Review
Hematology
Hannah Fassel, Catherine McGuinn
Summary: Haemophilia is an inherited bleeding disorder caused by deficiency of coagulation factor VIII or IX. Traditional treatments involve replacing the missing factors, but face challenges due to short half-life and inhibitor development. Recent advances, such as factor concentrate half-life extension and gene therapy, offer new hope for improved quality of life and potential cure for haemophilia.
BRITISH JOURNAL OF HAEMATOLOGY
(2021)
Article
Hematology
Alessio Branchini, Massimo Morfini, Barbara Lunghi, Donata Belvini, Paolo Radossi, Loredana Bury, Maria Luisa Serino, Paola Giordano, Dorina Cultrera, Angelo Claudio Molinari, Mariasanta Napolitano, Elisabetta Bigagli, Giancarlo Castaman, Mirko Pinotti, Francesco Bernardi
Summary: Circulating dysfunctional factor IX (FIX) can affect the distribution of infused FIX in hemophilia B (HB) patients, with recurrent substitutions at FIX activation sites associated with variable FIX activity and antigen levels. The study investigated the expression of missense mutations at FIX activation sites and the contribution of F9 genotypes on FIX pharmacokinetics in HB patients, finding that specific features of the dysfunctional R191/R226 variants may have pleiotropic effects on HB patients' phenotypes and substitutive treatment.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Hematology
Xueqing Dou, Wenhui Zhang, Man-Chiu Poon, Xinsheng Zhang, Runhui Wu, Xiaoqin Feng, Linhua Yang, Peng Cheng, Shu Chen, Ying Wang, Hu Zhou, Meijuan Huang, Yanping Song, Chenghao Jin, Donglei Zhang, Lingling Chen, Wei Liu, Lei Zhang, Feng Xue, Renchi Yang
Summary: This study investigates the risk factors and management experience of factor FIX inhibitors in Chinese patients with hemophilia B. The researchers found that large deletions in the F9 gene were significantly associated with inhibitor development. Additionally, low-dose immune tolerance induction therapy may be a feasible approach for eradicating FIX inhibitors.
Article
Hematology
Amy Dericquebourg, Mathilde Fretigny, Nicolas Chatron, Brigitte Tardy, Christophe Zawadzki, Herve Chambost, Christine Vinciguerra, Yohann Jourdy
Summary: This study aimed to characterize deep intronic variants in hemophilia B patients for whom genetic investigations failed. Whole F9 sequencing was performed in 17 genetically unsolved hemophilia B patients. A total of 9 candidate variants were identified and their pathogenic impact was studied. Five variants were classified as likely pathogenic and four variants remained of unknown significance. The study successfully identified the hemophilia B-causing variant in 76% of the families included.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Hematology
Connie H. Miller, J. Michael Soucie, Vanessa R. Byams, Amanda B. Payne, Robert F. Sidonio, Tyler W. Buckner, Christopher J. Bean
Summary: Characterization of females with haemophilia receiving care at HTCs in the United States showed differences from males in severity, age, and infection history.
Review
Hematology
Connie H. Miller, Christopher J. Bean
Summary: In cases of hemophilia, women and girls may have genetic causes leading to the condition, with 16% of mild hemophilia A patients being female.
Article
Hematology
Upendra K. Katneni, Aikaterini Alexaki, Ryan C. Hunt, Nobuko Hamasaki-Katagiri, Gaya K. Hettiarachchi, Jacob M. Kames, Joseph R. McGill, David D. Holcomb, John C. Athey, Brian Lin, Leonid A. Parunov, Tal Kafri, Qi Lu, Robert Peters, Mikhail V. Ovanesov, Daron I. Freedberg, Haim Bar, Anton A. Komar, Zuben E. Sauna, Chava Kimchi-Sarfaty
Summary: In this study, we evaluated the effects of gene recoding on F9 protein and found that it can alter protein conformation, translation kinetics, and immunogenicity. Moreover, posttranslational modifications were also influenced by gene recoding. These findings have general applicability and implications for other gene-recoded recombinant proteins.
Article
Pharmacology & Pharmacy
Sjoerd F. Koopman, Tine M. H. J. Goedhart, Laura H. Bukkems, Trevor M. Mulders, Frank W. G. Leebeek, Karin Fijnvandraat, Michiel Coppens, Mary Mathias, Peter W. Collins, R. Campbell Tait, Catherine N. Bagot, Nicola Curry, Jeanette Payne, Pratima Chowdary, Marjon H. Cnossen, Ron A. A. Mathot
Summary: This study evaluated the predictive performance of a population pharmacokinetic (PK) model for a recombinant factor IX Fc fusion protein (rFIX-Fc) and developed a new model using real-world data. The published model significantly underpredicted FIX activity levels, while the new model better described rFIX-Fc PK, especially for children aged <12 years.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2023)
Article
Hematology
Kristina Kihlberg, Fariba Baghaei, Maria Bruzelius, Eva Funding, Pal Andre Holme, Riitta Lassila, Myriam Martin, Vuokko Nummi, Susanna Ranta, Karin Strandberg, Nadine Gretenkort Andersson, Erik Berntorp, Jan Astermark
Summary: This study investigated the presence of neutralizing and non-neutralizing antibodies in severe hemophilia B patients and evaluated the outcome of immune tolerance induction (ITI) and complications in relation to the F9 variant. The study found a high proportion of F9 gene defects in severe hemophilia B patients in the Nordic countries, which may explain the relatively high prevalence of inhibitors. ITI success was independent of the F9 variant and could be achieved despite allergic manifestations and previous ITI failures. No non-neutralizing antibodies were observed.
