摘要:

Prothrombin (factor II) deficiency was first described in 1947 by Quicket al., although the first prothrombin abnormality was reported in 1969 by Shapiroet al.The condition is still considered very rare. In spite of its rarity, the defect has allowed important improvements in our understanding of both congenital and acquired prothrombin deficiencies. The diagnosis of prothrombin deficiency or abnormality can be made using a combination of clotting, chromogenic and immunological assays. In cases of true deficiency, a parallel decrease in all these assays is observed, regardless of the activating agent. If discrepancies among the clotting assays are noted, particularly using viper venoms, a dysprothrombinemia should be suspected. Usually, activity levels less than 10% of normal are found in homozygotes, and between 40 and 60% in heterozygotes. Factor II levels in congenital dysprothrombinemias are more variable since one may encounter homozygotes, heterozygotes and compound heterozygotes between a heterozygous abnormality and heterozygous ‘true’ deficiency or between two distinct abnormalities. Usually the levels of factor II vary between 1 and 50% of normal. Antigen levels in congenital dysprothrombinemias will be normal, near normal or slightly decreased but always higher than the clotting counterpart. Cases with a parallel decrease in prothrombin activity and antigen should not be considered as examples of hypoprothrombinemia. The gene involved in the synthesis of prothrombin is located in chromosome 11. It is composed of 10 exons and 8 introns. Molecular biology studies have discovered several point mutations in some of the dysprothrombinemias. Bleeding manifestations may be severe in homozygous ‘true’ deficiency and may be more variable in dysprothrombinemias. Heterozygotes are usually asymptomatic. Prognosis is variable and generally in agreement with the prothrombin activity level. In homozygous true deficiency, hemarthroses and intracranial bleeding have been described. Substitution therapy is based on the administration of prothrombin complex concentrates or of plasma. The long half-life of prothrombin injected, about 70 h, allows the achievement of hemostatically effective levels (about 50% of normal) without difficulty.

ISSN:0957-5235    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

We studied the effect of synthetic pentasaccharide, a low-molecular-weight heparin (enoxaparin), unfractionated heparin and recombinant hirudin on the generation of factor VIIa (FVIIa) and prothrombin activation after in-vitro clotting of human platelet-poor plasma. FVIIa was measured with a new clotting assay that uses recombinant tissue factor truncated to interact only with FVIIa. Residual prothrombin was measured using the conventional clotting assay. FVIIa and residual FII were measured in the liquid - called pseudo-serum (Ψ-serum) - obtained 1 h after clotting of normal platelet-poor plasma. A kinetic study of the generation of FVIIa was also performed. Coagulation was initiated by triggering the extrinsic, the intrinsic and both associated clotting pathways. Levels of FVIIa in the Ψ-sera (55 ± 15, 258 ± 18, and 164 ± 18 ng/ml, in the extrinsic, intrinsic and intrinsic + thromboplastin Ψ-serum respectively; values are means ± SEM) were significantly increased compared with those in the platelet-poor plasma (3 ng/ml). Pentasaccharide, low-molecular-weight heparin and unfractionated heparin inhibited the generation of factor VIIa or its activity, or both, in a dose-dependent manner in all the experimental systems (60–90% inhibition). A kinetic study revealed that the inhibition of the generation of FVIIa by pentasaccharide and heparins starts 1 min after triggering either the extrinsic or the intrinsic clotting pathway. The downregulation of FVIIa by heparins was effected mainly by their anti-Xa activity, but also by their inhibitory effect on the generation of prothrombinase. Pentasaccharide, enoxaparin and unfractionated heparin significantly inhibited prothrombin activation in both extrinsic and intrinsic experimental system. Hirudin had no inhibitory effect either on the generation of FVIIa or on prothrombin activation in any experimental system.

ISSN:0957-5235    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

The effect of percutaneous mitral valvuloplasty (PMV) on markers of coagulation and platelet activation was investigated to assess whether coagulation or platelet activation take place during and after PMV even under conditions of full heparinization. Before PMV, all the hemostatic parameters studied were in the normal range compared with those of a control group. Two hours after PMV the levels of prothrombin fragment F1 and 2 (F1+2) (1.6 ± 0.6 nmol/1 versus 0.8 ± 0.3 nmol/1,P< 0.005), plasma thrombin-antithrombin III (TAT) complexes (5.4 ± 3.2 ng/ml versus 2.2 ± 0.9 ng/ml) and β-thromboglobulin (119 ± 70 ng/ml versus 42.2 ± 41 ng/ml) had increased significantly compared with those measured at basal conditions. Activated partial thromboplastin time was significantly prolonged (152 ± 40 s versus 21 ± 5 s), reflecting full heparinization. Levels of fibrinogen, F1+2, TAT and β-thromboglobulin remained increased 72 h after PMV. We conclude that patients with severe, symptomatic mitral stenosis undergoing PMV need a more specific antithrombotic therapy or a more prolonged and perhaps less intensive heparinization.

