Incidence of thromboembolic complications in patients with atrial fibrillation or mechanical heart valves with a subtherapeutic international normalized ratio: A prospective multicenter cohort study

Subtherapeutic international normalized ratio (INR) is frequently encountered in clinical practice, and patients with high-risk atrial fibrillation (AF) and with mechanical heart valve (MHV) with inadequate anticoagulation may be exposed to an increased risk of thromboembolic events (TE). However, there are no prospective data evaluating this risk. Consecutive patients with a history of stable anticoagulation, but with a subtherapeutic INR, were prospectively included. Data on use and dose of low-molecular weight heparin (LMWH) bridging therapy were collected. The incidence of objectively confirmed TE and of major bleeding events within 90 days after the index INR was assessed. Five hundred…

Long-term outcomes of patients with cerebral vein thrombosis: a multicenter study.

Summary.  Background:  Little information is available on the long-term clinical outcome of cerebral vein thrombosis (CVT). Objectives and methods:  In an international, retrospective cohort study, we assessed the long-term rates of mortality, residual disability and recurrent venous thromboembolism (VTE) in a cohort of patients with a first CVT episode. Results:  Seven hundred and six patients (73.7% females) with CVT were included. Patients were followed for a total of 3171 patient-years. Median follow-up was 40 months (range 6, 297 months). At the end of follow-up, 20 patients had died (2.8%). The outcome was generally good: 89.1% of patients had a complete recovery (modified Rankin Scor…

Determining sulfur-containing amino acids by capillary electrophoresis: A fast novel method for total homocyst(e)ine human plasma

A high-performance capillary electrophoresis (HPCE) method based on laser-induced fluorescence detection is presented here. It enables the determination of sulfur-containing amino acids within 15 min. Fluorescence of sulfur-containing amino acids in plasma is linear over a range of 50-150 micromol/L for L-methionine, 5-100 micromol/L for L-homocysteine, and 50-200 micromol/L for L-cysteine. For homocysteine, we were able to detect 1 fmol injected, equivalent to a plasma concentration of 10 nmol/L. A similar sensitivity is present for cysteine, an even lower one being found for methionine. The intra- and interassay relative standard deviations are < 1%. High-performance liquid chromatography…

Prevalence of Apolipoprotein E Alleles in Healthy Subjects and Survivors of Ischemic Stroke

Background and Purpose —The ε4 allele of the apolipoprotein E (apoE) has been related to the occurrence of myocardial infarction, but its association with ischemic stroke is controversial. We have evaluated the relation between apoE alleles and the occurrence of cerebrovascular ischemia. Methods —The apoE ε genotypes of 100 patients with a documented history of ischemic stroke without clinically apparent dementia (stroke+) and 108 subjects without such history (stroke−) were determined. The relative frequency of the apoE alleles and genotypes was estimated in 398 healthy subjects aged &lt;40 years from the same ethnic background. Results —The frequency of the apoE ε4 allele in stroke+ (0.1…

The PAI-1 gene locus 4G/5G polymorphism is associated with a family history of coronary artery disease.

Abstract —A family history of ischemic events is a major determinant of coronary artery disease (CAD). Plasma levels of plasminogen activator inhibitor 1 (PAI-1) modulate this risk. A deletion/insertion polymorphism within the PAI-1 locus (4G/5G) affects the expression of this gene. We investigated the relationship between the PAI-1 4G/5G polymorphism in 1179 healthy employees of our institution and the occurrence of CAD in their first-degree relatives. A family history of documented ischemic coronary disease was assessed by a modified WHO questionnaire. The PAI-1 4G/5G polymorphism was evaluated by polymerase chain reaction and endonuclease digestion. The group with a first-degree relativ…

The Use of Frozen-Thawed Platelet-Derived Phospholipids as a Confirmatory Test for the Diagnosis of Lupus Anticoagulants. Comparison with Two Commercial Confirmatory System Tests

Lupus anticoagulants (LAs) belong to acquired circulating anticoagulants interfering with phospholipid-dependent coagulation tests. Owing to the remarkable variability among patients, SSC guidelines recommend more than one test to detect and confirm the presence of LAs. However, this is an expensive procedure and greatly raises the work load of the laboratory. A standardised platelet-derived phospholipid preparation was obtained and platelet neutralisation (PNP) procedures with APTT and DRVVT reagents were performed on plasmas from 16 patients with LAs and from 41 control subjects. In comparisons, STAclot-PNP and DVVconfirm clotting assays were conducted. PNP by using APTT or DRVVT reagents…

Pathogen safety of long-term treatments for bleeding disorders: (un)predictable risks and evolving threats.

Substantial improvements in the safety of blood and plasma products for the management of bleeding disorders have been achieved in recent decades. This has led some clinicians to believe that the infectious threat is over and that inhibitor formation is the foremost complication of hemophilia therapy. On the contrary, elimination of all microbes from blood is difficult, potentially impossible, and there are always threats from emerging pathogens. The risk of infection transmission is also increasing due to greater exposure to products, increasing prophylaxis and high-dose regimens for immune tolerance, and longevity of hemophilia patients. Current products can be considered "reasonably safe…

Coexistence of thrombophilic gene polymorphisms among 559 unrelated consecutive patients with a history of thrombosis.

Fibrinogen plasma levels in an apparently healthy general population: Relation to environmental and genetic determinants

SummaryElevated fibrinogen levels are an independent risk factor for cardiovascular ischemic disease. We investigated the relationship between cardiovascular ischemic risk factors, the fibrinogen Bβ-chain G/A-455 polymorphism and plasma fibrinogen levels in 989 apparently healthy subjects. Fibrinogen values were higher in subjects with C reactive protein (C-RP) &gt; 0.33 mg/dl, BMI &gt; 23.9 kg/m2, total cholesterol &gt; 4.84 mmol/l, triglycerides &gt;1.02 mmol/l, PAI-1 antigen &gt;12.2 ng/ml, carriers of the A allele, first-degree relative history of coronary artery disease, or consuming &gt;10 cigarettes per day (p &lt;0.01). Men and ethanol drinkers showed lower plasma fibrinogen levels …

Fibrinogen Naples I (Bβ A68T) Nonsubstrate Thrombin-Binding Capacities

Fibrinogen Naples I (Bbeta A68T) is characterized by defective thrombin binding and fibrinopeptide cleavage at the fibrinogen substrate site in the E domain. We evaluated the fibrinogen of three homozygotic members of this kindred (II.1, II.2, II.3) who have displayed thrombophilic phenotypes and two heterozygotic subjects (I.1, I.2) who were asymptomatic. Electron microscopy of Naples I fibrin networks showed relatively wide fiber bundles, probably due to slowed fibrin assembly secondary to delayed fibrinopeptide release. We evaluated 125I-thrombin binding to the fibrin from subjects I.1, I.2, II.1, and II.2 by Scatchard analysis with emphasis on the high-affinity site in the D domain of f…

Current concepts in the prevention of pathogen transmission via blood/plasma-derived products for bleeding disorders

The pathogen safety of blood/plasma-derived products has historically been a subject of significant concern to the medical community, Measures such as donor selection and blood screening have contributed to increase the safety of these products, but pathogen transmission does still occur. Reasons for this include lack of sensitivity/specificity of current screening methods, lack of reliable screening tests for some pathogens (e.g. prions) and the fact that many potentially harmful infectious agents are not routinely screened for. Methods for the purification/inactivation of blood/plasma-derived products have been developed in order to further reduce the residual risk, but low concentrations…