Hemophilia B (Factor IX Deficiency) Differential Diagnoses

1. Shen G, Gao M, Cao Q, Li W. The Molecular Basis of FIX Deficiency in Hemophilia B. Int J Mol Sci. 2022 Mar 2. 23 (5):[QxMD MEDLINE Link]. [Full Text].

2. Chavali S, Sharma A, Tabassum R, Bharadwaj D. Sequence and structural properties of identical mutations with varying phenotypes in human coagulation factor IX. Proteins. 2008 Oct. 73 (1):63-71. [QxMD MEDLINE Link].

3. BIGGS R, DOUGLAS AS, MACFARLANE RG, DACIE JV, PITNEY WR, MERSKEY. Christmas disease: a condition previously mistaken for haemophilia. Br Med J. 1952 Dec 27. 2 (4799):1378-82. [QxMD MEDLINE Link]. [Full Text].

4. Ewenstein BM, Wong WY, Schoppmann A. Bypassing agent prophylaxis for preventing arthropathy in patients with inhibitors. Haemophilia. 2010 Jan. 16(1):179-80. [QxMD MEDLINE Link].

5. Smith SB, Gailani D. Update on the physiology and pathology of factor IX activation by factor XIa. Expert Rev Hematol. 2008 Oct. 1 (1):87-98. [QxMD MEDLINE Link]. [Full Text].

6. Bauer KA, Kass BL, ten Cate H, Hawiger JJ, Rosenberg RD. Factor IX is activated in vivo by the tissue factor mechanism. Blood. 1990 Aug 15. 76 (4):731-6. [QxMD MEDLINE Link].

7. Wildgoose P, Nemerson Y, Hansen LL, Nielsen FE, Glazer S, Hedner U. Measurement of basal levels of factor VIIa in hemophilia A and B patients. Blood. 1992 Jul 1. 80 (1):25-8. [QxMD MEDLINE Link]. [Full Text].

8. Davie EW. A brief historical review of the waterfall/cascade of blood coagulation. J Biol Chem. 2003 Dec 19. 278 (51):50819-32. [QxMD MEDLINE Link]. [Full Text].

9. Hoffman M, Monroe DM 3rd. A cell-based model of hemostasis. Thromb Haemost. 2001 Jun. 85 (6):958-65. [QxMD MEDLINE Link].

10. Bos MHA, van 't Veet C, Reitsma PH. Molecular biology and biochemistry of the coagulation factors and pathways of hemostasis. Kaushansky K, Lichtman MA, Prchal JT, Levi MM, Press OW, Burns LJ, Caligiuri MA, eds. Williams Hematology. 9th ed. New York, NY: McGraw-Hill Professional; 2016.

11. Reijnen MJ, Maasdam D, Bertina RM, Reitsma PH. Haemophilia B Leyden: the effect of mutations at position +13 on the liver-specific transcription of the factor IX gene. Blood Coagul Fibrinolysis. 1994 Jun. 5 (3):341-8. [QxMD MEDLINE Link].

12. Goodeve AC. Hemophilia B: molecular pathogenesis and mutation analysis. J Thromb Haemost. 2015 Jul. 13 (7):1184-95. [QxMD MEDLINE Link]. [Full Text].

13. Christophe OD, Lenting PJ, Cherel G, Boon-Spijker M, Lavergne JM, Boertjes R, et al. Functional mapping of anti-factor IX inhibitors developed in patients with severe hemophilia B. Blood. 2001 Sep 1. 98 (5):1416-23. [QxMD MEDLINE Link].

14. Venkateswaran L, Wilimas JA, Jones DJ, Nuss R. Mild hemophilia in children: prevalence, complications, and treatment. J Pediatr Hematol Oncol. 1998 Jan-Feb. 20(1):32-5. [QxMD MEDLINE Link].

15. Zdziarska J, Chojnowski K, Klukowska A, Łetowska M, Mital A, Podolak-Dawidziak M, et al. Therapeutic properties and safety of recombinant factor VIII and factor IX. Pol Arch Med Wewn. 2009 Jun. 119 (6):403-9. [QxMD MEDLINE Link].

