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Biomedical subjects

E Vahtera

Publications and source records attributed to E Vahtera.

At least 37 records · Page 2Linked to original sources
PubMed1995

Habitual diet, platelet function, fibrinogen and factor VII coagulant activity in young Finns.

OBJECTIVES: The objective of the study was to determine whether an association between diet and platelet function, plasma fibrinogen level and factor VII coagulant activity (VII:C) could be established in young subjects. DESIGN: Data on the habitual diet of the subjects were collected either by a questionnaire on food habits (n = 204) or by a 48-h dietary recall interview (n = 53). SUBJECTS: The subjects were participants in the project 'Cardiovascular Risk in Young Finns' (age range 15-30 years). A total of 204 subjects having a questionnaire on food habits participated in the platelet function tests and 53 also participated in a 48-h dietary recall interview. Plasma fibrinogen concentration and factor VII: C were measured from 79 subjects. MAIN OUTCOME MEASURES: Platelet function was tested by turbidometric measurement of platelet aggregation using ADP and collagen as aggregation agents. RESULTS: Platelet aggregation with ADP (at up to 4.0 mumol L-1) and collagen (at up to 5.0 micrograms mL-1 platelet-rich plasma PRP) showed that the diet characterized as 'saturated', i.e. containing high-fat milk and saturated fat, was associated with platelets less sensitive to aggregating agents in vitro when compared to the unsaturated type of diet. Collagen- but not ADP-induced aggregation decreased with age of the subjects (P = 0.026-0.057, regression coefficient). An inverse regression coefficient between plasma factor VII:C (101%; range 64-145%) and serum triglycerides (P = 0.006) and the intake of rye (g 1000 kcal-1; P = 0.03) were found. CONCLUSIONS: In this study we showed that platelet reactivity and factor VII:C already differ considerably between subjects at a young age, and diet may explain some of this variation.

Adolescent↗
PubMed1995

Association of hormone replacement therapy with hemostatic and other cardiovascular risk factors. The FINRISK Hemostasis Study.

The risk of cardiovascular diseases in women is small until menopause but increases considerably afterwards. When all age groups are considered, cardiovascular diseases are responsible for approximately half of the total mortality in women. It has been suggested that hormone replacement therapy (HRT) in perimenopausal and postmenopausal women could be useful in the prevention of cardiovascular diseases, but its effects are insufficiently known. We performed a cross-sectional study on the associations of menopause and HRT with cardiovascular risk factors, in particular with hemostatic factors, on female participants of the FINRISK Hemostasis Study. The participants, aged 45 to 64 years, were recruited from the Finnish population register by random sampling from three geographically defined areas. The participation rate of women was 83.2%. Of the 1202 women included in the study, 29.2% were current users of HRT. Differences in cardiovascular risk factors by menopausal status and by HRT use were examined after adjustment for age, study area, current smoking, body mass index, self-reported diabetes, and years of education. Postmenopausal women not using exogenous sex hormones had on average a total cholesterol level 0.5 mmol/L (8.9%) higher and an LDL cholesterol level 0.4 mmol/L (11.4%) higher than premenopausal women. Women reporting irregular menstruation (presumably due to perimenopause) had higher adjusted plasma fibrinogen, factor VII coagulant activity, and factor VII antigen than women with regular menstruation or no menstrual periods.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Coagulation↗
PubMed1994

Deficiency in the A-subunit of coagulation factor XIII: two novel point mutations demonstrate different effects on transcript levels.

Congenital deficiency in coagulation factor XIII is a rare autosomal recessive bleeding disorder. Although the defect was characterized over 30 years ago, little is known about the molecular basis of the disorder. Here, we show two novel point mutations in the gene of the A-subunit of factor XIII in the genetically isolated population of Finland. All eight factor XIII-deficient families identified in Finland were studied. The exons of the gene of A-subunit were amplified individually by polymerase chain reaction and subsequently screened by single-strand conformation polymorphism. Sequence analysis of the abnormally migrating fragments showed two point mutations resulting in an amino acid alteration. A C-to-T transition at Arg-661 in exon XIV created a premature stop codon. This mutation was detected in six of the eight families, thus being the major alteration causing FXIII deficiency in Finland. In two of the six families, the patients were compound heterozygotes with the Arg-661-Stop mutation in one allele and either a T-to-C point mutation in exon VI or a thus far uncharacterized mutation in the other allele. The T-to-C transition in exon VI resulted in a substitution of threonine for methionine 242. The transition was found in one family only, where it was in the heterozygote form combined with the Arg-661-Stop mutation. To evaluate the consequences of these mutations, steady-state FXIII mRNA levels were quantitated by solid-phase minisequencing. In addition to the termination of translation 70 amino acids before the initial stop codon, the Arg-661-Stop mutation causes a 10- to 30-fold reduction in FXIII mRNA levels. This is also likely to result in a low translation level in the truncated polypeptide. In contrast, Met-242-Thr mutation does not seem to affect the level of mRNA. Here, the absence of a functional and immunodetectable protein is probably caused by an altered conformation of the mutant polypeptide, resulting in early degradation of the defective protein.

