Bulletin references April 2023

A full list of references for the April Bulletin is available here.

You can download a copy of the April 2023 Bulletin from our Bulletin pages.

The science behind the cure

Haemophilia and gene therapy 

  1. Biggs R, Douglas AS, Macfarlane RG, Dacie JV, Pitney WR, Merskey H. Christmas disease: a condition previously mistaken for haemophilia. Br Med J 1952;2:1378–1382.
  2. Castaman G, Matino D. Hemophilia A and B: molecular and clinical similarities and differences. Haematologica 2019;104:1702–1709. 
  3. Soucie JM, Miller CH, Dupervil B, Le B, Buckner TW. Occurrence rates of haemophilia among males in the United States based on surveillance conducted in specialized haemophilia treatment centres. Haemophilia 2020;26:487–493. 
  4. Berntorp E, Shapiro AD. Modern haemophilia care. Lancet 2012;379:1447–1456.
  5. Rosendaal F, Smit C, Briet E. Hemophilia treatment in historical perspective: a review of medical and social developments. Ann Hematol.1991;62:5–15;
  6. Brinkhous K. A Short History of Jemophilia, With Some Comments on the Word 'Hemophilia'. Handbook of Hemophilia. New York, USA: Elsevier, 1975.
  7. Hoffman M, Monroe DM, 3rd. A cell-based model of hemostasis. Thromb Haemost 2001;85:958–965.
  8. Fischer K, Ljung R, Platokouki H, Liesner R, Claeyssens S, Smink E et al. Prospective observational cohort studies for studying rare diseases: the European PedNet Haemophilia Registry. Haemophilia 2014;20:e280–e6.
  9. Biggs R, Macfarlane R. Haemophilia and related conditions: a survey of 187 cases. Br J Haematol 1958;4:1–27. 
  10. White GCI, Rosendaal F, Aledort LM, Lusher JM, Rothschild C, Ingerslev J. Definitions in hemophilia. Thromb Haemost 2001;85:560.
  11. Soucie JM, Nuss R, Evatt B, Abdelhak A, Cowan L, Hill H et al. Mortality among males with hemophilia: relations with source of medical care. The Hemophilia Surveillance System Project Investigators. Blood 2000;96:437–442.
  12. Chorba TL, Holman RC, Strine TW, Clarke MJ, Evatt BL. Changes in longevity and causes of death among persons with hemophilia A. Am J Hematol 1994;45:112–121. 
  13. Darby SC, Kan SW, Spooner RJD, Giangrande PLF, Lee CA, Makris M et al. The impact of HIV on mortality rates in the complete UK haemophilia population. AIDS 2004;18:525–533. 
  14. Ling G, Tuddenham EGD. Factor VIII: the protein, cloning its gene, synthetic factor and now - 35 years later - gene therapy; what happened in between? Br J Haematol 2020;189:400–407. 
  15. Kitazawa T, Igawa T, Sampei Z, Muto A, Kojima T, Soeda T et al. A bispecific antibody to factors IXa and X restores factor VIII hemostatic activity in a hemophilia A model. Nature Med 2012;18:1570–1574. 
  16. Sampei Z, Igawa T, Soeda T, Okuyama-Nishida Y, Moriyama C, Wakabayashi T et al. Identification and multidimensional optimization of an asymmetric bispecific IgG antibody mimicking the function of factor VIII cofactor activity. PloS One. 2013;8:e57479. 
  17. Rodriguez-Merchan EC, Valentino LA. Emicizumab: Review of the literature and critical appraisal. Haemophilia 2019;25:11–20. 
  18. Shapiro AD. Concizumab: a novel anti-TFPI therapeutic for hemophilia. Blood Adv 2021;5:279. 
  19. Mahlangu JN. Progress in the development of anti-tissue factor pathway inhibitors for haemophilia management. Front Med 2021;8:670526. 
  20. Naso MF, Tomkowicz B, Perry WL, Strohl WR. Adeno-associated virus (AAV) as a vector for gene therapy. BioDrugs 2017;31:317–334. 
  21. Eaton DL, Wood WI, Eaton D, Hass PE, Hollingshead P, Wion K et al. Construction and characterization of an active factor VIII variant lacking the central one-third of the molecule. Biochemistry 1986;25:8343–8347.
  22. BioMarin Announces Stable and Durable Annualized Bleed Control for ROCTAVIAN™ in Largest Phase 3 Gene Therapy Study in Adults with Severe Hemophilia A; 134-Participant Study Met All Primary and Secondary Efficacy Endpoints at [press release]. 2023. 
  23. European Medicines Agency. Roctavian 2022. Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/roctavian-0
  24. Miesbach WA, Recht M, Key NS, Sivamurthy K, Monahan PE, Pipe SW. Durability of Factor IX activity and bleeding rate in people with severe or moderately severe hemophilia B after 5 years of follow-up in the phase 1/2 study of AMT-060, and after 3 years of follow-up in the phase 2b and 2 years of follow-up in the phase 3 studies of etranacogene dezaparvovec (AMT-061). Blood 2022;140:4913–4914. 


