2,275 results match your criteria Hemophilia Type A


Identification of six novel factor viii gene variants using next generation sequencing and molecular dynamics simulation.

Acta Biochim Pol 2019 Feb 22. Epub 2019 Feb 22.

1Department of Medical Genetics, Faculty of Medicine, Umm Al-Qura University, P.O. Box 715, Makkah 21955, Saudi Arabia; 2Science and Technology Unit, Umm Al Qura University, P.O. Box 715, Makkah 21955, Saudi Arabia.

Hemophilia A is an X-linked recessive hemorrhagic disorder caused by variants in the F8 gene. To identify known and novel causative variants in hemophilia A, we have carried out genetic analysis among Saudi patients. Twenty-one patients, who were negative for inv-1/inv-22, were selected for analysis by next generation sequencing, thereafter confirmed by Sanger sequencing. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.18388/abp.2018_2339DOI Listing
February 2019

A phase III study comparing secondary long-term prophylaxis versus on-demand treatment with vWF/FVIII concentrates in severe inherited von Willebrand disease.

Blood Transfus 2019 Feb 4:1-8. Epub 2019 Feb 4.

Division of Haematology and Transfusion Medicine, "Luigi Sacco" University Hospital, Milan, Italy.

Background: There is a lack of prospective clinical trials specifically designed to evaluate the benefits of prophylaxis with vWF/FVIII concentrates in patients with inherited von Willebrand disease (vWD). The aim of the study was to compare efficacy of secondary long-term prophylaxis (PRO) with vWF/FVIII in the prevention of bleeding episodes in severe vWD patients to standard of care (on-demand treatment; ODT).

Materials And Methods: In this 12-month, phase III, open-label study (PRO. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.2450/2019.0183-18DOI Listing
February 2019
1 Read

Analysis of von Willebrand Disease in the South Moravian Population (Czech Republic): Results from the BRNO-VWD Study.

Thromb Haemost 2019 Feb 5. Epub 2019 Feb 5.

Haemostasis Unit, Antwerp University Hospital, Edegem, Belgium.

Background:  von Willebrand disease (VWD) is an inherited bleeding disorder caused by a quantitative (type 1 and 3) or qualitative (type 2) defect of von Willebrand factor (VWF). The heterogeneity of laboratory phenotyping makes diagnosing difficult.

Objective:  A cross-sectional, family-based VWD study in a collaboration between University Hospital Brno (Czech Republic) and Antwerp University Hospital (Belgium) to improve the understanding of laboratory phenotype/genotype correlation. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-0039-1678528DOI Listing
February 2019
1 Read

Tissue factor pathway inhibitor is the main determinant of thrombin generation in haemophilic patients.

Haemophilia 2019 Jan 28. Epub 2019 Jan 28.

INSERM, U1059, SAINBIOSE, Université de Lyon, UJM-Saint-Etienne, Saint-Etienne, France.

The thrombin generation (TG) assay evaluates haemostatic balance, which is influenced by the levels of many coagulation factors and inhibitors. Our objective was to identify the determinant factors of TG in haemophilia A (HA) and haemophilia B (HB) patients and to compare them to those in healthy controls. Coagulation factor and inhibitor levels, and TG, were measured in platelet-poor plasma from 40 patients with HA, 32 patients with HB and 40 healthy subjects. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1111/hae.13679DOI Listing
January 2019
1 Read

Sports participation and physical activity in adult Dutch and Swedish patients with severe haemophilia: A comparison between intermediate- and high-dose prophylaxis.

Haemophilia 2019 Jan 28. Epub 2019 Jan 28.

Van Creveldkliniek, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.

Introduction: Differences in treatment and outcome have been reported for persons with haemophilia (PWH) on intermediate-dose (Dutch) and high-dose (Swedish) prophylaxis, but the potential influence of sports participation has not been considered.

Aim: To compare sports participation and clinical outcome between adult Dutch and Swedish PWH.

Methods: Self-reported sports participation (type and frequency per week), physical functioning (SF-36 : 100-0), joint status (HJHS: 0-144), perceived limitations (HAL : 100-0) and physical activity (IPAQ) were recorded. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1111/hae.13683DOI Listing
January 2019

Viral Vector-Based Delivery of CRISPR/Cas9 and Donor DNA for Homology-Directed Repair in an In Vitro Model for Canine Hemophilia B.

Mol Ther Nucleic Acids 2018 Dec 20;14:364-376. Epub 2018 Dec 20.

Institute for Virology and Microbiology, Center for Biomedical Education and Research (ZBAF), Department of Human Medicine, Faculty of Health, Witten/Herdecke University, 58453 Witten, Germany. Electronic address:

Gene therapy represents an attractive alternative to treat hemophilia B. Here we established three hepatocyte-derived cell lines based on Huh7, PLC/PRF/5, and Hep3B cells stably carrying a mutated canine FIX (cFIXmut) transgene containing a single point mutation in the catalytic domain. Based on these in vitro models resembling a commonly used canine large animal model, the tetracycline-controlled transcriptional activator (Tet-on)-inducible CRISPR/Cas9 system and an optimized donor were used to correct mutated cFIX gene through homology-directed repair (HDR). Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.omtn.2018.12.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356096PMC
December 2018
1 Read

Serum Sclerostin Level and Bone Mineral Density in Pediatric Hemophilic Arthropathy.

