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J Clin Med 2020 Jul 8;9(7). Epub 2020 Jul 8.

Department of Food and Drug, University of Parma, 43124 Parma, Italy.

Lipid metabolism derangement contributes to increased cardiovascular risk in Rheumatoid Arthritis (RA). It is still debated whether and how tocilizumab, an interleukin-6 receptor inhibitor used in active RA, impacts cardiovascular risk. We studied the effect of tocilizumab on the regulation of macrophage cholesterol homeostasis, measuring patient serum ability to respectively load (cholesterol loading capacity, CLC) and discharge (cholesterol efflux capacity, CEC) cells with cholesterol. Read More

Mol Ther Methods Clin Dev 2020 Jun 13;17:1139-1154. Epub 2020 May 13.

Translational Vectorology Research Unit, Children's Medical Research Institute, The University of Sydney, Westmead, NSW 2145, Australia.

Use of the prototypical adeno-associated virus type 2 (AAV2) capsid delivered unexpectedly modest efficacy in an early liver-targeted gene therapy trial for hemophilia B. This result is consistent with subsequent data generated in chimeric mouse-human livers showing that the AAV2 capsid transduces primary human hepatocytes with low efficiency. In contrast, novel variants generated by directed evolution in the same model, such as AAV-NP59, transduce primary human hepatocytes with high efficiency. Read More

Thromb Haemost 2020 Jul 1;120(7):1056-1065. Epub 2020 Jun 1.

Department of Pediatric Hematology, Erasmus University Medical Center - Sophia Children's Hospital, Rotterdam, The Netherlands.

Background:  von Willebrand factor (VWF) is crucial for optimal dosing of factor VIII (FVIII) concentrate in hemophilia A patients as it protects FVIII from premature clearance. To date, it is unknown how VWF behaves and what its impact is on FVIII clearance in the perioperative setting.

Aim:  To investigate VWF kinetics (VWF antigen [VWF:Ag]), VWF glycoprotein Ib binding (VWF:GPIbM), and VWF propeptide (VWFpp) in severe and moderate perioperative hemophilia A patients included in the randomized controlled perioperative OPTI-CLOT trial. Read More

Front Immunol 2020 7;11:563. Epub 2020 May 7.

Department of Pediatric Hematology, Amsterdam UMC, Emma Children's Hospital, University of Amsterdam, Amsterdam, Netherlands.

In hemophilia A the presence of non-neutralizing antibodies (NNAs) against Factor VIII (FVIII) may predict the development of neutralizing antibodies (inhibitors) and accelerate the clearance of administrated FVIII concentrates. This systematic review aimed to assess: (1) the prevalence and incidence of NNAs in patients with congenital hemophilia without inhibitors and (2) the association between NNAs and patient and treatment characteristics. We conducted a search in MEDLINE, Embase, Web of Science and the Cochrane database. Read More

Pediatr Radiol 2020 Jul 11;50(8):1148-1155. Epub 2020 May 11.

Department of Radiology, The Children's Hospital of Philadelphia, 34th Street and Civic Center Boulevard, Philadelphia, PA, 19104, USA.

Background: Clotting factor replacement forms the pillar of treatment for children with hemophilia. Most children can be treated using peripheral venipuncture, but very young children and children with poor venous access might require a central venous catheter. Short-term and long-term complications of implantable venous access device placement (also known as port placement) can result in important morbidity and mortality in children with hemophilia. Read More

Glycoconj J 2020 Aug 6;37(4):471-483. Epub 2020 May 6.

School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD, 4072, Australia.

Human Factor IX is a highly post-translationally modified protein that is an important clotting factor in the blood coagulation cascade. Functional deficiencies in Factor IX result in the bleeding disorder haemophilia B, which is treated with plasma-derived or recombinant Factor IX concentrates. Here, we investigated the post-translational modifications of human serum-derived Factor IX and report previously undescribed O-linked monosaccharide compositions at serine 141 and a novel site of glycosylation. Read More

Thromb Haemost 2020 May 5;120(5):728-736. Epub 2020 May 5.

Baxalta US Inc, a member of the Takeda group of companies, Lexington, Massachusetts, United States.

Background:  Factor VIII (FVIII) trough levels > 1 IU/dL in patients with severe hemophilia A receiving regular prophylaxis may optimize bleed protection.

