Low Dose Prophylaxis in Hemophilia Care
AbstractHemophilia is an inherited bleeding disorder which causes impaired blood clotting. The severity of disease depends on the type of Hemophilia, level of clotting factor concentrate (CFC), phenotypic heterogeneity and the development of inhibitors. The currently accepted standard of care of this disease is prophylaxis therapy (PT) with CFC. Prophylaxis therapy for Hemophilia is given in developed countries for the last few decades. On the contrary, episodic therapy (ET) is still the mode of treatment in middle and low income countries. ET is documented to have several potential risks such as increased bleeding rate, d...
Source: Indian Journal of Hematology and Blood Transfusion - June 15, 2019 Category: Hematology Source Type: research

Real-world utilities and health-related quality-of-life data in hemophilia patients in France and the United Kingdom
(Source: Patient Preference and Adherence)
Source: Patient Preference and Adherence - June 14, 2019 Category: International Medicine & Public Health Tags: Patient Preference and Adherence Source Type: research

Emicizumab for the prevention of bleeds in hemophilia A
. (Source: Expert Opinion on Biological Therapy)
Source: Expert Opinion on Biological Therapy - June 13, 2019 Category: Drugs & Pharmacology Authors: Johnny Mahlangu Source Type: research

Tissue Factor-Negative Cell-Derived Microparticles Play a Distinctive Role in Hemostasis: A Viewpoint Review
Semin Thromb Hemost DOI: 10.1055/s-0039-1688570Circulating 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. Evidence for a role of MPs in hemostasis includes: (1) two congenital bleeding disorders attributed to impaired release of MPs; (2) two recent studies of trauma patients relating naturally elevated endogenous ...
Source: Seminars in Thrombosis and Hemostasis - June 13, 2019 Category: Hematology Authors: Horstman, Lawrence L. McCauley, Robert F. Jy, Wenche Ahn, Yeon S. Tags: Review Article Source Type: research

Emicizumab for the prevention of bleeds in hemophilia A
. (Source: Expert Opinion on Biological Therapy)
Source: Expert Opinion on Biological Therapy - June 13, 2019 Category: Drugs & Pharmacology Authors: Johnny Mahlangu Source Type: research

Variable readthrough responsiveness of nonsense mutations in hemophilia A.
Abstract Readthrough therapy relies on the use of small molecules that enable premature termination codons in mRNA open reading frames to be misinterpreted by the translation machinery, thus allowing the generation of full-length, potentially functional proteins from mRNAs carrying nonsense mutations. In patients with hemophilia A, nonsense mutations potentially sensitive to readthrough agents represent about 16% of the point mutations. The aim of this study was to measure the readthrough effect of different compounds and to analyze the influence of premature termination codon context in selected nonsense mutation...
Source: Haematologica - June 13, 2019 Category: Hematology Authors: Martorell L, Cortina V, Parra R, Barquinero J, Vidal F Tags: Haematologica Source Type: research

Traumatic hyphema in a patient with severe hemophilia A: Clinical features and management.
CONCLUSION: In such cases with hemophilia A, traumatic hyphema, and intraocular pressure elevation despite medical intervention, an early surgical clot removal under intense factor VIII replacement could be performed. In the early postoperative period, factor replacement should be resumed in order to avoid re-bleeding. PMID: 31187640 [PubMed - as supplied by publisher] (Source: European Journal of Ophthalmology)
Source: European Journal of Ophthalmology - June 12, 2019 Category: Opthalmology Authors: Belviranli S, Ozkagnici A, Tokgoz H, Bitirgen G, Caliskan U Tags: Eur J Ophthalmol Source Type: research

Viruses, Vol. 11, Pages 545: Genetic Analysis of the Full-Length gag Gene from the Earliest Korean Subclade B of HIV-1: An Outbreak among Korean Hemophiliacs
In conclusion, signature pattern analysis for the gag gene revealed 12 signature pattern residues within the KSB and also confirmed the previous conclusion that the 20 HPs were infected with viruses due to incompletely inactivated clotting factor IX. This study is the first genetic analysis of the HIV-1 gag gene in Korea. (Source: Viruses)
Source: Viruses - June 11, 2019 Category: Virology Authors: Young-Keol Cho Jung-Eun Kim Brian T. Foley Tags: Article Source Type: research

