Biomedical subjects

E Vahtera

Publications and source records attributed to E Vahtera.

At least 19 recordsLinked to original sources

PubMed2005

Plasma fibrinogen level and the risk of major cardiovascular diseases and nonvascular mortality: an individual participant meta-analysis.

CONTEXT: Plasma fibrinogen levels may be associated with the risk of coronary heart disease (CHD) and stroke. OBJECTIVE: To assess the relationships of fibrinogen levels with risk of major vascular and with risk of nonvascular outcomes based on individual participant data. DATA SOURCES: Relevant studies were identified by computer-assisted searches, hand searches of reference lists, and personal communication with relevant investigators. STUDY SELECTION: All identified prospective studies were included with information available on baseline fibrinogen levels and details of subsequent major vascular morbidity and/or cause-specific mortality during at least 1 year of follow-up. Studies were excluded if they recruited participants on the basis of having had a previous history of cardiovascular disease; participants with known preexisting CHD or stroke were excluded. DATA EXTRACTION: Individual records were provided on each of 154,211 participants in 31 prospective studies. During 1.38 million person-years of follow-up, there were 6944 first nonfatal myocardial infarctions or stroke events and 13,210 deaths. Cause-specific mortality was generally available. Analyses involved proportional hazards modeling with adjustment for confounding by known cardiovascular risk factors and for regression dilution bias. DATA SYNTHESIS: Within each age group considered (40-59, 60-69, and > or =70 years), there was an approximately log-linear association with usual fibrinogen level for the risk of any CHD, any stroke, other vascular (eg, non-CHD, nonstroke) mortality, and nonvascular mortality. There was no evidence of a threshold within the range of usual fibrinogen level studied at any age. The age- and sex- adjusted hazard ratio per 1-g/L increase in usual fibrinogen level for CHD was 2.42 (95% confidence interval [CI], 2.24-2.60); stroke, 2.06 (95% CI, 1.83-2.33); other vascular mortality, 2.76 (95% CI, 2.28-3.35); and nonvascular mortality, 2.03 (95% CI, 1.90-2.18). The hazard ratios for CHD and stroke were reduced to about 1.8 after further adjustment for measured values of several established vascular risk factors. In a subset of 7011 participants with available C-reactive protein values, the findings for CHD were essentially unchanged following additional adjustment for C-reactive protein. The associations of fibrinogen level with CHD or stroke did not differ substantially according to sex, smoking, blood pressure, blood lipid levels, or several features of study design. CONCLUSIONS: In this large individual participant meta-analysis, moderately strong associations were found between usual plasma fibrinogen level and the risks of CHD, stroke, other vascular mortality, and nonvascular mortality in a wide range of circumstances in healthy middle-aged adults. Assessment of any causal relevance of elevated fibrinogen levels to disease requires additional research.

Adult↗

PubMed2005

The effects of aprotinin and tranexamic acid on thrombin generation and fibrinolytic response after cardiac surgery.

BACKGROUND: Thrombin formation during cardiac surgery could result in disordered hemostasis and thrombosis. The aim of the study was to examine the effects of aprotinin and tranexamic acid on thrombin generation and fibrinolytic activity in patients undergoing cardiac surgery. METHODS: Data were collected prospectively from 60 patients undergoing coronary artery bypass grafting using cardiopulmonary bypass (CPB). In a randomized sequence, 20 patients received aprotinin, 20 patients received tranexamic acid, and in 20 patients placebo was used. RESULTS: Significant thrombin activity was found in all the studied patients. Thrombin generation was less in the aprotinin group than in the tranexamic acid and the placebo group (thrombin/anti-thrombin III complexes 33.7 +/- 3.6, 53.6 +/- 7.0 and 44.2 +/- 5.3 microg/l 2 h after CPB and F1 + 2 fragment 1.50 +/- 0.10, 2.37 +/- 0.37 and 2.04 +/- 0.20 nmol/l 6 h after surgery, respectively). The inhibition of fibrinolysis was significant with both anti-fibrinolytic drugs (D-dimers 0.427 +/- 0.032, 0.394 +/- 0.039 and 2.808 +/- 0.037 mg/l 2 h after CPB, respectively). The generation of d-dimers was inhibited until 16 h after CPB in the aprotinin group. The plasminogen activation was significantly less in the aprotinin group (plasmin/anti-plasmin complexes 0.884 +/- 0.095, 2.764 +/- 0.254 and 1.574 +/- 0.185 mg/l 2 h after CPB, respectively). CONCLUSION: Thrombin formation is inevitable in coronary artery bypass surgery when CPB is used. The suppression of fibrinolytic activity, either with aprotinin or with tranexamic acid interferes with the hemostatic balance as evaluated by biochemical markers. Further investigations are needed to define the role of hemostatic activation in ischemic complications associated with cardiac surgery.