Indian J Pediatr 2019 Jan 22. Epub 2019 Jan 22.

Department of Clinical Pathology, Ain Shams University Hospitals, Faculty of Medicine, Ain Shams University, Cairo, Egypt.

Objective: To assess serum sclerostin levels in relation to severity of arthropathy and bone mineral density (BMD) in children with hemophilic arthropathy.

Methods: This cross-sectional study included 40 male children suffering from Hemophilia A, and 10 matched healthy controls. Assessment of factor VIII deficiency degree, frequency of bleeding, type of treatment, body mass index (BMI), disease severity using the Hemophilia Joint Health Score (HJHS) and lumbar spine (LS) Z score for bone mineral density (BMD) using dual-energy X-ray absorbiometry was done. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12098-019-02855-1DOI Listing
January 2019
3 Reads

Laboratory assay measurement of modified clotting factor concentrates: a review of the literature and recommendations for practice.

J Thromb Haemost 2019 Jan 22. Epub 2019 Jan 22.

Cambridge Haemophilia and Thrombophilia Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.

Over the past several years, novel modified clotting factor concentrates (CFCs) have been introduced into practice and are now widely prescribed in the countries where they are licensed. These products allow for less frequent infusions of CFC, thereby providing improved convenience and/or higher trough levels. They have been extensively studied for prophylaxis, episodic treatment of bleeding and for surgical prophylaxis. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1111/jth.14394DOI Listing
January 2019
2 Reads

Bleed volume of experimental knee haemarthrosis correlates with the subsequent degree of haemophilic arthropathy.

Haemophilia 2019 Jan 16. Epub 2019 Jan 16.

Global Drug Discovery, Novo Nordisk A/S, Maaloev, Denmark.

Background: Haemophilic arthropathy is the main morbidity of haemophilia. The individual pathological response to the same number of clinically evident joint bleeds is highly variable; thus, it remains unknown if certain joint bleeding characteristics are critical for the development of arthropathy.

Aim: To study the relation between bleed volume and subsequent development of arthropathy, we aimed to develop quantitative in vivo imaging of active joint bleeds in a mouse model of haemophilia. Read More

View Article

Download full-text PDF

Source
http://doi.wiley.com/10.1111/hae.13672
Publisher Site
http://dx.doi.org/10.1111/hae.13672DOI Listing
January 2019
4 Reads

Routine Preoperative Coagulation Tests in Children Undergoing Elective Surgery or Invasive Procedures: Are They Still Necessary?

Clin Med Insights Blood Disord 2019 5;12:1179545X18821158. Epub 2019 Jan 5.

Department of Central Military Laboratory and Blood Bank, Prince Sultan Military Medical City, Riyadh, Saudi Arabia.

Introduction: Preoperative coagulation screening tests in pediatric patients was once routine clinical practice globally and still used as standard practice in some countries before surgical procedures to assess of perioperative bleeding risk.

Objective: The study aimed to evaluate unselected routine preoperative coagulation testing in children undergoing elective or invasive surgery to predict abnormal perioperative bleeding. The study also aimed to provide a rational approach of determining bleeding and family history of coagulation disorders as a predictive risk for bleeding. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1177/1179545X18821158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6322095PMC
January 2019
2 Reads

Comparative accuracy of optical sensor-based wearable system for non-invasive measurement of blood glucose concentration.

Clin Biochem 2019 Jan 7. Epub 2019 Jan 7.

Maale Carmel Mental Health Center Affiliated to Bruce Rappaport Medical Faculty, Technion, Tirat Carmel, Israel.

Non-invasive biosensors for indirect evaluation of routinely-measured blood components by sweat analysis have broad potential clinical applications. This trial tested a wrist-borne non-invasive glucose monitor (NIGM) to measure blood glucose (BG) levels using photoplethysmographic (PPG) optical sensors. Our aim was to determine the accuracy of the device in comparison with a standard, invasive clinical method for blood glucose monitoring. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clinbiochem.2018.12.014DOI Listing
January 2019
7 Reads

Individual risk factors predictive of venous thromboembolism in patients with temporary lower limb immobilization due to injury: a systematic review.

J Thromb Haemost 2019 Feb 7;17(2):329-344. Epub 2019 Feb 7.

Thrombosis and Haemophilia Centre, St Thomas' Hospital, London, UK.

Essentials Thromboprophylaxis after lower limb injury is often based on complex risk stratification. Our systematic review identified variables predicting venous thromboembolism (VTE) in this group. Age and injury type were commonly reported to increase the odds of VTE (odds ratio 1. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1111/jth.14367DOI Listing
February 2019

Anaphylaxis after treatment with recombinant factor VIII: investigation and therapeutic challenge.

