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Ann Rheum Dis 2018 Dec 14. Epub 2018 Dec 14.

Center of Research of Immunopathology and Rare Diseases- Coordinating Center of the Network for Rare Diseases of Piedmont and Aosta Valley, Department of Clinical and Biological Sciences, University of Turin, Turin, Italy.

Thromb Res 2018 Dec 6;174:24-26. Epub 2018 Dec 6.

Haemophilia and Thrombosis Centre, S.Giovanni Bosco Hospital of Naples, Italy.

Background: Bypassing agents are the first line therapy in patients with acquired haemophilia A (AHA). Activated prothrombin complex concentrate (aPCC) proved to be effective as initial treatment, but 20% of patients (pts) had relapses. aPCC as short-term prophylaxis to reduce subsequent bleeds is still not clear. Read More

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

Haematologica 2018 Dec 13. Epub 2018 Dec 13.

Maastricht University;

In combination with microspotting, whole-blood microfluidics can provide high-throughput information on multiple platelet functions in thrombus formation. Based on assessment of the inter- and intra-subject variability in parameters of microspot-based thrombus formation, we aimed to determine the platelet factors contributing to this variation. Blood samples from 94 genotyped healthy subjects were analysed for conventional platelet phenotyping: i. Read More

Haematologica 2018 Dec 13. Epub 2018 Dec 13.

INSERM UMR S 1138, Centre de Recherche des Cordeliers, Paris, France;

Hemophilia A is a rare hemorrhagic disorder due to the lack of functional pro-coagulant factor VIII. Factor VIII replacement therapy in patients with severe hemophilia A results in the development of inhibitory anti-factor VIII IgG in up to 30% of the cases. To date, immune tolerance induction upon daily injection of large amounts of factor VIII is the only strategy to eradicate factor VIII inhibitors. Read More

Health Qual Life Outcomes 2018 Dec 13;16(1):229. Epub 2018 Dec 13.

Department of Pharmacy Administration, University of Mississippi, University, USA.

Background: This study examined the psychometric properties of version 2 of the SF-12 Health Survey (SF-12v2) among adults with hemophilia in the United States.

Methods: This study employed a cross-sectional design using web-based and paper-based self-administered surveys. Hemophilia patients were recruited using an online panel and at a hemophilia treatment clinic. Read More

N Z Med J 2018 Dec 14;131(1487):111-115. Epub 2018 Dec 14.

Obstetrician and Gynaecologist, Department of Obstetrics and Gynaecology, North Shore Hospital, Auckland.

Drugs 2018 Dec;78(18):1861-1872

Department of Medicine 1, Division of Hematology and Hemostasis, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.

Acquired hemophilia A (AHA) is a rare autoimmune disease caused by autoantibodies inhibiting the function of coagulation factor VIII. It is characterized by spontaneous bleeding in patients with no previous family or personal history of bleeding. Although several large registries have collected clinical data on AHA, limited information is available on the optimal management of AHA because controlled clinical trials are lacking. Read More

J Thromb Haemost 2018 Dec 7. Epub 2018 Dec 7.

Novo Nordisk Park, Måløv, Denmark.

Background: Factor VIII (FVIII) consists of the A1-A2-B-A3-C1-C2 domains. FVIII with an intermediate length B-domain of 226 amino acids (aa) has previously been evaluated in murine gene therapy studies.

Objective: To characterize FVIII with intermediate length B-domains in vitro and in vivo in F8-KO mice. Read More

Case Rep Hematol 2018 13;2018:6757345. Epub 2018 Nov 13.

Division of Hematology, Takasago-Seibu Hospital, Takasago 676-0812, Japan.

This report describes six elderly patients with acquired hemophilia A (AHA), including four individuals aged ≥90 years. Bleeding symptoms were subcutaneous or intramuscular hemorrhage (=4), hematuria (=1), and hemorrhagic shock after tooth extraction (=1). Factor VIII (FVIII) activity ranged from <1. Read More

Int J Lab Hematol 2018 Dec 7. Epub 2018 Dec 7.

Department Of Coagulation, Royal Hallamshire Hospital, Sheffield, UK.