16. Horava SD, Peppas NA. Design of pH-Responsive Biomaterials to Enable the Oral Route of Hematological Factor IX. Ann Biomed Eng. 2016 Feb 16. [QxMD MEDLINE Link].

17. Loveland KA, Stehbens J, Contant C, Bordeaux JD, Sirois P, Bell TS, et al. Hemophilia growth and development study: baseline neurodevelopmental findings. J Pediatr Psychol. 1994 Apr. 19(2):223-39. [QxMD MEDLINE Link].

18. Alam AU, Karkhaneh M, Attia T, Wu C, Sun HL. All-cause mortality and causes of death in persons with haemophilia: A systematic review and meta-analysis. Haemophilia. 2021 Nov. 27 (6):897-910. [QxMD MEDLINE Link].

19. [Guideline] Hanley J et al, on behalf of the UK Haemophilia Centre Doctors Organisation (UKHCDO). Emergency and out of hours care for patients with bleeding disorders – standards of care for assessment and treatment. UKHCDO. Available at http://www.ukhcdo.org/wp-content/uploads/2015/12/EmergencyCareStandardsFinalVersionJune2009-For-Website.pdf. April 2009; Accessed: December 21, 2022.

20. Park CH, Seo JY, Kim HJ, Jang JH, Kim SH. A diagnostic challenge: mild hemophilia B with normal activated partial thromboplastin time. Blood Coagul Fibrinolysis. 2010 Jun. 21 (4):368-71. [QxMD MEDLINE Link].

21. Berntorp E, Astermark J, Björkman S, Blanchette VS, Fischer K, Giangrande PL, et al. Consensus perspectives on prophylactic therapy for haemophilia: summary statement. Haemophilia. 2003 May. 9 Suppl 1:1-4. [QxMD MEDLINE Link].

22. Ljung RC. Prophylactic infusion regimens in the management of hemophilia. Thromb Haemost. 1999 Aug. 82(2):525-30. [QxMD MEDLINE Link].

23. Iorio A, Marchesini E, Marcucci M, Stobart K, Chan AK. Clotting factor concentrates given to prevent bleeding and bleeding-related complications in people with hemophilia A or B. Cochrane Database Syst Rev. 2011 Sep 7. 9:CD003429. [QxMD MEDLINE Link].

24. Miners AH, Sabin CA, Tolley KH, Lee CA. Assessing the effectiveness and cost-effectiveness of prophylaxis against bleeding in patients with severe haemophilia and severe von Willebrand's disease. J Intern Med. 1998 Dec. 244(6):515-22. [QxMD MEDLINE Link].

25. Valentino LA, Rusen L, Elezovic I, Smith LM, Korth-Bradley JM, Rendo P. Multicentre, randomized, open-label study of on-demand treatment with two prophylaxis regimens of recombinant coagulation factor IX in haemophilia B subjects. Haemophilia. 2014 Jan 13. [QxMD MEDLINE Link].

26. Hand L. Prophylaxis trumps on-demand dosing for hemophilia B in RCT. Medscape Medical News. January 31, 2014. [Full Text].

27. Otto MA. FDA Approves First Gene Therapy for Hemophilia B. Medscape Medical News. November 23, 2022. Available at https://www.medscape.com/viewarticle/984531.

28. Santagostino E, Martinowitz U, Lissitchkov T, Pan-Petesch B, Hanabusa H, Oldenburg J, et al. Long acting recombinant coagulation factor IX albumin fusion protein (rIX-FP) in hemophilia B: results of a phase 3 trial. Blood. 2016 Jan 11. [QxMD MEDLINE Link].

29. Windyga J, Solano Trujillo MH, Hafeman AE. BAX326 (RIXUBIS): a novel recombinant factor IX for the control and prevention of bleeding episodes in adults and children with hemophilia B. Ther Adv Hematol. 2014 Oct. 5 (5):168-80. [QxMD MEDLINE Link]. [Full Text].

