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Am J Transplant 2020 Jun 3. Epub 2020 Jun 3.

General, Visceral and Transplant Surgery, Dept. of Surgery, Medical University of Graz.

Immunosuppression and frequent comorbidities in transplant recipients potentially increase the risk of fatal outcomes of pandemic coronavirus disease 2019 (COVID-19) [1]. A 1965 born male had suffered from haemophilia A. In the nineteen-seventies, he acquired hepatitis C virus (HCV) infection, probably via factor VIII supplementation, and in 1985 human immunodeficiency virus (HIV) infection. Read More

Blood Adv 2020 Jun;4(11):2451-2459

Hemophilia and Thrombosis Center, University of Colorado Anschutz Medical Campus, Aurora, CO.

The Joint Outcome Study (JOS), a randomized controlled trial, demonstrated that children with severe hemophilia A (HA) initiating prophylactic factor VIII (FVIII) prior to age 2.5 years had reduced joint damage at age 6 years compared with those treated with episodic FVIII for bleeding. The Joint Outcome Continuation Study (JOS-C) evaluated early vs delayed prophylaxis effects on long-term joint health, following JOS participants to age 18 years in an observational, partially retrospective study. Read More

Haemophilia 2020 Jun 3. Epub 2020 Jun 3.

Pediatrics and Pathology, University of Michigan, Ann Arbor, Michigan, USA.

The promise of gene therapy is a single treatment ('one and done') that leads to steady-state expression of endogenous factor VIII or factor IX sufficient to achieve a functional cure (free of recurrent haemophilic bleeding) if not normalized haemostasis. The elimination of the need for continued prophylaxis, or factor replacement following trauma or prior to surgery would lead to annual cost savings. Such optimized health and well-being would be reaching a level of health equity that was unimaginable several decades ago. Read More

Haemophilia 2020 Jun 2. Epub 2020 Jun 2.

World Federation of Hemophilia, Montreal, QC, Canada.

Haemophilia is at the dawn of a new era in therapeutic management, one that can generate greater protection from bleeding and a functional cure in some individuals. Prior advances in protein engineering and monoclonal antibody technology have facilitated therapeutic options to maintain decreased risk of bleeding and less burdensome treatment. The use of gene transfer, first proposed in 1971 for monogenic diseases, is emerging as an effective long-term treatment for a variety of diseases. Read More

Thromb Haemost 2020 Jun 1. 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 14;11:810. Epub 2020 May 14.

Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université de Paris, Paris, France.

In humans, maternal IgGs are transferred to the fetus from the second trimester of pregnancy onwards. The transplacental delivery of maternal IgG is mediated by its binding to the neonatal Fc receptor (FcRn) after endocytosis by the syncytiotrophoblast. IgGs present in the maternal milk are also transferred to the newborn through the digestive epithelium upon binding to the FcRn. Read More

Haemophilia 2020 Jun 1. Epub 2020 Jun 1.

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

Clin Transl Sci 2020 May 30. Epub 2020 May 30.

Hematology and Transfusion Medicine, Paul-Ehrlich-Institut, Federal Institute for Vaccines and Biomedicines, Langen, Germany.

Emerging treatment options for hemophilia, including gene therapy, modified factor products, antibody-based products, and other nonreplacement therapies, are in development or on their way to marketing authorization. For proof of efficacy, annual bleeding rates (ABRs) have become an increasingly important endpoint in hemophilia trials. We hypothesized that ABR analyses differ substantially between and within medicinal product classes and that the ABR observation period constitutes a major bias. Read More

PLoS One 2020 29;15(5):e0233866. Epub 2020 May 29.

Department of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, California, United States of America.

Several candidate HIV subunit vaccines based on recombinant envelope (Env) glycoproteins have been advanced into human clinical trials. To facilitate biopharmaceutical production, it is necessary to produce these in CHO (Chinese Hamster Ovary) cells, the cellular substrate used for the manufacturing of most recombinant protein therapeutics. However, previous studies have shown that when recombinant Env proteins from clade B viruses, the major subtype represented in North America, Europe, and other parts of the world, are expressed in CHO cells, they are proteolyzed and lack important glycan-dependent epitopes present on virions. Read More

Haemophilia 2020 May 29. Epub 2020 May 29.