Aged↗

PubMed2003

Beta-2-glycoprotein I antibodies in patients with thrombosis.

The laboratory diagnosis of antiphospholipid antibody syndrome currently requires two consecutive positive results in either lupus anticoagulant or anticardiolipin antibody assays. Antibodies against beta-2-glycoprotein I (abeta2-GPI) are suggested as a new marker for the syndrome. The inclusion of abeta2-GPI in the official diagnostic criteria has so far been precluded owing to lack of an international standard and also technical difficulties. Samples from 5367 consecutive patients sent to a national reference laboratory mainly because of various thrombotic events were studied. An IgG abeta2-GPI ELISA assay was performed in addition to lupus anticoagulant (dRVVT and PTT-LA) and IgG anticardiolipin antibody determinations to evaluate patient groups in which the new assay might be of value. From a total of 90 patients, 2.2% of the samples were abeta2-GPI positive; 51 patients had abeta2-GPI as the only positive antiphospholipid antibody marker; 20 patients had had a venous thrombosis and 14 an arterial thrombosis, 4 had pregnancy complications and 2 had thrombocytopenia. Relatively young patients with cerebrovascular ischaemic events seemed especially to present sole abeta2-GPI positivity. The abeta2-GPI positivity remained fairly constant in the 23 patients from whom follow-up samples were taken. It is concluded that the IgG abeta2-GPI assay seems to be a potentially important additional diagnostic tool for the antiphospholipid antibody syndrome.

Adolescent↗

PubMed2003

Effects of gestational age and prenatal and perinatal events on the coagulation status in premature infants.

OBJECTIVE: To study prospectively the effects of prematurity and perinatal events on the coagulation status of premature infants. PATIENTS AND MAIN OUTCOME MEASURES: Blood samples from premature infants born before 37 gestational weeks were taken for analysis of coagulation factors II, V, VII, and X and platelet count. RESULTS: A total of 125 premature infants, 71 boys, were studied at the median postnatal age of 40 minutes (range 12-100). The lowest median activities of coagulation factors II, V, VII, and X and the platelet count were observed, as expected, in infants (n = 21) born at 24-27 weeks gestation. Twin B (n = 14) had lower median activities of coagulation factors II, V, VII, and X than twin A. Infants with evidence of mild asphyxia (Apgar score at 5 minutes < 7 or cord pH < 7.26) had significantly (p < 0.05) lower levels of coagulation factors II, V, VII, and X and platelet counts than infants without asphyxia. Infants who were small for gestational age (SGA) had significantly (p < 0.05) lower levels of coagulation factors V and VII and platelet counts than infants of appropriate size for gestational age. Other prenatal and perinatal variables examined (sex, maternal hypertension and/or pre-eclampsia, antenatal steroid use, mode of delivery, Apgar scores) did not show any significant associations with coagulation status, which may be explained by the small number of infants studied. CONCLUSIONS: The data strongly suggest that there are distinct differences in specific coagulation tests in different patient populations, which could assist in the identification of extremely preterm, SGA, or asphyxiated preterm infants who may be susceptible to haemorrhagic problems perinatally.