BMJ Case Rep 2018 Dec 14;11(1). Epub 2018 Dec 14.

Application Lab, R&D Department, Roxall Group, Bilbao, Spain.

We report a 10-year-old patient with haemophilia A developing anaphylaxis to recombinant factor VIII (octocog alfa). Allergic reactions, and especially anaphylactic events, are rare in patients with haemophilia A. The nature of these reactions is not fully understood. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1136/bcr-2018-227426DOI Listing
December 2018
1 Read

AAV8 Gene Therapy for Crigler-Najjar Syndrome in Macaques Elicited Transgene T Cell Responses That Are Resident to the Liver.

Mol Ther Methods Clin Dev 2018 Dec 5;11:191-201. Epub 2018 Dec 5.

Gene Therapy Program, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Systemic delivery of adeno-associated viral (AAV) vectors has been evaluated for the treatment of several liver diseases, including homozygous familial hypercholesterolemia, ornithine transcarbamylase deficiency, and hemophilia. Here, we evaluated this approach for the treatment of Crigler-Najjar syndrome. We administered wild-type rhesus macaques with 1. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.omtm.2018.10.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6282099PMC
December 2018
2 Reads

Factor VIII with a 237 amino acid B-domain has an extended half-life in F8-knockout mice.

J Thromb Haemost 2019 Feb 25;17(2):350-360. Epub 2019 Jan 25.

Novo Nordisk A/S, Novo Nordisk Park, Måløv, Denmark.

Essentials Factor (F)VIII with an intermediate-length B-domain showed higher levels in murine gene therapy. FVIII with different B-domain lengths were analysed. FVIII variants with B-domains between 186 and 240 amino acids (aa) have extended half-life in mice. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1111/jth.14355DOI Listing
February 2019
1 Read

Evaluation of EC50 of factor VIII as predictor of prophylaxis efficacy in patients with severe haemophilia A.

Eur J Pharm Sci 2019 Feb 7;128:215-221. Epub 2018 Dec 7.

La Paz University Hospital, Haematology and Haemotherapy Department, Madrid, Spain. Electronic address:

Trough factor (F) VIII level is a not reliable bleeding risk indicator to predict prophylaxis efficacy in severe haemophilia A (SHA), therefore, accurate biomarkers are much needed. Thrombelastography (TEG) monitors both thrombin and clot formation addressing the global haemostatic status but its usefulness to tailor prophylaxis in haemophilia has been poorly evaluated. In this study, correspondence between individual pharmacodynamic/pharmacokinetic profile of FVIII and joint condition, physical activity and bleeding phenotype of SHA patients under prophylactic treatment was assessed. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejps.2018.12.003DOI Listing
February 2019
1 Read

Potential limits of AAV-based gene therapy with the use of new transgenes expressing factor IX fusion proteins.

Haemophilia 2019 Jan 6;25(1):e11-e18. Epub 2018 Dec 6.

Research Department of Haematology, University of London Cancer Institute, London, UK.

Introduction: The variety of treatment for haemophilia B (HB) has recently improved with the emergence of both AAV-based gene therapy and bioengineered human factor IX (hFIX) molecules with prolonged half-life due to fusion to either albumin (Alb) or immunoglobulin Fc fragment (Fc).

Aim: Adeno-associated viral vectors (AAV) mediating expression of hFIX-Alb and hFIX-Fc fusion proteins was investigated for gene therapy of HB to explore if their extended half-life translates to higher plasma levels of FIX.

Methods: Single-stranded cross-packaged AAV2/8 vectors expressing hFIX-Alb, hFIX-Fc and hFIX were evaluated in vitro, and in mice. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1111/hae.13651DOI Listing
January 2019
2 Reads

Genotype analysis and identification of novel mutations in a multicentre cohort of patients with hereditary factor X deficiency.

Blood Coagul Fibrinolysis 2019 Jan;30(1):34-41

St. George's Haemophilia Centre, St. George's University Hospitals NHS Foundation Trust, London, UK.

: The objective was to examine the genotypic and phenotypic characteristics of individuals with hereditary factor X deficiency (FXD), a rare autosomal recessive bleeding disorder caused by mutations in the F10 gene located on chromosome 13q34-ter. To date, 149 F10 mutations have been identified as contributory to FXD. Three open-label phase 3 trials enrolled individuals with mild, moderate, or severe FXD. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1097/MBC.0000000000000787DOI Listing
January 2019
2 Reads

Acquired Hemophilia A in Aged People: A Systematic Review of Case Reports and Case Series.

Semin Hematol 2018 Oct 21;55(4):197-201. Epub 2018 Feb 21.

Faculty of Medicine, University of Reims Champagne-Ardenne, Reims, France; Department of Research and Public Health, University Hospitals of Reims, Robert Debré Hospital, Reims, France.