Physical activity improved by adherence to prophylaxis in an Italian population of children, adolescents and adults with severe haemophilia A: the SHAPE Study.
DISCUSSION: PWH with better orthopaedic scores reported better physical performance. Adherence to long-term prophylaxis proved to be high and correlated with a reduction in bleeds, target joints, school/work days lost, and with a performance improvement in endurance sports activities over time. PMID: 31184581 [PubMed - as supplied by publisher] (Source: Blood Transfusion)
Source: Blood Transfusion - June 5, 2019 Category: Hematology Authors: Zanon E, Tagliaferri A, Pasca S, Ettorre CP, Notarangelo LD, Biasioli C, Aru AB, Milan M, Linari S, Rocino A, Gagliano F, Di Minno G, Gamba G, Santoro RC, Schinco P, Marietta M, Seuser A, von Mackensen S Tags: Blood Transfus Source Type: research

Lupus anticoagulant-hypoprothrombinemia syndrome and similar diseases: experiences at a single center in Japan.
Abstract Patients with lupus anticoagulant (LA), a thrombotic risk factor, along with decreased prothrombin (FII) activity are classified as lupus anticoagulant-hypoprothrombinemia syndrome (LAHPS) and occasionally show bleeding symptoms, although this is not essential for diagnosis. We treated 20 cases of LAHPS over a 3-year period. Median FII activity was 20.9% and the anti-prothrombin antibody (anti-II Ab), shown by ELISA findings, was detected in 55%. Bleeding symptoms were observed in 20%, although that finding was not correlated with FII activity or anti-FII Ab quantity. We also observed 21 LA cases with dec...
Source: International Journal of Hematology - June 4, 2019 Category: Hematology Authors: Ieko M, Yoshida M, Naito S, Ohmura K, Takahashi N Tags: Int J Hematol Source Type: research

[Haemophilia: Reasons for visits to the paediatric emergency department].
CONCLUSION: Haemophilic patients went to the Emergency Department for common paediatric causes, but also requested consultation on specific problems related to haemophilia, with musculoskeletal problems/injury or bleeding being the main issues. The paediatric Emergency Department is an indispensable component of haemophilia care. PMID: 31171477 [PubMed - as supplied by publisher] (Source: Anales de Pediatria)
Source: Anales de Pediatria - June 3, 2019 Category: Pediatrics Authors: García Sánchez P, Martín Sánchez J, Rivas Pollmar MI, Álvarez Román MT, Jiménez Yuste V Tags: An Pediatr (Barc) Source Type: research

External Jugular Vein Aneurysm in a Child With Hemophilia A
An external jugular vein (EJV) aneurysm is an extremely rare disease. Ultrasonography with color doppler methods is considered the criterion standard for diagnosis of a venous aneurysm. The treatment of choice for an EJV aneurysm is surgical excision. Herein, we report an unusual case of an EJV aneurysm in a child with hemophilia A. Because the incidence of an EJV aneurysm is low, it is important to distinguish it from other neck lesions, including congenital disease. In addition, it should be noted that in hemophilia patients, an EJV aneurysm may occur in a spontaneous or small trauma. (Source: Journal of Craniofacial Surgery)
Source: Journal of Craniofacial Surgery - June 1, 2019 Category: Surgery Tags: Brief Clinical Studies Source Type: research

Peri-cardiac surgery coagulation management in a severe hemophilia A patient: A case report
We report a 54-year-old male with severe HA with FVIII activity of 0.8% when he was first diagnosed, who underwent successful mitral valve repair and coronary artery bypass graft with FVIII replacement perioperatively. Diagnoses: Transthoracic echocardiography and coronary angiography confirmed the HA patient with the diagnosis of severe mitral valve regurgitation and left anterior descending artery stenosis. Interventions: Before surgery, a bolus of 1000 IU FVIII was injected, which obtained an FVIII of 80%. After induction, a 3750 IU bolus of FVIII was injected and subsequent FVIII level reached 135%. Mitral valve ...
Source: Medicine - June 1, 2019 Category: Internal Medicine Tags: Research Article: Clinical Case Report Source Type: research