30. Urasinski T, Stasyshyn O, Andreeva T, Rusen L, Perina FG, Oh MS, et al. Recombinant factor IX (BAX326) in previously treated paediatric patients with haemophilia B: a prospective clinical trial. Haemophilia. 2015 Mar. 21 (2):196-203. [QxMD MEDLINE Link].

31. Rebinyn (nonacog beta pegol; recombinant glycopegylated factor IX) [package insert]. Plainsboro, NJ: Novo Nordisk, Inc. 2017 June. Available at [Full Text].

32. Chapman WC, Singla N, Genyk Y, McNeil JW, Renkens KL Jr, Reynolds TC, et al. A phase 3, randomized, double-blind comparative study of the efficacy and safety of topical recombinant human thrombin and bovine thrombin in surgical hemostasis. J Am Coll Surg. 2007 Aug. 205(2):256-65. [QxMD MEDLINE Link].

33. O'Connell N, Mc Mahon C, Smith J, Khair K, Hann I, Liesner R, et al. Recombinant factor VIIa in the management of surgery and acute bleeding episodes in children with haemophilia and high responding inhibitors. Br J Haematol. 2002 Mar. 116(3):632-5. [QxMD MEDLINE Link].

34. Siddiqui MA, Scott LJ. Recombinant factor VIIa (Eptacog Alfa): a review of its use in congenital or acquired haemophilia and other congenital bleeding disorders. Drugs. 2005. 65(8):1161-77. [QxMD MEDLINE Link].

35. McQuilten ZK, Barnes C, Zatta A, Phillips LE. Off-Label Use of Recombinant Factor VIIa in Pediatric Patients. Pediatrics. 2012 Jun. 129(6):e1533-e1540. [QxMD MEDLINE Link].

36. Coppola A, Margaglione M, Santagostino E, Rocino A, Grandone E, Mannucci PM, et al. Factor VIII gene (F8) mutations as predictors of outcome in immune tolerance induction of hemophilia A patients with high-responding inhibitors. J Thromb Haemost. 2009 Nov. 7(11):1809-15. [QxMD MEDLINE Link].

37. Carcao M, St Louis J, Poon MC, Grunebaum E, Lacroix S, Stain AM, et al. Rituximab for congenital haemophiliacs with inhibitors: a Canadian experience. Haemophilia. 2006 Jan. 12(1):7-18. [QxMD MEDLINE Link].

38. Aggarwal A, Grewal R, Green RJ, Boggio L, Green D, Weksler BB, et al. Rituximab for autoimmune haemophilia: a proposed treatment algorithm. Haemophilia. 2005 Jan. 11(1):13-9. [QxMD MEDLINE Link].

39. Stachnik JM. Rituximab in the treatment of acquired hemophilia. Ann Pharmacother. 2006 Jun. 40(6):1151-7. [QxMD MEDLINE Link].

40. Personal communication with Dr. Troy H. Guthrie, Jr. MD, Medical Director Baptist Cancer Institute, Jacksonville, Florida.

41. Shapiro AD, Angchaisuksiri P, Astermark J, Benson G, Castaman G, Chowdary P, et al. Subcutaneous concizumab prophylaxis in hemophilia A and hemophilia A/B with inhibitors: Phase 2 trial results. Blood. 2019 Aug 23. 3 (21):3241-3247. [QxMD MEDLINE Link].

42. Shapiro AD, Angchaisuksiri P, Astermark J, Benson G, Castaman G, Eichler H, et al. Long-term efficacy and safety of subcutaneous concizumab prophylaxis in hemophilia A and hemophilia A/B with inhibitors. Blood Adv. 2022 Jun 14. 6 (11):3422-3432. [QxMD MEDLINE Link]. [Full Text].

43. EU/3/17/1940. European Medicines Agency. Available at https://www.ema.europa.eu/en/medicines/human/orphan-designations/eu3171940. December 1, 2018; Accessed: August 23, 2022.

44. Shapiro AD. Concizumab: a novel anti-TFPI therapeutic for hemophilia. Blood Adv. 2021 Jan 12. 5 (1):279. [QxMD MEDLINE Link]. [Full Text].