ISSN:0957-5235    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Heparin has been used extensively for prophylaxis and treatment of deep vein thrombosis. However, heparin has several limitations including a short intravenous half-life, inability to inhibit clot-bound thrombin, and bleeding. We have developed a covalent antithrombin-heparin complex (ATH) that has a longer intravenous half-life and greater anticoagulant activity than heparin. The antithrombotic activity of ATH was tested in a rabbit jugular vein thrombosis treatment model. Administration of ATH caused a 17% reduction in clot weight compared with an increase of 24, 60, 172 and 135% for administration of antithrombin plus heparin heparin, antithrombin and saline, respectively. Clot weight and fibrin accretion were both significantly lower in the ATH group than in the antithrombin plus heparin group (P< 0.05). The peak anti-factor-Xa activity was fourfold higher in the ATH group than in the antithrombin plus heparin group. Using a rabbit bleeding ear model, there was no significant difference in cumulative blood loss between ATH and antithrombin plus heparin groups, at similar plasma anti-factor-Xa levels. In conclusion, ATH has superior antithrombotic activity and similar bleeding effect compared with heparin on a mass basis. The enhanced antithrombotic activity of ATH may be a result of its increased anticoagulant activity or its longer half life, or both.

ISSN:0957-5235    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Several recent studies have reported contradicting results concerning the relevance of the plasminogen activator inhibitor-1 (PAI-1) 4G/5G-polymorphism for myocardial infarction. In addition, the common factor V Q506 (FV:Q506) mutation is frequently discussed as a risk factor for arterial thrombosis, but evidence is rare. In order to further highlight the role of both polymorphisms in myocardial infarction, we investigated 241 young male myocardial infarction patients (≤ 45 years-of-age) aged 38.6 ± 4.4 years (mean ± SD) for the presence of both genotypes. The control group consisted of 179 healthy men aged 47.1 ± 6.4 years (mean ± SD) of the same ethnic background as the patients. Neither the distribution of the PAI-1 4G/5G-polymorphism nor the prevalence of the FV:Q506 mutation was significantly different between young patients and controls (4G/4G-genotype:x2= 2.08, NS; odds ratio 1.36, 95% confidence interval 0.89–2.06; FV:Q506 mutation:x2= 0.33, NS; odds ratio 1.33, 95% confidence interval 0.64–2.78). Moreover, the PAI-1 4G/5G-distribution did not differ significantly between patients and controls in subgroups by tertiles of triglyceride levels. In conclusion, in the present study neither homozygosity for the 4G allele of the PAI-1 4G/5G-polymorphism nor the FV:Q506 mutation led to an increased risk of myocardial infarction in young men.

ISSN:0957-5235    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

A semiquantitative enzyme-linked immunosorbent assay (ELISA) test (Instant IA D-dimer) and a new quantitative rapid and individual test (STA-Liatest DDi) were compared with the reference microplate ELISA (Asserachrom D-Di) for D-dimer testing in 142 patients clinically suspected of pulmonary embolism, on the basis of clinical symptoms and signs, electrocardiogram, blood gases and chest X-Ray abnormalities. The cut-off value for the quantitative tests was 500 ng/ml and Instant IA was interpreted by three readers. Pulmonary embolism was confirmed by lung scan or angiography in 60 patients (42%). The sensitivities of ELISA and STA-Liatest DDi were 92% [95% confidence interval (CI) 82–97%] and 93% (95% CI 84–98%), respectively. The three readings of Instant IA D-dimer disagreed in 27 (19%) of the patients and sensitivity varied from 83 to 93% according to the readers. In the 115 patients with concordant readings, sensitivity was 92% (95% CI 82–98%). These results suggest that STA Liatest DDi may be used instead of microplate ELISA for the exclusion of pulmonary embolism, whereas the use of Instant IA D-dimer for this purpose is limited by the number of discordant results.

