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Cardiovasc Diabetol 2022 May 20;21(1):79. Epub 2022 May 20.

Division of Endocrinology and Diabetology, Interdisciplinary Metabolic Medicine Trials Unit, Medical University of Graz, Graz, Austria.

Background: In patients with type 2 diabetes mellitus (T2DM) an association between severe hypoglycaemic episodes and the risk of cardiovascular (CV) morbidity and mortality has been previously established.

Methods: We aimed to investigate the influence of hypoglycaemia on several diabetes-related and platelet-related miRNAs selected based on bioinformatic analysis and literature search, including hsa-miR-16, hsa-miR-34a, hsa-miR-129-2, hsa-miR-15a, hsa-miR-15b, hsa-miR-106a, miR-223, miR-126. Selected miRNAs were validated by qRT-PCR in 14 patients with T2DM on metformin monotherapy, without established CV disease and antiplatelet therapy during a stepwise hypoglycaemic clamp experiment and a follow-up 7 days after the clamp event. Read More

Biochem Biophys Res Commun 2022 Feb 20. Epub 2022 Feb 20.

School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China; Engineering Research Center of Cell and Therapeutic Antibody of Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China. Electronic address:

Hemophilia A is a bleeding disorder caused by quantitative or qualitative deficiencies in coagulation factor VIII (FVIII). Low FVIII expression due to its unstable mRNA and binding with immunoglobulin-binding protein (BiP) compromises gene therapy endeavors in hemophilia A. Site-directed mutagenesis have demonstrated an improvement in the expression of FVIII proteins. Read More

J Trop Pediatr 2022 Apr;68(3)

Department of Pathology, University College of Medical Sciences and Guru Teg Bahadur Hospital, Dilshad Garden, New Delhi 110095, India.

Introduction: Low dose factor VIII prophylactic therapy in hemophilia has not been well established till date. This randomized controlled trial compared the efficacy of twice vs. thrice weekly schedule of low dose prophylactic factor VIII in children with hemophilia A as evaluated by the bleeding rate and clinico-radiological evaluation. Read More

J Blood Med 2022 11;13:255-265. Epub 2022 May 11.

Department of Pediatrics, Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.

In acquired hemophilia A (AHA), autoantibodies to coagulation factor VIII (FVIII) neutralize FVIII activity leading to a potentially severe bleeding diathesis that carries a high rate of morbidity and mortality. This disorder is rare and occurs mainly in adults over 60 years of age or in the postpartum period. The diagnosis should be suspected in patients with new-onset bleeding without a personal or family history of bleeding and can be confirmed via specific assays for FVIII inhibitors. Read More

Int J Hematol 2022 May 19. Epub 2022 May 19.

Department of Laboratory Medicine, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan.

In hemophilia A, bleeding mostly correlates with factor VIII activity (FVIII:C), although some patients show discrepancy in bleeding severity and FVIII:C. We report a novel procoagulant mechanism associated with F8 p.H118R (c. Read More

J Blood Med 2022 9;13:229-241. Epub 2022 May 9.

Sol Price School of Public Policy, University of Southern California, Los Angeles, CA, USA.

Purpose: We compare the impact of hemophilia on comorbidities, joint problems, health-related quality of life (HRQoL) and health-care utilization between two age groups: 40-49 years and ≥50 years.

Patients And Methods: The HUGS VII study recruited persons with hemophilia A or B age ≥40 years. Participants completed surveys to collect data on sociodemographic and clinical characteristics, hemophilia treatment regimen, pain, joint problems, comorbidities, HRQoL, depression and anxiety, at baseline and 6-months later. Read More

Cancer Drug Resist 2022 7;5(1):214-228. Epub 2022 Mar 7.

Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, Dublin D02YNVV, Ireland.

Multiple Myeloma (MM) is a common haematological malignancy that is associated with a high rate of venous thromboembolism (VTE) with almost 10% of patients suffering thrombosis during their disease course. Recent studies have shown that, despite current thromboprophylaxis strategies, VTE rates in MM remain disappointingly high. The pathophysiology behind this consistently high rate of VTE is likely multifactorial. Read More

Haemophilia 2022 May 16. Epub 2022 May 16.

Department of Haematology, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

Introduction: Perioperative dosing recommendations vary across Nordic haemophilia treatment centres (HTCs) for extended half-life (EHL) factor concentrates in haemophilia A/B (HA/HB) patients.

