Article
Hematology
Anne-Fleur Zwagemaker, Fabienne R. Kloosterman, Samantha C. Gouw, Sara Boyce, Paul Brons, Marjon H. Cnossen, Peter W. Collins, Jeroen Eikenboom, Charles Hay, Rutger C. C. Hengeveld, Shannon Jackson, Caroline A. M. Klopper-Tol, Marieke J. H. A. Kruip, Britta Laros-van Gorkom, Christoph Male, Laurens Nieuwenhuizen, Susan Shapiro, Karin Fijnvandraat, Michiel Copens
Summary: This study investigated the discrepancy between one-stage and chromogenic assays of coagulation factor activity in moderate and mild hemophilia A and B patients. The results showed that only a small number of patients exhibited a discrepancy between the two assays, and this discrepancy was largely determined by laboratory variables.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2023)
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
Genetics & Heredity
Linna Lu, Lingyu Wang, Wukang Shen, Shuai Fang, Lidong Zhao, Xuchen Hu, Linhua Yang, Gang Wang
Summary: This study identified a novel Met394Thr variant as a causative mutation for Hemophilia B. The variant was found in a Chinese family with moderate Hemophilia B and was shown to affect the spatial conformation of the FIX protein. Further understanding of the molecular pathogenesis of FIX deficiency may offer new insights for precision therapy of Hemophilia B.
MOLECULAR GENETICS & GENOMIC MEDICINE
(2023)
Article
Hematology
Chur Woo You, Seung-Beom Hong, Suyeong Kim, Ho-Jin Shin, Jin Seok Kim, Jung Woo Han, Soo-Jeong Kim, Do Young Kim, Martin Lee, Howard Levy
Summary: Dalcinonacog alfa (DalcA), a recombinant human factor IX variant, was developed for increased procoagulant activity and longer duration of action. The study demonstrated that DalcA achieved protective FIX activity levels between 11% and 18%, reducing the risk of spontaneous bleeds.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2021)
Article
Hematology
Steffi Knoll Machado, Hendrik Peil, Timo Kraushaar, Philipp Claar, Marcel Mischnik, Holger Lind, Eva Herzog, Michael Bacher, Marc Wolfgang Nolte, Maximilian Bielohuby, Sabine Pestel, Padmapriya Ponnuswamy
Summary: This study evaluates the efficacy of extravascular FIX using animal models of tail clip bleeding and ferric chloride-induced thrombosis. The results demonstrate that mutated rFIX protein with enhanced binding (rFIX(K5R)) to extravascular space confers prolonged hemostatic efficacy in vivo, while rFIX(K5A) rapidly loses its efficacy. This finding is important for a better understanding of hemostasis mechanisms.
THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Pharmacology & Pharmacy
T. Preijers, M. W. F. van Spengler, K. Meijer, K. Fijnvandraat, K. Fischer, F. W. G. Leebeek, M. H. Cnossen, R. A. A. Mathot
Summary: The study aims to establish adequate limited sampling strategies (LSSs) for estimating individual pharmacokinetic (PK) parameters of EHL-FIX concentrates using in silico evaluation.
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY
(2022)
Review
Hematology
Mikhail V. Ovanesov, Joseph W. Jackson, Basil Golding, Timothy K. Lee
Summary: This article discusses the factors to consider when choosing an assay for potency assignment and postadministration monitoring of new factor products, including the validity of the assay calibrated with the IS, the meaning of potency values in IU, standards of care for patients, clinical relevance between the assigned potency value and recovery value from clinical laboratories, and patient safety.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2021)
Article
Microbiology
Xiaofeng Dong, Julia Tree, Logan Banadyga, Shihua He, Wenjun Zhu, Tom Tipton, Jade Gouriet, Xiangguo Qiu, Michael J. J. Elmore, Yper Hall, Miles Carroll, Julian A. A. Hiscox
Summary: Ebola virus infection can have severe consequences and result in Ebola virus disease, with varying outcomes of survival or death. The emergence of mutants during the 2013-2016 West African Ebola outbreak has been associated with changes in virulence and different organ responses.