Objectives:  In this post hoc analysis of patients receiving tertiary prophylaxis for approximately 1 year, the relationship between estimated FVIII levels and reported bleeds was investigated to predict the potential for zero bleeds.

Methods:  Sixty-three patients (median [range] age, 28 [7-59] years) with severe hemophilia A (229 bleeds) were included. Read More

Haemophilia 2020 May 24;26(3):487-493. Epub 2020 Apr 24.

Division of Hematology, University of Colorado School of Medicine, Aurora, CO, USA.

Introduction: Estimates of the size and characteristics of the US haemophilia population are needed for healthcare planning and resource needs assessment. A network of comprehensive haemophilia treatment centres (HTCs) located throughout the United States receives federal support for diagnosis and management of haemophilia and other rare bleeding disorders.

Aim: Estimate the incidence and prevalence of haemophilia among US males using the HTC network. Read More

PLoS Genet 2020 04 8;16(4):e1008690. Epub 2020 Apr 8.

Institute of Virology, Hannover Medical School, Hannover, Germany.

Loss-of-function mutations in the human coagulation factor 9 (F9) gene lead to hemophilia B. Here, we dissected the consequences and the pathomechanism of a non-coding mutation (c.2545A>G) in the F9 3' untranslated region. Read More

Biochem Biophys Res Commun 2020 Jun 2;526(3):633-640. Epub 2020 Apr 2.

Institute of Molecular Medicine and Oncology, Chongqing Medical University, Chongqing, 400016, China.

Factor VIII (FVIII) functions as a cofactor within the intrinsic pathway of blood coagulation in process of FX activation by FIXa, for which deficiency results in the bleeding disorder hemophilia A. The gene of FVIII contains 26 exons that code for a 19 amino acid signal peptide and a 2332 amino acid polypeptide with a domain structure designated A1-A2-B-A3-C1-C2, of which the A domains are homologous with each other, as are the C domains. It has been well-documented that both the domains are the necessary elements for FVIII activities. Read More

Cochrane Database Syst Rev 2020 03 18;3:CD010215. Epub 2020 Mar 18.

McMaster University, Department of Health Research Methods, Evidence and Impact (HEI), 1280 Main Street West, CRL - 140, Hamilton, ON, Canada, L8S 4K1.

Background: Managing hemophilia is challenging both in terms of medical treatment and its broad impact on many aspects of the individual's life, including self-perception. Several psychosocial issues are potentially relevant in the clinical management of hemophilia, including it being a chronic and incurable condition; e.g. Read More

J Card Surg 2020 May 16;35(5):1129-1131. Epub 2020 Mar 16.

Department of Cardiovascular Surgery, The University of Alabama at Birmingham, Birmingham, Alabama.

Hemophilia B is a rare X-linked recessive disorder that places surgical patients at an increased risk of bleeding. Patients with hemophilia are now achieving near-normal life expectancies and therefore the number of these patients requiring cardiac surgery due to the development of age-related cardiovascular disease may increase. We present the case of a young male with hemophilia B who was diagnosed with severe symptomatic mitral regurgitation and underwent successful robotic mitral valve repair. Read More

Cardiovasc Hematol Disord Drug Targets 2020 Mar 4. Epub 2020 Mar 4.

La Paz University Hospital, Madrid, Physical Medicine and Rehabilitation. Spain.

Background: It is important to discard those practices that do not add value. As a result, several initiatives have emerged. All of them try to improve patient safety and the use of health resources. Read More

Hamostaseologie 2020 Feb 28;40(1):88-96. Epub 2020 Jan 28.

Paediatric Haemophilia Centre, Dr. von Hauner Children's Hospital Munich, LMU, Munich, Germany.

With the recent approval of improved therapeutic options for patients suffering from haemophilia A such as the extended half-life, recombinant factor concentrates, non-factor VIII replacement therapies like Emicizumab and after consideration of the currently running clinical trials investigating even more advanced approaches, counselling of parents of a newly diagnosed boy with haemophilia A has not become less demanding. Parents need to be informed about the pathophysiology, the chronic nature and the potential risks that are commonly associated with this disease and its treatment, depending on disease severity. Above all, the safety and efficacy of the medicinal drug(s) to be used are of utmost importance, given the impact of non-virus-inactivated plasma-derived factor concentrates in the 1980s. Read More

Res Pract Thromb Haemost 2020 Jan 6;4(1):46-53. Epub 2019 Nov 6.

Department of Pathology and Laboratory Medicine University of North Carolina Chapel Hill North Carolina.