  25. Pipe SW. Delivering on the promise of gene therapy for haemophilia. Haemophilia 2021;27:114–121. 
  26. Sharma A, Easow Mathew M, Sriganesh V, Reiss UM. Gene therapy for haemophilia. Cochrane Database Syst Rev 2020;4:Cd010822. 
  27. Monahan PE, Négrier C, Tarantino M, Valentino LA, Mingozzi F. Emerging immunogenicity and genotoxicity considerations of adeno-associated virus vector gene therapy for hemophilia. J Clin Med 2021;10:2471. 
  28. Stanford S, Pink R, Creagh D, Clark A, Lowe G, Curry N et al. Adenovirus-associated antibodies in UK cohort of hemophilia patients: A seroprevalence study of the presence of adenovirus-associated virus vector–serotypes AAV5 and AAV8 neutralizing activity and antibodies in patients with hemophilia A. Res Pract Thromb Haemost 2019;3:261–267. 
  29. von Drygalski A, Gomez E, Giermasz A, Castaman G, Key NS, Lattimore SS et al. Stable and durable factor IX levels in hemophilia B patients over 3 years post etranacogene dezaparvovec gene therapy. Blood Adv 2022 (Epub ahead of print). 
  30. Chowdary P, Shapiro S, Makris M, Evans G, Boyce S, Talks K et al. Phase 1–2 trial of AAVS3 gene therapy in patients with hemophilia B. New Eng J Med 2022;387:237–247. 
  31. Ozelo MC, Mahlangu J, Pasi KJ, Giermasz A, Leavitt AD, Laffan M et al. Valoctocogene roxaparvovec gene therapy for hemophilia A. New Engl J Med 2022;386:1013–1025. 
  32. Pierce G, Iorio A. Past, present and future of haemophilia gene therapy: From vectors and transgenes to known and unknown outcomes. Haemophilia. 2018;24:60–67. 
  33. Schmidt M, Foster G, Coppens M, Thomsen H. Liver safety case report from the phase 3 HOPE-B gene therapy trial in adults with hemophilia B. Res Pract Thromb Haemost 2021;5:93
  34. uniQure. UniQure announces findings from reported case of hepatocellular carcinoma (HCC) in hemophilia B gene therapy program. Press Release. 2021. 
  35. A statement for the haemophilia community from BioMarin regarding a serious adverse event, deemed unrelated, by the Independent Data Safety Monitoring Committee, to the BioMarin haemophilia A gene therapy phase 1 / 2 trial (Clinical studies are ongoing) [press release]. 2022. 
  36. An update for the hemophilia community from BioMarin regarding a serious adverse event in the ongoing hemophilia A gene therapy [valoctocogene roxaparvovec, BMN 270] Phase 3 study that was deemed, by the Independent Data Safety Monitoring Committee and the company, very unlikely to be related to the investigational therapy. [press release]. 2022. 

