The EAHAD blood coagulation factor VII variant database.

Hereditary blood coagulation factor VII (FVII) deficiency is a rare autosomal recessive bleeding disorder resulting from variants in the gene encoding FVII (F7). Integration of genetic variation with functional consequences on protein function is essential for the interpretation of the pathogenicity of novel variants. Here, we describe the integration of previous locus-specific databases for F7 into a single curated database with enhanced features.

The European Association for Haemophilia and Allied Disorders (EAHAD) Coagulation Factor Variant Databases: Important resources for haemostasis clinicians and researchers.

Introduction: Advances in genomic sequencing have facilitated the sequencing of genes associated with disorders of haemostasis. The identification of variants within genes and access to curated data incorporating structural, functional, evolutionary as well as phenotypic data has become increasingly important in order to ascribe pathogenicity.

Aim: The European Association for Haemophilia and Allied Disorders (EAHAD) Coagulation Factor Variant Database Project aims to provide a single port of entry to a web-accessible resource for variants in genes involved in clinical bleeding disorders.

European retrospective study of real-life haemophilia treatment.

Introduction: Haemophilia treatment varies significantly between individuals, countries and regions and details of bleed rates, factor consumption and injection frequency are often not available.

Aim: To provide an overview of the FVIII/FIX treatment practice and outcome for patients with haemophilia A (HA) or haemophilia B (HB) across Europe.

Methods: Non-interventional, 12-month retrospective study where anonymized data were retrieved from haemophilia centres/registers in Belgium, France, Germany, Italy, Spain, Sweden and the United Kingdom.

Hepatitis C infection and outcomes in the Scottish haemophilia population.

Patients with bleeding disorders previously frequently became infected with hepatitis C virus. We identified the number of patients infected in Scotland and assessed several aspects of the outcomes of HCV infection and its treatment comparing these with cohorts infected for other reasons. We calculated the number of individuals infected in Scotland (cohort A) starting with the total number of patients treated in Scottish haemophilia centres registered on the UKHCDO database between 1970 and 1989.

Endogenous tissue plasminogen activator enhances fibrinolysis and limits thrombus formation in a clinical model of thrombosis.

Objective: Using a clinical model of deep arterial injury, we assessed the ability of exogenous and endogenous tissue plasminogen activator (t-PA) to limit acute in situ thrombus formation.

Approach And Results: Ex vivo thrombus formation was assessed in the Badimon chamber at low and high shear rates in 2 double-blind randomized cross-over studies of 20 healthy volunteers during extracorporeal administration of recombinant t-PA (0, 40, 200, and 1000 ng/mL) or during endogenous t-PA release stimulated by intra-arterial bradykinin infusion in the presence or absence of oral enalapril. Recombinant t-PA caused a dose-dependent reduction in thrombus area under low and high shear conditions (P<0.

Guidelines for the management of hemophilia.

Hemophilia is a rare disorder that is complex to diagnose and to manage. These evidence-based guidelines offer practical recommendations on the diagnosis and general management of hemophilia, as well as the management of complications including musculoskeletal issues, inhibitors, and transfusion-transmitted infections. By compiling these guidelines, the World Federation of Hemophilia aims to assist healthcare providers seeking to initiate and/or maintain hemophilia care programs, encourage practice harmonization around the world and, where recommendations lack adequate evidence, stimulate appropriate studies.

Plasma microparticles are not elevated in fresh plasma from patients with gynaecological malignancy--an observational study.

Objectives: Gynaecological cancer is common. It is highly amenable to effective treatment, but thrombosis remains a common complication. There is controversy about whether microparticles (MPs), particularly tissue factor (TF) positive MPs, are increased in patients with malignancy and/or thrombosis.

Microparticles, malignancy and thrombosis.

Microparticles (MPs) are considered to be important biological effectors of several different physiological and pathological processes. There is increasing evidence of their role in haemostasis and thrombosis, and also of their importance in cancer cell survival, invasiveness and metastasis. The level of circulating MPs has been assessed in many different disease states, and there are reports that patients with malignancy and patients with thrombosis have increased levels of circulating MPs and MP-dependent thrombogenic potential.

EUHASS: The European Haemophilia Safety Surveillance system.

Pharmacovigilance is an essential element of any drug treatment and considering the history of adverse events due to products used to treat inherited bleeding disorders, it should be an integral component of modern haemophilia treatment. Because inherited bleeding disorders and adverse events are rare, a multicentre, preferably multinational, adverse event reporting scheme for all clotting factor products is required. EUHASS is a European, prospective, multicentre adverse event reporting scheme in the field of inherited bleeding disorders.

Effects of acute insulin-induced hypoglycemia on indices of inflammation: putative mechanism for aggravating vascular disease in diabetes.

Objective: To examine the effects of acute insulin-induced hypoglycemia on inflammation, endothelial dysfunction, and platelet activation in adults with and without type 1 diabetes.