Acquired hemophilia A (AHA) is a rare disease that requires urgent management. Currently, there is no consensus regarding optimal management in aged people. This systematic review aimed to describe diagnosis, clinical features, management, and endpoints in population aged 65 years or over with AHA. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1053/j.seminhematol.2018.02.004DOI Listing
October 2018

Effect of Lanadelumab Compared With Placebo on Prevention of Hereditary Angioedema Attacks: A Randomized Clinical Trial.

JAMA 2018 11;320(20):2108-2121

Department of Dermatology and Allergy, Dermatological Allergology, Charité-Universitätsmedizin Berlin, Berlin, Germany.

Importance: Current treatments for long-term prophylaxis in hereditary angioedema have limitations.

Objective: To assess the efficacy of lanadelumab, a fully human monoclonal antibody that selectively inhibits active plasma kallikrein, in preventing hereditary angioedema attacks.

Design, Setting, And Participants: Phase 3, randomized, double-blind, parallel-group, placebo-controlled trial conducted at 41 sites in Canada, Europe, Jordan, and the United States. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1001/jama.2018.16773DOI Listing
November 2018
5 Reads

Cardiovascular disease-related hospitalization and mortality among persons with von Willebrand disease: A nationwide register study in Sweden.

Haemophilia 2019 Jan 23;25(1):109-115. Epub 2018 Nov 23.

Department of Translational Medicine, Skåne University Hospital, Lund University, Malmö, Sweden.

Introduction: It has been hypothesized that persons with von Willebrand disease (VWD) may be protected against arterial thrombosis despite having atherosclerosis.

Aim: To calculate a nationwide estimate of the absolute and comparative burden of cardiovascular disease (CVD) hospitalization and mortality among persons with VWD using birthdate and sex-matched comparisons from the general population in Sweden.

Methods: Persons with VWD regardless of the type and severity, diagnosed by a medical doctor, who lived in Sweden for some time during the observation period 1987 through 2008 were included. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1111/hae.13642DOI Listing
January 2019
10 Reads
2.603 Impact Factor

Fusion of Factor IX to Factor XIII-B Sub-Unit Improves the Pharmacokinetic Profile of Factor IX.

Thromb Haemost 2018 Dec 19;118(12):2053-2063. Epub 2018 Nov 19.

EA4609-Hemostase et Cancer, Universite Claude Bernard Lyon I, Lyon, France.

Prophylaxis is currently considered the optimal care for severe haemophilia. For patients and their families one of the major difficulties with prophylaxis is the need for frequent venipunctures. The half-life of standard factor IX (FIX) concentrates is approximately 18 hours, which requires 2 or 3 intravenous infusions per week to achieve bleeding prevention in patients with severe haemophilia B. Read More

View Article

Download full-text PDF

Source
http://www.thieme-connect.de/DOI/DOI?10.1055/s-0038-1675787
Publisher Site
http://dx.doi.org/10.1055/s-0038-1675787DOI Listing
December 2018
10 Reads

Suppressing protein Z-dependent inhibition of factor Xa improves coagulation in hemophilia A.

J Thromb Haemost 2019 Jan 16;17(1):149-156. Epub 2018 Dec 16.

Division of Hematology, Department of Medicine, Washington University School of Medicine, St Louis, MO, USA.

Essentials Protein Z (PZ) catalyzes PZ-dependent proteinase inhibitor (ZPI) inactivation of factor (F)Xa. Gene-deletion of PZ or ZPI improves coagulation in hemophilia (FVIII knockout) mice. A PZ blocking antibody enhances thrombin generation in human hemophilia plasma. Read More

View Article

Download full-text PDF

Source
http://doi.wiley.com/10.1111/jth.14337
Publisher Site
http://dx.doi.org/10.1111/jth.14337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6322933PMC
January 2019
18 Reads

Musculoskeletal ultrasonography for arthropathy assessment in patients with hemophilia: A single-center cross-sectional study from Shanxi Province, China.

Medicine (Baltimore) 2018 Nov;97(46):e13230

Department of Hematology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.

Magnetic resonance imaging (MRI) is currently considered the gold standard for assessing hemophilic arthropathy (HA) severity; however, MRI is often costly, time-consuming, and difficult to perform in children. In the present study, we evaluated the joint status of hemophilic patients from Shanxi Province, China, using musculoskeletal ultrasonography (MSKUS) and identified the factors that most strongly correlated with disease severity.The study included 104 patients with hemophilia, who underwent MSKUS examination. Read More

View Article

Download full-text PDF

Source
http://Insights.ovid.com/crossref?an=00005792-201811160-0004
Publisher Site
http://dx.doi.org/10.1097/MD.0000000000013230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6257645PMC
November 2018
9 Reads

Sports participation and physical activity in patients with von Willebrand disease.

Haemophilia 2019 Jan 14;25(1):101-108. Epub 2018 Nov 14.

Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands.

Introduction: Patients with bleeding disorders may experience limitations in sports participation and physical activity. Several studies on sports participation have been performed in haemophilia patients, but studies in patients with von Willebrand disease (VWD) are lacking.