Management of haemophilia in children
Haemophilia is an inherited bleeding disorder associated with a reduction or absence of coagulation factor VIII or IX. In severe haemophilia, recurrent, spontaneous bleeding occurs into joints, without treatment this leads to crippling joint deformity. Haemophilia is an X-linked disorder yet there is no family history in approximately one third of cases where haemophilia arises as a result of a new genetic mutation. Without treatment, the prognosis is poor but the development of factor concentrates and ‘non-factor replacement therapy’ has transformed the outlook. (Source: Paediatrics and Child Health)
Source: Paediatrics and Child Health - June 1, 2019 Category: Pediatrics Authors: Kate Khair Tags: Symposium: Haematology Source Type: research

Protocolized use of Factor Eight Inhibitor Bypassing Activity (FEIBA) for the reversal of warfarin induced coagulopathy
Coagulopathy due to warfarin in patients with major bleeding was traditionally reversed with fresh frozen plasma and intravenous (IV) vitamin K, but prothrombin complex concentrates (PCC) are increasingly used in the treatment of these patients. Factor Eight Inhibitor Bypassing Activity (FEIBA) is an activated four-factor PCC most commonly used in patients with hemophilia. We aimed to evaluate the efficacy and safety of FEIBA and IV vitamin K for the reversal of warfarin-associated coagulopathy in patients with major bleeding, by measuring the percentage of patients who achieved target INR  ≤ 1.5 and the incidence o...
Source: The American Journal of Emergency Medicine - May 31, 2019 Category: Emergency Medicine Authors: Natalie N. Htet, David Barounis, Catherine Knight, Ben-Paul Umunna, Mary Hormese, Elise Lovell Source Type: research

Off-pump technique and replacement therapy for coronary artery bypass surgery in a patient with hemophilia B
AbstractAntithrombotic treatment and perioperative management in patients with hemophilia remains a challenge. As life expectancy in these patients is increasing, a concern about cardiovascular diseases is emerging. Herein we present the case of a 68  year-old patient with mild hemophilia B and multivessel coronary disease who underwent coronary artery bypass grafting (CABG) surgery. Off-pump surgery with continuous infusion FIX treatment was performed successfully with stable factor IX levels, and no bleeding or thrombotic complications. There is a paucity of cases reported regarding management of CABG in this popula...
Source: Journal of Thrombosis and Thrombolysis - May 31, 2019 Category: Hematology Source Type: research

Prophylactic administration of glycoPEGylated factor IX provides protection and joint outcome superior to recombinant factor IX after induced joint bleeding.
CONCLUSIONS: These results indicate that, in comparison to rFIX, the prophylactic use of extended half-life FIX provides superior protection from bleeding-induced joint damage, manifested by improved correction of histologic parameters. This article is protected by copyright. All rights reserved. PMID: 31148392 [PubMed - as supplied by publisher] (Source: Thrombosis and Haemostasis)
Source: Thrombosis and Haemostasis - May 31, 2019 Category: Hematology Authors: Sun J, Livingston EW, Broberg ML, Johansen PB, Ley CD, Knudsen T, Ezban M, Bateman TA, Monahan PE, Taves S Tags: J Thromb Haemost Source Type: research

Polymorphisms in MAPK9 (rs4147385) and CSF1R (rs17725712) are associated with the development of inhibitors in patients with haemophilia A in North China.
CONCLUSION: We confirmed an association of CSF1R rs17725712 and MAPK9 rs4147385 with inhibitor development in haemophilia A patients in North China. PMID: 31149782 [PubMed - as supplied by publisher] (Source: International Journal of Laboratory Hematology)
Source: International Journal of Laboratory Hematology - May 31, 2019 Category: Hematology Authors: Zhao M, Zhang Y, Liu Y, Sun G, Tian H, Hong L Tags: Int J Lab Hematol Source Type: research

Dysfunctional endogenous FIX impairs prophylaxis in a mouse hemophilia B model
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 (FIXWT) 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. Thus, the vascular cache of FIX bound to Col4 is several-fold the FIX level measured in plasma. In a mouse model of prophylactic therapy (testing hemostasis by saphenou...
Source: Blood - May 30, 2019 Category: Hematology Authors: Cooley, B., Broze, G. J., Mann, D. M., Lin, F.-C., Pedersen, L. G., Stafford, D. W. Tags: Thrombosis and Hemostasis, Vascular Biology Source Type: research