A. Bianchi Bonomi Hemophilia and Thrombosis Center, Maggiore Hospital Policlinico, Foundation IRCCS Ca'Granda, Milan, Italy.

The performance of surgery and invasive procedures in patients with haemophilia is currently facing new challenges globally. The first is the appropriate application of low-dose protocols of clotting factor concentrates (CFC) achieving adequate perioperative haemostasis in resource constraint environments. The increasing availability of CFC through humanitarian aid programmes allows more invasive surgeries to be performed for which efficacy and safety data should be more widely collected and reported. Read More

Haemophilia 2020 May 29. Epub 2020 May 29.

Colorado Coagulation, Laboratory Corporation of America® Holdings, Englewood, CO, USA.

The treatment options for the haemostatic disorders, haemophilia A and haemophilia B, have progressed rapidly over the last decade. The introduction of extended half-life recombinant factor VIII (FVIII) and factor IX (FIX) concentrates to replace these missing clotting factors highlighted discordance between one-stage activated partial thromboplastin time (APTT)-based clotting factor assays and chromogenic factor assays with some products. This raised awareness of the importance of investigation of potential reagent or assay differences by pharmaceutical companies. Read More

Blood Coagul Fibrinolysis 2020 May 27. Epub 2020 May 27.

Baxalta Innovations GmbH, Vienna, Austria.

: Accurate monitoring of coagulation, needed for optimal management of patients with haemophilia A with inhibitors, presents a challenge for treating physicians. Although global haemostatic assays may be used in this population, their utility with nonfactor therapies has yet to be established in the clinical setting. The aim of this study was to assess options for potential haemostatic activity monitoring and feasibility for factor VIII (FVIII)-equivalency measurement with a sequence identical analogue (SIA) to emicizumab using different coagulation assays. Read More

Haematologica 2020 May 28. Epub 2020 May 28.

Department of Health Sciences, Università del Piemonte Orientale, Novara, Italy;

A major challenge in the development of a gene therapy for hemophilia A (HA) is the selection of cell type- or tissue-specific promoters to ensure factor VIII (FVIII) expression without eliciting an immune response. As liver sinusoidal endothelial cells (LSECs) are the major FVIII source, understanding the transcriptional F8 regulation in these cells would help optimize the minimal F8 promoter (pF8) to efficiently drive FVIII expression. In silico analyses predicted several binding sites (BS) for the E26 transformation-specific (Ets) transcription factors Ets-1 and Ets-2 in the pF8. Read More

J Thromb Thrombolysis 2020 May 27. Epub 2020 May 27.

School of Medical Sciences, University of Campinas, Campinas, Brazil.

The role of inflammation in thrombotic complications of primary antiphospholipid syndrome (PAPS) is controversial. The aim of this study was to evaluate levels of inflammation and coagulation markers in patients with thrombotic PAPS (t-PAPS). Patients with t-PAPS and individuals with no history of thrombosis were enrolled. Read More

Swiss Med Wkly 2020 05 26;150:w20293. Epub 2020 May 26.

Department of Medicine, Spital Emmental, Burgdorf, Switzerland.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as a global phenomenon has presented clinicians around the world with multiple challenges. Thromboembolic events are recognised complications of viral infection, but the diagnosis of an acute pulmonary thrombotic complication in the context of coronavirus disease 2019 (COVID-19) can be challenging because of the similarities of presentation, logistical considerations of diagnosis in a patient isolated for infection control reasons and the effects of cognitive errors in diagnostic reasoning. We present the case of a patient who was diagnosed with a pulmonary thrombotic complication during inpatient care for COVID-19. Read More

Acta Clin Belg 2020 May 27:1-3. Epub 2020 May 27.

Department of Hematology, Hôpital Erasme, Université Libre De Bruxelles , Brussels, Belgium.

This case report illustrates the difficulty associated with diagnosing acquired hemophilia A by reviewing the case of an 80-year-old man admitted to the hospital for anemia. A prolonged activated partial thromboplastin time (aPTT) was not noticed until the patient developed a severe hemorrhagic syndrome. Read More

Clin J Gastroenterol 2020 May 26. Epub 2020 May 26.

Department of Biochemistry, Jichi Medical University, Shimotsuke, Tochigi, Japan.