Aim: We assessed the sports participation and physical activity of a large cohort of VWD patients. Read More

View Article

Download full-text PDF

Source
http://doi.wiley.com/10.1111/hae.13629
Publisher Site
http://dx.doi.org/10.1111/hae.13629DOI Listing
January 2019
16 Reads

Coagulation phenotype of wild-type mice on different genetic backgrounds.

Lab Anim 2018 Nov 12:23677218811059. Epub 2018 Nov 12.

Shire, Vienna, Austria.

Genetically engineered mouse models are used to investigate beneficial treatment in haemophilia by comparison with wild-type mice. It has been recognized that wild-type and haemophilic mice of different genetic backgrounds show different bleeding phenotypes. We assessed ex-vivo coagulation parameters in nine wild-type substrains of 129S1/Sv, BALB/c and C57BL/6 mice applying thromboelastography (TEG), activated partial thromboplastin time (aPTT), prothrombin time (PT) and fibrinogen levels. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1177/0023677218811059DOI Listing
November 2018
8 Reads

Severe haemophilia A in a neonate presenting as haemopneumothorax after tracheo-oesophageal fistula-oesophageal atresia repair.

BMJ Case Rep 2018 Nov 8;2018. Epub 2018 Nov 8.

Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.

A male infant with oesophageal atresia and distal tracheo-oesophageal fistula (TEF type C) underwent right thoracotomy and transpleural repair of TEF on day 4 of life. He did not have a family history of coagulation disorders. A preoperative finding of prolonged partial thromboplastin time (PTT)>200 s was overlooked, and he went to surgery. Read More

View Article

Download full-text PDF

Source
http://casereports.bmj.com/lookup/doi/10.1136/bcr-2018-22552
Publisher Site
http://dx.doi.org/10.1136/bcr-2018-225526DOI Listing
November 2018
10 Reads

Recombinant factor VIII Fc fusion protein drives regulatory macrophage polarization.

Blood Adv 2018 Nov;2(21):2904-2916

Bioverativ, a Sanofi company, Waltham, MA; and.

The main complication of replacement therapy with factor in hemophilia A (HemA) is the formation of inhibitors (neutralizing anti-factor VIII [FVIII] antibodies) in ∼30% of severe HemA patients. Because these inhibitors render replacement FVIII treatment essentially ineffective, preventing or eliminating them is of top priority in disease management. The extended half-life recombinant FVIII Fc fusion protein (rFVIIIFc) is an approved therapy for HemA patients. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1182/bloodadvances.2018024497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6234359PMC
November 2018
6 Reads

von Willebrand factor clearance - biological mechanisms and clinical significance.

Br J Haematol 2018 Oct;183(2):185-195

Haemostasis Research Group, Irish Centre for Vascular Biology, Royal College of Surgeons in Ireland, Dublin, Ireland.

The mechanisms involved in regulating von Willebrand factor (VWF) clearance remain poorly understood. However recent studies have shown that macrophages play a critical role in regulating the half-life of VWF, and have identified specific lectin (including asialoglycoprotein, macrophage galactose-type lectin, Sigec-5 and C-type lectin domain family 4 member M) and scavenger receptors (including low-density lipoprotein receptor-related protein-1, scavenger receptor A1 and stabilin-2) that are involved in VWF clearance. Further studies will be required to determine the relative importance of these individual receptors with respect to physiological and pathological VWF clearance. Read More

View Article

Download full-text PDF

Source
http://doi.wiley.com/10.1111/bjh.15565
Publisher Site
http://dx.doi.org/10.1111/bjh.15565DOI Listing
October 2018
3 Reads

Evaluation of a semi-automated von Willebrand factor multimer assay, the Hydragel 5 von Willebrand multimer, by two European Centers.

Res Pract Thromb Haemost 2018 Oct 12;2(4):790-799. Epub 2018 Aug 12.

Department of Coagulation Sheffield Haemophilia and Thrombosis Centre Sheffield UK.

Background: The phenotypic diagnosis of von Willebrand disease (VWD) is a multistep process with classification dependent on the quantification of von Willebrand factor (VWF) multimeric structure. VWF multimer analysis is a technically challenging, lengthy and non-standardised assay, usually performed in specialist laboratories. Recently, a new semi-automated multimer assay, the Hydragel 5 von Willebrand multimers (H5VWM) has become available. Read More

View Article

Download full-text PDF

Source
http://doi.wiley.com/10.1002/rth2.12141
Publisher Site
http://dx.doi.org/10.1002/rth2.12141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6178608PMC
October 2018
4 Reads

An update on the role of RANKL-RANK/osteoprotegerin and WNT-ß-catenin signaling pathways in pediatric diseases.

World J Pediatr 2018 Oct 20. Epub 2018 Oct 20.

Pediatric Section, Department of Biomedical Sciences and Human Oncology, University "A. Moro" of Bari, Piazza G. Cesare 11, 70124, Bari, Italy.

