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Pediatric Thrombocytosis Differential Diagnoses

  • Author: Susumu Inoue, MD; Chief Editor: Max J Coppes, MD, PhD, MBA  more...
Updated: Mar 31, 2014

Diagnostic Considerations

In patients with secondary thrombocytosis (eg, iron deficiency anemia), if the patient has a thrombotic episode, other etiologies need to be considered (eg, hereditary thrombophilic disorder, antiphospholipid syndrome) because thrombosis as a complication of reactive thrombocytosis is extremely rare in children.

Reactive thrombocytosis is always temporary. If thrombocytosis persists long after the primary causes subsided or if it persists longer than 3 months, consider primary thrombocytosis, and particularly TPO or MPL mutation or polymorphism.

Differential Diagnoses

Contributor Information and Disclosures

Susumu Inoue, MD Professor of Pediatrics and Human Development, Michigan State University College of Human Medicine; Clinical Professor of Pediatrics, Wayne State University School of Medicine; Director of Pediatric Hematology/Oncology, Associate Director of Pediatric Education, Department of Pediatrics, Hurley Medical Center

Susumu Inoue, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Clinical Oncology, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Society for Pediatric Research

Disclosure: Nothing to disclose.

Specialty Editor Board

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.

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; Associate Clinical Professor, Department of Pediatrics, Creighton University School of Medicine; 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 Society of Pediatric Hematology/Oncology, American Federation for Clinical Research, Council on Medical Student Education in Pediatrics, Hemophilia and Thrombosis Research Society, American Academy of Pediatrics, American Association for Cancer Research, American Society of Hematology

Disclosure: Nothing to disclose.

Chief Editor

Max J Coppes, MD, PhD, MBA Executive Vice President, Chief Medical and Academic Officer, Renown Heath

Max J Coppes, MD, PhD, MBA is a member of the following medical societies: American College of Healthcare Executives, American Society of Pediatric Hematology/Oncology, Society for Pediatric Research

Disclosure: Nothing to disclose.

Additional Contributors

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

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

Disclosure: Nothing to disclose.

  1. Teofili L, Foa R, Giona F, Larocca LM. Childhood polycythemia vera and essential thrombocythemia: does their pathogenesis overlap with that of adult patients?. Haematologica. 2008 Feb. 93(2):169-72. [Medline].

  2. Vlacha V, Feketea G. Thrombocytosis in pediatric patients is associated with severe lower respiratory tract inflammation. Arch Med Res. 2006 Aug. 37(6):755-9. [Medline].

  3. Wang JL, Huang LT, Wu KH, et al. Associations of reactive thrombocytosis with clinical characteristics in pediatric diseases. Pediatr Neonatol. 2011 Oct. 52(5):261-6. [Medline].

  4. Tchebiner JZ, Nutman A, Boursi B, et al. Diagnostic and prognostic value of thrombocytosis in admitted medical patients. Am J Med Sci. 2011 Nov. 342(5):395-401. [Medline].

  5. Williams B, Morton C. Cerebral vascular accident in a patient with reactive thrombocytosis: a rare cause of stroke. Am J Med Sci. 2008 Sep. 336(3):279-81. [Medline].

  6. Henry DH, Dahl NV, Auerbach MA. Thrombocytosis and venous thromboembolism in cancer patients with chemotherapy induced anemia may be related to ESA induced iron restricted erythropoiesis and reversed by administration of IV iron. Am J Hematol. 2012 Mar. 87(3):308-10. [Medline].

  7. Go RS. Idiopathic cyclic thrombocytopenia. Blood Rev. 2005 Jan. 19(1):53-9. [Medline].

  8. Teofili L, Larocca LM. Advances in understanding the pathogenesis of familial thrombocythaemia. Br J Haematol. 2011 Mar. 152(6):701-12. [Medline].

  9. El-Harith el-HA, Roesl C, Ballmaier M, et al. Familial thrombocytosis caused by the novel germ-line mutation p.Pro106Leu in the MPL gene. Br J Haematol. 2009 Jan. 144(2):185-94. [Medline].

  10. Abe M, Suzuki K, Inagaki O, Sassa S, Shikama H. A novel MPL point mutation resulting in thrombopoietin-independent activation. Leukemia. 2002 Aug. 16(8):1500-6. [Medline].

  11. Ding J, Komatsu H, Wakita A, et al. Familial essential thrombocythemia associated with a dominant-positive activating mutation of the c-MPL gene, which encodes for the receptor for thrombopoietin. Blood. 2004 Jun 1. 103(11):4198-200. [Medline].

  12. Fujiwara T, Harigae H, Kameoka J, et al. A case of familial thrombocytosis: possible role of altered thrombopoietin production. Am J Hematol. 2004 Aug. 76(4):395-7. [Medline].

  13. Ghilardi N, Wiestner A, Kikuchi M, Ohsaka A, Skoda RC. Hereditary thrombocythaemia in a Japanese family is caused by a novel point mutation in the thrombopoietin gene. Br J Haematol. 1999 Nov. 107(2):310-6. [Medline].

