamer 188. Depletion flocculation may be a significant mechanism for biological regulation of fibrin network permeability by non-specific macromolecules such as soluble proteins or fibrin intermediaries.

ISSN:0957-5235    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Activated protein C resistance (APCR) has proved to be a frequent finding in association with thrombosis. The majority of patients with APCR have been found to be homozygous or heterozygous for the polymorphic variant factor V Q506(factor V Leiden; FVQ506). However a small number of patients have APCR as assessed by functional tests but do not possess the FVQ506polymorphism. Some of these cases are due to the presence of a lupus type anticoagulant but in this report we demonstrate that the remainder are almost entirely (nine out of ten) associated with an elevated level of FVIIIc. Spiking experiments in normal patient plasma and venous occlusion tests demonstrated that elevation of the FVIIIc results in a reduced APCR ratio and shortening of the APTT. Variation in FVIIIc, in conjunction with other factors, may therefore explain the variable phenotype associated with FVQ506and the phenomenon of thrombosis associated APCR in the absence of FVQ506. We conclude that FVIIIc as well as FVQ506should be taken into account when assessing thrombotic risk. APCR, elevated FVIIIc and shortened APTT have all been previously identified with an increased risk of thrombosis. It follows that resistance to APC may arise from a number of factors and is in itself a risk factor for thrombosis. The net effect of these factors is assessed in the functional test for APCR and it may be premature therefore to replace functional tests for APCR with DNA analysis alone.

ISSN:0957-5235    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Urokinase, or two-chain urokinase-type plasminogen activator (tcu-PA), is an effective thrombolytic agent. Its single-chain precursor (scu-PA), unlike tcu-PA, is able to selectively activate fibrin-bound plasminogen. The induced clot lysis is amplified by plasmin-triggered conversion of scu-PA to tcu-PA. The aim of our study was to compare the hemostatic effects of recombinant unglycosylated scu-PA, INN saruplase, and urokinase, at doses considered optimal (80 mg saruplase and 3 million units urokinase) in patients with acute myocardial infarction, within 6 h of onset of pain. Complete sample sets from more than 230 patients in each treatment group have been analyzed. The median hemostatic changes caused by saruplase and urokinase were virtually identical indicating that saruplase is converted earlyin vivoto its active tcu-PA derivative with the dose regimen used. Fibrinogen degradation products were higher for saruplase with a maximum at 2 h. They rose markedly after saruplase from 0.43 mg/l at 0 h to a maximum of 160 mg/l at 2 h, whereas the increase after urokinase (from 0.45 mg/l to 89.0 mg/l) was significantly smaller (P< 0.001).

ISSN:0957-5235    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

The effect of simvastatin, a potent inhibitor of 3-hydroxy 3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) was evaluated in an experimental model of myointimal hyperplasia in cholesterol-fed rabbits. Myointimal hyperplasia was induced by an air-drying injury of the left carotid artery followed by a 2%-cholesterol diet for 14 days. A 2-week oral treatment with simvastatin (6 mg/kg/day, p.o.) significantly lowered the circulating levels of cholesterol and triglycerides (41% and 49% inhibition respectively) as well as the low density lipoprotein (LDL)-cholesterol and high density lipoprotein (HDL)-cholesterol levels. Simvastatin also strongly affected the uptake of cholesterol in the arteries occurring as a consequence of vascular injury (44% inhibition,P< 0.001). Morphometric analysis revealed that both the intima and the media areas increased substantially 2 weeks after the lesion and showed a considerable smooth muscle cell accumulation in the neointima together with the presence of numerous foam cells. A 16-day oral treatment with simvastatin strongly reduced smooth muscle cells hyperplasia occurring in both the media and the intima following deendothelialization (19% and 60% inhibition respectively) suggesting that simvastatin may be a useful inhibitor of restenosis which occurs following vascular injury.