Percutaneous radiofrequency ablation (RFA) is a good indication for hepatocellular carcinoma (HCC) in cases involving ≦ 3 tumors of ≦ 30 mm in size, many hepatologists are hesitant to perform the procedure for patients with hemorrhagic disorders. We herein report the successful treatment of HCC by laparoscopic RFA in a patient with hemophilia A. A 48-year-old man with moderate form of hemophilia A had a single HCC at segment 8. Read More

Blood 2020 May 26. Epub 2020 May 26.

University of Michigan Medical Center, Ann Arbor, Michigan, United States.

Deep vein thrombosis and pulmonary embolism, collectively defined as venous thromboembolism (VTE), are the third leading cause of cardiovascular death in the United States. Common genetic variants conferring increased varying degrees of VTE risk have been identified by genome-wide association studies (GWAS). Rare mutations in the anticoagulant genes PROC, PROS1 and SERPINC1 result in perinatal lethal thrombosis in homozygotes and markedly increased VTE risk in heterozygotes. 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

Blood Adv 2020 May;4(10):2272-2285

Department of Medicine, Veterans Affairs Boston Healthcare System and Harvard Medical School, Boston, MA.

Factor VIII (FVIII) replacement therapy for hemophilia A is complicated by development of inhibitory antibodies (inhibitors) in ∼30% of patients. Because endothelial cells (ECs) are the primary physiologic expression site, we probed the therapeutic potential of genetically restoring FVIII expression selectively in ECs in hemophilia A mice (FVIIInull). Expression of FVIII was driven by the Tie2 promoter in the context of lentivirus (LV)-mediated in situ transduction (T2F8LV) or embryonic stem cell-mediated transgenesis (T2F8Tg). Read More

Andrologia 2020 May 26:e13670. Epub 2020 May 26.

Department of Anatomy, Faculty of Medicine, Yozgat Bozok Üniversity, Yozgat, Turkey.

In this study, we aimed to evaluate the effect of carob extract against intratesticular histological, apoptotic, biochemical and spermatogenic changes in rats exposed to nicotine. Twenty-eight rats were divided into four groups and were administered saline, nicotine, carob, or nicotine + carob once a day for 35 days. Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX), GSH, total anti-oxidative status (TAS), total oxidative status (TOS), oxidative stress index (OSI), IL-6, TNF-α and seminal parameters were evaluated. Read More

JAAPA 2020 Jun;33(6):24-26

At the University of Colorado School of Medicine in Aurora, Colo., Zachary P. Asher practices in the Department of Surgery, Tyler W. Buckner practices in the Department of Medicine, and Robert C. McIntyre, Jr., practices in the Department of Surgery. The authors have disclosed no potential conflicts of interest, financial or otherwise.

Acquired hemophilia A in postoperative patients can cause major bleeding and an accurate diagnosis is required for effective treatment. Standard treatment is costly, difficult to obtain, and takes 4 to 6 weeks to be effective. This article describes a patient successfully treated with recombinant factor VIIa, porcine factor VIII, plasmapheresis, rituximab, and high-dose corticosteroids. Read More

J Manag Care Spec Pharm 2020 May 26:1-12. Epub 2020 May 26.

CHOC Children's Hospital, Orange, California.

Background: Hemophilia A (HA) can result in bleeding events because of low or absent clotting factor VIII (FVIII). Prophylactic treatment for severe HA includes replacement FVIII infusions and emicizumab, a bispecific factor IXa- and factor X-directed antibody.

Objective: To develop an economic model to predict the short- and long-term clinical and economic outcomes of prophylaxis with emicizumab versus short-acting recombinant FVIII among persons with HA in the United States. Read More

Thromb Res 2020 May 11;192:52-60. Epub 2020 May 11.

Unité d'Hémostase Clinique, Hôpital Cardiologique Louis Pradel, Université Lyon 1, Lyon, France.

Replacement therapy with concentrates of factor VIII or IX remains the gold standard for severe haemophilia management. The recent development of clotting factor products with extended half-life, widely available on the market since 2 years, facilitates adherence, improves considerably the patients' quality of life, and simplifies the management of breakthrough bleedings or surgery. These molecules have also brought to the limelight the concepts of optimization and personalization of anti-haemophilic prophylaxis. Read More

J Thromb Haemost 2020 May 23. Epub 2020 May 23.