Asphyxia Neonatorum↗

PubMed2003

Association of markers of systemic inflammation, C reactive protein, serum amyloid A, and fibrinogen, with socioeconomic status.

STUDY OBJECTIVE: Systemic inflammation may play an important part in the development of cardiovascular disease. It has also been shown that socioeconomic status predicts cardiovascular events independently of established risk factors. The aim of this study was to analyse the association of three sensitive markers of systemic inflammation: C reactive protein (CRP), serum amyloid A protein (SAA), and fibrinogen, with socioeconomic status. DESIGN: Cross sectional study. SETTING: Eastern and southern Finland. PARTICIPANTS: 1503 men aged 45 to 74 years who participated in a cardiovascular risk factor survey in 1997. Based on the levels of education and family income, the men were classified to three socioeconomic groups. MAIN RESULTS: Mean concentrations of CRP (p for the trend <0.001), SAA (p for the trend 0.018), and fibrinogen (p for the trend <0.001) decreased substantially with increasing socioeconomic status. The trends in CRP and fibrinogen remained statistically significant after adjustment for smoking, waist to hip ratio, and prevalent longstanding diseases, and a non-significant trend was found for SAA (p for the trend 0.118). The inverse association between inflammation markers and socioeconomic status was particularly strong among the men below 60 years of age. CONCLUSIONS: Systemic inflammation is a potential mediator, especially among young and middle aged men, for the association between socioeconomic status and cardiovascular disease.

Acute-Phase Proteins↗

PubMed2001

The association of c-reactive protein, serum amyloid a and fibrinogen with prevalent coronary heart disease--baseline findings of the PAIS project.

Recent data suggest that infections, inflammation and the immune system are involved in the process of atherosclerosis. The aim of the present study was to analyze the association of coronary heart disease (CHD) with three inflammation markers, C-reactive protein (CRP), serum amyloid-A (SAA) and plasma fibrinogen. The cross-sectional study included 1400 men aged 45-74 years, who participated in a cardiovascular risk factor survey in Finland in 1997. Participants with prevalent CHD had markedly higher CRP, SAA and fibrinogen levels than participants without CHD. In logistic regression models, the age, smoking, serum cholesterol and systolic blood pressure adjusted odds ratios (2nd, 3rd and 4th quartile as compared with the 1st quartile) of CHD increased gradually with increasing quartile of CRP (1.90, 2.27, 2.64), SAA (1.68, 1.83, 2.41), and fibrinogen (1.60, 1.95, 2.14). The associations weakened somewhat after further adjustment for indicators of obesity, particularly waist hip-ratio. CRP, SAA and fibrinogen levels were markedly lower among CHD patients using cholesterol-lowering medication as compared to non-users. In conclusion, CRP, SAA and fibrinogen, which are markers of inflammation, were positively and significantly associated with prevalent CHD. Central obesity needs to be considered as a confounding factor in the observed associations. These findings support the hypothesis that cholesterol-lowering drugs have an anti-inflammatory effect.

Adult↗

PubMed2001

Weight change and blood coagulability and fibrinolysis in healthy obese women.