45. Lowes R. FDA OKs first cloned factor IX for bleeding prophylaxis. Medscape Medical News. June 27, 2013. Available at http://www.medscape.com/viewarticle/806996. Accessed: July 9, 2013.

46. US Food and Drug Administration. FDA approves first recombinant coagulation factor IX that is specifically indicated for routine use in preventing bleeding episodes (prophylaxis) [press release]. June 27, 2013. Available at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm358918.htm. Accessed: July 9, 2013.

47. Powell JS, Pasi KJ, Ragni MV, Ozelo MC, Valentino LA, Mahlangu JN, et al. Phase 3 study of recombinant factor IX Fc fusion protein in hemophilia B. N Engl J Med. 2013 Dec 12. 369(24):2313-23. [QxMD MEDLINE Link].

48. Brooks M. First Long-Acting Hemophilia B Drug (Alprolix) Clears FDA. Medscape Medical News. Mar 31 2014. [Full Text].

49. Antunes SV, Tangada S, Stasyshyn O, Mamonov V, Phillips J, Guzman-Becerra N, et al. Randomized comparison of prophylaxis and on-demand regimens with FEIBA NF in the treatment of haemophilia A and B with inhibitors. Haemophilia. 2014 Jan. 20(1):65-72. [QxMD MEDLINE Link].

50. Antunes SV, Tangada S, Stasyshyn O, Mamonov V, Phillips J, Guzman-Becerra N, et al. Randomized comparison of prophylaxis and on-demand regimens with FEIBA NF in the treatment of haemophilia A and B with inhibitors. Haemophilia. 2014 Jan. 20(1):65-72. [QxMD MEDLINE Link].

51. Duncan N, Kronenberger W, Roberson C, Shapiro A. VERITAS-Pro: a new measure of adherence to prophylactic regimens in haemophilia. Haemophilia. 2010 Mar. 16(2):247-55. [QxMD MEDLINE Link].

52. Hazendonk HCAM, Preijers T, Liesner R, Chowdary P, Hart D, Keeling D, et al. Perioperative replacement therapy in haemophilia B: An appeal to "B" more precise. Haemophilia. 2018 Jul. 24 (4):611-618. [QxMD MEDLINE Link]. [Full Text].

53. Négrier C, Abdul Karim F, Lepatan LM, Lienhart A, López-Fernández MF, Mahlangu J, et al. Efficacy and safety of long-acting recombinant fusion protein linking factor IX with albumin in haemophilia B patients undergoing surgery. Haemophilia. 2016 Jul. 22 (4):e259-66. [QxMD MEDLINE Link].

54. Curtin J, Santagostino E, Karim FA, Li Y, Seifert W, Négrier C. Simplifying surgery in haemophilia B: Low factor IX consumption and infrequent infusions in surgical procedures with rIX-FP. Thromb Res. 2020 Apr. 188:85-89. [QxMD MEDLINE Link].

55. Valentino LA, Cooper DL, Goldstein B. Surgical experience with rFVIIa (NovoSeven) in congenital haemophilia A and B patients with inhibitors to factors VIII or IX. Haemophilia. 2011 Jul. 17 (4):579-89. [QxMD MEDLINE Link].

56. Den Uijl I, Mauser-Bunschoten EP, Roosendaal G, Schutgens R, Fischer K. Efficacy assessment of a new clotting factor concentrate in haemophilia A patients, including prophylactic treatment. Haemophilia. 2009 Nov. 15(6):1215-8. [QxMD MEDLINE Link].

57. Ingerslev HJ, Hindkjaer J, Jespersgaard C, Lind MP, Kølvraa S. [Preimplantation genetic diagnosis. The first experiences in Denmark]. Ugeskr Laeger. 2001 Oct 1. 163(40):5525-8. [QxMD MEDLINE Link].

58. Lissens W, Sermon K. Preimplantation genetic diagnosis: current status and new developments. Hum Reprod. 1997 Aug. 12(8):1756-61. [QxMD MEDLINE Link].

59. Wells D, Delhanty JD. Preimplantation genetic diagnosis: applications for molecular medicine. Trends Mol Med. 2001 Jan. 7(1):23-30. [QxMD MEDLINE Link].