Aim: To summarise Nordic real-world surgical experiences with EHL recombinant factor VIII/IX Fc (rFVIIIFc/rFIXFc) fusion proteins using retrospective data from clinical records at four HTCs in Finland, Sweden and Norway.

Methods: Factor dosing and surgical outcomes were recorded from HA/HB patients who underwent surgery and were treated with rFVIIIFc/rFIXFc. Read More

Curr Drug Deliv 2022 May 13. Epub 2022 May 13.

Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran.

Purpose: To obtain the safe and qualified blood products (e.g., platelets, plasma, and red blood cell), various limitations such as limited shelf life (especially for platelets) and stability must be addressed. Read More

Clin Chem Lab Med 2022 May 16. Epub 2022 May 16.

Department of Clinical Laboratory, The First Hospital of China Medical University, Shenyang, P.R. China.

Haemophilia 2022 May 13. Epub 2022 May 13.

Division of Haemostaseology, Medical Department I, University Hospital Leipzig, Leipzig, Germany.

Background: Guidelines recommend that patients with haemophilia should preferably receive vaccination subcutaneously. COVID-19 and other vaccines, however, are only licenced for intramuscular application.

Aims: To assess the safety of intramuscular COVID-19 vaccination in patients living with haemophilia. Read More

Hum Mol Genet 2022 May 12. Epub 2022 May 12.

Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA.

Plasma levels of fibrinogen, coagulation factors VII and VIII, and von Willebrand factor (vWF) are four intermediate phenotypes that are heritable and have been associated with the risk of clinical thrombotic events. To identify rare and low-frequency variants associated with these hemostatic factors, we conducted whole exome sequencing in 10 860 individuals of European ancestry (EA) and 3529 African Americans (AAs) from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium and the National Heart, Lung, and Blood Institute's Exome Sequencing Project (ESP). Gene-based tests demonstrated significant associations with rare variation (minor allele frequency < 5%) in FGG (with fibrinogen, p = 9. Read More

Blood Transfus 2022 Apr 19. Epub 2022 Apr 19.

Department of Haemostasis and Transfusion, Lille University Hospital, Lille, France.

Background: Plasma-derived von Willebrand factor (VWF) (Wilfactin, LFB, France) was developed for prophylaxis and treatment of haemorrhages in both adults and adolescents with von Willebrand disease (VWD). Replacement therapy in paediatric patients is a key element of the clinical trial programme.

Material And Methods: Patients aged <6 years with severe VWD were enrolled in a multinational, open-label study to evaluate the in vivo recovery for Wilfactin, and its efficacy in preventing and treating bleeding episodes and during surgery. Read More

Haemophilia 2022 May 10. Epub 2022 May 10.

Paediatric Haematology-Oncology Division, Department of Child Health, Dr. Cipto Mangunkusumo Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.

Background: Pharmacokinetic (PK) studies of low-dose prophylaxis (LDP) of coagulation factor VIII (FVIII) in children with severe haemophilia A (SHA) are scarce.

Objective: This study aims to investigate the PK profile of children with SHA receiving LDP of FVIII.

Methods: Paediatric patients receiving FVIII infusions (10 IU/kg twice weekly) were included. Read More

Prog Biomater 2022 May 10. Epub 2022 May 10.

Department of Radiopharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

Despite the importance of the proper quality of blood products for safe transfusion, conventional methods for preparation and their preservation, they lack significant stability. Non-metal nanoparticles with particular features may overcome these challenges. This review study for the first time provided a comprehensive vision of the interaction of non-metal nanoparticles with each blood product (red blood cells, platelets and plasma proteins). Read More

J Comp Eff Res 2022 May 10. Epub 2022 May 10.

Department of Real-World Data Oncology-Hematology, F Hoffmann-La Roche Ltd., Basel, CH-4070, Switzerland.

To determine if emicizumab was channeled to clinically complex people with hemophilia A upon approval. Claims data (16 November 2017, through 31 December 2019) from US-based insurance databases were analyzed to compare the clinical complexity of people with hemophilia A initiating emicizumab with matched individuals receiving factor VIII (FVIII) episodically or prophylactically. People with hemophilia A with evidence of previous bypassing agent use (indicating FVIII inhibitors) were excluded. Read More

Blood Adv 2022 May 9. Epub 2022 May 9.

Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands.