Genet Mol Biol 2018 Nov 14. Epub 2018 Nov 14.

Grupo de Patología Molecular, Universidad Nacional de Colombia, Bogotá, D.C., Colombia.

Hemophilia A (HA) is an X-linked recessive disorder and the second most common coagulation disorder with an incidence of 1 in 5,000 live born males. Worldwide, there are 178,500 affected individuals, 60% with the severe form of the disease. Intron 22 and 1 inversions (Inv22 and Inv1) are the most frequent molecular alterations found in severe HA patients with a frequency of 45-50% and 0. Read More

Thromb J 2018 4;16:31. Epub 2018 Dec 4.

11Clinical Development, Bayer AG, Pharmaceuticals, Wuppertal, Germany.

Background: The EINSTEIN-Jr program will evaluate rivaroxaban for the treatment of venous thromboembolism (VTE) in children, targeting exposures similar to the 20 mg once-daily dose for adults.

Methods: This was a multinational, single-dose, open-label, phase I study to describe the pharmacodynamics (PD), pharmacokinetics (PK) and safety of a single bodyweight-adjusted rivaroxaban dose in children aged 0.5-18 years. Read More

Eur J Pharm Sci 2018 Dec 7. 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

Platelets 2018 Dec 6:1-9. Epub 2018 Dec 6.

b Institute of Cardiovascular Sciences, College of Medical and Dental Sciences , University of Birmingham , Birmingham , UK.

Heavy menstrual bleeding (HMB) is often undiagnosed in women and can cause discomfort and distress. A haemostatic cause for excessive bleeding is often not routinely investigated and can lead to hysterectomy at an early age. A prospective cohort study was carried out to determine whether certain patients with unexplained HMB have an underlying platelet function defect (PFD). Read More

Haemophilia 2018 Dec 6. 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

Haemophilia 2018 Dec 6. Epub 2018 Dec 6.

Department of Sports Medicine, University of Wuppertal, Wuppertal, Germany.

Introduction: The objective of this work was to examine the interrelations of posturographic and surface EMG (SEMG) characteristics of ankle muscles in patients with haemophilia while standing naturally.

Methods: Surface EMG of five bilaterally recorded ankle muscles was conducted in 24 patients with haemophilia (PwH, age: 42 [11] years, mean [SD], 22 A, 2 B, 21 severe, 3 moderate) with median (quartiles) WFH orthopaedic joint score of 30 (20/39) points and 24 non-haemophilic controls (Con, age: 42 [12]). Force plate (IBS) signals were captured simultaneously during bipedal stance with eyes open. Read More

Haemophilia 2018 Dec 6. Epub 2018 Dec 6.

Department of Medicine, McMaster University, Hamilton, Ontario, Canada.

Background: The Patient Reported Outcomes, Burdens and Experiences (PROBE) study aims to develop and validate questionnaire for assessing health status in patients with haemophilia and participants without bleeding disorders.

Objective: To investigate the test-retest properties of the PROBE questionnaire.

Methods: The PROBE questionnaire covers four domains and is comprised of 29 questions. Read More

Blood Coagul Fibrinolysis 2018 Nov 29. Epub 2018 Nov 29.

Real Fundación Victoria Eugenia.

Prophylaxis entails long-term continuous intravenous administration of concentrates of the deficient factor with a view to preventing spontaneous bleeds and the development of hemophilic arthropathy. Initiation of prophylaxis at an early age and continuous uninterrupted factor administration in patients with hemophilia have been hailed as essential by such organizations.The most widely used prophylaxis regimens include the Swedish (Malmö), the Dutch and the Canadian protocols. Read More

Blood Coagul Fibrinolysis 2018 Nov 29. Epub 2018 Nov 29.

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

Haemophilia 2018 Dec 3. Epub 2018 Dec 3.

Universitaire Ziekenhuizen Leuven, Leuven, Belgium.

Haemophilia 2018 Dec 3. Epub 2018 Dec 3.

Department of Pediatrics, Nara Medical University, Kashihara, Nara, Japan.

Haemophilia 2018 Dec 3. Epub 2018 Dec 3.

Department of Trauma & Orthopaedics, Royal Free Hospital, London, UK.