Total hip arthroplasty for a woman with hemophilia A -case report-
Publication date: July 2019Source: Annals of Medicine and Surgery, Volume 43Author(s): Akio Kanda, Kazuo Kaneko, Osamu Obayashi, Atsuhiko Mogami, Itaru MorohashiAbstractHemophilia A is a congenital bleeding disorder caused by an X-linked hereditary pattern. Female hemophilia A carriers are usually asymptomatic, although some have far lower levels of clotting factor because more X chromosomes with the normal gene are switched off, a phenomenon referred to as "lyonization.” During a medical checkup at our hospital, a 56-year-old Japanese woman with coxalgia was also diagnosed as an obligate hemophilia A carrier ba...
Source: Annals of Medicine and Surgery - May 29, 2019 Category: General Medicine Source Type: research

Emicizumab for hemophilia A without inhibitors.
Authors: Cafuir L, Kruse-Jarres R, Mancuso ME, Kempton CL Abstract Introduction: Hemophilia A (HA) is an inherited bleeding disorder that, if not properly treated, is associated with debilitating joint damage due to recurrent hemarthroses as well as life-threatening bleeds including intracranial hemorrhage. For decades, the only method to prevent bleeding events was to infuse factor (F) VIII concentrates intravenously two to three times weekly. Although successful in reducing bleeding frequency, preventing a high proportion of joint disease, and extending life expectancy, standard continuous prophylaxis with FVIII ...
Source: Expert Review of Hematology - May 29, 2019 Category: Hematology Tags: Expert Rev Hematol Source Type: research

F8 Inversions at Xq28 Causing Hemophilia A Are Associated With Specific Methylation Changes: Implication for Molecular Epigenetic Diagnosis
Diverse DNA structural variations (SVs) in human cancers and several other diseases are well documented. For genomic inversions in particular, the disease causing mechanism may not be clear, especially if the inversion border does not cross a coding sequence. Understanding about the molecular processes of these inverted genomic sequences, in a mainly epigenetic context, may provide additional information regarding sequence-specific regulation of gene expression in human diseases. Herein, we study one such inversion hotspot at Xq28, which leads to the disruption of F8 gene and results in hemophilia A phenotype. To determine...
Source: Frontiers in Genetics - May 29, 2019 Category: Genetics & Stem Cells Source Type: research

Increased Accumulation and Retention of rhFVIIa (eptacog beta) in Knee Joints of Hemophilia A Mice Compared to Wild-Type Mice.
In conclusion, the present data demonstrate a dose-dependent accumulation of rhFVIIa in knee joints, and the hemophilic condition enhances the entry of rhFVIIa from circulation to the extravascular. The present data will be useful in improving rhFVIIa prophylaxis. PMID: 31129915 [PubMed - as supplied by publisher] (Source: Thrombosis and Haemostasis)
Source: Thrombosis and Haemostasis - May 26, 2019 Category: Hematology Authors: Magisetty J, Pendurthi UR, Madhunapantula SV, Grandoni J, Rao LVM Tags: Thromb Haemost Source Type: research

Total hip arthroplasty in a woman with hemophilia A: case report
Publication date: Available online 24 May 2019Source: Annals of Medicine and SurgeryAuthor(s): Akio Kanda, Kazuo Kaneko, Osamu Obayashi, Atsuhiko Mogami, Itaru MorohashiAbstractHemophilia A is a congenital bleeding disorder caused by an X-linked hereditary pattern. Female hemophilia A carriers are usually asymptomatic, although some have far lower levels of clotting factor because more X chromosomes with the normal gene are switched off, a phenomenon referred to as "lyonization.” During a medical checkup at our hospital, a 56-year-old Japanese woman with coxalgia was also diagnosed as an obligate hemophilia A ca...
Source: Annals of Medicine and Surgery - May 25, 2019 Category: General Medicine Source Type: research

Safety analysis of rFVIIa with emicizumab dosing in congenital hemophilia A with inhibitors: Experience from the HAVEN clinical program.
CONCLUSION: rFVIIa use in the context of emicizumab prophylaxis does not change the rFVIIa safety profile as described in the product information. This article is protected by copyright. All rights reserved. PMID: 31124272 [PubMed - as supplied by publisher] (Source: Thrombosis and Haemostasis)
Source: Thrombosis and Haemostasis - May 24, 2019 Category: Hematology Authors: Levy GG, Asikanius E, Kuebler P, Benchikh El Fegoun S, Esbjerg S, Seremetis S Tags: J Thromb Haemost Source Type: research