Detailed information on the onset, frequency and severity of bleeding in non-severe hemophilia is limited. We aimed to assess the bleeding phenotype of people with non-severe hemophilia, and to analyse the association between baseline factor VIII/IX levels and the joint bleeding rate. In the DYNAMO study, an international multicenter cohort, we included males with non-severe hemophilia (factor VIII/IX (FVIII/IX) 0. Read More

Int J Hematol 2022 May 9. Epub 2022 May 9.

Department of Laboratory Medicine, Tokyo Medical University, Tokyo, Japan.

Type 3 von Willebrand disease (VWD), a rare and severe subtype, can produce inhibitors in roughly 5% to 10% of cases. We present a case of type 3 VWD with inhibitors in late pregnancy, which was successfully managed with a combination of neutralization and factor (F)VIII replacement during cesarean delivery. The patient, a 30-year-old woman, had no history of inhibitors despite over 100 exposures to VWF/FVIII. Read More

Eur J Haematol 2022 May 9. Epub 2022 May 9.

Haemophilia Center, General Medicine, Department of Medicine, University of Padua Medical School. Padua, Italy.

Objectives: The present review aims to summarize the state-of-the-art VWD treatment focusing on specific clinical settings (obstetrics, surgery, long-term prophylaxis and comorbidities) as well as on the use of a VWF concentrate with low FVIII content.

Methods: Literature research and case reports.

Results And Conclusions: Considering that patients affected by VWD have an intact ability to synthesize FVIII, in order to avoid excessive levels of FVIII, a highly purified plasma VWF concentrate with low FVIII content could be particularly useful in those patients and clinical circumstances at high thrombotic risk as well as for long-term prophylaxis. Read More

Cureus 2022 Apr 7;14(4):e23926. Epub 2022 Apr 7.

Hematology Oncology, State University of New York (SUNY) Upstate Medical University, Syracuse, USA.

This case report describes a 72-year-old female patient diagnosed with small cell lung carcinoma who was found to have elevated partial thromboplastin time (PTT) after reporting diarrhea and melanotic stool. Further investigations revealed the presence of a factor VIII inhibitor, possibly resulting from a side effect of immunotherapy or of possible paraneoplastic origin. The patient's PTT remained elevated following a course of steroid treatment, raising the likelihood of paraneoplastic etiology. Read More

Haemophilia 2022 May 8. Epub 2022 May 8.

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

Background: To account for interindividual variability in the pharmacokinetics (PK) of factor concentrates, PK-guided dosing is increasingly implemented in haemophilia patients. Calculations are based on provided label potency, but legislation allows a potency difference of ±20% between label and actual potency. It is unknown if these differences affect PK guidance. Read More

Expert Rev Hematol 2022 May 17:1-11. Epub 2022 May 17.

School of Medicine, University of Electronic Science and Technology of China, Sichuan, China.

Introduction: Hemophilia A (HA) or B (HB) is an X-linked recessive disorder caused by a defect in the factor VIII (FVIII) or factor IX (FIX) gene which leads to the dysfunction of blood coagulation. Protein replacement therapy (PRT) uses recombinant proteins and plasma-derived products, which incurs high cost and inconvenience requiring routine intravenous infusions and life-time treatment. Understanding of detailed molecular mechanisms on FVIII gene function could provide innovative solutions to amend this disorder. Read More

Haemophilia 2022 May;28 Suppl 4:26-34

Haemophilia Comprehensive Care Centre, Haematology Centre, Beijing Children's Hospital, National Centre for Children's Health, Capital Medical University, Beijing, China.

Introduction: Prophylaxis has become standard of care for persons with severe phenotype haemophilia (PWsH). However, 'standard prophylaxis' with either factor or non-factor therapies (emicizumab) is prohibitively expensive for much of the world. We sought to evaluate whether haemophilia care can be provided at a lower cost yet achieve good results using Lower dose/Lower frequency prophylaxis (LDP) and with increasing use of antifibrinolytics (Tranexamic acid and Epsilon amino caproic acid). Read More

Haemophilia 2022 May;28 Suppl 4:35-43

Coagulation Products Safety Supply and Access Committee, World Federation of Hemophilia, Montreal, Quebec, Canada.