ISSN:0957-5235    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

When compared with 67 age-and sex-matched normal weight control subjects, the 71 overweight patients displayed obviously higher levels of plasma fibronectin. For a similar body mass index (BMI) the 16 overweight men younger than 45 years had a significantly (P< 0.01) higher plasma fibronectin level (455 ± 99.3 mg/l; mean ± SD) than the 16 age-matched overweight women (351 ± 105 mg/l) while there was no significant difference between the 22 overweight men (446 ± 89.2 mg/l) and the 17 overweight women (475 ±111 mg/l) older than 45 years. Particularly high plasma fibronectin levels were noted in the five women with upper body (android) obesity. Plasma fibronectin was positively correlated with BMI, serum triglyceride concentration, plasma fibrinogen and serum cholinesterase activity. It is considered that metabolic disturbances related to upper body obesity may lead to an enhanced hepatic secretion of VLDL and of several plasma proteins including fibronectin.

ISSN:0957-5235    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Heparin-induced thrombocytopenia is very uncommon with low-molecular-weight heparin, especially when given for prophylaxis of venous thromboembolism. In two of the four published cases, with thrombotic complications, thrombocytopenia may have been related to cross-reactivity between unfractionated heparin and low-molecular-weight heparin. We report one patient who received low-molecular-weight heparin for prophylaxis against venous thromboembolism without any previous injection of unfractionated heparin, and experienced thrombocytopenia with thrombotic complications. Heparin-induced thrombocytopenia was confirmed by several laboratory assays. This observation emphasizes the need for platelet count monitoring during low-molecular-weight heparin therapy.

ISSN:0957-5235    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Circulating levels of the adhesion molecule P-selectin (CD62P) are increased in the plasma of patients with atherosclerosis, but its relationship to the anatomical location of symptomatic disease or extent of symptomatic disease is unknown. The influence of the risk factors for atherosclerosis on soluble P-selectin is also unclear. To clarify these questions we analysed plasma samples from 170 patients with symptomatic peripheral vascular disease and 119 asymptomatic controls who were, as a group, age-and sex-matched. Soluble P-selectin (ELISA) was increased in 83 patients with symptomatic disease of the iliac and/or femoral arteries alone (P< 0.05, ANOVA) but not in 37 patients with symptomatic carotid artery disease alone compared with controls. Soluble P-selectin was equally raised in 120 patients with disease at one arterial site and in 50 patients with disease at two or more arterial sites (bothP< 0.05) compared with controls. Smoking and atherosclerosis were both independent predictors of raised soluble P-selectin. We conclude that increased soluble P-selectin may have value as a marker of peripheral vascular disease of the iliac and/or femoral arteries in group comparisons only, as the poor discrimination and wide variation of data make comparisons at the individual level difficult.

ISSN:0957-5235    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Plasma activated factor VIIa (FVIIa) levels were measured in various diseases using mutant tissue factor (TF). FVIIa levels in thrombotic patients and patients with idiopathic thrombocytopenic purpura were significantly higher than those in healthy control subjects. The plasma FVIIa levels in thrombotic patients treated with warfarin were similar to those of control subjects. The plasma FVIIa levels in pregnant women and patients with systemic lupus erythematosus, infection or malignancies were high. However, the levels in patients with disseminated intravascular coagulation (DIG) were not significantly increased. DIC patients are in a severe hypercoagulable state, and exhibit severe consumption of coagulation factors. The slightly increased FVIIa level in the DIC patients observed is probably considered to be caused by consumption of coagulation factors. The plasma FVIIa level was poorly correlated with other hemostatic parameters except for protein C in our analysis of all cases. In the analysis of DIC and thrombotic patients treated without warfarin, the plasma FVIIa level was negatively correlated with TF antigen. Plasma FVIIa levels might reflect hypercoagulability in thrombotic diseases, and a normalized FVIIa level in patients with thrombotic diseases should be considered to be associated with DIC.

ISSN:0957-5235    

出版商:OVID    

年代:1996

数据来源: OVID

ISSN:0957-5235    

出版商:OVID    

年代:1996

数据来源: OVID