European Concerted Action on Anticoagulation (ECAA)-the multicentre calibration of rabbit and human ECAA reference thromboplastins. Steering Committee.

Two candidate ECAA reference preparations have been calibrated in a multicentre exercise at 14 representative national laboratories to provide reference thromboplastin for a large field study in 16 European countries. Two preparations were required because of the established differences in ISI arising from the two main routes of calibration via rabbit and human IRP. To be comparable with working reagents in everyday use a human plain recombinant reagent of low ISI and a rabbit plain preparation of moderately high ISI were selected.

Fibrinolytic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. ECAT Study Group. European Concerted Action on Thrombosis and Disabilities.

Background: Disturbances of the fibrinolytic system that lead to decreased removal of fibrin deposits may be important risk factors for coronary thrombosis. There is as yet no consensus on the prognostic value of fibrinolytic parameters, which may be attributed in part to the choice of confounding variables controlled for.

Methods And Results: The ECAT study is a prospective multicenter study of 3043 patients with angina pectoris followed for 2 years.

No influence of proinsulin and insulin on plasma levels of plasminogen activator inhibitor type 1 and tissue plasminogen activator in young women before and during intake of contraceptive steroids.

Clinical observations in patients predisposed to cardiovascular disorders and recent experimental observations suggest that proinsulin and insulin participate in the regulation of fibrinolysis in vivo. In the present study, we examined if proinsulin and insulin affect the constitutive (fasting) secretion of plasminogen activator inhibitor type 1 (PAI-1) and tissue plasminogen activator (t-PA) in young healthy women (N = 17). We also measured the antigen concentrations of PAI-1 and t-PA during slow and fast changes in proinsulin and insulin levels induced by oral (OGTT) and intravenous (IVGTT) glucose tolerance tests.

Contraception guidance in women with pre-existing disturbances in carbohydrate metabolism.

Objectives: To review our studies on the clinical and metabolic impact of contraceptive methods in women with insulin dependent diabetes mellitus (IDDM) and women with previous gestational diabetes mellitus (GDM) in order to provide suggestions for the contraceptive counselling of these women.

Methods: The clinical events following first insertions of copper IUDs were studied in 103 women with IDDM and in 119 non-diabetic women. Moreover we studied the effects on glycometabolic control and lipid metabolism in women with well-controlled IDDM using low-dose oral contraceptives (OCs) containing ethinylestradiol combined with norethisterone (n = 10), levonorgestrel (n = 9) or gestodene (n = 11).

Plasma resistance to activated protein C: an important link between venous thromboembolism and combined oral contraceptives--a short review.

The discovery of plasma resistance towards activated protein C, APC resistance, and its main genetic background, the presence of a single-point mutation in the gene coding for coagulation factor V, factor V Leiden, has, together with renewed documentation of a link between oral contraceptive use and thrombosis, increased the understanding of the pathophysiology, but also the demands to the prescribers, of the pill. Only with knowledge about hemostasis, thrombophilia, DNA technology, its use and limitations, epidemiology, and absolute risk, can general practitioners perform good clinical practice. This short survey tries to cover some of these aspects and to suggest directions for future research.

Elevated fibrinogen and the relation to acute phase response in diabetic nephropathy.

Insulin-dependent diabetic patients with nephropathy have a high risk of cardiovascular disease. Chronic inflammation is a part of the pathogenesis of atherosclerosis, and presently we have studied the relation between the inflammatory state, measured as levels of interleukin-6 and C-reactive protein and fibrinogen in diabetic nephropathy. Thirty-three insulin-dependent diabetic patients with diabetic nephropathy (urinary albumin excretion rate (AER) > 300 mg/24-h) and 22 patients with incipient diabetic nephropathy (AER 30-300 mg/24-h) were compared with 14 non-diabetic controls and 17 diabetic patients with normal AER (<30 mg/24-h).

Hemifacial spasm: magnetic resonance angiography.

Twenty-three consecutive patients with hemifacial spasm were studied. Magnetic resonance imaging angiography of the brain was performed in 20 patients and 15 controls. The angiograms were evaluated by two independent observers and blinded for side-location of the spasm.

Does low protein concentration of tissue-type plasminogen activator predict a low risk of spontaneous deep vein thrombosis?

Many reports have demonstrated an abnormal fibrinolysis in a subset of patients with deep vein thrombosis. We have studied systemic global fibrinolytic activity and protein concentrations of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) in plasma of 25 young patients with a previous instance of spontaneous deep vein thrombosis documented by phlebography and in 50 healthy controls. The two populations were comparable with respect to a number of base-line variables (age, height, weight, etc.

Elevated insulin levels in men: an 11-year follow-up study.

Background: Hyperinsulinaemia is linked to cardiovascular disease. This follow-up study examines factors influencing the fasting insulin level in men.

Methods: All men born in 1936 living in a certain area within the county of Copenhagen were invited for a health examination in 1976 and 1987; 425 men (73%) participated in both examinations.

Gender-related association between beta-fibrinogen genotype and plasma fibrinogen levels and linkage disequilibrium at the fibrinogen locus in Greenland Inuit.

