Thalassemia Intermedia Differential Diagnoses

1. Weatherall DJ, Clegg JB, eds. The Thalassaemia Syndromes. 4th ed. Oxford: Blackwell Science; 2001.

2. Yathiraj PH, Singh A, Vidyasagar S, Varma M, Mamidipudi V. Excellent and durable response to radiotherapy in a rare case of spinal cord compression due to extra-medullary hematopoiesis in β-thalassemia intermedia: case report and clinicoradiological correlation. Ann Palliat Med. 2017 Apr. 6 (2):195-9. [QxMD MEDLINE Link].

3. Tufekci O, Atabay B, Turker M, et al. Evaluation of the Clinical and Laboratory Characteristics of Previously Followed-up Thalassemia Intermedia Patients to Provide Them Better Care in the Future. J Pediatr Hematol Oncol. 2017 Aug. 39 (6):440-4. [QxMD MEDLINE Link].

4. [Guideline] Taher A, Musallam K, Cappellini MD. Guidelines for the Management of Non Transfusion Dependent Thalassaemia (NTDT). 2nd ed. Nicosia, Cyprus: Thalassaemia International Federation; 2017. [Full Text].

5. Modell B, Berdoukas V. The Clinical Approach to Thalassaemia. London: Grune and Stratton; 1984.

6. Delicou S. Extramedullary haemopoiesis in hemoglobinopathies. J Hematol Transfusion. 2017 Sep 21. [Full Text].

7. Cappellini MD, Grespi E, Cassinerio E, Bignamini D, Fiorelli G. Coagulation and splenectomy: an overview. Ann N Y Acad Sci. 2005. 1054:317-24. [QxMD MEDLINE Link].

8. Westerman M, Pizzey A, Hirschman J, et al. Microvesicles in haemoglobinopathies offer insights into mechanisms of hypercoagulability, haemolysis and the effects of therapy. Br J Haematol. 2008 Jul. 142(1):126-35. [QxMD MEDLINE Link]. [Full Text].

9. Tantawy AA, Adly AA, Ismail EA, Youssef OI, Ali ME. Soluble fms-Like Tyrosine Kinase 1 as a Link Between Angiogenesis and Endothelial Dysfunction in Pediatric Patients With β-Thalassemia Intermedia. Clin Appl Thromb Hemost. 2017 Jan 1. 1076029617692879. [QxMD MEDLINE Link].

10. Dunn J, Khan S, Ariff B, Strickland N, Al-Nahhas A. Pulmonary emboli and extramedullary haematopoiesis in beta-thalassaemia intermedia. Nucl Med Rev Cent East Eur. 2008. 11(1):34-6. [QxMD MEDLINE Link].

11. Goldschmidt N, Spectre G, Brill A, et al. Increased platelet adhesion under flow conditions is induced by both thalassemic platelets and red blood cells. Thromb Haemost. 2008 Nov. 100(5):864-70. [QxMD MEDLINE Link].

12. Gardenghi S, Marongiu MF, Ramos P, et al. Ineffective erythropoiesis in beta-thalassemia is characterized by increased iron absorption mediated by down-regulation of hepcidin and up-regulation of ferroportin. Blood. 2007 Jun 1. 109(11):5027-35. [QxMD MEDLINE Link].

13. Weizer-Stern O, Adamsky K, Amariglio N, et al. Downregulation of hepcidin and haemojuvelin expression in the hepatocyte cell-line HepG2 induced by thalassaemic sera. Br J Haematol. 2006 Oct. 135(1):129-38. [QxMD MEDLINE Link].

14. Meloni A, Pistoia L, Gamberini MR, et al. The Link of Pancreatic Iron with Glucose Metabolism and Cardiac Iron in Thalassemia Intermedia: A Large, Multicenter Observational Study. J Clin Med. 2021 Nov 26. 10 (23):[QxMD MEDLINE Link]. [Full Text].

15. Ansari S, Rashid N, Hanifa A, et al. Laboratory diagnosis for thalassemia intermedia: Are we there yet?. J Clin Lab Anal. 2019 Jan. 33 (1):e22647. [QxMD MEDLINE Link]. [Full Text].

16. Taher AT, Musallam KM, Karimi M, et al. Overview on practices in thalassemia intermedia management aiming for lowering complication rates across a region of endemicity: the OPTIMAL CARE study. Blood. 2010 Mar 11. 115 (10):1886-92. [QxMD MEDLINE Link]. [Full Text].

17. Cappellini MD, Bejaoui M, Agaoglu L, et al. Iron chelation with deferasirox in adult and pediatric patients with thalassemia major: efficacy and safety during 5 years' follow-up. Blood. 2011 Jul 28. 118(4):884-93. [QxMD MEDLINE Link].