OBJECTIVES: To study the effect of weight loss and subsequent weight maintenance or weight regain on the activities of FVII and plasminogen activator inhibitor 1 (PAI-1) and the concentration of fibrinogen over 12 months in obese women consuming a hypoenergetic, low-fat diet with or without orlistat. In addition, the relation between the changes of the activities of PAI-1 and FVII with the changes of other cardiovascular risk factors were examined. METHODS AND PROCEDURES: Design-a 12-month randomized double-blind weight reduction trial of placebo and orlistat. Subjects-51 healthy obese women (age 44+/-0.7 y, BMI 36.2+/-0.5 kg/m(2), mean+/-s.e.m.) Treatment-the participants were on a hypoenergetic diet (-600 kcal daily). The diet was adjusted for actual body weight (-300 kcal) at 6 months. Women were randomized to receive either orlistat 120 mg three times daily (n=25) or placebo three times daily (n=26) for 12 months according to a double-blind protocol after a 1 month run-in period. Measurements-changes of body weight, body composition, haemostatic and other cardiovascular risk factors were measured at 3-6 month intervals. The activity of plasma PAI-1 was measured by a chromogenic method, fibrinogen by the PT-derived method and the activity of FVII by the one-stage method. RESULTS: The changes in body weight between orlistat and placebo groups were not statistically significantly different. Orlistat did not influence haemostatic factors beyond its effect on weight loss. Therefore, the results of the orlistat and placebo groups were pooled. The average weight loss at 3, 6 and 12 months was 7.6, 9.5 and 10.0 kg, respectively (P<0.001). Between 6 and 12 months, 35% of women regained weight, 24% had stable weight and 41% continued to lose weight. No changes in the mean plasma fibrinogen concentration were observed at any time point during the trial. During the first 3 months the activities of PAI-1 and FVII decreased. The decline depended on the magnitude of weight loss. Between months 6 and 12 the changes of PAI-1 and FVII activities paralleled the changes of body weight. The activities rose with weight rebound but remained below the 6-month values if weight loss was sustained or continued. The changes of serum insulin were significantly correlated with the changes of both PAI-1 and FVII at 6 months and with PAI-1 at 12 months. CONCLUSIONS: The maintenance of modest weight loss is associated with long-term benefits in PAI-1 and FVII in obese women. The change of serum insulin is associated with the changes of PAI-1 activities. Fibrinogen is not affected by modest weight loss.

Adult↗

PubMed2001

Utility of the Arg/Gln polymorphism of the factor VII (FVII) gene, serum lipid levels and body mass index in the prediction of the FVII:C and FVII:Ag in North Karelia; a cross-sectional and prospective study.

The arginine/glutamine (Arg/Gln) polymorphism of the factor VII (FVII) gene is associated with variation in coagulation activity (FVII:C) and antigen concentration (FVII:Ag) of the FVII protein. We estimated frequency distributions of the Arg and Gln alleles and respective genotypes in North Karelia, and evaluated the utility of this polymorphism, serum lipids, and body mass index (BMI) in the prediction of the distributions of FVII:C and FVII:Ag in a cross-sectional study and in a prospective cohort study. The sample comprised 203 males and 262 females (aged 45-64 years) who were seen twice, in 1992 and 1995. The Arg/Arg genotype and the Arg allele frequencies were among the highest reported so far (86 and 93% respectively, in men; and 89 and 94% respectively, in women). Intragenotypic means of both FVII:C and FVII:Ag were significantly higher in the Arg/Arg genotype than in the Arg/Gln genotype in both genders. Also, intragenotypic variances were different in different genotypes in females. Regression relationships between the FVII:C and FVII:Ag and serum triglyceride, and total cholesterol levels and BMI were positive in both genotypes in both genders, which has not been found in other populations. In prospective analyses, average changes in the FVII:C and FVII:Ag were genotype specific in both genders, as were also regression relationships between these changes and changes in triglyceride level in females (P = 0.065 for FVII:C and P = 0.061 for FVII:Ag). A consequence of these complex genetic architectures is that predictive utility of the Arg/Gln genotypes depends on population, gender, serum lipid levels, and BMI, and changes in these factors over time.

Alleles↗

PubMed2000

Single founder mutation (W380G) in type II protein C deficiency in Finland.