Background: Bone remodeling is a lifelong process due to the balanced activity of osteoclasts (OCs), the bone-reabsorbing cells, and osteoblasts (OBs), and the bone-forming cells. This equilibrium is regulated by numerous cytokines, but it has been largely demonstrated that the RANK/RANKL/osteoprotegerin and Wnt/β-catenin pathways play a key role in the control of osteoclastogenesis and osteoblastogenesis, respectively. The pro-osteoblastogenic activity of the Wnt/β-catenin can be inhibited by sclerostin and Dickkopf-1 (DKK-1). Read More

View Article

Download full-text PDF

Source
http://link.springer.com/10.1007/s12519-018-0198-7
Publisher Site
http://dx.doi.org/10.1007/s12519-018-0198-7DOI Listing
October 2018
7 Reads

A Rare Case of Giant Solid Hemangioblastoma Accompanied with Hemophilia Type A.

NMC Case Rep J 2018 Oct 13;5(4):95-97. Epub 2018 Sep 13.

Department of Neurosurgery, Kurashiki Central Hospital, Kurashiki, Okayama, Japan.

The surgical removal of giant solid hemangioblastoma involves a high risk of perioperative bleeding and requires attentive hemostasis. Here, we present a case of a giant solid hemangioblastoma accompanied with hemophilia which was previously undiagnosed. A 35-year-old man without any past medical history was admitted with diplopia and ocular motility disorder. Read More

View Article

Download full-text PDF

Source
https://www.jstage.jst.go.jp/article/nmccrj/5/4/5_cr.2018-00
Publisher Site
http://dx.doi.org/10.2176/nmccrj.cr.2018-0062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6187256PMC
October 2018
4 Reads

A decreased and less sustained desmopressin response in hemophilia A carriers contributes to bleeding.

Blood Adv 2018 Oct;2(20):2629-2636

Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada.

The cause of hemophilia A carrier bleeding is not well established. Desmopressin (DDAVP), used clinically to treat or prevent bleeding, can also be used as a medical stress surrogate. This study's objective was to compare the response to DDAVP in hemophilia A carriers with that in normal control patients. Read More

View Article

Download full-text PDF

Source
http://www.bloodadvances.org/lookup/doi/10.1182/bloodadvance
Publisher Site
http://dx.doi.org/10.1182/bloodadvances.2018023713DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6199650PMC
October 2018
11 Reads

Hemostatic abnormalities in patients with Ehlers-Danlos syndrome.

J Thromb Haemost 2018 Dec 8;16(12):2425-2431. Epub 2018 Nov 8.

A. Bianchi Bonomi Hemophilia and Thrombosis Center, University of Milan, Milan, Italy.

Essentials Ehlers-Danlos Syndrome (EDS) is a rare heterogeneous group of inherited collagen disorders. A cohort of EDS patients was investigated for bleeding tendency and hemostatic abnormalities. EDS is associated with an increased risk of bleeding. Read More

View Article

Download full-text PDF

Source
http://doi.wiley.com/10.1111/jth.14310
Publisher Site
http://dx.doi.org/10.1111/jth.14310DOI Listing
December 2018
4 Reads

Anti-tissue factor pathway inhibitor (TFPI) therapy: a novel approach to the treatment of haemophilia.

Authors:
Pratima Chowdary

Int J Hematol 2018 Oct 9. Epub 2018 Oct 9.

KD Haemophilia and Thrombosis Centre, Royal Free London NHS Foundation Trust, London, UK.

Novel approaches to the treatment of haemophilia are needed due to the limitations of the current standard of care, factor replacement therapy. Aspirations include lessening the treatment burden and effectively preventing joint damage. Treating haemophilia by restoring thrombin generation may be an effective approach. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12185-018-2548-6DOI Listing
October 2018
2 Reads

Paired CRISPR/Cas9 Nickases Mediate Efficient Site-Specific Integration of into rDNA Locus of Mouse ESCs.

Int J Mol Sci 2018 Oct 5;19(10). Epub 2018 Oct 5.

Center for Medical Genetics, School of Life Sciences, Central South University, Changsha 410000, China.

Hemophilia B (HB) is an X-linked recessive bleeding disorder, caused by gene deficiency. Gene therapy combined with the CRISPR/Cas9 technology offers a potential cure for hemophilia B. Now the Cas9 nickase (Cas9n) shows a great advantage in reducing off-target effect compared with wild-type Cas9. Read More

View Article

Download full-text PDF

Source
http://www.mdpi.com/1422-0067/19/10/3035
Publisher Site
http://dx.doi.org/10.3390/ijms19103035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6213315PMC
October 2018
4 Reads

Impact of Exercise/Sport on Well-being in Congenital Bleeding Disorders.

Semin Thromb Hemost 2018 Nov 4;44(8):796-801. Epub 2018 Oct 4.

Unità Operativa Complessa Medicina Trasfusionale, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.