18. Cappellini MD, Musallam KM, Poggiali E, Taher AT. Hypercoagulability in non-transfusion-dependent thalassemia. Blood Rev. 2012 Apr. 26 Suppl 1:S20-3. [QxMD MEDLINE Link].

19. Koren A, Levin C, Dgany O, Kransnov T, Elhasid R, Zalman L, et al. Response to hydroxyurea therapy in beta-thalassemia. Am J Hematol. 2008 May. 83(5):366-70. [QxMD MEDLINE Link].

20. Ren Q, Zhou YL, Wang L, et al. Clinical trial on the effects of thalidomide on hemoglobin synthesis in patients with moderate thalassemia intermedia. Ann Hematol. 2018 Oct. 97 (10):1933-9. [QxMD MEDLINE Link].

21. Haghi M, Feizi AA, Harteveld CL, Pouladi N, Feizi MA. Homozygosity for a rare beta 0-thalassemia mutation [frameshift codons 25/26 (+T)] causes beta-thalassemia intermedia in an Iranian family. Hemoglobin. 2009. 33(1):75-80. [QxMD MEDLINE Link].

22. Harteveld CL, Refaldi C, Cassinerio E, Cappellini MD, Giordano PC. Segmental duplications involving the alpha-globin gene cluster are causing beta-thalassemia intermedia phenotypes in beta-thalassemia heterozygous patients. Blood Cells Mol Dis. 2008 May-Jun. 40(3):312-6. [QxMD MEDLINE Link].

23. Finkenstedt A, Bianchi P, Theurl I, Vogel W, Witcher DR, Wroblewski VJ, et al. Regulation of iron metabolism through GDF15 and hepcidin in pyruvate kinase deficiency. Br J Haematol. 2009 Mar. 144(5):789-93. [QxMD MEDLINE Link].

24. Musallam KM, Taher AT, Duca L, Cesaretti C, Halawi R, Cappellini MD. Levels of growth differentiation factor-15 are high and correlate with clinical severity in transfusion-independent patients with ß thalassemia intermedia. Blood Cells Mol Dis. 2011 Dec 15. 47(4):232-4. [QxMD MEDLINE Link].

25. [Guideline] Gibson BE, Todd A, Roberts I, et al. Transfusion guidelines for neonates and older children. Br J Haematol. 2004 Feb. 124(4):433-53. [QxMD MEDLINE Link].

26. Origa R, Galanello R, Ganz T, Giagu N, Maccioni L, Faa G, et al. Liver iron concentrations and urinary hepcidin in beta-thalassemia. Haematologica. 2007 May. 92(5):583-8. [QxMD MEDLINE Link]. [Full Text].

27. Preza GC, Ruchala P, Pinon R, et al. Minihepcidins are rationally designed small peptides that mimic hepcidin activity in mice and may be useful for the treatment of iron overload. J Clin Invest. 2011 Dec 1. 121(12):4880-8. [QxMD MEDLINE Link]. [Full Text].

28. Uzun E, Balcı YI, Yuksel S, Aral YZ, Aybek H, Akdag B. Glomerular and tubular functions in children with different forms of beta thalassemia. Ren Fail. 2015 Sep 12. 1-5. [QxMD MEDLINE Link].

29. Girard JM, Drevin G, Brasme JF, et al. Clinical and biological specificity of beta-thalassemia intermedia: a case report. Ann Biol Clin (Paris). 2016 Dec 1. 74 (6):688-92. [QxMD MEDLINE Link].

30. Cela E, Bellon JM, de la Cruz M, et al. National registry of hemoglobinopathies in Spain (REPHem). Pediatr Blood Cancer. 2017 Jul. 64 (7):[QxMD MEDLINE Link].

31. Aessopos A, Kati M, Farmakis D. Heart disease in thalassemia intermedia: a review of the underlying pathophysiology. Haematologica. 2007 May. 92(5):658-65. [QxMD MEDLINE Link]. [Full Text].

32. Succar J, Musallam KM, Taher AT. Thalassemia and venous thromboembolism. Mediterr J Hematol Infect Dis. 2011. 3(1):e2011025. [QxMD MEDLINE Link]. [Full Text].

33. Karimi M, Khanlari M, Rachmilewitz EA. Cerebrovascular accident in beta-thalassemia major (beta-TM) and beta-thalassemia intermedia (beta-TI). Am J Hematol. 2008 Jan. 83(1):77-9. [QxMD MEDLINE Link].

34. Morris CR, Gladwin MT, Kato GJ. Nitric oxide and arginine dysregulation: a novel pathway to pulmonary hypertension in hemolytic disorders. Curr Mol Med. 2008 Nov. 8(7):620-32. [QxMD MEDLINE Link].