60. Arruda VR, Samelson-Jones BJ. Obstacles and future of gene therapy for hemophilia. Expert Opin Orphan Drugs. 2015. 3 (9):997-1010. [QxMD MEDLINE Link].

61. Nathwani AC, Reiss UM, Tuddenham EG, et al. Long-term safety and efficacy of factor IX gene therapy in hemophilia B. N Engl J Med. 2014 Nov 20. 371 (21):1994-2004. [QxMD MEDLINE Link]. [Full Text].

62. Pipe SW, Recht M, Key NS, Leebeek FWG, Castaman G, Lattimore SU, et al. First data from the phase 3 HOPE-B gene therapy trial: Efficacy and safety of etranacogene dezaparvovec (AAV5-Padua hFIX variant; AMT-061) in adults with severe or moderate-severe hemophilia B treated irrespective of pre-existing anti-capsid neutralizing antibodies. Presented December 8, 2020 at the 62nd American Society of Hematology Annual Meeting and Exposition. [Full Text].

63. 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. N Engl J Med. 2022 Jul 21. 387 (3):237-247. [QxMD MEDLINE Link]. [Full Text].

64. Croteau SE. Hemophilia A/B. Hematol Oncol Clin North Am. 2022 Aug. 36 (4):797-812. [QxMD MEDLINE Link].

65. Morishige S, Mizuno S, Ozawa H, Nakamura T, Mazahery A, Nomura K, et al. CRISPR/Cas9-mediated gene correction in hemophilia B patient-derived iPSCs. Int J Hematol. 2019 Oct 29. [QxMD MEDLINE Link].

66. Chen X, Niu X, Liu Y, Zheng R, Yang L, Lu J, et al. Long-term correction of haemophilia B through CRISPR/Cas9 induced homology-independent targeted integration. J Genet Genomics. 2022 Jun 9. [QxMD MEDLINE Link].

67. [Guideline] Hanley J, McKernan A, Creagh MD, Classey S, McLaughlin P, Goddard N, et al. Guidelines for the management of acute joint bleeds and chronic synovitis in haemophilia: A United Kingdom Haemophilia Centre Doctors' Organisation (UKHCDO) guideline. Haemophilia. 2017 Jul. 23 (4):511-520. [QxMD MEDLINE Link]. [Full Text].

68. Hart DP, Matino D, Astermark J, Dolan G, d'Oiron R, Hermans C, et al. International consensus recommendations on the management of people with haemophilia B. Ther Adv Hematol. 2022. 13:20406207221085202. [QxMD MEDLINE Link]. [Full Text].

69. Castaman G, Mancuso ME, Giacomelli SH, Tosetto A, Santagostino E, Mannucci PM, et al. Molecular and phenotypic determinants of the response to desmopressin in adult patients with mild hemophilia A. J Thromb Haemost. 2009 Nov. 7(11):1824-31. [QxMD MEDLINE Link].

Robert A Zaiden, MD Adjunct Associate Professor, Division of Cancer Medicine, Baptist MD Anderson Cancer Center

Robert A Zaiden, MD is a member of the following medical societies: American College of Physicians, American Society of Clinical Oncology

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Srikanth Nagalla, MD, MS, FACP Chief of Benign Hematology, Miami Cancer Institute, Baptist Health South Florida; Clinical Professor of Medicine, Florida International University, Herbert Wertheim College of Medicine

Srikanth Nagalla, MD, MS, FACP is a member of the following medical societies: American Society of Hematology, Association of Specialty Professors

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Alexion; Alnylam; Kedrion; Sanofi; Dova; Apellis; Pharmacosmos<br/>Serve(d) as a speaker or a member of a speakers bureau for: Sobi; Sanofi; Rigel.

Dimitrios P Agaliotis, MD, PhD, FACP Consulting Staff, Department of Medicine, Baptist Health System

Disclosure: Nothing to disclose.

Jeffrey L Arnold, MD, FACEP Chairman, Department of Emergency Medicine, Santa Clara Valley Medical Center

Jeffrey L Arnold, MD, FACEP is a member of the following medical societies: American Academy of Emergency Medicine and American College of Physicians

Disclosure: Nothing to disclose.