The present study investigated the genetic basis for type II protein C deficiency in Finland, where this form has an unusually high incidence. We demonstrated that, first, a single novel mutation W380G in the protein C gene (PROC) explained 25/26 index patients, estimated to represent two thirds of all families with type II deficiency in Finland. Second, extended chromosomal conservation, i.e. a specific haplotype, around the W380G mutation was indicated in unrelated patients. Third, a local geographical origin for the W380G mutation was suggested by genealogical data. These results are in contrast to the heterogeneity in type II protein C deficiency elsewhere, but closely parallel disorders of the Finnish disease heritage. The high frequency of the type II disease can be explained by founder effect and subsequent enrichment of a single mutation in Finland. The present study also provided a simple means for genetic diagnosis of this disease and the genetic test can be included in the routine screenings in this population.

Chromosome Mapping↗

PubMed1999

Symptoms of chronic bronchitis, haemostatic factors, and coronary heart disease risk.

Positive association has been suggested between a variety of infections and coronary heart disease. Disturbances in blood coagulation system may form a link between infections and coronary heart disease. The aim of this study was to analyze whether chronic bronchitis, defined by the occurrence of symptoms, is associated with selected haemostatic factors in a cross-sectional population study of 2379 Finnish men and women aged between 45 and 64 years. Plasma fibrinogen level was significantly higher, 3.70 versus 3.35 g/l (P < 0.001) in men and 3.64 versus 3.44 g/l (P < 0.001) in women, among subjects with symptoms of chronic bronchitis than among those without symptoms. The association was independent of age, smoking, body mass index, physical exercise, and alcohol consumption. Also plasminogen was higher among men with symptoms than among those without but the difference disappeared after adjustment for age and smoking. Factor VII coagulant activity and factor VII antigen level did not differ between subjects with and without symptoms. Thus, fibrinogen may be associated with a possible mechanism to link chronic bronchitis to coronary heart disease risk, even though the causality of the association cannot be verified in a cross-sectional study.

Blood Coagulation Factors↗

PubMed1998

Intra- and interindividual variability of hemostatic factors and traditional cardiovascular risk factors in a three-year follow-up.

Elucidation of the key role of thrombosis in cardiovascular disease events has arisen considerable interest in hemostatic factors and in the repeatability of their determinations. Data on long-term repeatability has, however, remained scanty. We examined twice 208 men and 265 women in North Karelia, eastern Finland. The baseline examination was a part of the FINRISK 1992 Hemostasis Study and the age-range of participants was between 45-64 years. The re-examination took place three years later in 1995. Both surveys followed the same protocol and were carried out during the same season. Spearman rank correlation coefficients between 1992 and 1995 measurements of fibrinogen, factor VII coagulant activity (FVII:C), factor VII antigen (FVII:Ag), and plasminogen were among men 0.72, 0.77, 0.46 and 0.56, respectively. For total cholesterol, HDL-cholesterol, triglycerides and diastolic blood pressure the corresponding coefficients were 0.74, 0.83, 0.66, and 0.54. In women, the coefficient of fibrinogen was lower than in men, 0.62, otherwise the results were similar. Of men belonging to the highest quarter of fibrinogen, FVII:C, FVII:Ag and plasminogen in 1992, 65%, 60%, 53% and 60% belonged to the highest quarter of respective distributions also in 1995. In women, the corresponding proportions were 64%, 65%, 46% and 58%. The modest repeatability of FVII:Ag and plasminogen was mainly due to the high intraindividual variability. However, in comparisons of plasma levels between two groups, relatively small sample sizes seemed to give adequate statistical power to detect possible differences in FVII:Ag and plasminogen. In conclusion, the long-term repeatability of fibrinogen and FVII:C is similar to that of triglycerides and even better than that of diastolic blood pressure, but somewhat lower than the repeatability of total cholesterol. FVII:Ag and plasminogen did not have very good repeatability and more than one measurement of them should be considered if they are used as predictors of cardiovascular disease in prospective studies.

Cardiovascular Diseases↗

PubMed1997

Effects of dietary fat modification on fibrinogen, factor VII, and plasminogen activator inhibitor-1 activity in subjects with impaired glucose tolerance.