35. Parker TM, Ward LM, Johnston DL, Ventureya E, Klaassen RJ. A case of Moyamoya syndrome and hemoglobin E/beta-thalassemia. Pediatr Blood Cancer. 2009 Mar. 52(3):422-4. [QxMD MEDLINE Link].

36. Metarugcheep P, Chanyawattiwongs S, Srisubat K, Pootrakul P. Clinical silent cerebral infarct (SCI) in patients with thalassemia diseases assessed by magnetic resonance imaging (MRI). J Med Assoc Thai. 2008 Jun. 91(6):889-94. [QxMD MEDLINE Link].

37. Singer ST, Ataga KI. Hypercoagulability in sickle cell disease and beta-thalassemia. Curr Mol Med. 2008 Nov. 8(7):639-45. [QxMD MEDLINE Link].

38. Memish ZA, Saeedi MY. Six-year outcome of the national premarital screening and genetic counseling program for sickle cell disease and ß-thalassemia in Saudi Arabia. Ann Saudi Med. 2011 May-Jun. 31(3):229-35. [QxMD MEDLINE Link]. [Full Text].

39. Badens C, Joly P, Agouti I, et al. Variants in genetic modifiers of ß-thalassemia can help to predict the major or intermedia type of the disease. Haematologica. 2011 Nov. 96(11):1712-4. [QxMD MEDLINE Link]. [Full Text].

40. Hankins JS, McCarville MB, Loeffler RB, et al. R2* magnetic resonance imaging of the liver in patients with iron overload. Blood. 2009 May 14. 113(20):4853-5. [QxMD MEDLINE Link]. [Full Text].

41. Wood JC, Mo A, Gera A, Koh M, Coates T, Gilsanz V. Quantitative computed tomography assessment of transfusional iron overload. Br J Haematol. 2011 Jun. 153(6):780-5. [QxMD MEDLINE Link].

42. Deborah Chirnomas S, Geukes-Foppen M, Barry K, Braunstein J, Kalish LA, Neufeld EJ, et al. Practical implications of liver and heart iron load assessment by T2*-MRI in children and adults with transfusion-dependent anemias. Am J Hematol. 2008 Oct. 83(10):781-3. [QxMD MEDLINE Link].

43. Pennell DJ, Carpenter JP, Roughton M, Cabantchik Z. On improvement in ejection fraction with iron chelation in thalassemia major and the risk of future heart failure. J Cardiovasc Magn Reson. 2011 Sep 12. 13:45. [QxMD MEDLINE Link]. [Full Text].

44. Baldini M, Marcon A, Ulivieri FM, et al. Bone quality in beta-thalassemia intermedia: relationships with bone quantity and endocrine and hematologic variables. Ann Hematol. 2017 Jun. 96 (6):995-1003. [QxMD MEDLINE Link].

45. Algiraigri AH, Wright NAM, Paolucci EO, Kassam A. Hydroxyurea for nontransfusion-dependent β-thalassemia: a systematic review and meta-analysis. Hematol Oncol Stem Cell Ther. 2017 Apr 6. [QxMD MEDLINE Link].

46. Karimi M, Darzi H, Yavarian M. Hematologic and clinical responses of thalassemia intermedia patients to hydroxyurea during 6 years of therapy in Iran. J Pediatr Hematol Oncol. 2005 Jul. 27(7):380-5. [QxMD MEDLINE Link].

47. Meiler SE, Wade M, Kutlar F, et al. Pomalidomide augments fetal hemoglobin production without the myelosuppressive effects of hydroxyurea in transgenic sickle cell mice. Blood. 2011 Jul 28. 118(4):1109-12. [QxMD MEDLINE Link]. [Full Text].

48. Cappellini MD. Long-term efficacy and safety of deferasirox. Blood Rev. 2008 Dec. 22 Suppl 2:S35-41. [QxMD MEDLINE Link].

49. Taher AT, Porter J, Viprakasit V, Kattamis A, Chuncharunee S, Sutcharitchan P, et al. Deferasirox reduces iron overload significantly in nontransfusion-dependent thalassemia: 1-year results from a prospective, randomized, double-blind, placebo-controlled study. Blood. 2012 Aug 2. 120(5):970-7. [QxMD MEDLINE Link].

50. Taher AT, Porter JB, Viprakasit V et al. Deferasirox continues to reduce iron overload in non-transfusion-dependent thalassemia: a one-year, open-label extension to a one-year, randomized double-blind, placebo-controlled study (THALASSA). Poster presented at the 54th American Society of Hematology Annual Meeting and Exposition in Atlanta, GA (8-11 December 2012). Abstract #3258.

