摘要:

Venous thromboembolism (VTE) is a significant cause of morbidity and mortality in hospitalized patients. For many years, stasis in the deep veins of the legs has been recognized as being a necessary but not a sufficient cause of thrombosis. The recent demonstration of the high prevalence of a mutation at Arg506in the factor V gene ('factor V Leiden') in patients presenting with VTE has emphasized the protective role of activated protein C in neutralizing thrombin, and has highlighted the importance of genetic factors in the pathogenesis of venous thrombosis. For many if not most patients, the prothrombotic stimulus of a surgical operation with the accompanying stasis may be a sufficient cause for VTE if endogenous anticoagulant mechanisms are impaired. In populations with a high prevalence of the FV:Q506allele there is now a strong case for screening individuals for the mutant gene if they have a personal or family history of VTE, especially before surgery, during pregnancy or before prescribing oral contraceptives.

ISSN:0957-5235    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Serum or plasma sialic acid (SA) has been shown to be a possible risk factor for cardiovascular disease and to be elevated in diabetes mellitus. We postulated that plasma SA may be related to plasma fibrinogen, another reputed cardiovascular risk factor. We decided to test this hypothesis in 27 patients with non-insulin-dependent diabetes mellitus (NIDDM) and 27 age-and sex-matched control subjects. Plasma fibrinogen was significantly elevated in the diabetic patients compared with the control subjects (3.4 ± 1.5 g/l versus 2.2 ± 0.60 g/l,P< 0.001). Similarly, plasma SA was elevated in the diabetic patients in comparison with the control subjects (0.74 ± 0.14 g/l versus 0.62 ± 0.08 g/l,P< 0.001). There was a strong univariate correlation between plasma fibrinogen and plasma SA in both NIDDM patients (r= 0.80,P< 0.001) and control subjects (r= 0.54,P< 0.01).

ISSN:0957-5235    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

The effect of oral contraceptive therapy was studied in five patients with homozygous activated protein C resistance. Patients with this congenital abnormality, in contrast to those with antithrombin, protein C or protein S deficiencies, showed only a mild thrombotic tendency. In fact, only two of six observations (one patient took the pill on two separate occasions many years apart) showed deep vein thrombosis. No patient had pulmonary embolism. Two additional patients had a superficial vein thrombosis of the legs. In two instances, a superficial vein thrombosis and a deep vein thrombosis, concomitant risk factors were present (immobilization and surgery for an ovarian cyst, respectively). However, compared with heterozygous for the same abnormality, the symptomatic homozygous patients with APC resistance appeared to develop thrombosis after a shorter period of oral contraception.

ISSN:0957-5235    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

The very early anticoagulant response was analysed in non-pregnant female New Zealand rabbits infused with rabbit brain tissue thromboplastin for a period of 10 min (n= 6), 20 min (n= 6), and 30 min (n= 6). The rabbits infused with thromboplastin responded with a significant drop in mean arterial pressure (P< 0.05), an increase in blood paO2(P< 0.05) and a decrease in paCO2(P< 0.05), while control animals remained stable with respect to these variables. The thromboplastin-treated animals had an immediate drop in platelet count (P< 0.05), plasma fibrinogen (P< 0.05) and a prolongation in prothrombin time (P< 0.05) and activated partial thromboplastin time (P< 0.05). The concentrations in a number of proteins involved in the anticoagulant response (antithrombin, plasminogen, antiplasmin) as well as global fibrinolytic activity did not change significantly following 10, 20 and 30 min infusion of thromboplastin, while the concentration of protein C decreased continuously during the infusion periods (P< 0.05) to reach the lowest level (∼60%) in animals infused with thromboplastin for 30 min. The animals infused with tissue thromboplastin had microthrombi in 1–6% of the renal glomeruli, but the number of microthrombi did not differ significantly between animals infused for 10, 20 and 30 min. It is concluded that the protein C system may play a key role during the initial phase of intravascular coagulation and immediate activation of protein C may protect against excessive deposition of fibrin.

