Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We identified a group of 24 young (less than 50 years of age) women with isolated, premature atherosclerotic aortoiliac occlusive disease and attempted to identify distinguishing hemostatic characteristics. Most of these patients (62%) presented with acute thromboembolic events (blue toe syndrome, n = 6; macroemboli, n = 6; or aortoiliac thrombosis, n = 3). Aortoiliac reconstruction (aortoiliac endarterectomy, n = 10, aortobifurcation bypass grafts, n = 6; and percutaneous angioplasty, n = 4) was complicated by early thrombosis in 6 of 20 cases (30%), (1 of 10 endarterectomies, 4 of 6 bypass grafts, and 1 of 4 angioplasties). Fresh thrombus overlying an atherosclerotic plaque was a common finding at surgery. This observation and the relatively high incidence of thromboembolic events led us to hypothesize that a characteristic hemostatic profile might underlie the remarkably similar clinical presentations of these women. Levels of antiphospholipid antibodies (anticardiolipin antibodies and lupus anticoagulant), plasminogen activator inhibitor-1, fibrinogen, antithrombin III, protein C, protein S, plasminogen, prothrombin fragment F1 + 2, and D-dimer were determined for these young women and for 21 age-matched white female control subjects without vascular disease and nine white male patients with aortoiliac occlusive disease (mean 61 years, range 43 to 74 years). The incidence of anticardiolipin antibodies was 42% (8 of 19) in the female patients, which was significantly elevated (p = 0.028). The female (62.5%) and male (100%) patients had significantly elevated D-dimer levels (p < 0.001). Deficiencies of antithrombin III, protein C, and protein S were rare. A unique pattern of premature aortoiliac atherosclerosis exists in some young women. Intra-arterial thromboembolic events are common at presentation and complicate surgical management. The role of antiphospholipid antibodies remains uncertain.
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PMID:Young women with advanced aortoiliac occlusive disease: new insights. 898 71

Recently, we found an increase in tissue factor pathway inhibitor (TFPI) activity in patients with insulin-dependent diabetes mellitus (IDDM). This increase in TFPI activity could be the result of increased thrombin formation and/or altered binding of TFPI to glycosaminoglycans. We studied TFPI activity (chromogenic assay) in relation to prothrombin F1 + 2 fragments and endogenous thrombin potential (ETP), in 46 IDDM patients, and 18 age and sex-matched healthy controls. Prothrombin, antithrombin and thrombomodulin were also determined. In IDDM patients, TFPI activity and F1 + 2 levels were significantly higher, while ETP, prothrombin antigen levels, and antithrombin activity were lower as compared to the controls. In IDDM patients with microalbuminuria, a manifestation of generalized angiopathy, TFPI activity, F1 + 2 and thrombomodulin levels were higher than in patients with only retinopathy or patients without complications. No correlation between TFPI activity, F1 + 2 levels and thrombomodulin was found, while TFPI activity was negatively correlated with ETP (r = -0.27). Microalbuminuria was significantly correlated with TFPI activity (r = 0.46), F1 + 2 (r = 0.56), and thrombomodulin (r = 0.52). In TFPI-depleted plasma, ETP increased, indicating that ETP is affected by TFPI. In conclusion, the increase in TFPI activity in IDDM patients may not be considered to be a reaction on a procoagulant state. It is hypothesized that vascular damage, leading to alterations in glycosaminoglycans, is in part responsible for the changes in TFPI activity, F1 + 2 levels and ETP.
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PMID:Increased tissue factor pathway inhibitor (TFPI) and coagulation in patients with insulin-dependent diabetes mellitus. 906 96

Male (NZW x BXSB)F1 (W/BF1) mice develop a systemic lupus-like syndrome characterized by thrombocytopenia, coronary vascular disease, nephritis, and anticardiolipin antibodies. Three stable hybridoma cell lines secreting monoclonal anticardiolipin antibodies were developed from these mice by fusing their splenic lymphocytes with nonsecreting myeloma cell line, NS-1. Monoclonal antibody A1.17 reacted with cardiolipin in a beta2-Glycoprotein I-dependent manner. The epitope for this antibody consisted of beta2-glycoprotein I bound to cardiolipin or immobilized on plastic plates. Other anionic phospholipid-binding proteins, such as prothrombin or annexin V, had no significant effect in the reactivity of these antibodies. The specificity is similar to the autoimmune anticardiolipin antibodies described in patients with systemic lupus erythematosus and other infectious diseases. In contrast, monoclonal antibodies A1.72 and A1.84 reacted with cardiolipin in the absence of beta2-glycoprotein I. Beta2-glycoprotein I, either in the fluid phase or bound to cardiolipin, inhibited the binding of these antibodies. The specificity of the latter two antibodies was similar to that described in patients with syphilis and allied disorders. Both types of antibodies had lupus anticoagulant properties. Thus lupus-prone male (NZW x BXSB)F1 (W/BF1) mice develop both beta2-glycoprotein I-dependent and beta2-glycoprotein I-independent anticardiolipin antibodies.
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PMID:Characterization of beta2-glycoprotein I-dependent and -independent "antiphospholipid" antibodies from lupus-prone NZW/BXSB F1 hybrid male mice. 932 49