Our aim was to assess the impact of a monounsaturated fat-enriched (Mono) diet and a diet recommended by the National Cholesterol Education Program (NCEP) on plasma levels of fibrinogen and activities of factor VII (FVII:C) and plasminogen activator inhibitor-1 (PAI-1) and the impact of genetic polymorphisms of these variables (HaeIII, MspI, and 4G/5G polymorphisms, respectively) in 28 subjects with impaired glucose tolerance ([IGT] 17 men and 11 women; mean age, 55.6 +/- 5.5 years). A diet rich in fat and saturated fatty acids served as a baseline diet for 3 weeks. Thereafter, subjects were randomized for the next 8 weeks to either the Mono diet (n = 12) or NCEP diet (n = 18). Fibrinogen levels or PAI-1 activities did not change with either of the diets, but fibrinogen levels were higher (3.4 +/- 0.5 v 4.0 +/- 0.6 g/L, P = .007 at baseline) throughout the study in heterozygous subjects with respect to HaeIII polymorphism. This polymorphism and age accounted for 38% of the variation of fibrinogen levels. MspI polymorphism together with body mass index explained 51% of the variation of FVII:C, which was higher in subjects with the M1M1 genotype compared with M1M2/M2M2 genotypes (127% +/- 21% v 90% +/- 12%, P < .001). FVII:C showed a decrease with the NCEP diet (P < .05), but the decline was confined to M1M1 subjects. PAI-1 activity did not differ significantly between the genotypes. The insulin sensitivity index (SI) obtained by the minimal model method was the main explanatory variable of PAI-1 activity. To conclude, despite good compliance, the fat-modified diet did not alter plasma levels of fibrinogen or PAI-1 in white subjects with IGT. FVII:C levels decreased with the NCEP diet, but this was confined to subjects with the M1M1 genotype.

Analysis of Variance↗

PubMed1997

Association of the fatty acid composition of serum phospholipids with hemostatic factors.

It has been suggested that the fatty acid composition of serum phospholipids is an independent risk factor for cardiovascular disease. We examined the association of the fatty acid composition of serum phospholipids with fibrinogen, factor VII antigen (FVII:Ag), factor VII coagulant activity (FVII:C), plasminogen, and lipoprotein(a) [Lp(a)] in 338 men and 363 women 45 to 64 years old. Palmitic acid, the most abundant saturated fatty acid, was positively associated in univariate analyses with plasminogen, which explained 5.2% of its variance among men (P<.0001) and 5.8% among women (P<.0001). Linoleic acid, which is the most abundant polyunsaturated fatty acid, was negatively associated with plasminogen and fibrinogen. This explained 1.1% of the variance in fibrinogen among men (P=.04) and 3.2% among women (P=.0006) and 4.1% of the variance in plasminogen in both sexes (P<.0001). Dihomogammalinolenic acid was positively associated with FVII:Ag and explained 3.7% of its variance among men (P=.0003) and 4.6% among women (P<.0001). Furthermore, dihomogammalinolenic acid was positively and significantly associated with FVII:C, fibrinogen, and plasminogen among women but not among men. All these associations remained significant after adjustment for multiple potential confounding factors such as age, smoking, serum lipids, and body mass index. In conclusion, our findings suggest that linoleic acid, palmitic acid, and dihomogammalinoleic acid are significant independent determinants of hemostatic profile. It is not clear, however, to what extent these results reflect the effects of fatty acids on coagulation and to what extent they reflect the activity of inflammatory processes in the arteries.

8,11,14-Eicosatrienoic Acid↗

PubMed1996

Fibrinolysis, antithrombin III, and protein C in neonates during cardiac operations.