ISSN:0957-5235    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

The aim of this study was to compare thein vitroeffects of different classes of contrast media on both the blood coagulation system and on platelet function. Global tests (APTT, TT) and FpA and F1 + 2 generation measurements showed that ioxaglate (ionic dimer) presents the highest anticoagulant potential. The anticoagulant effects of nonionic agents were less marked, iodixanol (nonionic dimer) being significantly less anticoagulant than iohexol (nonionic monomer). Major platelet activation was observed with release of PF4, serotonin and PDGF-AB when iohexol was incubated for 1 min in whole blood. Iodixanol showed no effect over the same period, while moderate platelet activation was observed after 30 min. Under the same experimental conditions, ioxaglate had no effect on platelets even after incubation for 30 min, whereas activation was observed with the 9 g/l saline control at this time. Prevention of thrombin formation and platelet activation is only achieved with ioxaglate, the ionic dimer. These findings may be clinically important in the thrombotic environment of radiological procedures and may explain the increased thrombotic risks observed with nonionic agents in interventional procedures.

ISSN:0957-5235    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

There is some clinical evidence that cyclosporine A (CyA) is associated with thrombotic complications of bone marrow and renal transplantation. We investigated plasma concentrations of lipoprotein(a) [Lp(a)], a potentially atherothrombotic lipoprotein, and hemostatic and vascular status in ten patients with aplastic anemia receiving CyA, eleven patients not taking it, and 38 age-matched healthy controls. Patients receiving CyA had significantly higher concentrations of plasma fibrinogen (P< 0.05), prothrombin fragment 1+2 (F1 + 2;P< 0.05), plasminogen activator inhibitor-1 (PAI-1;P< 0.05), and von Willebrand factor antigen (P< 0.05) than did patients not taking CyA. Plasma concentrations of Lp(a) were higher in CyA-treated patients than those not receiving it (P< 0.05) or healthy controls (P< 0.05). The difference in the Lp(a) concentration between controls and patients who did not receive CyA-treatment was not significant. Our results suggest that hypercoagulability is likely to occur during CyA therapy. Further, the presence of high concentrations of Lp(a) may accelerate the process of atherosclerosis and increase thrombotic events in patients receiving long-term CyA.

ISSN:0957-5235    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Nitric oxide (NO) is known as a regulator of platelet function by its anti-adhesive, anti-aggregating, and disaggregating properties. We investigated the modulating effects of the NO-releasing compound SIN-1 (3-morpholino-sydnonimine) on platelet surface glycoprotein (GP) expression during stimulation with human α-thrombin. Analysis was performed with two-color flow cytometry using fluoresceine-isothiocyanate (FITC) and phycoerythrin-(PE)-conjugated monoclonal antibodies (MoAbs) directed against GPIb (CD42b), GP IIb-IIIa (CD41), P-selectin (CD62P), and MoAb PAC-1 directed against activated GP IIb-IIIa. Preincubation of platelets with SIN-1 (IC50: 1 μM) significantly decreased expression of both total and activated GP IIb—IIIa, and P-selectin in platelets stimulated with thrombin (ED50: 0.05 U/ml), whereas thrombin-induced downregulation of GP lb was not attenuated. P-selectin expression increased in thrombin-stimulated platelets over time; in contrast, activated GP IIb-IIIa decreased after an initial peak, indicating that thrombin-induced GP IIb-IIIa activation is spontaneously reversible. SIN-1 reduced P-selectin expression only when added before or at the same time as thrombin, whereas conformationally changed GP IIb-IIIa was significantly reversed at up to 60 minutes after stimulation by SIN-1. In conclusion, NO attenuates activation marker expression in a dose and time dependent manner. GP IIb-IIIa is highly sensitive to NO which not only prevents receptor activation but also promotes reversal of activated GP IIb-IIIa complex.