Patients with haemophilia who have developed inhibitors against factor VIII (FVIII) or factor IX present a significant concern to those surgeons who operate on them. The evidence base for bypassing agents such as recombinant factor VIIa and activated prothrombin complex concentrate has amassed over several decades. The literature is open to positive interpretation on the successful use of these agents in the treatment of inhibitor-positive patients. Read More

Hematology Am Soc Hematol Educ Program 2018 Nov;2018(1):412-417

Primary Care Sports Medicine, Baylor Scott & White Health, Waco, TX; and.

Traditionally, the athlete who requires long-term anticoagulation has been told to forgo participation in contact and collision sports. However, a strategy of short-term interruption of anticoagulant therapy may be designed for some athletes, allowing them return to full athletic activity. A personalized pharmacokinetic/pharmacodynamic study of a direct oral anticoagulant (DOAC) may allow athletic participation when plasma drug concentration is minimal and resumption of treatment after the risk of bleeding sufficiently normalizes. Read More

Pediatr Rev 2018 Dec;39(12):588-600

Department of Pediatrics, Holtz Children's Hospital-Jackson Memorial Medical Center, Miami, FL.

Blood Adv 2018 Nov;2(Suppl 1):39-41

Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Can J Ophthalmol 2018 Dec 27;53(6):600-604. Epub 2018 Mar 27.

Mohs Unit, Sheba Medical Center, Tel Hashomer, affiliated to the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.

Objective: Postoperative ecchymoses or hematomas can prolong healing from surgery, and a search for locally administered agents that decrease bleeding is warranted. The objective of this study is to evaluate whether preoperative subcutaneous injection of tranexamic acid (TXA) reduces intra- and postoperative bleeding or ecchymoses in skin-only upper eyelid blepharoplasty surgery.

Design: This is a prospective randomized, double-blind, controlled study. Read More

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

Blood Cells Mol Dis 2018 Nov 16;75:11-12. Epub 2018 Nov 16.

Department of Hemostasis and Thrombosis, National Institute of Immunohaematology (ICMR), KEM Hospital, Mumbai, India. Electronic address:

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2018 Dec;26(6):1863-1867

Department of Hematology, People's Hospital of Wuhan University, Wuhan 430000, Hubei Province, China

In recent years, with the development of gene editing technology, the site-specific genome can be modified. The curability of genetic disease may be achieved by the use of gene editing techniques. As the simplicity, high specificity and economical efficiency, much attention has been paid to the CRISPR/Cas9 system, which was been widely used in research of molecular biology and other fields of life science. Read More

Rev Assoc Med Bras (1992) 2018 Oct;64(10):872-875

Rio de Janeiro Federal University (UFRJ), Nuclear Medicine Department, Rio de Janeiro - RJ, Brasil.

FASEB J 2018 Dec 5:fj201801391R. Epub 2018 Dec 5.

Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

Adeno-associated viral vectors (AAVs) achieve stable therapeutic expression without long-term toxicity in adults with hemophilia. To avert irreversible complications in congenital disorders producing early pathogenesis, safety and efficacy of AAV-intrauterine gene transfer (IUGT) requires assessment. We therefore performed IUGT of AAV5 or -8 with liver-specific promoter-1 encoding either human coagulation factors IX (hFIX) or X (hFX) into Macaca fascicularis fetuses at ∼0. Read More

Eur J Epidemiol 2018 Dec 5. Epub 2018 Dec 5.

Haemophilia Treatment Centre, APHM, Children Hospital La Timone, Aix Marseille University, INSERM, INRA, C2VN, Marseille, France.

FranceCoag is an ongoing open prospective multicentre cohort project aimed at improving epidemiological knowledge about inherited bleeding disorders in France. The main objective of this article was to evaluate the project's progress as of the 30th December 2016. Between 1994 and this date, of the 10,047 patients included in the study, 384 (3. Read More

Haematologica 2018 Dec 4. Epub 2018 Dec 4.