MICROBIOLOGY SPECTRUM
(2023)
Article
Hematology
Neha Iyer, Ayah Al Qaryoute, Meghana Kacham, Pudur Jagadeeswaran
Summary: Gene and protein sequence analysis revealed that zebrafish f9a and f9b are homologous to human F9, while f9l is similar to human F10. Knockdown and immunodepletion of f9a and Fixa prolonged partial thromboplastin time, while knockdown of f9l and Fixl prolonged multiple coagulation tests. Age-dependent increases in expression of these genes were observed, suggesting potential use of zebrafish model for studying factors involved in aging-related gene expression.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2021)
Article
Hematology
David E. Schmidt, Asa Truedsson, Annelie Stralfors, Johanne Andersen Hojbjerg, Nida Soutari, Margareta Holmstrom, Susanna Ranta, Anna Letelier, Annette Bowyer, Rolf Ljung, Jovan Antovic, Maria Bruzelius
Summary: This study found that there is a discrepancy in factor IX activity (FIX:C) between the one-stage assay (OSA) and chromogenic substrate assay (CSA) in moderate and mild hemophilia B (HB) patients. FIX:C measured by CSA was consistently lower than by OSA, leading to misdiagnosis of a more severe hemophilia type in some patients. Therefore, it is suggested to use both OSA and CSA FIX:C together with genotyping to classify HB severity and provide essential information for clinical management.
THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Biochemistry & Molecular Biology
Guomin Shen, Meng Gao, Qing Cao, Weikai Li
Summary: This article systematically summarizes the structural and functional characteristics of FIX and the pathogenic mechanisms of identified mutations in hemophilia B patients. It discusses various mechanisms of FIX deficiency caused by different types of mutations, such as deletions, insertions, duplications, and point mutations, and their effects on bleeding phenotypes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Hematology
Karen Aymonnier, Charlotte Kawecki, Veronique Arocas, Yacine Boulaftali, Marie Christine Bouton
Summary: Hemostasis is a regulated process involving a balance between procoagulant and anticoagulant systems. Hemophilia, a well-known bleeding disorder, is caused by deficiencies in FVIII or FIX and recent studies suggest that targeting natural serpins could rebalance coagulation in hemophilia.
THROMBOSIS AND HAEMOSTASIS
(2021)
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
Biotechnology & Applied Microbiology
Ghada Y. El-Kamah, Rehab M. Mosaad, Mohamed B. Taher, Khalda S. Amr
Summary: This study conducted the first molecular analysis of the F9 gene in HB Egyptian patients, identifying four causative mutations and pinpointing differences in gene loci, which can aid in genetic counseling and prenatal decision-making.
JOURNAL OF GENETIC ENGINEERING AND BIOTECHNOLOGY
(2021)
Review
Hematology
Daniel Kraemmer, Oliver Koenigsbruegge, Florian Moik, Brigitte Wildner, Cihan Ay, Ingrid Pabinger
Summary: This review summarized the current evidence on the efficacy of PK-guided prophylaxis compared to non-PK-guided prophylaxis. The review found insufficient evidence to support the clinical benefit of PK-guided prophylaxis over fixed-dose prophylaxis.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Hematology
Karina Meijer, Waander van Heerde, Keith Gomez
Summary: Rare bleeding disorders have significant morbidity but are often underdiagnosed globally. Advances in genomic testing and specialist laboratory assays have greatly improved the diagnostic capabilities, leading to the discovery of new genetic causes for rare diseases and a better understanding of their underlying molecular pathology.
Editorial Material
Hematology
Keith Gomez, Mike Laffan, Charlotte Bradbury
BRITISH JOURNAL OF HAEMATOLOGY
(2021)
Review
Obstetrics & Gynecology
Deborah Obeng-Tuudah, Brwa A. Hussein, Amir Hakim, Keith Gomez, Rezan Abdul Kadir
Summary: Hermansky-Pudlak syndrome (HPS) is a rare autosomal-recessive disorder characterized by bleeding diathesis and oculocutaneous albinism in women. Management strategies for women with HPS include desmopressin and platelet transfusions, with close collaboration between obstetrics and gynecology and hematology teams recommended. Heavy menstrual bleeding and post-partum hemorrhage may lead to diagnosis of HPS in affected women.
INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS
(2021)
Article
Hematology
Karyn Megy, Kate Downes, Marie-Christine Morel-Kopp, Jose M. Bastida, Shannon Brooks, Loredana Bury, Eva Leinoe, Keith Gomez, Neil V. Morgan, Maha Othman, Willem H. Ouwehand, Juliana Perez Botero, Jose Rivera, Harald Schulze, David-Alexandre Tregouet, Kathleen Freson
Summary: The implementation of high-throughput sequencing technologies has identified many new genes related to rare bleeding, thrombotic, and platelet disorders, but the lack of well-curated databases and submission processes hampers further research progress in understanding these disorders.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2021)
Article
Medicine, General & Internal
Lise J. Estcourt, Alexis F. Turgeon, Zoe K. McQuilten, Bryan J. McVerry, Farah Al-Beidh, Djillali Annane, Yaseen M. Arabi, Donald M. Arnold, Abigail Beane, Philippe Begin, Wilma van Bentum-Puijk, Lindsay R. Berry, Zahra Bhimani, Janet E. Birchall, Marc J. M. Bonten, Charlotte A. Bradbury, Frank M. Brunkhorst, Meredith Buxton, Jeannie L. Callum, Michael Chasse, Allen C. Cheng, Matthew E. Cove, James Daly, Lennie Derde, Michelle A. Detry, Menno De Jong, Amy Evans, Dean A. Fergusson, Matthew Fish, Mark Fitzgerald, Claire Foley, Herman Goossens, Anthony C. Gordon, Iain B. Gosbell, Cameron Green, Rashan Haniffa, Heli Harvala, Alisa M. Higgins, Thomas E. Hills, Veronica C. Hoad, Christopher Horvat, David T. Huang, Cara L. Hudson, Nao Ichihara, Emma Laing, Abigail A. Lamikanra, Francois Lamontagne, Patrick R. Lawler, Kelsey Linstrum, Edward Litton, Elizabeth Lorenzi, Sheila MacLennan, John Marshall, Daniel F. McAuley, John F. McDyer, Anna McGlothlin, Shay McGuinness, Gail Miflin, Stephanie Montgomery, Paul R. Mouncey, Srinivas Murthy, Alistair Nichol, Rachael Parke, Jane C. Parker, Nicole Priddee, Damian F. J. Purcell, Luis F. Reyes, Peter Richardson, Nancy Robitaille, Kathryn M. Rowan, Jennifer Rynne, Hiroki Saito, Marlene Santos, Christina T. Saunders, Ary Serpa Neto, Christopher W. Seymour, Jon A. Silversides, Alan A. Tinmouth, Darrell J. Triulzi, Anne M. Turner, Frank van de Veerdonk, Timothy S. Walsh, Erica M. Wood, Scott Berry, Roger J. Lewis, David K. Menon, Colin McArthur, Ryan Zarychanski, Derek C. Angus, Steve A. Webb, David J. Roberts, Manu Shankar-Hari
Summary: Among critically ill adults with confirmed COVID-19, treatment with 2 units of high-titer, ABO-compatible convalescent plasma had a low likelihood of providing improvement in the number of organ support-free days.
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
(2021)
Review
Hematology
Keith Gomez
Summary: In the last decade, the number of patients with heritable platelet disorders in national databases of bleeding disorders has significantly increased. This revolution has been made possible through the use of high-throughput sequencing strategies and efforts to standardize diagnostic testing. New microscopy techniques could improve the diagnostic yield of peripheral blood smears and assist in determining the need for specialist testing.
Correction
Hematology
Renu Riat, Keith Gomez
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Article
Hematology
Karina Meijer, Waander van Heerde, Keith Gomez
Summary: Advancements in genomic testing and specialist laboratory assays have greatly improved the diagnostic accuracy of rare bleeding disorders, leading to the discovery of new genetic causes and a better understanding of the underlying molecular pathology.