Fibrinolysis and coagulation were studied in 10 neonates undergoing cardiac operations for congenital heart defects. Coagulation was activated during cardiopulmonary bypass as evidenced by highly increased prothrombin fragment 1 + 2 levels compared with preoperative values. Prothrombin fragment 1 + 2 levels remained elevated until postoperative day 3. Unlike coagulation, fibrinolysis was not activated during cardiopulmonary bypass but did show late activation on postoperative day 3, as evidenced by elevated levels of the fibrin degradation product D-dimer. Lack of fibrinolytic activation during bypass and its appearance on postoperative day 3 were partly explained by changes observed in tissue plasminogen activator and its inhibitor. During bypass, levels of tissue plasminogen activator and its inhibitor increased by 3.4-fold and 3.2-fold, respectively. In the postoperative period, levels of plasminogen activator inhibitor normalized rapidly whereas tissue plasminogen activator remained elevated, resulting in late fibrinolytic activation on postoperative day 3. In accordance with elevated prothrombin fragment 1 + 2, platelet count, antithrombin III, protein C, prothrombin, and factor VII were decreased on postoperative day 2, indicating ongoing consumptive coagulopathy. Nine patients had antithrombin III and six had protein C levels below age-specific normal ranges, consistent with an acquired deficiency state. Three had central venous thrombosis by postoperative day 4 or 5. In all three, thrombosis was preceded by antithrombin III deficiency, protein C deficiency, and highly elevated plasminogen activator inhibitor (3.7 to 37 times the mean of the other patients) on postoperative days 1 to 3. In conclusion, cardiopulmonary bypass in neonates caused rapid and profound alterations in the coagulation and fibrinolytic systems and initiated consumptive coagulopathy lasting until at least postoperative day 3. Thrombophilic abnormalities in antithrombin III, protein C, and fibrinolysis were frequently found and were associated with serious thrombotic complications.

Antithrombin III↗

PubMed1996

Plasma ascorbate protects coagulation factors against photooxidation.

It has been suggested that proteins, unlike lipids, are not protected against oxidative damage by antioxidants in plasma. We have studied the effect of photodynamic virus inactivation treatment of fresh human plasma on coagulation factor activities. Photodynamic treatment generates singlet oxygen which causes inactivation of fibrinogen and factor VII. Other coagulation factors or anticoagulant proteins are clearly less affected. We found that there is an inverse correlation between the extent of coagulation factor inactivation during the treatment and the plasma ascorbate concentration. The inactivation of coagulation factors was prevented in a dose-dependent manner by adding ascorbate to the plasma before the treatment. Ascorbate was consumed during the treatment at an apparently linear rate. Oxidation of urate and coagulation factors was enhanced when ascorbate had disappeared from plasma. These results indicate that ascorbate is a primary antioxidant against photooxidation in plasma and that it effectively prevents oxidative damage to coagulation factors and other proteins.

Antioxidants↗

PubMed1995

Fibrinogenemia Tampere--a dysfibrinogenemia with defective gelation and thromboembolic disease.

Fibrinogen Tampere was found in a woman with severe thromboembolic disease. The thrombin induced clotting time of her plasma and purified fibrinogen was slightly prolonged. The activation of fibrinogen Tampere appeared to be normal but subsequent gelation was defective. We studied fibrin gels formed at different ionic strengths and at different fibrinogen and calcium concentrations by liquid permeation, turbidity, and 3D laser microscopy. Crosslinking was studied by SDS-gel electrophoresis. The gels formed from fibrinogen Tampere were at ionic strength above 0.2 much tighter and had lower fiber mass-length ratios than normal gels as judged by permeability and turbidity data. At ionic strength 0.15 and at different calcium concentrations analysis by permeability showed the same results for fibrinogen Tampere as for normal gels. Analysis by turbidity at ionic strength 0.15 suggested swelling of the fibers at low calcium concentrations. 3D microscopy revealed perturbed clot architecture under all conditions. In fibrin gels from fibrinogen Tampere, the gamma-chain crosslinking was normal but the crosslinking of alpha-chains was delayed at ionic strength 0.2 and also at lower ionic strengths on lowering the calcium concentration. The abnormal gelation may be due to a mutation in the fibrinogen molecule. Tendency to form tight fibrin gels and/or insufficient crosslinked fibrin matrix may be pathogenetic in this thrombotic disease.