Recently a novel polymorphism in the 3'-untranslated region of the prothrombin gene (a G to A transition at position 20210) was discovered, and an association with venous thrombosis and cardiovascular disease was found. The prevalence of the polymorphic allele in different human populations is unknown. We investigated the prevalence of the A 20210 allele of the prothrombin gene in 420 unrelated individuals (840 chromosomes) who belong to four different ethnic groups: Whites, African and Brazilian Blacks, Asians and Amerindians. PCR amplification followed by HindIII digestion was employed. The polymorphism was found in heterozygosity in 2 out of 120 Whites or a prevalence of 1.6% (allele frequency 0.8%), similar to that observed for other Caucasian populations. The A allele was absent among the other ethnic groups analyzed. Our data indicate that in non-Caucasians the prevalence of the 20210 G-->A mutation in the prothrombin gene, if any, must be extremely low. The absence of this novel genetic risk factor for venous and arterial thrombotic disease among non-Caucasians may contribute to explaining geographical and ethnic differences in the risk of vascular disease.
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PMID:Prevalence of the G20210A polymorphism in the 3'-untranslated region of the prothrombin gene in different human populations. 969 Nov 39

The 20210 G/A prothrombin gene mutation is associated with an increased risk of venous thrombosis but whether there is an association of the mutation with premature coronary artery disease and acute myocardial infarction remains unclear. To further assess the role of the G/A genotype as a risk factor for arterial vascular disease, we performed a case-control study of 644 patients aged less than 50 years with angiographically proven coronary artery disease, 402 of whom had myocardial infarction, and 679 unrelated healthy control subjects aged less than 50 years, randomly selected from the electoral roll. The prevalence of the G/A genotype was 2.5% in patients with coronary artery disease, and 3.2% in control subjects (odds ratio 0.8; 95% confidence interval 0.35 to 1.83). The mutation was not more frequent among patients with a history of myocardial infarction (2.2%, odds ratio 0.7; 95% confidence interval 0.27 to 2.05), and there was no evidence of an interaction between the prothrombin mutation and conventional cardiovascular disease risk factors. There was no association between genotype and extent of angiographic coronary artery disease (p=0.73). We conclude that the 20210 G/A prothrombin gene mutation is not a major risk factor for premature coronary artery disease in our predominantly Caucasian Australian population.
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PMID:No association between the 20210 G/A prothrombin gene mutation and premature coronary artery disease. 986 53

We report a patient who had an ischemic stroke aged 22 years, an inherited type I protein C deficiency and a heterozygous genotype of prothrombin gene 20210A. In view of recent reports of an increased risk for ischemic cerebral vascular disease in patients with the prothrombin 20210A mutation, we suggest that many of the reported cases of ischemic stroke and protein C deficiency may have had additional prothrombotic disorders such as the prothrombin mutation. The current data concerning the magnified risk for stroke in patients with the prothrombin 20210A mutation suggests the need to study all patients with premature stroke for this mutation and the other risk factors for thrombosis. This would include homocysteine, lupus inhibitor, anticardiolipin antibodies, and possibly the natural inhibitors of coagulation. It is possible that patients with the prothrombin 20210A mutation and ischemic cerebral vascular disease would benefit from long-term anticoagulation therapy in a similar way to patients with the antiphospholipid syndrome.
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PMID:Ischemic stroke in a young patient with protein C deficiency and prothrombin gene mutation G20210A. 989 Jul 20

The normal aging process alters blood coagulation system in humans; this may be of great concern in the view of the known association of vascular disease with advancing age. The plasma concentration of several coagulation factors, namely fibrinogen, factor VII, factor VIII, factor IX, high molecular-weight kininogen, and prekallikrein, increase in healthy humans, paralleling the physiological aging process. Plasma parameters of clotting activation in vivo, such as prothrombin fragment 1 + 2, fibrinopeptide A, thrombin-antithrombin III complex, and D-dimer, are positively correlated with age. Nevertheless, among centenarians, biochemical signs of marked hypercoagulability are associated with a healthy state. Natural anticoagulants, including antithrombin III, heparin cofactor II, protein C, protein S, and tissue factor pathway inhibitor, can modulate the reactions of blood coagulation system. The occurrence of menopause is accompanied by a significant increase in antithrombin III plasma level; the mean antithrombin III levels in older women exceed levels in male contemporaries. In healthy elderly subjects heparin cofactor II plasma concentrations are lower than in young subjects, independently of gender. Protein C levels raise with age in both sexes, as well as free protein S levels. In women, statistically significant increases in the plasma concentration of the tissue factor pathway inhibitor have been observed, whereas no significant age-related change has been found in men. The fact that many subjects with congenital defects of natural anticoagulants do not undergo thromboembolic events in young age suggests that in healthy individuals a raise in natural anticoagulants can balance the age-related increase of procoagulant factors.
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PMID:Natural anticoagulants, aging, and thromboembolism. 995 32