The RESTORE trial – the first human trials on in vitro red cells for transfusion 

  1. Olivier EN, Marenah L, McCahill A, Condie A, Cowan S, Mountford JC. High-efficiency serum-free feeder-free erythroid differentiation of human pluripotent stem cells using small molecules. Stem Cells Transl Med 2016;5:1394–1405. 
  2. Hawksworth J, Satchwell TJ, Meinders M, Daniels DE, Regan F, Thornton NM et al. Enhancement of red blood cell transfusion compatibility using CRISPR-mediated erythroblast gene editing. EMBO Mol Med 2018;10:e8454. 
  3. Locke M, Reddy PS, Badawy SM. Adherence to iron chelation therapy among adults with thalassemia: A systematic review. Hemoglobin 2022;46:201–213. 
  4. Reddy PS, Locke M, Badawy SM. A systematic review of adherence to iron chelation therapy among children and adolescents with thalassemia. Ann Med 2022;54:326–342. 
  5. Cogan N, Kupzig S, Parsons SF, Anstee DJ. A robust ex vivo culture system for production of mature human reticulocytes from a single donor. Blood 2011;118:2096. 
  6. Griffiths RE, Kupzig S, Cogan N, Mankelow TJ, Betin VM, Trakarnsanga K et al. Maturing reticulocytes internalize plasma membrane in glycophorin A-containing vesicles that fuse with autophagosomes before exocytosis. Blood 2012;119:6296–6306. 

Antimicrobial resistance – the slow pandemic 

  1. Antimicrobial Resistance Collaborators. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet 2022;399:629–655.  

On the agenda

We can end cervical cancer

  1. Jo’s Trust. We Can End Cervical Cancer – The Opportunities and Challenges to Eliminating Cervical Cancer in the UK. Available at: https://www.jostrust.org.uk/sites/default/files/jos-1422-01_-_elimination_report_v5_2.pdf 
  2. World Health Organization. Global Strategy to Accelerate the Elimination of Cervical Cancer as a Public Health Problem. Available at: https://www.who.int/publications/i/item/978924001410

Clinical effectiveness

Adherence to prescribing and monitoring standards for liposomal amphotericin B prior to and during the COVID-19 pandemic 

  1. Mendelson M, Matsoso MP. The World Health Organization Global Action Plan for antimicrobial resistance. S Afr Med J 2015;105:325. 
  2. De Pauw B, Walsh TJ, Donnelly JP, Stevens DA, Edwards JE, Calandra T et al. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis 2008;46:1813–1821. 
  3. Kooraki S, Hosseiny M, Velez EM, Gupta A, Gilkeson R, Raman SS et al. COVID-19 pandemic revisited: lessons the radiology community has learned a year later. Emerg Radiol 2021;28:1083–1086. 


Personalised histopathology reporting for personalised medicine

  1. Mason AE, Varma M. Histopathology reporting for personalised medicine: focus on clinical utility. J Clin Pathol 2022;75:525–528.  
  2. Varma M, Williamson S. Clinical utility of histopathology data: urological cancers. J Clin Pathol 2022;75:506–513. 
  3. Deb R, Tan PH. Clinical utility of breast pathology data: implications for practising pathologists. J Clin Pathol 2022;75:514–518. 
  4. Loughrey MB, Wong NACS. Clinical utility of GI pathology data: implications for practising pathologists. J Clin Pathol 2022;75:519–524. 
  5. Shah VI, McCluggage WG. Clinical utility of pathology data: endometrial and tubo-ovarian carcinomas. J Clin Pathol 2022;75:529–536.
  6. Hunter K, Jamieson L, Wong N, Varma M, Bateman A. Best practice Recommendations: The Role of the Cellular Pathologist in the Cancer Multidisciplinary Team. London, UK: The Royal College of Pathologists. Available online at: https://www.rcpath.org/profession/guidelines/cross-specialty-publications.html 
  7. Varma M, McCluggage WG, Shah V, Berney DM. Pathologists can get it right the first time. J Clin Pathol 2021;74:271–272. 

Report on the 2nd Symposium on Developing a Sustainable UK Diagnostic Sector: the regional dimension – West Midlands leading the way?

  1. Deloitte. The Future of Diagnostics. Available at: https://www2.deloitte.com/uk/en/pages/life-sciences-and-healthcare/articles/future-of-diagnostics.html
  2. NHS England. Core20PLUS5 (Adults) – An Approach to Reducing Healthcare Inequalities. Available at: https://www.england.nhs.uk/about/equality/equality-hub/national-healthcare-inequalities-improvement-programme/core20plus5/ 
  3. Diagnostics Commission. The Lancet Commission on Diagnostics. Available at: https://diagnosticscommission.org