ISSN:0957-5235    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

RNA-based studies are an important tool for the identification and functional characterization of mutations underlying inherited disease. These studies could in principle be compromised by ‘aberrant splicing’ (the generation of alternatively spliced transcripts lacking any obvious function) during normal expression of the genes under investigation. Using a highly sensitive RT-PCR assay, we show here that aberrant splicing is a frequent occurrence during expression of the protein C (PROC) and protein S (PROS) genes. Aberrantly spliced transcripts were present in different cell types including liver, the main expressing tissue for both protein C and protein S. In an attempt to compare individual mRNA splicing patterns,PROCandPROSRNA from easily accessible cells of different healthy control individuals was studied. However, variation between different RT-PCR assays from the same individual precluded both the relative quantitation of the aberrant transcripts and the analysis of interindividual differences. Our findings are consistent with the notion that a low level of aberrantly spliced transcripts are routinely generated duringPROCandPROSgene expression. The possibility that these transcripts may complicate the RT-PCR analysis of pathological transcripts must be taken into account when RNA-based strategies of disease analysis are considered.

ISSN:0957-5235    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Plasma antithrombin-III (AT-III), protein S, and protein C were measured during myocardial stunning (MS) and acute myocardial infarction (AMI). The effects of magnesium (Mg), diltiazem, and a Mac-1 inhibitor on their plasma levels were elucidated. Forty-nine open-chest swine underwent brief (8 min), or prolonged (50 min) coronary artery occlusion followed by reperfusion. During MS an increase in the plasma AT-III (from 98.5 ± 3.38% to 138.1 ± 3.6%) during the early occlusion phase, without any further changes was observed. The profile of total protein S was not changed during MS. Protein C increased at the end of occlusion (from 45.3 ± 1.8% to 55.7 ± 1.4%) reaching a peak (64.5 ± 1.4%) at the beginning of reperfusion. When compared with controls, no significant differences were found in the antithrombotics profile during MS after pretreatment with Mac-1 inhibitor. For the AMI, the AT-III decreased during occlusion (from 98.5 ± 3.4% to 61.0 ± 3.6%). The protein S decreased during occlusion with the lowest level at 1 h of reperfusion (from 71.8 ± 2.2% to 46.7 ± 1.0%), followed by an increase during late reperfusion (59.2 ± 1.5%). Contrarily, protein C increased during occlusion and early reperfusion (from 44.7 ± 2.6% to 79.4 ± 2.4%), but declined to 49.6 ± 2.5% thereafter. In both Mg and diltiazem-treated swine, protein C was higher at the end of occlusion and during the entire reperfusion period compared with controls. Mg and diltiazem therapy was associated with the slight elevation of plasma AT-III. The patterns for protein S level during ischemia-reperfusion were similar with the controls. Protein S was higher at the end of occlusion and through the entire reperfusion in the NPC 15669-treated animals when compared with the controls. Mac-1 inhibition was associated with the elevated protein C during late reperfusion. Ability of Mg, diltiazem, and a Mac-1 inhibitor to favorably modulate the plasma level of antithrombotics have direct clinical implications for the use of these agents in patients with acute coronary artery syndromes.

ISSN:0957-5235    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Lipoprotein(a) [Lp(a)], and to a lesser extent low-density lipoprotein (LDL), have been shown to compete with plasminogen for binding to the extracellular matrix (ECM). Evidence exists that modification of lipoproteins alters their atherogenic properties. Therefore in the present study the effect of modifying Lp(a) and LDL by copper-inducedin vitrooxidation on their ability to compete with plasminogen for binding to the ECM was studied. Oxidation of Lp(a) resulted in increased competitiveness for plasminogen binding. This effect was dependent on the Lp(a) concentration used, as well as the extent of oxidation. In the highest Lp(a) concentration used (100 nmol/l apo B100), inhibition of plasminogen binding was further increased with almost 30% compared with native Lp(a). In contrast, oxidation of LDL resulted in an additional inhibition of plasminogen binding of about 10% at all concentrations used. In separate experiments Lp(a) and LDL were modified by neuraminidase treatment. After desialylation a strong tendency for better competitiveness of Lp(a) was observed. Desialylation of LDL had no effect on its ability to compete with plasminogen for binding to the ECM. Modification of the additional and distinguishing apolipoprotein [i.e. apo(a)] in Lp(a) by oxidation and desialylation most likely explains the difference in behaviour of Lp(a) and LDL. It is concluded that modification by oxidation, and to a lesser extent desialylation, increases the anti-fibrinolytic potential of Lp(a).

ISSN:0957-5235    

出版商:OVID    

年代:1996

数据来源: OVID