Hemophilia Treatment Centre, University Hospital of Caen, Caen, France.

Background: A triple-secured plasma-derived von Willebrand factor (pdVWF) almost devoid of FVIII (WILFACTIN®) was approved in France in 2003, and then in other countries for the treatment of patients with von Willebrand disease (VWD).

Objective: To investigate long-term safety and efficacy of the product in real-life over the first 5 post-approval years.

Patients/methods: This prospective, observational, national post-marketing study (PMS) enrolled patients of all ages and VWD types. Read More

Haemophilia 2020 May 23. Epub 2020 May 23.

Pediatric Department, Sheikh Zayed hospital, Cairo, Egypt.

Background: Subclinical synovitis occur long before clinical haemophilic arthropathy (HA). New biomarkers are needed for early detection of HA.

Aim: To compare the levels of tissue inhibitors of metalloproteinase-1 (TIMP-1) and vascular endothelial growth factor (VEGF)in severe haemophilia A boys on prophylaxis and on-demand therapy to healthy boys and correlate them with the haemophilia joint health score (HJHS) & the Denver magnetic resonance imaging (MRI) scale; hence, determine their values in early detection of HA. Read More

PLoS One 2020 22;15(5):e0233576. Epub 2020 May 22.

Sol Sherry Thrombosis Research Center, Temple University, Philadelphia, PA, United States of America.

Human coagulation factor VIII (FVIII) is a key co-factor in the clotting cascade, the deficiency of which leads to Hemophilia A. Human plasma-derived (pdFVIII) and recombinant FVIII (rFVIII) had been used as effective products to prevent and treat bleeding episodes. Both FVIII products share identical amino acid sequences and appear to be equivalent as of clinical efficiency. Read More

Blood 2020 May;135(21):1825-1827

The Children's Hospital of Philadelphia; University of Pennsylvania.

Haemophilia 2020 May 20. Epub 2020 May 20.

State Key Laboratory of Experimental Hematology, Tianjin Laboratory of Blood Disease Gene Therapy, CAMS Key Laboratory of Gene Therapy for Blood Diseases, National Clinical Research Center for Hematological Disorders, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.

Introduction: The management of haemophilia is critical to minimize the risk of disability and reduce the burden on China's healthcare system.

Aim: This study was based on a single centre in China and was conducted to understand the evolution of real-world haemophilia care over the past 15 years.

Methods: We retrospectively analysed clinical characteristics, diagnosis, treatment and medical expenditures of 428 patients with haemophilia from January 2004 to December 2018 from the Institute of Hematology & Blood Diseases Hospital in Tianjin, China. Read More

Front Immunol 2020 28;11:618. Epub 2020 Apr 28.

The Children's Hospital of Philadelphia, Philadelphia, PA, United States.

Hemophilia A (HA) is an X-linked bleeding disorder due to deficiencies in coagulation factor VIII (FVIII). The major complication of current protein-based therapies is the development of neutralizing anti-FVIII antibodies, termed inhibitors, that block the hemostatic effect of therapeutic FVIII. Inhibitors develop in about 20-30% of people with severe HA, but the risk is dependent on the interaction between environmental and genetic factors, including the underlying gene mutation. Read More

Indian J Hematol Blood Transfus 2020 Apr 18;36(2):374-376. Epub 2019 Sep 18.

2Department of Hemato-Oncology, Amrita Institute of Medical Sciences, Amrita Vishwa Vidyapeetham, Kochi, India.

To address the scarcity of real world data on adult prophylaxis from developing world, a short term intermediate dose prophylaxis in adult haemophilia A patients was initiated. A total of eight patients aged > 18 years with moderate/severe haemophilia A were given an average dose of 23 IU/kg recombinant factor VIII (rFVIII) concentrate twice weekly for 2 months. A clinical audit was done on completion of four months. Read More

Haemophilia 2020 May 18. Epub 2020 May 18.

Quest Diagnostics, Secaucus, NJ, USA.

Introduction: The time-dependent nature of factor VIII (FVIII) inhibitors is well described, and the standard FVIII Bethesda assay used to measure inhibitors incorporates a 2-hour incubation. Despite case reports and reviews describing the immediate-acting nature of factor IX (FIX) inhibitors, many coagulation laboratories continue to use a traditional prolonged incubation for FIX Bethesda assays. To our knowledge, a comprehensive evaluation of the FIX Bethesda assay without incubation has not been reported. Read More

Am J Hematol 2020 May 17. Epub 2020 May 17.