Article
Medicine, General & Internal
Charlotte A. Bradbury, Patrick R. Lawler, Simon J. Stanworth, Bryan J. McVerry, Zoe McQuilten, Alisa M. Higgins, Paul R. Mouncey, Farah Al-Beidh, Kathryn M. Rowan, Lindsay R. Berry, Elizabeth Lorenzi, Ryan Zarychanski, Yaseen M. Arabi, Djillali Annane, Abi Beane, Wilma Van Bentum-Puijk, Zahra Bhimani, Shailesh Bihari, Marc J. M. Bonten, Frank M. Brunkhorst, Adrian Buzgau, Meredith Buxton, Marc Carrier, Allen C. Cheng, Matthew Cove, Michelle A. Detry, Lise J. Estcourt, Mark Fitzgerald, Timothy D. Girard, Ewan C. Goligher, Herman Goossens, Rashan Haniffa, Thomas Hills, David T. Huang, Christopher M. Horvat, Beverley J. Hunt, Nao Ichihara, Francois Lamontagne, Helen L. Leavis, Kelsey M. Linstrum, Edward Litton, John C. Marshall, Daniel F. McAuley, Anna McGlothlin, Shay P. McGuinness, Saskia Middeldorp, Stephanie K. Montgomery, Susan C. Morpeth, Srinivas Murthy, Matthew D. Neal, Alistair D. Nichol, Rachael L. Parke, Jane C. Parker, Luis Reyes, Hiroki Saito, Marlene S. Santos, Christina T. Saunders, Ary Serpa-Neto, Christopher W. Seymour, Manu Shankar-Hari, Vanessa Singh, Timo Tolppa, Alexis F. Turgeon, Anne M. Turner, Frank L. van de Veerdonk, Cameron Green, Roger J. Lewis, Derek C. Angus, Colin J. McArthur, Scott Berry, Lennie P. G. Derde, Steve A. Webb, Anthony C. Gordon
Summary: The study results showed that among critically ill patients with COVID-19, treatment with an antiplatelet agent compared with no antiplatelet agent did not significantly improve the number of organ support-free days within 21 days. The use of antiplatelet therapy in critically ill patients with COVID-19 did not show significant benefits.
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
(2022)
Review
Hematology
Rezan Abdul-Kadir, Keith Gomez
Summary: This systematic review investigated the prevalence and management of bleeding symptoms associated with gynecological and obstetric issues in women with Congenital factor VII (FVII) deficiency. The results showed that women with FVII deficiency often experience heavy menstrual bleeding, ovarian bleeding, and postpartum hemorrhage, which can impact their quality of life. However, the management of these bleeding complications is inconsistent due to the lack of treatment guidelines.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Medicine, General & Internal
Pratima Chowdary, Banwari Agarwal, Maria Rita Peralta, Sanjay Bhagani, Simon Lee, James Goldring, Marc Lipman, Emal Waqif, Mark Phillips, Helen Philippou, Jonathan H. Foley, Nicola J. Mutch, Robert A. S. Ariens, Kathleen A. Stringer, Federico Ricciardi, Marie Watissee, Derralynn Hughes, Amit Nathwani, Anne Riddell, David Patch, Jim Buckley, Mark De Neef, Rahul Dimber, Cecilia Diaz-Garcia, Honey Patel, Aarti Nandani, Upuli Dissanayake, Nick Chadwick, Ahmed A. A. M. M. Alkhatip, Peter Watkinson, Eamon Raith, Suveer Singh, Tony Wolff, Rajeev Jha, Simon E. Brill, Ameet Bakhai, Alison Evans, Farhat Gilani, Keith Gomez
Summary: Nebulized recombinant tissue plasminogen activator (rt-PA) has the potential to improve lung injury and oxygenation in COVID-19 patients. Preliminary studies show better outcomes in patients receiving non-invasive respiratory support (NIRS). Randomized clinical trials are needed to confirm the clinical effects.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Hematology
Evelien Krumb, Nishita Mehta, Ciaran Hutchinson, Bilal Jradeh, Ewa Jaslowska, Keith Gomez, Rezan Abdul-Kadir
Summary: This article describes a case of fetal death at 26 weeks due to massive intracranial hemorrhage (ICH) in patients with severe congenital factor X deficiency. Gene panel analysis of postmortem samples revealed a pathologic F10 gene variant that causes a significant reduction in FX levels. The parents were heterozygous for this variant and had no personal or family history of abnormal bleeding. This is the first reported case of severe FX deficiency resulting in ICH diagnosed through postmortem genetic analysis, highlighting the importance of exploring the etiology of fetal or neonatal ICH and treating potential coagulopathy in children.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2023)
Meeting Abstract
Hematology
Imran Malik, Paul Priest, Ian Jennings, Keith Gomez
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Obstetrics & Gynecology
Timothy A. C. Snow, Rezan A. Abdul-Kadir, Keith Gomez, Adrian England
Summary: This case study presents a 33-year-old woman in her third pregnancy with platelet storage pool disorder, who successfully minimised her risk of major obstetric haemorrhages through a peripartum plan devised by an extensive multi-disciplinary team. The use of point-of-care thromboelastography was also highlighted as a valuable tool in guiding management decisions and facilitating individualised risk-benefit discussions for anaesthetic choices.
OBSTETRIC MEDICINE
(2022)
Correction
Hematology
Renu Riat, Keith Gomez
BRITISH JOURNAL OF HAEMATOLOGY
(2022)