Adult↗

PubMed1995

Cellular fibronectin in serum and plasma: a potential new tumour marker?

The concentration of cellular fibronectin (cFN) containing the extra domain A (EDA) was measured in 479 plasma and 300 serum samples from healthy blood donors by a competitive enzyme immunoassay (EIA). Serum and plasma samples contained low concentrations of EDAcFN. The mean concentration of EDAcFN was higher in plasma (2.46 mg l-1) than in serum (0.30 mg l-1). No significant differences between sexes or age groups were found. The EDAcFN concentrations were also measured in 120 patients with various malignancies. The mean values in serum were 4.28 mg l-1, 2.01 mg l-1 and 5.18 mg l-1 in patients with digestive tract malignancies, breast cancer and a group of miscellaneous cancers respectively. In plasma, the corresponding values were 12.26 mg l-1, 4.38 mg l-1 and 11.12 mg l-1 respectively. The serum EDAcFN concentration was higher than the 97.5th percentile level of healthy blood donors in 86% of patients with digestive tract and in 76% with miscellaneous malignancies. In patients with breast cancer 60% had elevated levels of EDAcFN. The corresponding figures for plasma samples in patients with digestive tract and miscellaneous malignancies were 79% and 71% respectively. In patients with breast cancer only 30% had elevated plasma levels of EDAcFN. The mean values in serum and plasma of 20 patients with benign diseases were below the cut-off levels. Consistent with the EIA results, Western blotting revealed increased amounts of EDAcFN in blood samples from cancer patients. Pregnancy did not affect the EDAcFN concentration. The mean values in 20 pregnant women were below the cut-off levels.

Antibodies, Monoclonal↗

PubMed1995

Haemostatic and other cardiovascular risk factors, and socioeconomic status among middle-aged Finnish men and women.

BACKGROUND: The higher morbidity and mortality due to cardiovascular diseases (CVD) in lower social classes has been shown repeatedly in Finland. Lower socioeconomic groups also have a more adverse CVD risk factor profile. The association between socioeconomic factors and risk of CVD is only partly explained by the traditional risk factors. Fibrinogen may be of particular importance as an underlying mechanism that mediates this association. MATERIAL AND METHODS: The association of socioeconomic status (SES), as measured by years of education and family income with coronary risk factors was studied among a random population-based sample (N = 2365) of Finnish men and women aged 45 to 64. Subjects were studied in three parts of Finland; North Karelia, the Helsinki area, and South-West Finland, in connection with a larger cardiovascular monitoring programme. Years of education was divided into four categories (< or = 7, 8-9, 10-12, > or = 13) and family income into quartiles. The coronary risk factors studied were serum total cholesterol, HDL-cholesterol, triglycerides, blood pressure, prevalence of hypertension, smoking, body mass index (BMI), waist-to-hip ratio, prevalence of obesity, alcohol use and the following haemostatic factors: plasma fibrinogen, factor VII coagulant activity (factor VII:C), factor VII antigen (factor VII:Ag) and plasminogen. RESULTS: Adjusting for age and area of residence, both men and women of low SES tended either to have more adverse risk factor levels or there was no association. The only exception was proportion of heavy drinkers, which was higher among higher social class women. The inverse association of SES were especially strong and consistent with smoking among men, and with BMI in both sexes. Of the haemostatic factors studied, plasma fibrinogen was inversely associated with SES in both sexes. The association disappeared after adjustment for smoking among men but not among women. Among women, plasma factor VII:Ag was inversely associated with income. No other statistically significant associations of haemostatic factors with SES were observed. CONCLUSIONS: Low SES groups had more adverse levels of most of the CVD risk factors. Haemostatic factors appeared to be associated with SES especially among women.

Blood Proteins↗