Numerous methods for evaluation of global fibrinolytic activity in whole blood or plasma have been proposed, with the majority based on tissue-type plasminogen activator (t-PA) addition to initiate fibrinolysis. We propose that such an approach is useful to reveal hypofibrinolysis, but t-PA concentrations should be kept to a minimum. In this paper, we describe a low-concentration t-PA plasma turbidity assay to evaluate several congenital factor deficiencies, including plasminogen activator inhibitor-1 (PAI-1) and plasminogen deficiency, as well as hemophilia A and B. Read More

Transfus Apher Sci 2020 Jun 9;59(3):102728. Epub 2020 Jan 9.

Pediatric Hematology Specialist, Ankara Dışkapı Child Health and Diseases Hematology Oncology Training And Research Hospital, Ankara, Turkey.

Objective: This study aims to investigate the distribution, clinical characteristics and outcome of inherited coagulation disorders (ICD) in Turkish children.

Subjects And Methods: Data from all children (age<18 years) with ICD examined in our center were retrospectively reviewed.

Results: There were 403 children with ICD (233 males and 170 females) with a median age of four years at diagnosis. Read More

Haemophilia 2020 Mar 21;26(2):354-362. Epub 2020 Jan 21.

Western Australian Centre for Thrombosis and Haemostasis (WACTH), Murdoch University, Perth, WA, Australia.

Introduction: Investigation of factors (F) VIII and IX is common, with testing important for diagnosis or exclusion of haemophilia A or B, associated acquired conditions and factor inhibitors. Rivaroxaban, a common direct anti-Xa agent, causes significant interference in clotting assays, including substantial false reduction of factor levels.

Aim: To assess whether rivaroxaban-induced interference of FVIII and FIX testing could be neutralized. Read More

Haemophilia 2020 Jan 19;26(1):56-63. Epub 2019 Nov 19.

Boston Hemophilia Center, Boston Children's Hospital, Boston, MA, USA.

Background: Use of population pharmacokinetics (PopPK) to facilitate PK-informed prophylaxis in clinical practice has gained momentum among haemophilia providers due to the accessibility of tools such as the Web Accessible Population Pharmacokinetic Service-Hemophilia (WAPPS-Hemo) and availability of extended half-life (EHL) factor concentrates. It is unknown how clinicians implement PopPK.

Aim: To investigate the evolution of PopPK use in clinical practice by comparing blood sampling strategies, patient features, and factor group between initial and recent periods of WAPPS-Hemo availability. Read More

Blood Coagul Fibrinolysis 2019 Dec;30(8):385-392

Department of Paediatrics, University of Occupational and Environmental Health, Japan, Fukuoka.

: The novel agent pd-FVIIa/FX is a 1 : 10 protein weight mixture of activated factor VII (FVIIa) and factor X (FX) derived from donated blood plasma. A phase III clinical trial of pd-FVIIa/FX revealed high efficacy for bleeding episodes in haemophilia patients with inhibitors. However, up to now, only one case of this new agent being used for surgery had been reported. Read More

Mol Ther Methods Clin Dev 2019 Dec 26;15:221-231. Epub 2019 Sep 26.

uniQure biopharma B.V., Paasheuvelweg 25A, 1105 BP Amsterdam, the Netherlands.

Gene therapy for severe hemophilia B is advancing and offers sustained disease amelioration with a single treatment. We have reported the efficacy and safety of AMT-060, an investigational gene therapy comprising an adeno-associated virus serotype 5 capsid encapsidating the codon-optimized wild-type human factor IX (WT h) gene with a liver-specific promoter, in patients with severe hemophilia B. Treatment with 2 × 10 gc/kg AMT-060 showed sustained and durable FIX activity of 3%-13% and a substantial reduction in spontaneous bleeds without T cell-mediated hepatoxicity. Read More

Thromb Haemost 2019 Dec 28;119(12):1956-1967. Epub 2019 Oct 28.

EA 4609-Hémostase et Cancer, SFR Lyon Est, Université Claude Bernard Lyon I, Lyon, France.

Gene therapy using recombinant adeno-associated virus (AAV) has induced sustained long-term coagulation human factor IX (hFIX) levels in hemophilia B (HB) patients. However, asymptomatic transient liver toxicity was observed at high vector doses, highlighting the need to improve the potency of these vectors. We report the generation of an AAV transgene cassette containing the hyperfunctional hFIX-E456H variant showing improved binding to platelets, with a comparison to wild-type hFIX (hFIX-WT) and hFIX-R384L variant (Padua) transgenes, containing truncated-intron 1 (I1). Read More

Thromb Haemost 2019 Dec 22;119(12):1981-1993. Epub 2019 Oct 22.