ISSN:0957-5235    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Epidemiological studies have demonstrated that levels of plasma fibrinogen, von Willebrand factor (vWf), plasminogen activator inhibitor-1 (PAI-1) and tissue-type plasminogen activator (tPA) are associated with the incidence of vascular disease. Since oncostatin M dramatically induces fibrinogen biosynthesis by hepatocytes and could be implicated in vascular injury leading to atherosclerosis, we have analyzed the effect of oncostatin M on PAI-1, vWf and tPA secretion by endothelial cells. A 2-h incubation of human umbilical vein endothelial cells with oncostatin M increases thrombin-induced secretion of vWf to the same extent as tumour necrosis factor-aor interleukin-1 (137 ± 26% of control for 5 ng/ml oncostatin M,P< 0.001,n= 5). The effects on tPA and PAI-1 secretion were different depending on the type of endothelial cells tested. On human umbilical vein endothelial cells, oncostatin M induced an increase in PAI-1 and a decrease in tPA secretion, which could explain the thrombogenicity of oncostatin M on large vessels. On a human microvasculature endothelial cell line, oncostatin M did not modify PAI-1 but induced an increase in tPA secretion. This observation of the effects of oncostatin M on both macro- and microvasculature could explain the increased levels of vWf, PAI-1 and tPA in the plasma of atherosclerotic subjects identified in epidemiological studies, suggesting that oncostatin M could play a key role in the development of atherosclerotic lesions.

ISSN:0957-5235    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

The purpose of this study was to investigate the role of genetic polymorphisms associated with venous and arterial thrombosis in patients with retinal vein occlusion (RVO). One-hundred and two consecutive patients with RVO were examined for factor V G1691A and factor II G20210A, methylenetetrahydrofolate reductase (MTHFR) C677T and apolipoprotein E4by amplification of specific DNA fragments and restriction analysis. The risks exerted by these polymorphisms and by the conventional risk factors of RVO were evaluated by comparing their frequencies among patients and controls and by estimating the respective odds ratios. We found that the prevalences of the factor V G1691A, factor II G20210A, and apolipoprotein E4polymorphisms were similar in the study and control groups. Logistic regression analysis involving the parameters for which significant differences were detected disclosed an odds ratio of 1.9 for MTHFR C677T homozygosity (95% confidence interval 0.95–3.81), an odds ratio of 2.12 for hypertension (95% confidence interval 1.16–3.73) and an odds ratio of 3.25 for a family history of stroke (95% confidence interval 1.07–9.51). Our data suggests that homozygosity for the MTHFR C677T polymorphism is a risk factor of RVO in addition to arterial hypertension and a family history of stroke.

ISSN:0957-5235    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

The distinction between a specific factor inactivator and a non-specific inhibitor is important when confronted by a patient with a history of bleeding and abnormal in-vitro coagulation tests. We report on two patients who presented with bleeding and a prolonged activated partial thromboplastin time. Initial factor assays suggested combined deficiency of factors VIII and IX as a result of the presence of inactivators. The use of dilution studies, chromogenic assays, a novel in-house enzyme-linked-immunosorbent-assay-based technique and phospholipid neutralization, demonstrated that Case 1 had a genuine factor VIII inactivator resulting in factor VIII levels of less than 1 IU/dl but no factor IX deficiency. Case 2 had normal levels of factor VIII on further testing and no specific inactivator to either factor VIII or IX but a potent antiphospholipid antibody which had interfered with the phospholipid-dependent in-vitro assays. Care must be taken in the interpretation of laboratory assays in the presence of antiphospholipid antibodies to ensure that the correct diagnosis is made and inappropriate treatment avoided.

ISSN:0957-5235    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

In addition to calcium, other physiologically important divalent cations (magnesium and zinc) are known to influence fibrin formation and structure. We have studied the effect of different concentrations (0–20 μmol/l) of zinc ions (Zn2+) in the absence and presence of calcium on the gel structure formed in purified fibrinogen-enzyme systems. For that purpose, we used turbidity measurement, liquid permeation and confocal three-dimensional microscopy of the gel as well as sodium dodecyl sulphate (SDS)-gel electrophoresis. The results of turbidity measurements indicated that the clotting time decreased with increasing concentrations of Zn2+. The fiber mass: length ratio (μ) values showed that the porosity of the gels increased in a concentration-dependent manner, i.e. at higher concentrations of Zn2+, larger pores with thicker fibrin fibers were formed. Three-dimensional microscopy data of the gels were in good agreement with the μ data. On SDS-gel electrophores of reduced fibrin, no cross-linking was observed in the presence of zinc ions only (without the addition of calcium ions), nor were D-D dimer bands observed in non-reduced plasmin digested fibrin samples in the presence of zinc ions only. The above results show that zinc changes the fibrin gel structure and that this effect appears to be independent of calcium.

ISSN:0957-5235    

出版商:OVID    

年代:1998

数据来源: OVID