摘要:

To investigate the relationship between changes in plasma concentrations of polymorphonuclear elastase (PMN-E) and haemostatic effects during haemodialysis (HD), changes in the plasma concentrations of elastase-alpha1proteinase inhibitor complex (E-α1PI) and fibrinogen (Fbg), cross-linked fibrin degradation products (XDP), thrombin-antithrombin III complex (TAT), plasmin-α2plasmin inhibitor complex (PIC) and soluble thrombomodulin (TM) in 49 patients with end-stage chronic glomerulonephritis maintained on chronic HD were measured. Plasma concentrations of TAT, PIC, TM and E-α1PI significantly increased during a single HD. There was a statistically significant correlation between change in plasma E-α1PI concentration and changes in plasma concentrations of TAT, PIC and TM during a single HD, as well as between changes in plasma concentrations of TM and TAT during a single HD. These observations suggested that activation of coagulation and fibrinolysis, endothelial cell damage, and activation of polymorphonuclear cells occur during HD. Activation of polymorphonuclear cells may induce activation of coagulation and fibrinolysis, leading to endothelial cell damage, augmented by release of proteases such as elastase.

ISSN:0957-5235    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

The aim of this study was to synthesize and investigate hybrid peptides which contain the RGD (Arg-Gly-Asp) sequence coupled with lysine residues in special arrangements (antiplasmin carboxyterminal peptide) in an effort to simultaneously inhibit platelet aggregation and promote fibrinolysis. Thein vitrohaemostatic modifying properties of the synthesized peptides were tested by ADP-induced platelet aggregation, plasmin-generation tests and fibrin-clot lysis assays. The hybrid peptide RGDFAP, composed of RGDF (Arg-Gly-Asp-Phe) coupled to a synthetic peptide residue of the carboxyterminal part of antiplasmin (AP26) inhibited platelet activation and increased plasmin generation andin vitrofibrin-clot lysis.

ISSN:0957-5235    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

The long-term effects of fish-oil supplementation on haemostatic parameters and bleeding episodes were investigated in patients undergoing coronary artery bypass surgery. They were investigated before and 9 months after the operation. Following randomization post-operatively, 260 patients received 4 g fish-oil concentrate per day, whereas 251 patients comprised the control group. All patients received either aspirin (300 mg/day) or warfarin (international normalized ratio aimed at 2.5–4.2). Compliance was affirmed by determination of serum phospholipid fatty acids. No excess of bleeding episodes could be attributed to the use of fish oil, given in addition to either aspirin or warfarin. The supplementation of fish oil did not affect the bleeding time or plasma levels of beta-thromboglobulin, whereas an increase in the platelet count after the operation was slightly less pronounced in the fish-oil group. Apart from a small increase in PAI-1 antigen of borderline significance, no long-term effects by fish oil on parameters of coagulation and fibrinolysis were seen.

ISSN:0957-5235    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Protein C deficiency is an autosomally inherited disorder that is associated with a high risk of recurrent venous thrombosis. The authors have shown that temperature gradient gel electrophoresis (TGGE) is a simple and rapid screening method for the detection of mutations in the protein C gene. Samples from eleven patients with sequence defined point mutations in the promoter region of exon I, and in exons II, III, VII, VIII and IX were analysed by TGGE. In all cases the mutations were readily detected. The exons IV, V and VI were not submissive to TGGE analysis due to amplification difficulties. However, specific computer calculations predict a more general applicability of TGGE for the detection of any mutation in the protein C gene. The presented data establish the usefulness of TGGE as a simple and rapid screening method for the detection of hereditary mutations in the protein C gene.

ISSN:0957-5235    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Ten per cent of patients with haemophilia A develop intracranial haemorrhage (ICH) with a mortality rate of 30% and an incidence of psycho-neurological sequelae in 50% of survivors. ICH may be spontaneous or in association with trauma and other pathology. The generally recommended management is conservative replacement therapy using bolus injections of factor VIII and no neurosurgical intervention. Adjusted dose continuous infusion therapy provides an alternative method of factor VIII administration that is simple, more cost effective and safer through the maintenance of stable plasma VIII:C levels. This method has been successfully used to cover general surgery and the conservative treatment of subarachnoid haemorrhage but is not widely used due to unfamiliarity with the technique. This paper describes the use of continuous infusion of factor VIII concentrates to cover the successful neurosurgical management of a young man with severe haemophilia A who presented with an ICH associated with a bleeding choroid plexus tumour. Surgery was complicated by the development of a factor VIII inhibitor which disappeared following treatment with an immune-tolerance induction programme.

ISSN:0957-5235    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

This paper reports the case of an adult patient with severe protein C (PC) deficiency. She had the first deep vein thrombosis when she was 14 years old and developed skin necrosis when oral anticoagulant treatment was started. The same sequence of thrombotic complications recurred several times. Analysis of the PC gene coding sequences allowed two mutations (Arg-1 to His and Arg 178 to Gln) to be identified in this compound heterozygote. Oral anticoagulant treatment during PC concentrate infusion and low-molecular-weight heparin administration was successful and uncomplicated.