Institut National de la Santé et de la Recherche Médicale, UMR_S 1176, Univ. Paris-Sud, Université Paris-Saclay, Le Kremlin-Bicêtre, France.

Engineered recombinant factor X (FX) variants represent a promising strategy to bypass the tenase complex and restore hemostasis in hemophilia patients. Previously, a thrombin-activatable FX variant with fibrinopeptide-A replacing the activation peptide (FX-delAP/FpA) has been described in this regard. Here we show that FX-delAP/FpA is characterized by a sixfold shorter circulatory half-life compared with wild-type FX, limiting its therapeutical applicability. Read More

Haemophilia 2019 Nov 22;25(6):919-927. Epub 2019 Oct 22.

Department of Biomedical and Biotechnological Sciences, Section of Pharmacology, University of Catania, Catania, Italy.

Introduction: Intra-articular injections of various drugs are commonly used in patients with degenerative osteoarthritis and also in haemophilic patients. Haemophilic arthropathy is a particular type of secondary osteoarthritis (OA), but the degeneration of strong synovial, cartilaginous and subchondral constituents is provoked by the direct action of iron and blood in the joint.

Aim Of The Study: The aim of this study is to review the literature regarding the use of various intra-articular drugs in joints affected by haemophilic arthropathy. Read More

Thromb Haemost 2019 Nov 6;119(11):1767-1772. Epub 2019 Oct 6.

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano, A. Bianchi Bonomi Hemophilia and Thrombosis Center and Fondazione Luigi Villa, Milan, Italy.

Thrombotic thrombocytopenic purpura (TTP) is a rare thrombotic microangiopathy (TMA) characterized by the severe deficiency of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) activity (< 10%). Rapid ADAMTS13 testing is crucial for an early diagnosis and optimal management of acute TTP. We evaluated the performance of the HemosIL AcuStar ADAMTS13 activity assay (Instrumentation Laboratory, Bedford, Massachusetts, United States), a fully automated chemiluminescent immunoassay with an analytical time of 33 minutes. Read More

J Family Med Prim Care 2019 Jul;8(7):2463-2467

Department of Pathology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India.

Introduction: Deficiency of factor VIII (Hemophilia A), factor IX (Hemophilia B) and Von Willebrand's factor are the most frequent coagulation defects. The incidence of inhibitors in patients of factor VIII deficiency is varies in different regions of India.

Aim: To determine the prevalence, clinical profile and incidence of formation of inhibitors in patients of Hemophilia in north eastern part of India. Read More

FASEB J 2019 11 26;33(11):12477-12486. Epub 2019 Aug 26.

Section of Genetics, Department of Pediatrics, School of Medicine, University of Colorado, Aurora, Colorado, USA.

Classic homocystinuria (HCU) is an inherited disorder characterized by elevated homocysteine (Hcy) in plasma and tissues resulting from cystathionine β-synthase (CBS) deficiency. There is no cure, and patients are predominantly managed by methionine-restricted diet (MRD) to limit the production of Hcy. In this study, we used the I278T mouse model of HCU to evaluate the long-term impact of a novel enzyme replacement therapy [truncated human CBS C15S mutant modified with linear 20-kDa -hydroxysuccinimide ester polyethylene glycol (OT-58)] on clinical end points relevant to human patients with HCU. Read More

Protein Pept Lett 2019 ;26(12):930-939

Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, Iran.

Background: Supercharged GFP proteins were known as effective carriers for delivery of macromolecules into eukaryotic cells as well as fluorescent fusion tags for in vitro and in vivo detection.

Objective: Herein, anti-viral effects of +36 GFP and its anti-tumor effects were studied in vitro and in vivo, respectively.

Methods: We evaluated anti-HIV, anti-HSV, and anti-HCV effects of +36 GFP in vitro using ELISA, and real time PCR as common techniques for their detection, respectively. Read More

Haemophilia 2019 Nov 21;25(6):e353-e360. Epub 2019 Aug 21.

Centre for Hereditary Blood Diseases, Basra Heath Directorate, Basra, Iraq.