Acquired Hemophilia A Associated with Dipeptidyl Peptidase-4 Inhibitors for the Treatment of Type 2 Diabetes Mellitus: A Single-Center Case Series in Japan
AbstractHerein we describe four patients with acquired hemophilia A (AHA) caused by factor VIII (FVIII) inhibitor and histories of dipeptidyl peptidase-4 inhibitor (DPP4-I) treatment for diabetes mellitus (DM). Drug exposure can cause a breakdown of immune tolerance to FVIII associated with CD4 T cells, resulting in the induction of autoantibodies against FVIII. In patient 1 in the present series, FVIII inhibitor disappeared after DPP4-I treatment. The DPP4-I treatment was stopped faster in patient 1 than it was in patient 2, whose FVIII inhibitor titer was higher than patient 1 ’s. Two patients died: patient 3 due t...
Source: Diabetes Therapy - May 23, 2019 Category: Endocrinology Source Type: research

Bullous Pemphigoid Associated with Acquired Hemophilia A: A Case Report and Review of the Literature
We report a 68-year-old Thai woman diagnosed and treated for bullous pemphigoid (BP) for 11 months who recently presented with a 3-day history of extensive hemorrhagic bullae and large intra-oral buccal hematoma. Laboratory investigations confirmed a prolonged activated partial thromboplastin time, a low factor VIII level, a high factor VIII inhibitor level, and elevated anti-BPAG180 and anti-BPAG230 titers, confirming the diagnosis of BP associated with AHA. Immunosuppressive therapy with systemic corticosteroids and cyclophosphamide combined with bypassing agents for bleeding control resulted in significant clinical impr...
Source: Case Reports in Dermatology - May 22, 2019 Category: Dermatology Source Type: research

[Research Articles] Phagocytosis-shielded lentiviral vectors improve liver gene therapy in nonhuman primates
Liver-directed gene therapy for the coagulation disorder hemophilia showed safe and effective results in clinical trials using adeno-associated viral vectors to replace a functional coagulation factor, although some unmet needs remain. Lentiviral vectors (LVs) may address some of these hurdles because of their potential for stable expression and the low prevalence of preexisting viral immunity in humans. However, systemic LV administration to hemophilic dogs was associated to mild acute toxicity and low efficacy at the administered doses. Here, exploiting intravital microscopy and LV surface engineering, we report a major ...
Source: Science Translational Medicine - May 22, 2019 Category: Biomedical Science Authors: Milani, M., Annoni, A., Moalli, F., Liu, T., Cesana, D., Calabria, A., Bartolaccini, S., Biffi, M., Russo, F., Visigalli, I., Raimondi, A., Patarroyo-White, S., Drager, D., Cristofori, P., Ayuso, E., Montini, E., Peters, R., Iannacone, M., Cantore, A., Na Tags: Research Articles Source Type: research

Contaminated blood scandal: Could some deaths have been prevented?
Campaigners are giving evidence to an inquiry into the haemophilia treatments that infected thousands of people with HIV and hepatitis C in the 1970s and 80s (Source: New Scientist - Health)
Source: New Scientist - Health - May 21, 2019 Category: Consumer Health News Source Type: research

Routine clinical care data for population pharmacokinetic modeling: the case for Fanhdi/Alphanate in hemophilia A patients
This study shows the feasibility of using real-world data for the development of a population PK model. Evaluation and comparison of the model for Bayesian forecasting resulted in similar results as a model developed using rich sampling data. (Source: Journal of Pharmacokinetics and Pharmacodynamics)
Source: Journal of Pharmacokinetics and Pharmacodynamics - May 21, 2019 Category: Drugs & Pharmacology Source Type: research

Systematic review and analysis of efficacy of recombinant factor IX products for prophylactic treatment of hemophilia B in comparison with rIX-FP.
CONCLUSION: This indirect comparison of Phase III trials indicates that rIX-FP efficacy compares favorably versus other rFIX products for prophylaxis in hemophilia B. PMID: 31094591 [PubMed - as supplied by publisher] (Source: Journal of Medical Economics)
Source: Journal of Medical Economics - May 18, 2019 Category: Health Management Tags: J Med Econ Source Type: research