Several hereditary disorders affecting coagulation factors have been identified as prothrombotic risk factors. Recently, the prothrombin 20210 A/G mutation has been identified as a second important polymorphism involved in venous thrombosis. This article reviews all published information about this new procoagulant mutation. Our group has been involved in a number of studies about the role and importance of polymorphisms in thromboembolic disease, including the analysis of the prothrombin 20210 A/G mutation. Moreover, an extensive Medline literature search was made to complete the review using the key words: prothrombin mutation, 20210, venous or arterial thrombosis. The combination of environmental and genetic risk factors determines the relative risk that any individual has of suffering a thrombotic episode. Some genetic mutations affecting coagulation factors have been described. Recently, Poort et al. described a new mutation in the 3'-untranslated region of the prothrombin gene. The prothrombin 20210 G/A mutation, associated with elevated levels of factor II in plasma, significantly increases the risk of developing venous thrombosis. In fact, this polymorphism is the second most important genetic risk factor for venous thrombosis in Caucasian populations. Moreover, and supporting the multifactorial feature of thromboembolic diseases, this mutation greatly increases the possibility of developing a thrombotic episode when combined with other environmental or genetic risk factors. The role of this procoagulant mutation in arterial vascular disease is, however, unclear.
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PMID:The prothrombin gene variant 20210A in venous and arterial thromboembolism. 1019 Sep 40

Lipid-lowering by postmenopausal hormone therapy (HRT) explains only partly the assumed coronary risk reduction associated with therapy. To explore other possible mechanisms, we studied associations of HRT use with inflammation and hemostasis risk markers in women >/=65 years of age. Subjects were selected from 3393 participants in the fourth year examination of the Cardiovascular Health Study, an observational study of vascular disease risk factors. After excluding women with vascular disease, we compared levels of inflammation and hemostasis variables in the 230 women using unopposed estrogen and 60 using estrogen/progestin, with those of 196 nonusers selected as controls. Compared with nonusers, unopposed estrogen use was associated with 59% higher mean C-reactive protein (P<0.001), but with modestly lower levels of other inflammation indicators, fibrinogen, and alpha-1 acid glycoprotein (P<0.001). Factor VIIc was 16% higher among estrogen users (P<0.001), but this was not associated with higher thrombin production (prothrombin fragment 1-2), or increased fibrin breakdown (D-dimer). Concentration of plasminogen activator inhibitor-1 was 50% lower in both using groups (P<0.001) compared with nonusers, and this was associated with higher plasmin-antiplasmin complex: 8% higher in estrogen and 18% higher in estrogen/progestin users (P<0. 05). Relationships between the markers and hormone use were less pronounced in estrogen/progestin users, with no association for C-reactive protein except in women in upper 2 tertiles of body mass index (P for interaction, 0.02). The direction and strength of the associations of HRT use with inflammation markers differed depending on the protein, so it is not clear whether HRT confers coronary risk reduction through an inflammation-sensitive mechanism. Associations with hemostasis markers indicated no association with evidence of procoagulation and a possible association with increased fibrinolytic activity.
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PMID:Hormone replacement therapy, inflammation, and hemostasis in elderly women. 1019 15

The effect of homocysteine-lowering treatment on thrombin generation was investigated in 17 subjects with hyperhomocysteinemia (aged 22-60 years), 11 of whom had symptomatic atherosclerotic vascular disease. All subjects had fasting total homocysteine levels above 16 micromol/L. The formation of thrombin was assessed by measuring thrombin-antithrombin III complexes and prothrombin fragment 1+2 in peripheral venous blood and in the bleeding time blood collected at 30-second intervals from skin incisions on a forearm. All the tests were performed before and after an 8-week treatment with folic acid p.o. 5 mg/day, vitamin B6 p.o. 300 mg/day, and vitamin B12 i.m. 1000 microg given on a weekly basis. Following the 8-week therapy, the median plasma homocysteine concentration became significantly reduced from 20 to 10 micromol/L, while plasma levels of fibrinogen, prothrombin, and antithrombin III as well as activity of protein C, S, and factor VII showed no changes. Vitamin treatment was associated with a significant fall in thrombin-antithrombin III complexes and prothrombin fragment 1+2 concentrations in peripheral venous blood. Bleeding time became prolonged by about 60 seconds. At sites of hemostatic plug formation, plasma concentrations of both thrombin markers significantly decreased. Compared with pretreatment values, significantly less thrombin was produced during the first 3 minutes of bleeding after homocysteine-lowering therapy. In subjects with hyperhomocysteinemia a reduction of plasma fasting homocysteine concentration by folic acid and vitamins B12 and B6 administration is associated with attenuation of thrombin generation both in peripheral blood and at sites of hemostatic plug formation.
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PMID:Treatment of hyperhomocysteinemia with folic acid and vitamins B12 and B6 attenuates thrombin generation. 1052 5


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