Introduction: Patients with haemophilia are at increased risk of being overweight or obese, which in turn may have a profound effect on morbidity and quality of life.

Aims: To assess the nutritional status of paediatric patients with haemophilia and identify possible risk factors that may adversely affect their nutritional status.

Methods: A case-control study was performed on 63 haemophilia patients and 135 control subjects aged 5-18 years. Read More

Transfus Apher Sci 2019 Oct 6;58(5):565-568. Epub 2019 Aug 6.

National Director of Health Policy, Canadian Hemophilia Society Montreal, Canada. Electronic address:

The World Federation of Hemophilia (WFH) states in its Guidelines for the Management of Hemophilia, Second Edition [1], that people with hemophilia are best managed in a comprehensive care setting. That team is typically comprised of a core group including a hematologist, nurse coordinator, physiotherapist, social worker, specialized lab technologist and data manager, and as needed, by other specialists. Hemophilia is an X-linked congenital bleeding disorder caused by a deficiency of coagulation factor VIII (FVIII) in hemophilia A or factor IX (FIX) in hemophilia B. Read More

Semin Thromb Hemost 2019 Jul 13;45(5):509-513. Epub 2019 Jun 13.

University of Miami Miller School of Medicine, Miami, Florida.

Circulating cell-derived microparticles (MPs) exhibit procoagulant activity and have been investigated for a possible role in some human pathologies. However, their potential role in hemostasis has been neglected and often denied. This review brings to attention a specific body of direct clinical evidence supporting an important but distinctive role of MPs in hemostasis. Read More

PLoS One 2019 13;14(6):e0218258. Epub 2019 Jun 13.

CESP, INSERM UMR 1018, Faculty of Medicine, Paris-Sud University, UVSQ, Paris-Saclay University, Villejuif, France.

Replacement therapy in severe hemophilia A leads to factor VIII (FVIII) inhibitors in 30% of patients. Factor VIII gene (F8) mutation type, a family history of inhibitors, ethnicity and intensity of treatment are established risk factors, and were included in two published prediction tools based on regression models. Recently investigated immune regulatory genes could also play a part in immunogenicity. Read More

Mol Ther Methods Clin Dev 2019 Jun 11;13:440-452. Epub 2019 Apr 11.

BioMarin Pharmaceutical Inc., Novato, CA, USA.

Adeno-associated virus (AAV)-based vectors are widely used for gene therapy, but the effect of pre-existing antibodies resulting from exposure to wild-type AAV is unclear. In addition, other poorly defined plasma factors could inhibit AAV vector transduction where antibodies are not detected. To better define the relationship between various forms of pre-existing AAV immunity and gene transfer, we studied valoctocogene roxaparvovec (BMN 270) in cynomolgus monkeys with varying pre-dose levels of neutralizing anti-AAV antibodies and non-antibody transduction inhibitors. Read More

An Pediatr (Barc) 2019 Dec 3;91(6):394-400. Epub 2019 Jun 3.

Servicio de Hematología y Hemoterapia, Hospital Universitario La Paz, Madrid, España.

Introduction: Haemophilia is a rare disease and its management can pose a challenge to Emergency Department paediatricians.

Aim: To describe the frequency and reasons for consultation by haemophilic children in the ED.

Materials And Methods: Longitudinal retrospective study was conducted in a paediatric Emergency Department of a tertiary care hospital. Read More

Haemophilia 2019 Jul 6;25(4):e247-e256. Epub 2019 Jun 6.

Pfizer Japan, Tokyo, Japan.

Introduction: In 2010, nonacog alfa became the first recombinant factor IX (rFIX) available in Japan for patients with haemophilia B.

Aim: To determine real-world safety (adverse events, incidence of inhibitors) and effectiveness of nonacog alfa in Japan.

Methods: This multicentre, prospective, observational, postmarketing surveillance study enrolled previously treated and untreated patients (PTPs and PUPs, respectively) who were observed for 1 and 2 years, respectively, after initiating nonacog alfa therapy. Read More

Thromb Res 2019 Jul 9;179:140-146. Epub 2019 May 9.

Institute of Experimental Haematology and Transfusion Medicine, University Hospital Bonn, Sigmund-Freud Street 25, D-53127 Bonn, Germany. Electronic address:

Introduction: The administration of FVIII leads to inhibitors in up to 30% of patients with hemophilia A (HA), the most severe treatment complication. FVIII-mannosylation fosters the presentation of FVIII to CD4-T-lymphocytes. Mannose as primary ligand for the mannose-binding lectin (MBL) activates the lectin pathway of complement. Read More

Thromb Haemost 2019 Aug 26;119(8):1283-1294. Epub 2019 May 26.

Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, Texas, United States.

Our earlier studies showed that recombinant human factor VIIa (rhFVIIa) administered intravascularly in mice disappeared rapidly from the circulation. However, a small fraction of rhFVIIa that entered extravascular remained functionally active for an extended period. The present study aims to investigate the dose-dependency of rhFVIIa accumulation and retention in mouse knee joints and test whether the hemophilic condition affects rhFVIIa sequestration in joints. Read More

Tidsskr Nor Laegeforen 2019 May 6;139(8). Epub 2019 May 6.

Background: As a result of good medical treatment, the life expectancy of patients with severe haemophilia is now approaching normal. This implies a growing need for treatment of lifestyle- and age-related disease. This article describes surgery in patients with severe haemophilia in the period 1997-2014. Read More

Haemophilia 2019 Jul 1;25(4):e231-e239. Epub 2019 May 1.

Multi-professional Residency Program in Health and in Health Professional Areas (HC/UFPR), Curitiba, Brazil.

Introduction: To date, none of the available assessment instruments to evaluate functional abilities for individuals with haemophilia has been translated and validated in Brazil.

Aim: To translate, and test the construct validity, internal consistency and the reliability of the Haemophilia Activities List (HAL) for the Brazilian population with severe and moderate haemophilia (type A or B) and to investigate differences in the self-perception of functional abilities in patients adults with haemophilia classified according to the presence of joint bleeding and the performance of orthopaedic surgeries.

Methods: The translation and transcultural adaptation following the steps: (a) translation; (b) synthesis (consensual version); (c) back-translation; (d) review by the committee of experts; (e) pretest in the target population; and (f) final version of the instrument. Read More

Int J Hematol 2019 Jul 20;110(1):59-68. Epub 2019 Apr 20.

Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, China.

Bleeding into the joints represents the major morbidity of severe hemophilia and predisposes it to hemophilic arthropathy (HA). In a reproducible hemarthrosis mouse model, we found distinct changes in thrombin activity in joint tissue homogenate following exposure of the joint to blood in wide type (WT) and hemophilic B mice. Specifically, at early time points (4 h and 24 h) after hemarthrosis, thrombin activity in WT mice quickly peaked at 4 h, and returned to baseline after 1 week. Read More

Cochrane Database Syst Rev 2019 04 19;4:CD011385. Epub 2019 Apr 19.

Van Creveldkliniek / Department of Haematology, University Medical Centre Utrecht, Heidelberglaan 100, Utrecht, Netherlands, 3584CT.

Background: Minor oral surgery or dental extractions (oral or dental procedures) are widely performed and can be complicated by hazardous oral bleeding, especially in people with an inherited bleeding disorder such as haemophilia or Von Willebrand disease (VWD). The amount and severity of singular bleedings depend on disease-related factors, such as the severity of the haemophilia, both local and systemic patient factors (such as periodontal inflammation, vasculopathy or platelet dysfunction) and intervention-related factors (such as the type and number of teeth extracted or the dimension of the wound surface). Similar to local haemostatic measures and suturing, antifibrinolytic therapy is a cheap, safe and potentially effective treatment to prevent bleeding complications in individuals with bleeding disorders undergoing oral or dental procedures. Read More

Exp Mol Med 2019 04 17;51(4):1-9. Epub 2019 Apr 17.

Department of Physiology, Yonsei University College of Medicine, 50-1 Yonsei-ro Seodaemun-gu, Seoul, 03722, Korea.

Target-specific genome editing, using engineered nucleases zinc finger nuclease (ZFN), transcription activator-like effector nuclease (TALEN), and type II clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9), is considered a promising approach to correct disease-causing mutations in various human diseases. In particular, hemophilia A can be considered an ideal target for gene modification via engineered nucleases because it is a monogenic disease caused by a mutation in coagulation factor VIII (FVIII), and a mild restoration of FVIII levels in plasma can prevent disease symptoms in patients with severe hemophilia A. In this study, we describe a universal genome correction strategy to restore FVIII expression in induced pluripotent stem cells (iPSCs) derived from a patient with hemophilia A by the human elongation factor 1 alpha (EF1α)-mediated normal FVIII gene expression in the FVIII locus of the patient. Read More

Blood 2019 05 16;133(22):2445-2451. Epub 2019 Apr 16.