THROMBOSIS RESEARCH
(2022)
Article
Medicine, General & Internal
Ki-Young Yoo, Soo-Young Jung, Jin-Young Choi, Hye-Ryeon Park, Young-Shil Park
Summary: This study investigated the validity of FVIII:C/VWF:Ag ratio and FVIII:C analyses as screening tests for haemophilia A carriers. The results showed that the FVIII:C/VWF:Ag ratio had high specificity but may also induce false-negative results.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Multidisciplinary Sciences
Romy M. W. de Laat-Kremers, Marisa Ninivaggi, Iris van Moort, Moniek de Maat, Bas de Laat
Summary: Factor (F) VIII deficiency in haemophilia A patients leads to reduced thrombin generation and a severe imbalance between procoagulant and anticoagulant processes, increasing the risk of bleeding. Targeting the anticoagulant pathway, such as with thrombin inhibitor antithrombin (AT), could restore the haemostatic balance, but individual variations in response to AT reduction suggest a need for personalized treatment. In silico simulations showed that lowering AT levels dose-dependently restored thrombin generation, indicating the potential future use of modeling thrombin dynamics in managing patients undergoing AT targeting therapy.
SCIENTIFIC REPORTS
(2021)
Article
Medicine, Research & Experimental
Eva Funding, Gillian Lowe, Lone H. Poulsen, Susan Shapiro, Johannes Oldenburg, Daniel Eriksson, Aletta Falk, Carly Rich
Summary: This study evaluated the effectiveness of budesonide in relieving symptoms, improving quality of life, and reducing the number of acute attacks in patients with asthma. The results showed significant improvements in symptoms, quality of life, and the number of acute attacks in patients using budesonide.
ADVANCES IN THERAPY
(2023)
Article
Hematology
Johnny Mahlangu, Howard Levy, Martin Lee, Frank Del Greco
Summary: The study demonstrated that subcutaneous dalcinonacog alfa is effective in raising FIX levels into the mild haemophilia range, comparable to intravenous extended half-life FIX clotting factors. Thrombogenicity markers remained normal throughout prophylactic injections or showed some initial increases followed by decreases with continued dosing. Overall, the treatment was well tolerated with a manageable safety profile.
Article
Hematology
Kristina Kihlberg, Fariba Baghaei, Maria Bruzelius, Eva Funding, Pal Andre Holme, Riitta Lassila, Vuokko Nummi, Susanna Ranta, Mehdi Osooli, Erik Berntorp, Jan Astermark
Summary: The Nordic cohort of persons with severe haemophilia B is well treated by prophylaxis, but the goal of zero bleeds for all is not yet achieved. The findings suggest that patients with severe haemophilia B experience milder arthropathy compared to patients with severe haemophilia A.
Article
Hematology
John Puetz, Dunlei Cheng
Summary: The study analyzed 922 haemophilia carriers in the ATHNdataset and found that 74% of carriers reported a normal bleeding score. Logistic regression identified age, factor activity level, ethnicity, and region of residence as risk factors for an abnormal score.
Letter
Hematology
Catherine Hildyard, Jessica Palmer, Sarah Alhulail, George Zumbadze, David Keeling
BRITISH JOURNAL OF HAEMATOLOGY
(2016)
Review
Hematology
David Keeling, Frederikus A. Klok, Gregoire Le Gal
Letter
Hematology
Susan Shapiro, Neha Bhatnagar, Asif Khan, James Beavis, David Keeling
BRITISH JOURNAL OF HAEMATOLOGY
(2018)
Letter
Hematology
P. M. Baker, D. M. Keeling
INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY
(2017)
Letter
Hematology
L. F. D. van Vulpen, D. Keeling, M. Makris
Letter
Hematology
John Willan, David Keeling
BRITISH JOURNAL OF HAEMATOLOGY
(2019)
Article
Hematology
H. C. A. M. Hazendonk, T. Preijers, R. Liesner, P. Chowdary, D. Hart, D. Keeling, M. H. E. Driessens, B. A. P. Laros-van Gorkom, F. J. M. van der Meer, K. Meijer, K. Fijnvandraat, F. W. G. Leebeek, R. A. A. Mathot, P. W. Collins, M. H. Cnossen
Article
Hematology
M. J. . R. Desborough, C. A. T. Hildyard, S. J. Stanworth
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2018)
Article
Hematology
T. Preijers, H. C. A. M. Hazendonk, R. Liesner, P. Chowdary, M. H. E. Driessens, D. Hart, D. Keeling, B. A. P. Laros-van Gorkom, F. J. M. van der Meer, K. Meijer, K. Fijnvandraat, F. W. G. Leebeek, P. W. Collins, M. H. Cnossen, R. A. A. Mathot
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2018)
Article
Hematology
John Willan, Harley Katz, David Keeling
BRITISH JOURNAL OF HAEMATOLOGY
(2019)
Article
Hematology
Alexander P. Bye, Amanda J. Unsworth, Michael J. Desborough, Catherine A. T. Hildyard, Niamh Appleby, David Bruce, Neline Kriek, Sophie H. Nock, Tanya Sage, Craig E. Hughes, Jonathan M. Gibbins
Editorial Material
Hematology
Noemi B. A. Roy, Nicola Curry, David Keeling
BRITISH JOURNAL OF HAEMATOLOGY
(2017)
Review
Hematology
Michael J. R. Desborough, David M. Keeling
BRITISH JOURNAL OF HAEMATOLOGY
(2017)
Article
Hematology
C. A. T. Hildyard, S. Shiekh, J. A. B. Browning, G. P. Collins
CLINICAL MEDICINE INSIGHTS-BLOOD DISORDERS
(2017)