51. Atichartakarn V, Angchaisuksiri P, Aryurachai K, Chuncharunee S, Thakkinstian A. In vivo platelet activation and hyperaggregation in hemoglobin E/beta-thalassemia: a consequence of splenectomy. Int J Hematol. 2003 Apr. 77(3):299-303. [QxMD MEDLINE Link].

52. Blendis LM, Modell CB, Bowdler AJ. Some effects of splenectomy in thalassaemia major. Br J Haematol. 1974 Sep. 28(1):77-87. [QxMD MEDLINE Link].

53. Sanefuji M, Ohga S, Kira R, et al. Moyamoya syndrome in a splenectomized patient with beta-thalassemia intermedia. J Child Neurol. Jan 2006. 21(1):75-7. [QxMD MEDLINE Link].

54. Graziadei G, Refaldi C, Barcellini W, et al. Does absolute excess of alpha chains compromise the benefit of splenectomy in patients with thalassemia intermedia?. Haematologica. 2012 Jan. 97(1):151-3. [QxMD MEDLINE Link]. [Full Text].

55. Luyendijk W, Went L, Schaad HD. Spinal cord compression due to extramedullary hematopoiesis in homozygous thalassemia. Case report. J Neurosurg. 1975 Feb. 42(2):212-6. [QxMD MEDLINE Link].

56. Cunningham MJ, Macklin EA, Neufeld EJ, et al. Complications of beta-thalassemia major in North America. Blood. 2004 Jul 1. 104(1):34-9. [QxMD MEDLINE Link].

57. Davison SM, Kelly DA. Management strategies for hepatitis C virus infection in children. Paediatr Drugs. 2008. 10(6):357-65. [QxMD MEDLINE Link].

58. Lai ME, Vacquer S, Carta MP, et al. Thalassemia intermedia is associated with a proatherogenic biochemical phenotype. Blood Cells Mol Dis. 2011 Apr 15. 46(4):294-9. [QxMD MEDLINE Link].

May C Chien, MD Clinical Assistant Professor, Department of Medicine, Division of Hematology, Clinical Assistant Professor, Department of Pediatrics, Division of Hematology and Oncology, Associate Director, Hematology Block, Science of Medicine Course, Stanford University School of Medicine

May C Chien, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Physicians, American Society of Clinical Oncology, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Children's Oncology Group, Sigma Xi, The Scientific Research Honor Society

Disclosure: Nothing to disclose.

Clara Yeong-Yi Lo, MD Clinical Assistant Professor, Department of Pediatric Hematology/Oncology, Lucile Packard Children’s Hospital at Stanford Medical Center

Clara Yeong-Yi Lo, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Children's Oncology Group, International Society on Thrombosis and Haemostasis

Disclosure: Nothing to disclose.

Vikramjit S Kanwar, MBBS, MBA, MRCP(UK) Professor Emeritus of Pediatrics, Albany Medical College; Chief of Pediatric Oncology, Homi Bhabha Cancer Hospital, Varanasi, India

Vikramjit S Kanwar, MBBS, MBA, MRCP(UK) is a member of the following medical societies: Children's Oncology Group, Indian Academy of Pediatrics, International Society of Pediatric Oncology

Disclosure: Nothing to disclose.

Hassan M Yaish, MD Medical Director, Intermountain Hemophilia and Thrombophilia Treatment Center; Professor of Pediatrics, University of Utah School of Medicine; Director of Hematology, Pediatric Hematologist/Oncologist, Department of Pediatrics, Primary Children's Medical Center

Hassan M Yaish, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Michigan State Medical Society, New York Academy of Sciences

Disclosure: Nothing to disclose.

James L Harper, MD Associate Professor, Department of Pediatrics, Division of Hematology/Oncology and Bone Marrow Transplantation, Associate Chairman for Education, Department of Pediatrics, University of Nebraska Medical Center; Assistant Clinical Professor, Department of Pediatrics, Creighton University; Director, Continuing Medical Education, Children's Memorial Hospital; Pediatric Director, Nebraska Regional Hemophilia Treatment Center

James L Harper, MD is a member of the following medical societies: American Academy of Pediatrics, American Association for Cancer Research, American Federation for Clinical Research, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Council on Medical Student Education in Pediatrics, and Hemophilia and Thrombosis Research Society

Disclosure: Nothing to disclose.

J Martin Johnston, MD Associate Professor of Pediatrics, Mercer University School of Medicine; Director of Pediatric Hematology/Oncology, Backus Children's Hospital; Consulting Oncologist/Hematologist, St Damien's Pediatric Hospital

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

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Pharmacy Editor, eMedicine

Disclosure: Nothing to disclose.

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