Physical activity provides many benefits in patients with congenital bleeding disorders. Patients with hemophilia are encouraged to participate in exercise and sports, especially those patients receiving prophylaxis. Several publications and guidelines have explored this issue in hemophilia patients, evaluating in particular the impact of physical activity on patients' well-being and quality of life. Read More

View Article

Download full-text PDF

Source
http://www.thieme-connect.de/DOI/DOI?10.1055/s-0038-1673628
Publisher Site
http://dx.doi.org/10.1055/s-0038-1673628DOI Listing
November 2018
12 Reads

The elevated prevalence of risk factors for chronic liver disease among ageing people with hemophilia and implications for treatment.

Medicine (Baltimore) 2018 Sep;97(39):e12551

Department of Haematology, Oslo University Hospital.

Chronic liver disease (CLD) is frequently seen in the hemophilia population. The ADVANCE Working Group conducted a cross-sectional study in which people with hemophilia (PWH) aged ≥40 years were included. This study aimed to assess the associations between CLD and its risk factors using data from the H3 study, and to suggest implications for optimal care. Read More

View Article

Download full-text PDF

Source
http://Insights.ovid.com/crossref?an=00005792-201809280-0007
Publisher Site
http://dx.doi.org/10.1097/MD.0000000000012551DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6181599PMC
September 2018
2 Reads

Long-Term Outcome after Joint Bleeds in Von Willebrand Disease Compared to Haemophilia A: A Post Hoc Analysis.

Thromb Haemost 2018 Oct 1;118(10):1690-1700. Epub 2018 Oct 1.

Department of Epidemiology, Van Creveldkliniek and Julius Center, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.

Long-term outcome after joint bleeds in von Willebrand disease (VWD) (von Willebrand factor activity ≤ 30 IU/dL) could differ from moderate or severe haemophilia A (HA) (factor VIII [FVIII] 1-5 IU/dL or FVIII < 1 IU/dL). We performed a post hoc analysis on Haemophilia Joint Health Score (HJHS, 0-124), X-ray Pettersson scores (PS, 0-13/joint) and the Haemophilia Activities List (HAL, 0-100), using multivariable regression to adjust for age (rate ratio [RR] or odds ratio [OR] [95% confidence interval]). We included 48 VWD (median age, 47 years, type 3 VWD,  = 19), 39 moderate HA (median, 39 years) and 59 severe HA patients (median, 25 years) with documented joint bleeds. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-0038-1670704DOI Listing
October 2018
9 Reads

The Impact of Bleeding Disorders on the Socioeconomic Status of Adult Patients.

Hamostaseologie 2018 Aug 27;38(3):150-157. Epub 2018 Sep 27.

II. Medical Department, Haemophilia Centre, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.

The impact of inherited bleeding disorders on the socioeconomic status (SES) of affected individuals is not clear. The SES of adult patients with congenital bleeding disorders (PWBD) from a centre in Germany (age 42.3 ± 15. Read More

View Article

Download full-text PDF

Source
http://www.schattauer.de/index.php?id=1214&doi=10.5482/H
Publisher Site
http://dx.doi.org/10.5482/HAMO-16-12-0047DOI Listing
August 2018
13 Reads

Recombinant Factor VIII Measurement in a Hemophilia A Patient Undergoing Cardiopulmonary Bypass-Supported Cardiac Surgery.

J Extra Corpor Technol 2018 09;50(3):170-177

Department of Health Sciences Graduate Program, College of Medicine, University of Saskatchewan, Saskatoon, Canada.

Patients with hemophilia A (Hem A) requiring cardiopulmonary bypass-supported cardiac surgery pose unique challenges for perioperative hemostatic management. This report describes a staged perioperative approach to clinical hematologic management as applied to an 80-year-old male of O-positive blood type with mild Hem A, who underwent successful, uncomplicated coronary artery bypass graft surgery. Hematologic management primarily consisted of normalization of plasma factor VIII levels followed by standard care. Read More

View Article

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6146271PMC
September 2018
3 Reads

Anti-ADAMTS13 Autoantibodies against Cryptic Epitopes in Immune-Mediated Thrombotic Thrombocytopenic Purpura.

Thromb Haemost 2018 Oct 20;118(10):1729-1742. Epub 2018 Sep 20.

Laboratory for Thrombosis Research, IRF Life Sciences, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium.

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is characterized by severe ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13) deficiency, the presence of anti-ADAMTS13 autoantibodies and an open ADAMTS13 conformation with a cryptic epitope in the spacer domain exposed. A detailed knowledge of anti-ADAMTS13 autoantibodies will help identifying pathogenic antibodies and elucidating the cause of ADAMTS13 deficiency. We aimed at cloning anti-ADAMTS13 autoantibodies from iTTP patients to study their epitopes and inhibitory characteristics. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-0038-1669459DOI Listing
October 2018
14 Reads

Platelet heterogeneity in activation-induced glycoprotein shedding: functional effects.

Blood Adv 2018 Sep;2(18):2320-2331

Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre, Maastricht, The Netherlands.