Introduction: Haemophilia therapy has evolved from rudimentary transfusion-based approaches to an unprecedented level of innovation with glimmers of functional cure brought by gene therapy. After decades of misfires, gene therapy has normalized factor (F)VIII and factor (F)IX levels in some individuals in the long term. Several clinical programmes testing adeno-associated viral (AAV) vector gene therapy are approaching completion with imminent regulatory approvals. Read More

Haemophilia 2022 May;28 Suppl 4:93-102

Division of Haematology, Haemostasis and Thrombosis Unit, Saint-Luc University Hospital, Université catholique de Louvain (UCLouvain), Brussels, Belgium.

New treatment possibilities and modalities are now available globally for patients with haemophilia requiring surgery or invasive procedures. The first is the appropriate application of low-dose protocols of clotting factor concentrates (CFC) achieving adequate perioperative haemostasis in resources constraint environments. The increasing availability of CFC through humanitarian aid programs allows more invasive surgeries to be performed for which efficacy and safety data should be more widely collected and reported. Read More

Haemophilia 2022 May;28 Suppl 4:77-92

Indiana Hemophilia & Thrombosis Center, Inc., Indianapolis, Indiana, USA.

Introduction: Recent technological innovations in haemophilia have advanced at an astounding pace, including gene therapy programmes and bioengineered molecules for prophylaxis, products that reduce treatment burden through half-life extension, unique mechanisms of action, and subcutaneous administration. Additional technological advancements have emerged that are anticipated to further transform haemophilia care.

Aim: Review new and emerging haemophilia therapies, including replacement and bypassing products, digital applications, utilisation of big data, and personalised medicine. Read More

Haemophilia 2022 May;28 Suppl 4:111-118

Aflac Cancer and Blood Disorders Center of Children's Healthcare of Atlanta and Department of Pediatrics, Emory University, Atlanta, Georgia, USA.

Factor (F) VIII inhibitors develop in around 30% of previously untreated patients (PUPs) with severe haemophilia, to a lesser extend in moderate and mild haemophilia A and in up to 10% in severe haemophilia B. Diagnostic challenges and questions remain including access to high quality testing, the role for functional inhibitor testing and binding antibody testing, and the adaptations needed in the presence of non-factor replacement therapy. Despite significant gains in knowledge there are still many unanswered questions underlying the immunologic mechanisms of inhibitor development and tolerance. Read More

Haemophilia 2022 May;28 Suppl 4:68-76

Surgical Research Laboratory and Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

Acquired bleeding disorders can accompany hematological, neoplastic, autoimmune, cardiovascular or liver diseases, but can sometimes also arise spontaneously. They can manifest as single factor deficiencies or as complex hemostatic abnormalities. This review addresses (a) acquired hemophilia A, an autoimmune disorder characterized by inhibitory autoantibodies against coagulation factor VIII; (b) acquired von Willebrand syndrome in patients with cardiovascular disorders, where shear stress abnormalities result in destruction of von Willebrand factor; and (c) liver function disorders that comprise complex changes in pro- and anti-hemostatic factors, whose clinical implications are often difficult to predict. Read More

Haemophilia 2022 May;28 Suppl 4:5-10

Laboratory for Hemostasis, Inflammation & Thrombosis, Unité Mixed de Recherche (UMR)-1176, Institut National de la Santé et de la Recherche Médicale (Inserm), Université Paris-Saclay, Le Kremlin-Bicêtre, France.

Deficiency or dysfunction of von Willebrand factor (VWF) is associated with a bleeding disorder known as von Willebrand disease (VWD). The clinical manifestations of VWD are heterogeneous, and are in part dictated by the structural or functional defects of VWF. The tools to control bleeding in VWD are dominated by VWF concentrates, desmopressin and antifibrinolytic therapy. Read More

Haemophilia 2022 May;28 Suppl 4:44-52

Katharine Dormandy Haemophilia and Thrombosis Centre, Royal Free Hospital, London, UK.

The first wave of gene therapies for haemophilia submitted for regulatory review utilize a liver-directed approach in which a functional gene copy of factor VIII (FVIII) or factor IX (FIX) is packaged inside a recombinant adeno-associated viral vector (rAAV). Following a single treatment event, these particles are taken up into liver cells, where the rAAV uncoats and delivers the DNA to the nucleus of the cell, where genetic elements that accompany the gene allow for efficient expression and secretion of FVIII or FIX protein into the plasma. An immune response to the vector capsid has been manifest by elevations in common liver enzymes that must be diligently followed postinfusion for weeks and months afterward and if signs of toxicity appear, will trigger a course of immunosuppression. Read More