Universite Paris Descartes, Sorbonne Paris Cite, INSERM U1138, Centre de Recherche des Cordeliers

Therapeutic factor VIII presents with elevated immunogenicity. Despite intensive research in the last decades, the reasons for which 5-30% of patients with hemophilia A (encompassing all severities) develop inhibitory anti-factor VIII antibodies (inhibitors) following replacement therapy remain an enigma. Under physiological conditions, endogenous factor VIII is recognized by the immune system. Read More

Mult Scler Relat Disord 2018 Nov 29;27:403-405. Epub 2018 Nov 29.

Department of Neurology, Division of Neuroscience, Institute of Experimental Neurology (INSPE), San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milan, Italy.

Alemtuzumab is a highly effective monoclonal antibody for the treatment of multiple sclerosis (MS). During the immune reconstitution following the use of this treatment severe secondary autoimmune diseases (SADs) can develop. We present the case of a patient affected by active MS who failed to achieve disease control with several disease-modifying drugs and was thereafter successfully treated with alemtuzumab, obtaining no evidence of disease activity and a high quality of life. Read More

Expert Rev Mol Diagn 2018 Dec 4. Epub 2018 Dec 4.

a 225 Second Avenue Waltham , MA 02451.

Clin Chem Lab Med 2018 Dec 4. Epub 2018 Dec 4.

Coagulation Reference Laboratory, Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, The Netherlands.

World J Clin Cases 2018 Nov;6(14):781-785

Department of Internal Medicine, Health Sciences University of Hokkaido, Toubetsu 0610293, Japan.

Acquired hemophilia A (AHA) is a rare, hemorrhagic autoimmune disease, whose pathogenesis involves reduced coagulation factor VIII (FVIII) activity related to the appearance of inhibitors against FVIII. Common etiological factors include autoimmune diseases, malignancy, and pregnancy. We report two cases of AHA in solid cancer. Read More

J Blood Med 2018 19;9:211-218. Epub 2018 Nov 19.

Clinical Development, Medical and Regulatory Affairs, Novo Nordisk Inc., Plainsboro, NJ, USA.

Background: One of the most common rare inherited bleeding disorders, congenital factor VII (FVII) deficiency typically has a milder bleeding phenotype than other rare bleeding disorders. Categorizing severity in terms of factor activity associated with hemophilia (severe <1%, moderate 1%-5%, mild 6%-40%) has led to the observation that bleeding phenotype does not follow closely with FVII activity. Over the past decade, large-scale global registries have investigated bleeding phenotype more thoroughly. Read More

Hamostaseologie 2018 Nov 30;38(4):211-222. Epub 2018 Nov 30.

Division of Clinical and Experimental Haemostasis, Hemotherapy and Transfusion Medicine, University Blood Center, and Haemophilia Comprehensive Care Center, Institute of Transplantation Diagnostics and Cell Therapeutics, Heinrich Heine University Medical Center, Düsseldorf, Germany.

Platelet signal transduction is the focus of this review. While 'classic' platelet signaling through G protein-coupled receptors in response to fluid-phase agonists has been extensively studied, signaling mechanisms linking platelet adhesion receptors such as GPIb-IX-V, GPVI and α2β1 to the activation of αIIbβ3 are less well established. Moreover, 'non-haemostatic' pathways can also activate platelets in various settings, including platelet-immune or platelet-tumour cell interactions, platelet responses to neutrophil extracellular traps, or stimulation by microbial pathogens. Read More

Vox Sang 2018 Nov 30. Epub 2018 Nov 30.

Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.

Background: Acquired haemophilia A (AHA) is an autoimmune bleeding disorder with significant morbidity and mortality. Bleeding AHA patients with high titre inhibitors can be treated with either activated prothrombin complex concentrate (aPCC) or recombinant activated factor VII (rFVIIa). Given that both replacement therapies have inherent benefits and limitations, a cost-effectiveness analysis (CEA) was performed in this population to compare rFVIIa with aPCC. Read More

J Cell Commun Signal 2018 Nov 29. Epub 2018 Nov 29.

Cancer Research Unit, VA Medical Center, Kansas City, MO, 64128, USA.