The platelet receptors glycoprotein Ibα (GPIbα) and GPVI are known to be cleaved by members of a disintegrin and metalloprotease (ADAM) family (ADAM10 and ADAM17), but the mechanisms and consequences of this shedding are not well understood. Our results revealed that (1) glycoprotein shedding is confined to distinct platelet populations showing near-complete shedding, (2) the heterogeneity between (non)shed platelets is independent of agonist type but coincides with exposure of phosphatidylserine (PS), and (3) distinct pathways of shedding are induced by elevated Ca, low Ca protein kinase C (PKC), or apoptotic activation. Furthermore, we found that receptor shedding reduces binding of von Willebrand factor, enhances binding of coagulation factors, and augments fibrin formation. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1182/bloodadvances.2017011544DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156892PMC
September 2018
2 Reads

The role of patient and healthcare professionals in the era of new hemophilia treatments in developed and developing countries.

Ther Adv Hematol 2018 Aug 2;9(8):239-249. Epub 2018 Jul 2.

Professor of Pediatrics, UC San Diego, 3020 Children's Way, MC 5035, San Diego, CA 92123, USA.

Medical decisions in hemophilia care are primarily related to the type of factor replacement and treatment regimen. With the growing number of treatment options for patients with hemophilia, decision making is more complex and requires careful consideration of benefits, risks, and patient goals. Shared decision making and decision-aid tools facilitate patient and healthcare provider communication. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1177/2040620718784830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6116757PMC
August 2018
16 Reads

Congenital coagulation factor X deficiency: Genetic analysis of five patients and functional characterization of mutant factor X proteins.

Haemophilia 2018 Sep 28;24(5):774-785. Epub 2018 Aug 28.

Department of Clinical Laboratory Science, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa, Japan.

Congenital factor X (FX) deficiency is a rare bleeding disorder that is inherited as an autosomal recessive trait. In this study, a genetic analysis of the FX gene was performed in five families with this disorder. Four heterozygous mutations [p. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1111/hae.13606DOI Listing
September 2018
4 Reads

The frequency of joint hemorrhages and procedures in nonsevere hemophilia A vs B.

Blood Adv 2018 Aug;2(16):2136-2144

Department of Medicine, University of Minnesota, Minneapolis, MN.

Data are needed on minimal factor activity (FA) levels required to prevent bleeding in hemophilia. We aimed to evaluate associations between hemophilia type and FA level and joint bleeding and orthopedic procedures using longitudinal data. Data were collected over an 11-year period on males with nonsevere hemophilia A or B without inhibitors who were receiving on-demand factor replacement therapy. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1182/bloodadvances.2018020552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6113607PMC
August 2018
5 Reads

Optimizing outcome measurement with murine ferric chloride-induced thrombosis.

Blood Coagul Fibrinolysis 2018 Nov;29(7):636-643

McAllister Heart Institute.

: The murine FeCl3 model is a widely used model for studying arterial thrombosis, yet provides limited information from each mouse, often only a single time point for the onset of occlusion (defined as the time to occlusion; TTO). To optimize data from the murine ferric chloride model of thrombosis. FeCl3 injury was induced in the carotid arteries of wild-type and Factor IX (FIX) knockout mice, with infusion of recombinant FIX (rFIX) to normalize FIX deficiency at various times around FeCl3 injury. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1097/MBC.0000000000000768DOI Listing
November 2018
12 Reads

Hepatocellular targeted α-tocopherol based pH sensitive galactosylated lipids: design, synthesis and transfection studies.

Medchemcomm 2018 Feb 6;9(2):264-274. Epub 2017 Dec 6.

National Institute of Technology , Warangal-506004 , Telangana , India . Email:

Receptor mediated gene delivery to the liver offers advantages in treating genetic disorders such as hemophilia and hereditary tyrosinemia type I (HTI). Prior findings demonstrated that tethering the d-galactose head group to cationic lipids directs genes to the liver asialoglycoprotein receptors (ASGPRs). In our continued efforts to develop safer and efficient lipofectins, we demonstrated that cationic lipids bearing α-tocopherol, an antioxidant, as a hydrophobic domain could deliver genes efficiently with high safety profiles in multiple cell lines. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1039/c7md00503bDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6083795PMC
February 2018
8 Reads

Novel assays in the coagulation laboratory: a clinical and laboratory perspective.

Transfus Apher Sci 2018 Aug 20;57(4):480-484. Epub 2018 Jul 20.

University of Toronto, Department of Medicine, Toronto, Canada; St. Michael's Hospital Hemostasis and Thrombosis Laboratory, Toronto, Canada; Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Canada.

The ability to monitor Factor VIII (FVIII) and Factor IX (FIX) levels is integral to the clinical management of hemophilia A and B patients, respectively. Factor activity levels are checked during regular follow-up, post-infusion of factor concentrates, during pre- and post-operative assessments, and when the presence of an inhibitor is suspected. However, the ability to accurately and reproducibly measure factor activity levels with standard coagulation assays has been challenging due to the emergence of recombinant factor concentrates with extended half-lives. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.transci.2018.07.008DOI Listing
August 2018
39 Reads