Department of Biology and Pathology, University of North Carolina at Chapel Hill, Chapel Hill, NC.

Factor IX (FIX) binds to collagen IV (Col4) in the subendothelial basement membrane. In hemophilia B, this FIX-Col4 interaction reduces the plasma recovery of infused FIX and plays a role in hemostasis. Studies examining the recovery of infused BeneFix (FIX) in null (cross-reactive material negative, CRM) hemophilia B mice suggest the concentration of Col4 readily available for binding FIX is ∼405 nM with a 95% confidence interval of 374 to 436 nM. Read More

Haemophilia 2019 Jul 16;25(4):656-667. Epub 2019 Apr 16.

Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy.

Vaccination against communicable diseases is crucial for disease prevention, but this practice poses challenges to healthcare professionals in patients with haemophilia. Poor knowledge of the vaccination requirements for these patients and safety concerns often result in vaccination delay or avoidance. In order to address this issue, a panel of 11 Italian haemophilia and immunization experts conducted a Delphi consensus process to identify the main concerns regarding the safe use of vaccines in patients with haemophilia. Read More

Harefuah 2019 Mar;158(3):187-191

The National Hemophilia Center and Thrombosis Unit, and Amalia Biron Research Institute of Thrombosis and Hemostasis, Sheba Medical Center, Tel Hashomer and Sackler Faculty of Medicine, Tel Aviv University, Israel.

Introduction: Deep Venous Thrombosis (DVT) is rare among children, yet may yield high morbidity and mortality. Due to the limited data regarding pediatric DVT, its management has been adopted from adults' protocols. Recent research reported associations of DVT and strokes with genetic thrombophilia, especially in the presence of transient risk factors (e. Read More

BMJ Case Rep 2019 Mar 22;12(3). Epub 2019 Mar 22.

Department of Prosthodontics and Digital Technology, Stony Brook University, Stony Brook, New York, USA.

Haemorrhagic disorders combined with soft tissue inflammation and infection may lead to severe bleeding complications before, during or after dental treatment. In selected cases, a combined therapeutic approach involving clinical therapies and systemic and local medication could improve the treatment outcomes and the patient's quality of life. This clinical case report, presents for the first time a successful combined approach, completed in a 38-year-old male patient with severe type-B haemophilia in which an infected tooth was extracted, an immediate implant was inserted, bone grafting was performed and early implant loading was successfully applied. Read More

Haemophilia 2019 May 13;25(3):514-520. Epub 2019 Mar 13.

Secteur des Sciences de la Santé, Institut de Recherche Expérimentale et Clinique, Neuromusculoskeletal Lab (NMSK), Université catholique de Louvain, Brussels, Belgium.

Introduction: European guidelines on the care of haemophilia recommend ready access to a range of services provided by a multidisciplinary team of specialists including physiotherapy. However, the scope of physiotherapy provided is unknown.

Methods: The Physiotherapists Committee of the European Association for Haemophilia and Allied Disorders (EAHAD) conducted a web-based survey to quantify the role and scope of practice of physiotherapists involved in haemophilia care. Read More

Haemophilia 2019 May 12;25(3):e138-e145. Epub 2019 Mar 12.

Department of Pediatric-Hematology and Hemophilia Comprehensive Care Treatment Center, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.

Introduction And Aim: Suboptimal health-related quality of life and lowered employment rates found in a previous study in young adults (YA) with congenital coagulation disorders (CCD) in the Netherlands underline the need for more insight into professional functioning of YA with CCD and into determinants of professional functioning.

Methods: Young adults (18-30 years) with CCD participated in a cross-sectional study. Professional functioning was assessed with the Work Productivity and Activity Impairment questionnaire (WPAI). Read More

Haematologica 2019 11 7;104(11):2307-2313. Epub 2019 Mar 7.

Institute of Genetics, University of Bern, Bern, Switzerland.

Hemophilia B is a classical monogenic, X-chromosomal, recessively transmitted bleeding disorder caused by genetic variants within the coagulation factor IX gene (). Although hemophilia B has been described in dogs, it has not yet been reported in the Hovawart breed. Here we describe the identification of a Hovawart family transmitting typical signs of an X-linked bleeding disorder. Read More

Haemophilia 2019 Mar 28;25(2):343-348. 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