Development and evaluation of a generic population pharmacokinetic model for standard half-life factor VIII for use in dose individualization
AbstractHemophilia A is a rare bleeding disorder resulting from a lack of functional factor VIII (FVIII). Therapy consists of replacement with exogenous FVIII, but is complicated by high inter-patient variability. A population pharmacokinetics (PopPK) approach can facilitate the uptake of an individualized approach to hemophilia therapy. We developed a PopPK model using data from seven brands of standard half-life FVIII products. The final model consists of a 2-compartment structure, with a proportional residual error model and between-subject variability on clearance and central volume. Fat-free mass, age, and brand were ...
Source: Journal of Pharmacokinetics and Pharmacodynamics - May 18, 2019 Category: Drugs & Pharmacology Source Type: research

Gene Therapy: Paving New Roads in the Treatment of Hemophilia
Semin Thromb Hemost DOI: 10.1055/s-0039-1688445Hemophilia is a monogenic disease with robust clinicolaboratory correlations of severity. These attributes coupled with the availability of experimental animal models have made it an attractive model for gene therapy. The road from animal models to human clinical studies has heralded significant successes, but major issues concerning a previous immunity against adeno-associated virus and transgene optimization remain to be fully resolved. Despite significant advances in gene therapy application, many questions remain pertaining to its use in specific populations such as those ...
Source: Seminars in Thrombosis and Hemostasis - May 16, 2019 Category: Hematology Authors: Yamaguti-Hayakawa, Gabriela G. Ozelo, Margareth C. Tags: Review Article Source Type: research

Emicizumab (Hemlibra) for Subcutaneous Prophylaxis in Hemophilia A
Date: May 20, 2019 Issue #:  1572Summary:  The FDA has approved emicizumab-kxwh (Hemlibra– Genentech), a subcutaneously injected, factor IXa- and X-directed antibody, for routine prophylaxis to prevent or reduce bleeding episodes in patients with hemophilia A. Emicizumab is not recommended for treatment of bleeding. (Source: The Medical Letter)
Source: The Medical Letter - May 10, 2019 Category: Drugs & Pharmacology Authors: admin Tags: Beriplex Eloctate emicizumab Hemlibra Hemophilia Source Type: research

Current and emerging biologics for the treatment of hemophilia
. (Source: Expert Opinion on Biological Therapy)
Source: Expert Opinion on Biological Therapy - May 9, 2019 Category: Drugs & Pharmacology Authors: Giancarlo Castaman Silvia Linari Source Type: research

The role of variant alleles of the mannose-binding lectin in the inhibitor development in severe hemophilia A
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. MBL2 single nucleotide polymorphisms (SNPs) lead to low peripheral MBL-concentrations that may hamper the removal of mannosylated FVIII. (Source: Thrombosis Research)
Source: Thrombosis Research - May 8, 2019 Category: Hematology Authors: Gudrun Ulrich-Merzenich, Annekristin Hausen, Heike Zeitler, Georg Goldmann, Johannes Oldenburg, Anna Pavlova Tags: Full Length Article Source Type: research

Effects and Interferences of Emicizumab, a Humanised Bispecific Antibody Mimicking Activated Factor VIII Cofactor Function, on Coagulation Assays.
The objective of this study was to assess the effect of emicizumab on coagulation assays, including potential interference behavior that may produce inaccurate or misleading results. A variety of clotting-based, amidolytic/chromogenic, latex particle-enhanced turbidometric, and enzyme-linked immunosorbent methods were investigated. As expected based on its pharmacologic mechanism of action, emicizumab exhibited strong activity on the activated partial thromboplastin time (aPTT), which resulted in interference with several aPTT-based assays, most importantly the one-stage FVIII activity assay; these assays are not recommend...
Source: Thrombosis and Haemostasis - May 7, 2019 Category: Hematology Authors: Adamkewicz JI, Chen DC, Paz-Priel I Tags: Thromb Haemost Source Type: research

Kirurgiske inngrep hos pasienter med alvorlig bl ødersykdom 1997–2014.
This article describes surgery in patients with severe haemophilia in the period 1997-2014. MATERIAL AND METHOD: Data were retrieved from the registry linked to the national treatment service for surgery, intervention and advanced diagnostics for haemophilia. The patients were categorised according to type of haemophilia and type of intervention in orthopaedic and non-orthopaedic surgical procedures. RESULTS: A total of 825 surgical procedures were undertaken in 286 patients. The number of procedures increased from 21 in 1997 to 66 in 2014. This increase was associated with non-orthopaedic interventions: alt...
Source: Tidsskrift for den Norske Laegeforening - May 6, 2019 Category: General Medicine Authors: Andersen MF, Holme PA, Tjønnfjord GE Tags: Tidsskr Nor Laegeforen Source Type: research