Adolescent↗
PubMed1994

Haemostatic factors and prevalent coronary heart disease; the FINRISK Haemostasis Study.

We examined the association of haemostatic factors with prevalent coronary heart disease (CHD) in the population-based FINRISK Haemostasis Study. Of the 2365 participants aged 45-64 years, 88 men and 44 women with prevalent CHD were identified. The participants with CHD were older and had lower high density lipoprotein cholesterol, higher triglycerides and higher body mass index than the participants without CHD. Men with CHD had significantly higher plasma fibrinogen (P < 0.0001, adjusted for age and smoking) and lipoprotein (a) (Lp (a), P = 0.001, adjusted for age) concentrations than those without CHD. Among women, the findings were consistent with those of men, but only fibrinogen reached the conventional level of statistical significance (P = 0.04). No difference was observed in factor VII antigen, factor VII activity or in plasminogen. The association of Lp (a) with prevalent CHD was dependent on fibrinogen concentration (P = 0.02 for the interaction-term) and on non-HDL cholesterol concentration (P = 0.01 for the interaction-term). These cross-sectional results do not prove causality, but they demonstrate a considerable accumulation of prevalent CHD among persons with high Lp (a), fibrinogen and non-HDL cholesterol.

Antigens↗
PubMed1993

The effects of saturated fat and n-6 polyunsaturated fat on postprandial lipemia and hemostatic activity.

The effect of different fat loads on postprandial lipemia and hemostatic activity was examined in 10 middle-aged men using 3 different meals. One meal was rich in saturated fatty acids (cream), the other rich in n-6 polyunsaturated fatty acids (sunflower oil) and the third was fat-free containing only carbohydrates. Lipoprotein lipids and hemostatic parameters were measured during fasting and 2, 4, 6 and 8 h after the test meal. In fasting samples, several hemostatic parameters were significantly associated with lipoprotein lipids. Most notable were the strong associations of fibrinolysis parameters tissue plasminogen activator antigen and plasminogen activator inhibitor activity (PAI-1) with total and very low density lipoprotein (VLDL) triglycerides. During lipemia, the associations were approximately similar or slightly weaker than in the fasting state. Both fat loads resulted in similar postprandial lipid responses: VLDL and high density lipoprotein (HDL) triglycerides reached maximum at 4 h after the meal. VLDL cholesterol also increased 4 and 6 h after the fat loads. HDL3 cholesterol declined after the fatty meals but no change was observed in the HDL2 fraction. The fat-free meal gave no significant lipid changes during the time course studied. Factor VII activity (F VII:C) increased 6 and 8 h after the fatty meals, whereas a decrease was observed after the fat-free meal. The changes (+/- S.D.) at 8 h after cream, sunflower oil and fat-free meal were 5.2 +/- 3.3, 3.3 +/- 4.2 and -5.8 +/- 7.9 percentage points, respectively, and the effect of the meal on the changes was statistically significant (F (8,99) = 2.99, P = 0.0048). F VII antigen (F VII:Ag) tended to decline during the day but there was no difference between the meals. Factor VIII activity (F VIII:C) was highest after the polyunsaturated fat meal and lowest after the fat-free meal. PAI-1 declined during the day and the decline tended to be steepest after the fat-free morning meal. The effect of the meal on the changes in lipoprotein lipids and hemostatic factors varied significantly between individuals. In conclusion, postprandial lipemia after a single fatty meal was associated with procoagulatory change in F VII:C but there was no difference between saturated fat and n-6 polyunsaturated fat.

Adult↗
PubMed1993

Hydroxyethyl starch as a prime for cardiopulmonary bypass: effects of two different solutions on haemostasis.