The Ohio State University College of Medicine.

Increased awareness of von Willebrand Disease (VWD) has led to more frequent diagnostic laboratory testing, which insurers often dictate be performed at a facility with off-site laboratory processing instead of a coagulation facility with onsite processing. Off-site processing is more prone to preanalytical variables causing falsely low levels of von Willebrand Factor (VWF) due to the additional transport required. Our aim was to determine the percentage of discordance between off-site and onsite specimen processing for VWD in this multicenter, retrospective study. Read More

Front Immunol 2020 28;11:638. Epub 2020 Apr 28.

Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, WA, United States.

Hemophilia A is a genetic disorder that results in the deficiency of functional factor VIII protein, which plays a key role in blood coagulation. Currently, the majority of hemophilia A patients are treated with repeated infusions of factor VIII protein. Approximately 30% of severe hemophilia A patients develop neutralizing antibodies to factor VIII (known as factor VIII inhibitors) due to treatment, rendering factor VIII protein infusions ineffective. Read More

Blood Adv 2020 May;4(9):2111-2118

Hémostase Inflammation Thrombose, INSERM, Unité Mixte de Recherche Scientifique 1176, Université Paris-Saclay, Le Kremlin-Bicêtre, France.

Monitoring factor VIII (FVIII) activity has traditionally been complicated by discrepancies between assays for the various sorts of FVIII molecules. The advent of novel nonfactor therapies (emicizumab, fitusiran, and anti-tissue factor pathway inhibitor antibodies) in hemophilia A poses a new level of difficulty on the laboratory monitoring of these patients. To use the correct assays and for a proper interpretation of their results, it is pertinent to understand the mode of action of these nonfactor agents. Read More

Cochrane Database Syst Rev 2020 May 12;5:CD013238. Epub 2020 May 12.

Department of Medical Oncology, Royal North Shore Hospital, Sydney, Australia.

Background: Glioblastoma is an uncommon but highly aggressive type of brain tumour. Significant gains have been achieved in the molecular understanding and the pathogenesis of glioblastomas, however clinical improvements are difficult to obtain for many reasons. The current standard of care involves maximal safe surgical resection followed by chemoradiation and then adjuvant chemotherapy European Organisation for Research and Treatment of Cancer and the NCIC Clinical Trials Group (EORTC-NCIC) protocol with a median survival of 14. Read More

Am Surg 2020 Apr;86(4):e191-e193

Pediatr Radiol 2020 May 11. 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

J Stroke Cerebrovasc Dis 2020 May 8:104859. Epub 2020 May 8.

Department of Neurology, Inha University School of Medicine, 27 Inhang-ro, Jung-gu, Incheon 22332, Republic of Korea. Electronic address:

No previous study has reported endovascular treatment (EVT) in a patient with hemophilia who had an acute ischemic stroke (AIS). Herein, we report the case of a patient with hemophilia A who presented with hyperacute stroke due to a near occlusion of the proximal internal carotid artery (ICA). A 54-year-old man was admitted to our emergency department with a sudden onset of left-sided weakness that occurred 4 hours prior to admission. Read More

Diagn Pathol 2020 May 9;15(1):48. Epub 2020 May 9.

Department of Diagnostic Pathology, Kyoto University Hospital, 54 Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.

Background: Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare disorder of pulmonary vascular abnormality with persistent pulmonary hypertension of the newborn. The symptom usually presents within hours after birth, leading to an early demise. Heterozygous de novo point mutations and genomic deletions of the FOXF1 (forkhead box F1) gene or its upstream enhancer have been identified in most patients with ACD/MPV. Read More

Thromb Haemost 2020 Jun 8;120(6):968-976. Epub 2020 May 8.

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

Background:  Emicizumab prophylaxis is a promising treatment that reduces bleeding events in severely affected patients with hemophilia A (PwHA). It is anticipated that emicizumab could be similarly effective in mild/moderate PwHA (PwMHA) although this effect has not been investigated.

Aim:  We evaluated coagulant effects of emicizumabin PwMHA. Read More

Haematologica 2020 May 7. Epub 2020 May 7.