Emmanuel C Besa, MD Professor, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Clinical Oncology, American Society of Hematology, and New York Academy of Sciences

Disclosure: Nothing to disclose.

Gary D Crouch, MD Associate Professor, Program Director of Pediatric Hematology-Oncology Fellowship, Department of Pediatrics, Uniformed Services University of the Health Sciences

Gary D Crouch, MD is a member of the following medical societies: American Academy of Pediatrics and American Society of Hematology

Disclosure: Nothing to disclose.

Brendan R Furlong, MD Clinical Chief, Department of Emergency Medicine, Georgetown University Hospital.

Brendan R Furlong is a member of the following medical societies: American College of Emergency Physicians and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Mary A Furlong, MD Associate Professor and Program/Residency Director, Department of Pathology, Georgetown University School of Medicine

Mary A Furlong, MD is a member of the following medical societies: United States and Canadian Academy of Pathology

Disclosure: Nothing to disclose.

William G Gossman, MD Associate Clinical Professor of Emergency Medicine, Creighton University School of Medicine; Consulting Staff, Department of Emergency Medicine, Creighton University Medical Center

William G Gossman, MD is a member of the following medical societies: American Academy of Emergency Medicine

Disclosure: Nothing to disclose.

Lawrence F Jardine, MD, FRCPC Associate Professor, Department of Pediatrics, Schulich School of Medicine and Dentistry, University of Western Ontario; Head, Section of Pediatric Hematology and Oncology, Children's Hospital of Western Ontario; Associate Scientist, Child Health Research Institute

Lawrence F Jardine, MD, FRCPC is a member of the following medical societies: American Society of Hematology, American Society of Pediatric Hematology/Oncology, Canadian Medical Protective Association, Children's Oncology Group, College of Physicians and Surgeons of Ontario, Hemophilia and Thrombosis Research Society, Ontario Medical Association, and Royal College of Physicians and Surgeons of Canada

Disclosure: Baxter Honoraria Consulting; Bayer Honoraria Consulting; Novartis Honoraria Speaking and teaching

Adonis Lorenzana, MD Consulting Staff, Department of Pediatric Oncology, St John Hospital and Medical Center

Adonis Lorenzana, MD is a member of the following medical societies: American Academy of Pediatrics and American Society of Pediatric Hematology/Oncology

Disclosure: Nothing to disclose.

Saduman Ozturk, PA-C Physician Assistant, Bone Marrow Transplant Center, Florida Hospital Cancer Institute

Disclosure: Nothing to disclose.

Ronald A Sacher, MB, BCh, MD, FRCPC Professor, Internal Medicine and Pathology, Director, Hoxworth Blood Center, University of Cincinnati Academic Health Center

Ronald A Sacher, MB, BCh, MD, FRCPC is a member of the following medical societies: American Association for the Advancement of Science, American Association of Blood Banks, American Clinical and Climatological Association, American Society for Clinical Pathology, American Society of Hematology, College of American Pathologists, International Society of Blood Transfusion, International Society on Thrombosis and Haemostasis, and Royal College of Physicians and Surgeons of Canada

Disclosure: Glaxo Smith Kline Honoraria Speaking and teaching

Hadi Sawaf, MD Director, Pediatric Hematology Oncology, Van Elslander Cancer Center; Clinical Assistant Professor, Wayne State University School of Medicine

Hadi Sawaf, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Clinical Oncology, and American Society of Hematology

Disclosure: Nothing to disclose.

Karen Seiter, MD Professor, Department of Internal Medicine, Division of Oncology/Hematology, New York Medical College

Karen Seiter, MD is a member of the following medical societies: American Association for Cancer Research, American College of Physicians, and American Society of Hematology

Disclosure: Novartis Honoraria Speaking and teaching; Novartis Consulting fee Speaking and teaching; Ariad Honoraria Speaking and teaching; Celgene Honoraria Speaking and teaching

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

• Print this section
• Print the entire contents of
• Print the entire contents of article