Hydroxyethyl starch (HES) is efficacious as a volume expander in cardiac surgical patients, but it may impair the haemostatic mechanisms. However, this latter effect may be less conspicuous with low molecular weight (LMW) solutions than with high molecular weight (HMW) solutions. Therefore, LMW- and HMW-HES solutions were evaluated as priming solutions for cardiopulmonary bypass (CPB) with respect to their effect on haemostasis. Forty-five patients undergoing coronary bypass grafting were prospectively randomised to three groups and received in a double-blind manner as their CPB prime either 20 ml.kg-1 LMW-HES (Mw 120,000), 20 ml.kg-1 HMW-HES (Mw 400,000) or Ringer's acetate 2000 ml. The final volume of the prime was completed to 2000 ml with Ringer's acetate in the HES groups. Anaesthesia and CPB management were standardised. Plasma levels of von Willebrand factor antigen and factor VIII procoagulant activity were significantly more depressed after CPB in both HES-groups as compared with the crystalloid prime group. In addition, APTT was more prolonged and the maximal amplitude of thromboelastographic tracing was more decreased in the HES-groups. It is concluded that it may be advisable to avoid HES solutions in the CPB prime, especially in patients with an increased risk for bleeding after cardiac operations.

Cardiopulmonary Bypass↗
PubMed1992

Antiphospholipid antibodies and thrombosis in systemic lupus erythematosus: comparison of three lupus anticoagulant assays and anticardiolipin ELISA in 188 patients.

The presence of antiphospholipid antibodies (aPL) in 188 unselected patients with systemic lupus erythematosus was studied using the recalcification time, kaolin clotting time (KCT), dilute Russell's viper venom time (dRVVT) and anticardiolipin ELISA (aCL) to identify patients with a high or low risk of thrombosis among patients with aPL. aPL were detected by at least one method in 104 (55%) of the patients. Despite heterogeneity, lupus anticoagulant (LA) methods correlated reasonably well with each other (r = 0.736-0.968), but poorly with aCL (r = 0.241-0.549). Positivity in LA assays and immunoglobulin G (IgG)-aCL were associated with patients who experienced thrombosis (P less than 0.001 for all assays). Patients with both LA and aCL had experienced thrombosis more often than those having only one (odds = 6.3, P less than 0.001). When patients with aPL were ranked by relative strength of the finding and divided into tertiles, a history of thrombosis was associated with membership in the strongest tertile of at least one assay (odds = 4.2, P = 0.002). LA and aCL had similar sensitivities for thrombosis (61% and 63%, respectively), but LA was more specific than aCL (79% vs 53%). The best combination of two assays was KCT with dRVVT (61% sensitivity, 87% specificity). Maximal sensitivity (71%) for thrombosis could be achieved by adding IgG-aCL to these two assays, but specificity was lower (73%). In conclusion, a high thrombotic risk among patients with aPL was indicated by the simultaneous presence of both LA and aCL, strongly positive aPL, and, among aCL, IgG-class antibodies.

Adolescent↗
PubMed1991

Familial clustering of defective release of t-PA.

91 unrelated patients with idiopathic or familial deep vein thrombosis (DVT) and 72 (34 with DVT) relatives from 26 families were screened for hypofibrinolysis by measuring tissue plasminogen activator antigen (t-PA:Ag) after venous occlusion (VO) for 10 and 20 min and by measuring t-PA inhibitor activity (PAI) at rest. 21 healthy subjects served as controls. Defective release of t-PA:Ag was found in eight out of the 91 patients (9%). A partial family study of six of these eight patients was performed. This study included 10 family members with and 21 without DVT. A defective release of t-PA:Ag was found in 50% (5/10) of the family members with DVT, which is significantly more frequent than the 9% (8/91) prevalence in the unrelated patients (P less than 0.001). Furthermore, 24% (5/21) of asymptomatic members of these families also had defective release of t-PA:Ag. In the 18 families where the propositus had a normal level of t-PA:Ag, none of the 24 studied family members with DVT had defective release of t-PA:Ag. In contrast to the defective release of t-PA:Ag, increased basal level of PAI did not show familial clustering. In conclusion, low release of t-PA during VO shows familial clustering in a proportion of the cases.

Adult↗
PubMed1989

Familial hypofibrinolysis and venous thrombosis.

Nine patients with, and 11 without, venous thromboses (DVT) from two families were studied. In family 1, four members with, and one without, DVT had t-PA activity below the lower limit of the controls (21.3 IU/ml, n = 19) after 20 min venous occlusion (VO). After VO t-PA antigen (t-PA:Ag) was below the lowest value of the controls (22.8 ng/ml) in all five cases with low t-PA activity. All the family members, both with and without thrombosis, had normal t-PA inhibitor activities (PAI). In family 2 t-PA activity after VO was low in three symptomatic and four asymptomatic family members. t-PA:Ag was also low in four of these. PAI level was normal in all but one family member. Mild type I von Willebrand's disease was discovered in four members of family 2. Deficient t-PA:Ag response was found in two of these. Antithrombin III, protein C and protein S were normal in both families. It is concluded that low fibrinolytic capacity, independent of PAI, is associated with familial DVT. Our data suggests autosomal dominant inheritance.