Green Templeton College, University of Oxford, Oxford, UK.

Acquired hemophilia A (AHA), a rare bleeding disorder caused by neutralizing autoantibodies against coagulation factor VIII (FVIII), occurs in both men and women without a previous history of bleeding. Patients typically present with an isolated prolonged activated partial thromboplastin time (APTT) due to FVIII deficiency. Neutralizing antibodies (inhibitors) are detected using the Nijmegen-modified Bethesda assay. Read More

J Thromb Haemost 2020 May 7. Epub 2020 May 7.

Grifols, Discovery Research Group, Raleigh, North Carolina, USA.

Background: Emicizumab is an alternative non-factor approach for treating patients with hemophilia A. However, there is a potential risk of thrombotic events when emicizumab is concomitantly administered with pro-hemostatic therapies.

Objectives: To assess the hemostatic effect in vitro when a plasma-derived factor VIII concentrate containing von Willebrand factor (pdFVIII/VWF) was added to hemophilia A plasma (HAp) in combination with emicizumab. Read More

J Thromb Haemost 2020 May 7. Epub 2020 May 7.

Hematology and Transfusion Medicine, L. Sacco University Hospital, Department of Oncology and Oncohematology, University of Milan, Milano, Italy.

Background: Type 3 von Willebrand's disease (VWD) patients present markedly reduced levels of von Willebrand factor and factor VIII. Because of its rarity, the bleeding phenotype of type 3 VWD is poorly described, as compared to type 1 VWD.

Aims: To evaluate the frequency and the severity of bleeding symptoms across age and sex groups in type 3 patients and to compare these with those observed in type 1 VWD patients; to investigate any possible clustering of bleeding symptoms within type 3 patients. Read More

Am J Case Rep 2020 May 7;21:e922326. Epub 2020 May 7.

Department of Hematology and Oncology, Lehigh Valley Health Network, Allentown, PA, USA.

BACKGROUND Acquired hemophilia A (AHA) is a rare autoimmune disease caused by immunoglobulins that bind and inactive factor VIII, thereby predisposing to life-threatening bleeding. Bleeding is typically stabilized by utilizing bypassing agents, such as recombinant factor VIIa (rVIIa). Select case reports have demonstrated the success of alternative prophylaxis for clearance of factor VIII inhibitors through the use of emicizumab, a current FDA approved medication for treatment of congenital hemophilia A. Read More

Blood Adv 2020 May;4(9):1870-1880

Research and Development, CSL Behring GmbH, Marburg, Germany.

A novel mechanism for extending the circulatory half-life of coagulation factor VIII (FVIII) has been established and evaluated preclinically. The FVIII binding domain of von Willebrand factor (D'D3) fused to human albumin (rD'D3-FP) dose dependently improved pharmacokinetics parameters of coadministered FVIII in all animal species tested, from mouse to cynomolgus monkey, after IV injection. At higher doses, the half-life of recombinant FVIII (rVIII-SingleChain) was calculated to be increased 2. Read More

Thorac Cancer 2020 May 6. Epub 2020 May 6.

Department of Internal Medicine VIII, Medical Oncology and Pneumology, Eberhard Karls University, Tübingen, Germany.

Epithelial growth factor receptor (EGFR) directed tyrosine kinase inhibitor (TKI) treatment is the standard approach in patients with advanced, EGFR-mutated non-small cell lung cancer (NSCLC). Although benefit/risk ratio is favorable for these TKI and side effects are manageable in the vast majority of patients, severe and even life-threatening side effects have been reported. TKI-induced interstitial lung disease (ILD) has been reported for single cases in modest severity, predominantly in EGFR-TKI pretreated patients. Read More

Thromb Haemost 2020 May 5;120(5):747-757. Epub 2020 May 5.

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

Background:  The currently published population pharmacokinetic (PK) models used for PK-guided dosing in hemophilia patients are based on clinical trial data and usually not externally validated in clinical practice. The aim of this study was to validate a published model for recombinant factor VIII-Fc fusion protein (rFVIII-Fc) concentrate and to develop an enriched model using independently collected clinical data if required.

Methods:  Clinical data from hemophilia A patients treated with rFVIII-Fc concentrate (Elocta) participating in the United Kingdom Extended Half-Life Outcomes Registry were collected. Read More