  14. Kikuchi M, Tayama T, Hayakawa H, et al. Familial thrombocytosis. Br J Haematol. 1995 Apr. 89(4):900-2. [Medline].

  15. Graziano C, Carone S, Panza E, et al. Association of hereditary thrombocythemia and distal limb defects with a thrombopoietin gene mutation. Blood. 2009 Aug 20. 114(8):1655-7. [Medline].

  16. Kondo T, Okabe M, Sanada M, et al. Familial essential thrombocythemia associated with one-base deletion in the 5'-untranslated region of the thrombopoietin gene. Blood. 1998 Aug 15. 92(4):1091-6. [Medline].

  17. Liu K, Kralovics R, Rudzki Z, et al. A de novo splice donor mutation in the thrombopoietin gene causes hereditary thrombocythemia in a Polish family. Haematologica. 2008 May. 93(5):706-14. [Medline].

  18. Robins EB, Niazi M. Essential thrombocythemia in a child with elevated thrombopoietin concentrations and skeletal anomalies. Pediatr Blood Cancer. 2008 Apr. 50(4):859-61. [Medline].

  19. Wiestner A, Schlemper RJ, van der Maas AP, Skoda RC. An activating splice donor mutation in the thrombopoietin gene causes hereditary thrombocythaemia. Nat Genet. 1998 Jan. 18(1):49-52. [Medline].

  20. Schlemper RJ, van der Maas AP, Eikenboom JC. Familial essential thrombocythemia: clinical characteristics of 11 cases in one family. Ann Hematol. 1994 Mar. 68(3):153-8. [Medline].

  21. Stuhrmann M, Bashawri L, Ahmed MA, et al. Familial thrombocytosis as a recessive, possibly X-linked trait in an Arab family. Br J Haematol. 2001 Mar. 112(3):616-20. [Medline].

  22. Tecuceanu N, Dardik R, Rabizadeh E, Raanani P, Inbal A. A family with hereditary thrombocythaemia and normal genes for thrombopoietin and c-Mpl. Br J Haematol. 2006 Nov. 135(3):348-51. [Medline].

  23. Kumar TS, Scott JX, Mathew LG. Caffey disease with raised immunoglobulin levels and thrombocytosis. Indian J Pediatr. 2008 Feb. 75(2):181-2. [Medline].

  24. Osovsky M, Tamary H, Merlob P. Neonatal thrombocytosis following G-CSF treatment. Clin Toxicol (Phila). 2007 Oct-Nov. 45(7):801-2. [Medline].

  25. Hwang SJ, Luo JC, Li CP, et al. Thrombocytosis: a paraneoplastic syndrome in patients with hepatocellular carcinoma. World J Gastroenterol. 2004 Sep 1. 10(17):2472-7. [Medline].

  26. Liautard C, Nunes AM, Vial T, et al. Low-molecular-weight heparins and thrombocytosis. Ann Pharmacother. 2002 Sep. 36(9):1351-4. [Medline].

  27. Haddad LB, Laufer MR. Thrombocytosis associated with malignant ovarian lesions within a pediatric/adolescent population. J Pediatr Adolesc Gynecol. 2008 Oct. 21(5):243-6. [Medline].

  28. Valade N, Decailliot F, Rebufat Y, et al. Thrombocytosis after trauma: incidence, aetiology, and clinical significance. Br J Anaesth. 2005 Jan. 94(1):18-23. [Medline].

  29. Dame C, Sutor AH. Primary and secondary thrombocytosis in childhood. Br J Haematol. Apr 2005. 129(2):165-77. [Medline].

  30. Dror Y, Zipursky A, Blanchette VS. Essential thrombocythemia in children. J Pediatr Hematol Oncol. Sep-Oct 1999. 21(5):356-63. [Medline].

  31. Sutor AH. Thrombocytosis in childhood. Semin Thromb Hemost. 1995. 21(3):330-9. [Medline].

  32. Wang JL, Huang LT, Wu KH, et al. Associations of reactive thrombocytosis with clinical characteristics in pediatric diseases. Pediatr Neonatol. 2011 Oct. 52(5):261-6. [Medline].

  33. Teofili L, Giona F, Martini M, et al. Markers of myeloproliferative diseases in childhood polycythemia vera and essential thrombocythemia. J Clin Oncol. 2007 Mar 20. 25(9):1048-53. [Medline].

  34. Eyster ME, Saletan SL, Rabellino EM, et al. Familial essential thrombocythemia. Am J Med. 1986 Mar. 80(3):497-502. [Medline].

  35. Lundstrom U. Thrombocytosis in low birthweight infants: a physiological phenomenon in infancy. Arch Dis Child. 1979 Sep. 54(9):715-7. [Medline].

  36. Matsubara K, Fukaya T, Nigami H, et al. Age-dependent changes in the incidence and etiology of childhood thrombocytosis. Acta Haematol. 2004. 111(3):132-7. [Medline].