Functional polymorphisms in the LDLR and pharmacokinetics of Factor VIII concentrates.
CONCLUSIONS: With the limitation of different FVIII concentrates and low number of patients, our data show plausible associations of LDLR polymorphisms with FVIII PK parameters, thus supporting their investigation as candidate functional determinants of FVIII PK. This article is protected by copyright. All rights reserved. PMID: 31055871 [PubMed - as supplied by publisher] (Source: Thrombosis and Haemostasis)
Source: Thrombosis and Haemostasis - May 4, 2019 Category: Hematology Authors: Lunghi B, Bernardi F, Martinelli N, Frusconi S, Branchini A, Linari S, Marchetti G, Castaman G, Morfini M Tags: J Thromb Haemost Source Type: research

Dental management of a patient with incidentally detected hemophilia: Report of a clinical case
This report describes the dental/medical management provided to a 23-year-old patient suffering from uncontrolled bleeding after an electrosurgical procedure (operculectomy) in relation to the mandibular right third molar, in which hemophilia was a true accidental finding. Various safety measures that need to be considered during the dental surgical management of hemophilic patients are discussed. (Source: Journal of Indian Society of Periodontology)
Source: Journal of Indian Society of Periodontology - May 2, 2019 Category: Dentistry Authors: Sreenivas Nagarakanti Hasya Sappati Sumanth Gunupati Bhumanapalli Venkata Ramesh Reddy Vijay Kumar Chava Source Type: research

Concurrent lymphoma and hemophilia B in a pediatric patient: A case report
Conclusion: Concurrent hemophilia and lymphoma are rare, especially in children. When encountering a patient with unexplained obstructive jaundice and massive ascites, the possibility of a tumor should be considered. Early diagnosis and adequate treatment of such tumor may improve prognosis. (Source: Medicine)
Source: Medicine - May 1, 2019 Category: Internal Medicine Tags: Research Article: Clinical Case Report Source Type: research

Genetic analysis of a hemophilia B family with a novel F9 gene mutation: A STROBE-compliant article
In this study, we made gene and prenatal diagnoses in a family with a novel F9 gene mutation, and report a novel F9 gene mutation. All exon sequences and flanking sequences of F9 gene were analyzed by Sanger sequencing in the proband; and then according to the F9 gene mutation in the proband, the F9 gene sequencing was performed on the family members. Based on the above results, the pathogenic mutation in F9 gene was finally identified, which was used for prenatal diagnosis. Sanger sequencing revealed c.1232G>C [p.Ser411Thr] mutation in F9 gene in the proband. c.1232G>C heterozygous mutation was also found in the p...
Source: Medicine - May 1, 2019 Category: Internal Medicine Tags: Research Article: Observational Study Source Type: research

Apparent synonymous mutation F9 c.87A > G causes secretion failure by in-frame mutation with aberrant splicing
Hemophilia B is an X-linked recessive bleeding disorder caused by coagulation factor IX (FIX) gene (F9) mutations. Several F9 synonymous mutations have been known to cause hemophilia B; however, the deleterious mechanisms underlying the development of hemophilia B have not been completely understood. To elucidate the molecular pathogenesis causing hemophilia B, we investigated the synonymous F9 mutation: c.87A>G, p.(Thr29=). (Source: Thrombosis Research)
Source: Thrombosis Research - May 1, 2019 Category: Hematology Authors: Koya Odaira, Shogo Tamura, Nobuaki Suzuki, Misaki Kakihara, Yuna Hattori, Mahiru Tokoro, Sachiko Suzuki, Akira Takagi, Akira Katsumi, Fumihiko Hayakawa, Shuichi Okamoto, Atsuo Suzuki, Takeshi Kanematsu, Tadashi Matsushita, Tetsuhito Kojima Tags: Full Length Article Source Type: research

Update on Molecular Testing in von Willebrand Disease
This article discusses the pros and cons of molecular testing in VWD considering the experience obtained through the multicenter project “Molecular and Clinical Profile of VWD in Spain (PCM-EVW-ES).” [...] Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.Article in Thieme eJournals: Table of contents  |  Abstract  |  Full text (Source: Seminars in Thrombosis and Hemostasis)
Source: Seminars in Thrombosis and Hemostasis - April 30, 2019 Category: Hematology Authors: Batlle, Javier P érez-Rodríguez, Almudena Corrales, Irene Borr às, Nina Costa Pinto, Joana L ópez-Fernández, María Fernanda Vidal, Francisco Tags: Review Article Source Type: research