Research Design And Methods: We studied 16 nondiabetic adults and 16 subjects with type 1 diabetes during euglycemia (blood glucose 4.5 mmol/l) and hypoglycemia (blood glucose 2.

Vascular dysfunction in chronic obstructive pulmonary disease.

Rationale: Cardiovascular disease is a major cause of morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD), which may in part be attributable to abnormalities of systemic vascular function. It is unclear whether such associations relate to the presence of COPD or prior smoking habit.

Objectives: To undertake a comprehensive assessment of vascular function in patients with COPD and healthy control subjects matched for smoking history.

Dissociation of phenotypic and functional endothelial progenitor cells in patients undergoing percutaneous coronary intervention.

Objectives: Endothelial progenitor cells (EPCs) are circulating mononuclear cells with the capacity to mature into endothelial cells and contribute to vascular repair. We assessed the effect of local vascular injury during percutaneous coronary intervention (PCI) on circulating EPCs in patients with coronary artery disease.

Design And Setting: Prospective case-control study in a university teaching hospital.

Consensus protocol for the use of recombinant activated factor VII [eptacog alfa (activated); NovoSeven] in elective orthopaedic surgery in haemophilic patients with inhibitors.

Patients with haemophilia complicated by inhibitors have a significant burden of joint disease, which is associated with a negative impact on their quality of life. Successful elective orthopaedic surgery can result in decreased bleed frequency into a new joint, less time spent in hospital, increased mobility and improved well being. This paper describes a new protocol for use of recombinant activated factor VII (rFVIIa) in elective orthopaedic surgery, based on a review of published data as well as the personal experience of a group of expert physicians.

Vascular B1 kinin receptors in patients with congestive heart failure.

Animal models suggest a vasomotor role for the B1 kinin receptor in cardiovascular disease states. In patients with heart failure treated with angiotensin-converting enzyme inhibition (ACEi), or combined B1/B2 receptor antagonism, but not B2 receptor antagonism alone, causes vasoconstriction. However, B1 agonism has no effect on vasomotor or fibrinolytic function.

Acute endothelial tissue plasminogen activator release in pregnancy.

Objective: Pregnancy is associated with marked changes in vascular physiology and an increased risk of thrombosis. The aim of the study was to assess the effect of pregnancy on the acute release of tissue plasminogen activator (t-PA) from the endothelium.

Methods And Results: Ten primigravida pregnant women were recruited in the third trimester of pregnancy (week 36 +/- 1) and compared with 20 age-matched non-pregnant women (day 9.

An update on the assessment and management of the risk of transmission of variant Creutzfeldt-Jakob disease by blood and plasma products.

There have been four highly probable instances of variant Creutzfeldt-Jakob disease (vCJD) transmission by non-leucocyte depleted red cell concentrates and it is now clear that the infectious agent is transmissible by blood components. To date there in no reported evidence that the infectious agent has been transmitted by fractionated plasma products, e.g.

Risk factors and mechanisms of anaphylactoid reactions to acetylcysteine in acetaminophen overdose.

Background: Adverse effects to N-acetylcysteine (NAC) are well recognized, but their etiology and incidence are unclear.

Methods: The nature and severity of adverse effects were prospectively studied in 169 patients and potential reaction mediators studied in 22 patients.

Results: Adverse effects were minimal in 101 (59.

Marked impairment of protease-activated receptor type 1-mediated vasodilation and fibrinolysis in cigarette smokers: smoking, thrombin, and vascular responses in vivo.

Objectives: We sought to test the hypothesis that cigarette smoking adversely alters protease-activated receptor type 1 (PAR-1)-mediated vascular effects in vivo in humans.

Background: Distinct from its role in the coagulation cascade, thrombin exerts its major cellular and cardiovascular actions via PAR-1. The activation of PAR-1 causes endothelium-dependent arterial vasodilation and the release of endogenous fibrinolytic factors.

Role of the endothelium in the vascular effects of the thrombin receptor (protease-activated receptor type 1) in humans.

Objectives: The purpose of this study was to determine the role of the endothelium in the vascular actions of protease-activated receptor type 1 (PAR-1) activation in vivo in man.

Background: Thrombin is central to the pathophysiology of atherothrombosis. Its cellular actions are mediated via PAR-1.

Hyperfibrinolysis in alcoholic cirrhosis: relative plasminogen activator inhibitor type 1 deficiency.

Background: Over activity of the fibrinolytic system (hyperfibrinolysis) occurs in cirrhosis and has been shown to correlate with the risk of variceal hemorrhage. We have developed a model for assessing acute tissue plasminogen activator (t-PA) release in vivo in man. The aims of the study were to assess the contribution of basal and stimulated t-PA release to hyperfibrinolysis in patients with alcoholic cirrhosis.