Elevated plasma fibrinogen levels represent an increased risk for cardiovascular disease, but the mechanism explaining this association is still not clear. Genetic differences may play a role, because it has been shown that individuals who carry the rare alleles of polymorphisms in the genes for the B beta-chain (Bcl I and G/A-455) and the A alpha-chain (Taq I) of fibrinogen have higher plasma fibrinogen levels and that patients with peripheral arterial disease have a higher frequency of the rare allele of the Bcl I polymorphism than do healthy control subjects. We studied the Greenland Inuit, a population with a low incidence of ischemic heart disease; polymorphisms of the fibrinogen gene; and their association with plasma fibrinogen level.

Plasminogen activator activity and plasma-coagulum lysis measured by use of optimized fibrin gel structure preformed in microtiter plates.

We introduce a new fibrin plate assay performed in microtiter plates. By means of spectroscopic studies we optimized the structure of the fibrin gel and then used the optimized fibrin gel to determine plasminogen activator activity. Plasminogen activator solutions were applied on top of the fibrin gel, and the absorbance of the gel was recorded at 405 nm.

[Hemifacial spasms--clinical picture, diagnosis and treatment].

A rectrospective study of 23 consecutive patients with hemifacial spasm is presented. Based on this experience, a practical approach to the diagnosis, investigation and treatment with injections of botulinum toxin is described. Magnetic resonance imaging angiography of the brain was performed in 20 patients an 15 controls.

Fasting serum insulin levels and coronary heart disease in a Danish cohort: 17-year follow-up.

Aim: Our objective was to examine the association between the fasting serum insulin level and coronary heart disease (CHD) and cardiovascular disease in 40-year-old men and women.

Methods: In 1976, all of the men and women born in 1936 living in four municipalities in the County of Copenhagen were invited for a health examination. The participation rate was 87% (504 men and 548 women).

The protein concentration of blood coagulation factor VII can be measured equally well in plasma and serum.

In the Northwick Park Heart Study, the coagulant activity of factor VII (FVII:C) has been identified as a risk marker of ischaemic heart disease. In the fasting state, the protein concentration of FVII (FVII:Ag) might be an even better risk marker, because of the low coefficient of variation of the antigen assay. Today, most analyses are performed in plasma samples, as it is unknown whether FVII, to some extent, is consumed during coagulation.

Plasminogen activator inhibitor type-1 determines plasmin formation in patients with ischaemic heart disease.

The aim of the present study was to find out whether plasminogen activator inhibitor type-1 (PAI-1) controls the formation of plasmin in patients with ischaemic heart disease. We examined PAI activity, PAI-1 antigen, tissue type plasminogen activator (t-PA) activity, t-PA antigen, plasmin-alpha2-antiplasmin complex (PAP-complex) and fibrin degradation products D-dimer in 62 patients before (unstimulated) and after infusion of 1-desamino-8-D-arginine vasopressin (DDAVP; stimulated). DDAVP was used in a standardized dose to trigger the release of t-PA from the vascular endothelium.

Perturbed (procoagulant) endothelium and deviations within the fibrinolytic system during the third trimester of normal pregnancy. A possible link to placental function.

Purpose: To evaluate the endothelial cell state and the possible relation to placental function in the third trimester of normal pregnancy by an indirect assessment of endothelial cell function. STUDY-DESIGN. Twenty-six pregnant women entered the study in the 30th week of pregnancy.

[Food intake of Danes and cardiac risk factors].

We served a low-fat (28% of energy) high-fibre (3.3 g/MJ) diet according to Nordic Nutrition Recommendations (REC diet), and a high-fat diet (39% of energy) corresponding to the average Danish diet (DANE diet) to 21 healthy middle-aged individuals in a two times two weeks cross-over study. The REC diet resulted in lower serum concentrations of low density lipoprotein (LDL) cholesterol (medians: 2.

Effect of low-dose heparin on urinary albumin excretion in insulin-dependent diabetes mellitus.

We investigated the effect of heparin on urinary albumin excretion in patients with insulin-dependent diabetes mellitus. 39 patients with persistent urinary albumin excretion of 30-300 mg/24 h were randomly treated for 3 months with subcutaneous injections twice daily of isotonic saline, 5000 IU unfractionated heparin, or 2000 anti-Xa IU low-molecular-weight heparin. Unfractionated and low-molecular-weight heparin induced a significant reduction in urinary albumin excretion (p = 0.

Dietary changes in fasting levels of factor VII coagulant activity (FVII:C) are accompanied by changes in factor VII protein and other vitamin K-dependent proteins.

The mechanisms behind dietary effects on fasting coagulant activity of factor VII (FVII:C) are not clarified. In the present study of 15 young volunteers, two experimental diets differing in composition of saturated fatty acids (C18:0 [diet S] or C12:0 + C14:0 [diet ML]) were served for 3 weeks each. Fasting blood samples were collected before and after the dietary regimen and analysed for triglycerides, FVII:C, and protein concentrations of FVII, FII, FX, protein C, CRP, albumin, fibrinogen, and F1 + 2.