ISSN:0957-5235    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

It has been proposed that cyclic adenosine monophosphate (cAMP) is involved in the differentiation of several cell types and this study analysed whether von Willebrand factor (vWf) synthesis, which is a marker of the megakaryocyte maturation of these cells, would be enhanced by agents acting on cAMP formation. Different compounds known to stimulate cAMP accumulation in cells were used: dibutyryl cAMP (db-cAMP), isobutyl-methylxanthine (IBMX) or pentoxifylline (PTX) and forskolin. Treatments with db-cAMP or IBMX (10–1 000 μM) induced a dose-dependent increase in vWf synthesis. Associations of IBMX with forskolin produced a synergistic enhancement in vWf synthesis. PTX alone did not enhance vWf synthesis but a latent effect was revealed in the presence of forskolin or db-cAMP. The increase in vWf mRNA shown by Northern blot analysis demonstrates that the protein synthesis correlates with the transcript expression after db-cAMP or IBMX treatments. vWf synthesis paralleled the accumulation of cAMP in the cells. Moreover vWf expression induced by combination of IBMX with forskolin was associated with a moderate increase in the percentage of GPIIb/IIIa positive cells and in the ploidy level related to an important inhibition of cell growth. These data provide evidence that agents acting on cAMP metabolism induce vWf synthesis in the Dami megakaryoblastic cells.

ISSN:0957-5235    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Three unrelated families have been identified with mutations involving asparagine 187. Two of these families are asymptomatic and were identified during the screening of random blood donors, whilst the third has a history of recurrent thromboembolic disease. In two families the mutation (6460 AAC→GAC) results in an asparagine to aspartate substitution and is associated with normal immunological levels of antithrombin but a reduction in functional activity. In the third family the mutation (6462 AAC→AAA) results in an asparagine to lysine substitution at residue 187 and is associated with a parallel reduction in both immunological and functional antithrombin levels. Asparagine 187 is located in the middle of the F helix of antithrombin and forms the major link between the F helix and strand 3 of the A sheet. The F helix is seen to overlie the A sheet of the molecule and moves with strands 2 and 3 of this sheet as they open to allow entry of the reactive site loop to form strand 4. Substitutions of asparagine 187 are, therefore, likely to disrupt this sliding movement leading to a loss of inhibitory activity.

ISSN:0957-5235    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

A high intake of β-carotene has been associated with a decreased risk for cardiovascular disease. To evaluate whether β-carotene may exert a protective effect through an impact on haemostasis a randomized, placebo-controlled trial was conducted in male smokers (n= 149) using 20 mg/day β-carotene for 14 weeks. For comparisons, haemostatic indicators were also evaluated in a group of non-smokers (n= 54). Smokers compared with non-smokers had higher fibrinogen (3.5vs.3.1 mg/ml,P< 0.01), higher tissue-type plasminogen activator antigen (t-PA; 8.03vs.6.60 ng/ml,P< 0.05), lower levels of soluble fibrin (3.40vs.5.16 μg/ml,P< 0.01) and slightly higher plasma levels of total degradation products of fibrin and fibrinogen (TDP; 47.0vs.41.3 ng/ml,P= 0.21). Within the group of smokers, there were no initial differences in the four haemostatic indicators between the placebo (n= 77) and β-carotene (n= 72) groups, and in both groups there was virtually no change in the indicators during the 14 weeks treatment. It is concluded that the different haemostatic profile in smokers may partly explain their increased risk for cardiovascular disease. β-Carotene has no influence on the measured haemostatic indicators, and cardiovascular protection for β-carotene via a beneficial effect on haemostasis seems improbable.

ISSN:0957-5235    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

The purpose of this pilot study was to determine the effect of recombinant hirudin (r-hirudin) on coagulopathy and the relationship between concentrations of thrombin-antithrombin III (ATIII) complex (TAT) and thrombin-hirudin complex (THC) in patients with disseminated intravascular coagulation (DIC). Five patients with haematological malignancy associated with DIC were studied. r-Hirudin was administered by continuous intravenous infusion at a dose of 0.005 mg/kg/h for 4–9 days to each patient. Fibrin/fibrinogen degradation products (FDP), D-dimer, TAT and plasmin-α2antiplasmin complex (PAP) concentrations decreased after treatment with r-hirudin in four patients studied. However, in one patient, serum creatinine increased to 1.7 mg/dl and aPTT was prolonged to 74.4 s. Statistical analysis disclosed significant positive correlations between plasma concentrations of hirudin and THC, and between concentrations of THC and TAT. The concentrations of THC were much higher than those of TAT. In conclusion, these findings indicate that r-hirudin more strongly inhibited thrombin than did ATIII without heparin, and that administration of r-hirudin to renal insufficiency required individual adjustment of dosage. The present findings also suggest that r-hirudin can be considered a new agent for the treatment of DIC.

ISSN:0957-5235    

出版商:OVID    

年代:1995

数据来源: OVID