Search results for "coagulation factor"

Recombinant factor VIII: past, present and future of treatment of hemophilia A.

2018

The development of recombinant factor VIII (rFVIII) was initially driven by the necessity to treat hemophilia A (HA) patients with FVIII concentrates without the risk of transmitting infectious agents. Over the last three decades the safety of rFVIII has been further improved by completely removing animal or human proteins from the manufacturing process, so that patients would not be exposed to known or emerging pathogens. Recent efforts have concentrated on improving the expression of rFVIII, reducing its immunogenicity and enhancing its pharmacokinetic (PK) behavior. These new goals have been possible thanks to the develop-ment of biotechnology and a better knowledge of the function and s…

CD36-fibrin interaction propagates FXI-dependent thrombin generation of human platelets.

2019

Thrombin converts fibrinogen to fibrin and activates blood and vascular cells in thrombo-inflammatory diseases. Platelets are amplifiers of thrombin formation when activated by leukocyte- and vascular cell-derived thrombin. CD36 on platelets acts as sensitizer for molecules with damage-associated molecular patterns, thereby increasing platelet reactivity. Here, we investigated the role of CD36 in thrombin-generation on human platelets, including selected patients with advanced chronic kidney disease (CKD). Platelets deficient in CD36 or blocked by anti-CD36 antibody FA6.152 showed impaired thrombin generation triggered by thrombin in calibrated automated thrombography. Using platelets with …

sgp120 and the contact system in hereditary angioedema: A diagnostic tool in HAE with normal C1 inhibitor

2020

Mutations in Factor XII, plasminogen gene, angiopoietin-1 gene and kininogen 1 gene have been found in some patients with hereditary angioedema with normal C1 inhibitor (HAE-nl-C1inh), but the underlying disease mechanisms remain unclear. Additionally, there are no accepted biomarkers for this disease. Because the contact system has been implicated in hereditary angioedema with C1 inhibitor deficiency (HAE-C1inh), we studied the fragmentation patterns of serum glycoprotein 120 (sgp120), a protein that is highly susceptible to cleavage by kallikrein, in 31 HAE-C1inh and 13 HAE-nl-C1inh patient plasma samples. Compared to normal controls, the majority of plasma samples from patients with HAE-…

2018

Patients with inflammatory bowel disease (IBD) are susceptible to thromboembolism. Interestingly, IBD occurs less frequently in patients with inherited bleeding disorders. Therefore, we analyzed whether F9-deficiency is protective against the onset of acute colitis in a genetic hemophilia B mouse model. In the 3.5% dextran sulfate sodium (DSS)-induced colitis model, F9-deficient mice were protected from body-weight loss and had a reduced disease activity score. We detected decreased colonic myeloperoxidase activity and decreased CXCL1 levels in DSS-treated F9-deficient mice compared with wild-type (WT) littermate controls, indicating decreased neutrophil infiltration. Remarkably, we identif…

Safety of prothrombin complex concentrate in healthy subjects

2017

Keywords: anticoagulants; prothrombin complex concentrate; thrombosis; reversal; meta-analysis; bleeding disorders

Blood coagulation factor XII drives adaptive immunity during neuroinflammation via CD87-mediated modulation of dendritic cells

2016

Aberrant immune responses represent the underlying cause of central nervous system (CNS) autoimmunity, including multiple sclerosis (MS). Recent evidence implicated the crosstalk between coagulation and immunity in CNS autoimmunity. Here we identify coagulation factor XII (FXII), the initiator of the intrinsic coagulation cascade and the kallikrein–kinin system, as a specific immune cell modulator. High levels of FXII activity are present in the plasma of MS patients during relapse. Deficiency or pharmacologic blockade of FXII renders mice less susceptible to experimental autoimmune encephalomyelitis (a model of MS) and is accompanied by reduced numbers of interleukin-17A-producing T cells.…

The important impact of dental care on haemostatic treatment burden in patients with mild haemophilia

2022

Background: Mild haemophilia (MH) is mainly characterized by haemorrhages secondary to surgery/invasive procedures or trauma. Haemostatic treatment in MH ranges from on demand to short prophylaxis according to the type of bleeding events and the basal clotting factor level. Oral surgery and dental extractions can represent a frequent haemostatic challenge in MH requiring appropriate treatment. However, only few studies on limited numbers of patients are available in the literature regarding the implications of dental management in patients with MH. Objectives: The purpose of the study was to evaluate the impact of dental care on the burden of haemostatic treatment in patients affected by MH…

New data from the Italian National Register of Congenital Coagulopathies, 2016 Annual Survey

2018

BACKGROUND: In Italy, the National Register of Congenital Coagulopathies (NRCC) collects epidemiological and therapeutic data from patients affected by haemophilia A (HA), haemophilia B (HB), von Willebrand’s disease (vWD) and other rare coagulation disorders. Here we present data from the 2016 annual survey. MATERIALS AND METHODS: Data are provided by the Italian Haemophilia Centres, on a voluntary basis. Information flows from every Centre to a web-based platform of the Italian Association of Haemophilia Centres, shared with the Italian National Institute of Health, in accordance with current privacy laws. Patients are classified by diagnosis, disease severity, age, gender and treatment-r…

Obesity, hypertension and atherosclerosis

1993

Hypertension and obesity are associated with an increased risk of clinical cardiovascular complications due to atherosclerosis. Moreover has been reported that hypertension may predispose to atheroma development. In the present review some common aspects to hypertension and atherosclerosis including smooth muscle cell proliferation, endothelial damage and intervention of growth factors have been analyzed. Additional data have to be provided to explain if the connections between hypertension and atherosclerosis could be considered two effects with one unknown cause. In addition some aspects related to obesity and atherosclerosis have been dissected. In particular we have reported our results…

Kallikrein–kinin system and fibrinolysis in hereditary angioedema due to factor XII gene mutation Thr309Lys

2009

In a subgroup of hereditary angioedema (HAE) patients with normal C1-esterase inhibitor levels, HAE is caused by a Thr309Lys mutation in the coagulation factor XII (F12) gene. The aim of this study was to examine elements of the kallikrein-kinin system ('contact system') and the downstream-linked coagulation, complement and fibrinolytic systems in the plasma of six patients with HAE caused by the Thr309Lys mutation and healthy probands. Blood samples were taken from participants during the symptom-free interval between attacks. Samples were analyzed for activity and concentrations of components of the kallikrein-kinin system and linked enzyme systems. The mean FXII clotting activity was 90%…