PEGylation is a biochemical modification process of bioactive molecules with polyethylene glycol (PEG), which lends several desirable properties to proteins/peptides, antibodies, and vesicles considered to be used for therapy or genetic modification of cells. However, PEGylation of proteins is a complex process and can be carried out using more than one strategy that depends on the nature of the protein and the desired application. Proteins of interest are covalently conjugated or non-covalently complexed with inert PEG strings. Read More

BMC Hematol 2018 23;18:34. Epub 2018 Nov 23.

1Regenerative Medicine Cluster, Advanced Medical and Dental Institute, Universiti Sains Malaysia, 13200 Kepala Batas, PNG Malaysia.

Background: Massive bleeding is one of the commonest salvageable causes of death. The search for an ideal haemostatic agent during massive bleeding is still ongoing. One of the novel haemostatic medications is recombinant activated factor VII (rFVIIa). Read More

Int J Stem Cells 2018 Nov;11(2):235-241

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

Mbd3 (Methyl-CpG binding domain protein), a core member of NuRD (nucleosome remodelling and deacetylation) is essential for embryogenesis. However, its role in reprogramming of somatic cells into induced pluripotent stem cells (iPSC) remains controversial. Some reports suggest that Mbd3 inhibits pluripotency, whilst others show that it greatly enhances reprogramming efficiency. Read More

Thromb Res 2018 Nov 16;173:79-84. Epub 2018 Nov 16.

Department of Blood Coagulation, Ogikubo Hospital, Tokyo, Japan.

Introduction: Standard prophylaxis dosing based on bodyweight may result in over- or under-dosing due to interpatient variability. Adopting individual pharmacokinetic (PK) based tailoring may improve adherence to treatment guideline, and consequently clinical outcomes. Here we report clinical observations performed across the adoption of individual PK based tailoring in a single center in Japan. Read More

J Thromb Haemost 2018 Nov 29. Epub 2018 Nov 29.

Drug Discovery Austria, Shire, Vienna, Austria.

Development of factor VIII (FVIII) inhibitors following replacement therapy with FVIII is one of the major challenges faced when treating patients with hemophilia A. Inhibitors develop in 20-32% of previously untreated patients with severe and in 3-13% with moderate or mild hemophilia A (1,2). The cause of the immunogenicity is not well understood. Read More

Haemophilia 2018 Nov 29. Epub 2018 Nov 29.

Department of Haematology, Erasmus University Medical Centre Rotterdam, Rotterdam, The Netherlands.

Background: Both one-stage (OSA) and chromogenic substrate assays (CSA) are used to measure factor VIII (FVIII) activity. Factors explaining analytical variation in FVIII activity levels are still to be completely elucidated.

Aim: The aim of this study was to investigate and quantify the analytical variation in OSA and CSA. Read More

Clin Exp Pharmacol Physiol 2018 Nov 29. Epub 2018 Nov 29.

Department of Orthopaedics and Traumatology, Central Clinical Hospital of the Ministry of the Interior and Administration, Wołoska 137, 02-507, Warsaw, Poland.

Hemophilia A and B are rarely occurring X chromosome-linked congenital coagulation disorders dominated by spontaneous joint bleedings and chronic synovitis, leading to development of hemophilic arthropathy (HA). Progranulin (PGRN) is a growth factor with anti-inflammatory and immunomodulatory properties. PGRN is an important molecule in the pathogenesis of osteoarthritis (OA) and rheumatological disorders. Read More

Haemophilia 2018 Nov;24(6):862-872

Pfizer, Ballerup, Denmark.

Recombinant prophylactic treatment (PTX) has greatly improved morbidity, mortality and health-related quality of life (HRQoL) in patients with severe haemophilia. Yet, treatment adherence appears suboptimal in adolescents and young adults with haemophilia (YWH). Young patients experience major biopsychosocial changes challenging their adherence through the transition from parental to self-care, from paediatric to adult care. Read More

PLoS One 2018 28;13(11):e0207939. Epub 2018 Nov 28.

Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.

People with haemophilia (PWH) experience acute pain during joint bleeds and might develop chronic pain due to joint degeneration. However, there is a lack of standardized measures to comprehensively assess pain in PWH. This study aimed to develop a multidimensional questionnaire for haemophilia-related pain, the Multidimensional Haemophilia Pain Questionnaire (MHPQ), and to present initial validation data among adults. Read More