Prothrombin activation fragment 1 + 2 as a marker of coagulation activation in cord blood collection for banking.

There have been efforts to increase the quality of cord blood (CB) collections aimed at banking and transplantation. Yet, the effect of CB collection techniques on haemostatic activation is scarcely studied, despite the unique nature of the neonatal haemostatic system. The aim of this study was to explore coagulation system and platelet (PLT) activation during CB collection at a national CB bank. At three time points over a 9-year period (in 1998, 2000 and 2006), CB collections were assessed to evaluate the collection process during bank setup and changes in procedures. Thrombin generation and PLT activation were assessed with prothrombin activation fragment 1 + 2 (F1 + 2) and PLT factor 4 (PF4), respectively. The median F1 + 2 level was 2.8 nmol L(-1) in 1998 (n = 11), 0.7 nmol L(-1) in 2000 (n = 10) and 0.7 nmol L(-1) in 2006 (n = 6), the decrease being statistically significant (1998 vs 2000, P < 0.001; 1998 vs 2006, P = 0.01). The median PF4 level was 117 IU mL(-1) in 1998 and 104 IU mL(-1) in 2000. PF4 was not measured in 2006. The level of F1 + 2 correlated with that of PF4 (n = 21; Spearman's Rho = 0.59, P = 0.006). Haemostatic activation, assessed as a part of CB bank process control, decreased from the first to the subsequent sample series. F1 + 2 may be a candidate for quality control in CB banking; however, further studies are needed to optimise the analyses and to assess the effect of haemostatic activation on CB quality.

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.

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.

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.

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.

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.

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.

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)

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.