Comparative pharmacokinetics of two extended half-life FVIII concentrates (Eloctate and Adynovate) in adolescents with hemophilia A: is there a difference?
CONCLUSIONS: Eloctate and Adynovate have almost identical PK parameters. When switching from one to another no prophylaxis regimen change is needed. This article is protected by copyright. All rights reserved. PMID: 31038793 [PubMed - as supplied by publisher] (Source: Thrombosis and Haemostasis)
Source: Thrombosis and Haemostasis - April 30, 2019 Category: Hematology Authors: Carcao MD, Chelle P, Clarke E, Kim L, Tiseo L, Morfini M, Hossain T, Rand ML, Brown C, Edginton A, Lillicrap D, Iorio A, Blanchette VS Tags: J Thromb Haemost Source Type: research

Current and emerging biologics for the treatment of hemophilia
. (Source: Expert Opinion on Biological Therapy)
Source: Expert Opinion on Biological Therapy - April 30, 2019 Category: Drugs & Pharmacology Authors: Giancarlo Castaman Silvia Linari Source Type: research

Hematological Side Effects of Immune Checkpoint Inhibitors: The Example of Immune-Related Thrombocytopenia
Roser Calvo* Patient Safety, Safety Science, AstraZeneca Pharmaceuticals, Gaithersburg, MD, United States Immune-related hematological adverse events are amongst the rare but potentially life-threatening complications of immune checkpoint inhibitors. The spectrum of these toxicities is broadening as the number of patients exposed to these agents is increasing. Yet, they are still relatively unknown to many clinicians, possibly due to a lack of specific diagnostic criteria, which poses a challenge for their recognition and proper reporting, and partly due to their low incidence, often too low to be noted in most c...
Source: Frontiers in Pharmacology - April 26, 2019 Category: Drugs & Pharmacology Source Type: research

Severe haemophilia A caused by an unbalanced chromosomal rearrangement identified using nanopore sequencing.
CONCLUSION: we characterized a novel genomic rearrangement in which a 3.8Mb Xq11.1q12 gain inserted in the F8 intron 25 led to an aberrant fusion transcript in a patient with severe HA, using comprehensive molecular techniques. This study highlights the value of single molecule long-read sequencing technologies for molecular diagnosis of HA especially when conventional genetic approaches have failed. This article is protected by copyright. All rights reserved. PMID: 31021037 [PubMed - as supplied by publisher] (Source: Thrombosis and Haemostasis)
Source: Thrombosis and Haemostasis - April 25, 2019 Category: Hematology Authors: Chatron N, Schluth-Bolard C, Frétigny M, Labalme A, Vilchez G, Castet SM, Négrier C, Sanlaville D, Vinciguerra C, Jourdy Y Tags: J Thromb Haemost Source Type: research

Coagulation Pathways in Neurological Diseases: Multiple Sclerosis
Nicole Ziliotto1,2, Francesco Bernardi1, Dejan Jakimovski2 and Robert Zivadinov2,3* 1Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy 2Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, Buffalo Neuroimaging Analysis Center, University at Buffalo, State University of New York, Buffalo, NY, United States 3Clinical Translational Science Institute, Center for Biomedical Imaging, University at Buffalo, State University of New York, Buffalo, NY, United States Significant progress has been made in understanding the complex interactions between the coagulatio...
Source: Frontiers in Neurology - April 24, 2019 Category: Neurology Source Type: research

Gene Therapy Leaves a Vicious Cycle
Reena Goswami1, Gayatri Subramanian2, Liliya Silayeva1, Isabelle Newkirk1, Deborah Doctor1, Karan Chawla2, Saurabh Chattopadhyay2, Dhyan Chandra3, Nageswararao Chilukuri1 and Venkaiah Betapudi1,4* 1Neuroscience Branch, Research Division, United States Army Medical Research Institute of Chemical Defense, Aberdeen, MD, United States 2Department of Medical Microbiology and Immunology, University of Toledo College of Medicine and Life Sciences, Toledo, OH, United States 3Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States 4Department of Physiology and Biophysics, Case Western Reserve University, Clev...
Source: Frontiers in Oncology - April 24, 2019 Category: Cancer & Oncology Source Type: research