Adult↗
PubMed1988

Antithrombin III molecular variants with defective binding to heparin or to serine proteases: evidence of two different abnormal patterns identified by crossed immunoelectrofocusing.

Molecular heterogeneity of antithrombin III (AT III) was investigated by a technique of crossed immunoelectrofocusing (CIEF) in plasma samples of patients from 16 families with AT III congenital defect, including 8 AT III molecular variants. The AT III CIEF pattern was normal in all the patients with AT III quantitative deficiency, showing a balanced decrease of all the peaks. Out of the 8 AT III variants investigated, 6 had an abnormal pattern: the three variants with defective binding to heparin (AT III Roma, AT III Barcelona, AT III Malmö) shared a similar abnormal pattern; three variants with defective binding to serine proteases (AT III Pescara, AT III Milano, AT III Tampere) had a common abnormal pattern clearly different from the first one, whereas the other two variants deficient in the inactivation of the serine proteases (AT III Chicago, AT III Milano 2) showed a normal pattern. The first type of pathological pattern (type Roma) was characterized by the presence of an abnormal peak overlapping the normal isoforms present at pH 4.8-4.6 and by an additional peak at pH 4.5. The second type of pattern (type Pescara) showed an additional peak at pH 4.5 and an abnormal quantitative distribution of the isoantithrombins all throughout the pH range (5.2-4.6). In order to separate the abnormal AT III fraction from the normal one, plasma of a patient with Roma defect and serum of a patient with Pescara defect were passed throughout an heparin-ultrogel column.(ABSTRACT TRUNCATED AT 250 WORDS)

Antithrombin III↗
PubMed1988

Decrease of plasma prekallikrein and kallikrein inhibitors during intravenous phlebography.

Complex contact activation systems may have major involvement in side effects of i.v. contrast media. To investigate this, quantitative measurements of several factors (plasma prekallikrein, kallikrein inhibitory activity, haematocrit, alpha-2-macroglobulin, antithrombin III, alpha-1-antitrypsin and beta-thromboglobulin) were made before and after i.v. contrast phlebography in two groups of patients (each containing 21 patients) with no thrombosis, using a high- (meglumine iodamide) and a low-osmolality (ioxaglate) contrast medium. A statistically significant decrease in plasma prekallikrein was observed after the high-osmolality contrast medium, which is a sign of the activation of the kallikrein-kinin system and an indicator of the activation of the intrinsic coagulation. These events may play an important role in the adverse effects of contrast media.

Antithrombin III↗
PubMed1988

Heme arginate: effects on hemostasis.

Hematin, the drug used for acute porphyric attacks, has been shown to cause disturbances in hemostasis, mainly because of its degradation products. Lately a new heme compound, heme arginate, has been developed for the treatment of porphyrias. In experimental animal studies as well as in clinical use it has proved to be well tolerated. To find out whether heme arginate has any effects on hemostasis we have studied a number of parameters of coagulation and fibrinolysis after a heme arginate infusion in seven healthy volunteers. All parameters studied remained practically unchanged except the coagulation factor X, which showed a transient, insignificant decrease during the maximal heme concentration. We believe that the lack of side effects is due to a better stability of heme arginate, the degradation rates being 1% for heme arginate and 61% for hematin in four hours. Our data favor the use of heme arginate in acute porphyrias as well as in other deficiency states of heme.

Adult↗
PubMed1987

The blood F VIII:Ag/F VIII:C ratio as an early indicator of deep venous thrombosis during post-traumatic immobilization.

Twenty-two consecutive patients with spinal fractures (eight with spinal cord injuries) were studied. All patients were immobilized in bed for 6 weeks after trauma. The occurrence of deep venous thrombosis (DVT) was detected by the 125I-labeled fibrinogen test and confirmed by venography. F VIII:C, F VIII:Ag, and AT III activities were determined 2, 6, and 10 to 12 days after trauma. All paralyzed patients (n = 8) developed DVT and two of them had pulmonary embolism within 5 days after trauma. F VIII:Ag and F VIII:C disproportionally increased and the values of F VIII:Ag/F VIII:C ratio above 2 predicted DVT. AT III remained normal during the whole immobilization time and the values of DVT(+) and DVT(-) groups were comparable.

Adult↗
PubMed1982

The stability of factor IX concentrate during storage.

A storage study of factor IX concentrate was performed on 35 randomly selected batches that had been prepared between 1976 and 1980. Vacuum stability, dissolution time, F IX procoagulant activity, NAPTT, and thrombin generation were measured immediately after the manufacturing process and compared in this study with the results obtained from the spare samples analysed in 1981. No significant changes during storage at cold room temperature for up to 5 years were established. The product can thus be considered to be stable for 5 years at + 4 degrees C.

Drug Stability↗