  37. [Guideline] Wiedmeier SE, Henry E, Sola-Visner MC, Christensen RD. Platelet reference ranges for neonates, defined using data from over 47,000 patients in a multihospital healthcare system. J Perinatol. 2009 Feb. 29(2):130-6. [Medline].

  38. El-Moneim AA, Kratz CP, Boll S, Rister M, Pahl HL, Niemeyer CM. Essential versus reactive thrombocythemia in children: retrospective analyses of 12 cases. Pediatr Blood Cancer. 2007 Jul. 49(1):52-5. [Medline].

  39. Nakatani T, Imamura T, Ishida H, Wakaizumi K, Yamamoto T, Otabe O. Frequency and clinical features of the JAK2 V617F mutation in pediatric patients with sporadic essential thrombocythemia. Pediatr Blood Cancer. 2008 Dec. 51(6):802-5. [Medline].

  40. Messinezy M, Westwood N, Sawyer B, et al. Primary thrombocythaemia: a composite approach to diagnosis. Clin Lab Haematol. 1994 Jun. 16(2):139-48. [Medline].

  41. [Guideline] Matthews JH, Smith CA, Herst J, et al. The management of malignant thrombocytosis in Philadelphia chromosome-negative myeloproliferative disease: guideline recommendations. Evidence-based series; no. 6-9. 2008 Jan 15. Cancer Care Ontario (CCO):[Full Text].

  42. Saadi Z, Inaba K, Barmparas G, Salim A, Talving P, Plurad D. Extreme thrombocytosis in trauma patients: are antiplatelet agents the answer?. Am Surg. 2009 Oct. 75(10):1020-4. [Medline].

  43. Kastan MB, Zehnbauer BA, Leventhal BG, Corden BJ, Dover GJ. Philadelphia-chromosome positive essential thrombocythemia. Two cases in children. Am J Pediatr Hematol Oncol. 1989. 11(4):433-6. [Medline].

  44. Harrison CN, Gale RE, Machin SJ, Linch DC. A large proportion of patients with a diagnosis of essential thrombocythemia do not have a clonal disorder and may be at lower risk of thrombotic complications. Blood. 1999 Jan 15. 93(2):417-24. [Medline].

  45. Tefferi A, Silverstein MN, Hoagland HC. Primary thrombocythemia. Semin Oncol. 1995 Aug. 22(4):334-40. [Medline].

  46. Aksentijevich I, Masters SL, Ferguson PJ, Dancey P, Frenkel J, van Royen-Kerkhoff A. An autoinflammatory disease with deficiency of the interleukin-1-receptor antagonist. N Engl J Med. 2009 Jun 4. 360(23):2426-37. [Medline].

  47. Fu R, Zhang L, Yang R. Paediatric essential thrombocythaemia: clinical and molecular features, diagnosis and treatment. Br J Haematol. 2013 Nov. 163(3):295-302. [Medline].

  48. Klampfl T, Gisslinger H, Harutyunyan AS, et al. Somatic Mutations of Calreticulin in Myeloproliferative Neoplasms. New Engl J Med. 2013. 2013;369:2379-90:2379-90. [Full Text].

  49. Moliterno AR, Williams DM, Gutierrez-Alamillo LI, et al. Mpl Baltimore: A thrombopoietin receptor polymorphism associated with thrombocytosis. PNAS. 2004. 101:11444-11447.

  50. Munot P, De Vile C, Hemingway C, Gunny R, Ganesan V. Severe iron deficiency anaemia and ischaemic stroke in children. Arch Dis Child. 2011 Mar. 96(3):276-9. [Medline].

  51. Nangalia J, Massie CE, Baxter EJ, et al. Somatic CALR Mutations in Myeloproliferative Neoplasms with Nonmutated JAK2. N Engl J Med. 2013. 369:2391-405.

  52. Rossi-Semerano L, Piram M, Chiaverini C. et al. First clinical description of an infant with interleukin-36-receptor antagonist deficiency successfully treated with anakinra. Pediatrics. 2013. 132:e1043-7.

  53. Rumi E, Pietra D, Ferretti V, et al. JAK2 or CALR mutation status defines subtypes of essential thrombocythemia with substantially different clinical course and outcomes. Blood. 2014. 123:1544-51.

  54. Stockklausner C, Echner N, Klotter AC, Hegenbart U, Dreger P, Kulozik AE. Hereditary thrombocythemia caused by a thrombopoietin (THPO) gain-of-function mutation associated with multiple myeloma and congenital limb defects. Ann Hematol. 2012 Jul. 91(7):1129-33. [Medline].

  55. Unal S, Alanay Y, Cetin M, Boduroglu K, Utine E, Cormier-Daire V. Striking hematological abnormalities in patients with microcephalic osteodysplastic primordial dwarfism type II (MOPD II): a potential role of pericentrin in hematopoiesis. Pediatr Blood Cancer. 2014 Feb. 61(2):302-5. [Medline].

Algorithm for thrombocytosis workup and potential need for medication.
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