Medical Care

Normally, no treatment is necessary for reactive thrombocytosis. Rarely, in patients who have reactive thrombocytosis and a known risk factor for thrombosis, such as factor V Leiden mutation, the thrombotic risk may be increased. However, no information is currently available regarding the magnitude of the risk. Therefore, one should consider each case individually for prophylaxis of thrombosis.

In vasculitis syndrome with thrombocytosis (in particular, in Kawasaki syndrome), treatment with aspirin is recommended (see Kawasaki Disease). In primary thrombocytosis, prophylactic use of antithrombotic agents has not been well delineated. In general, platelet-lowering agents have been recommended for high-risk adult patients, ie, those with an increased cardiovascular risk or a previous history of thrombosis or who are older than 60 years (see Medication). Indications for thrombosis prophylaxis are not firmly established for children; the use of antithrombotics and anticoagulants should be individualized, weighing the risks and benefits.

In adult patients with posttrauma thrombocytosis (platelet count >1 million), treatment with aspirin showed no effect in the rate of mortality, complications, and length of ICU stay. However, these results are from a retrospective, nonrandomized study; thus, they do not answer whether aspirin is useful in this group of patients. Anticoagulation to prevent thrombosis with heparin or low–molecular-weight heparin is the standard of care for these adult patients, unless there are bleeding problems.

In patients in whom primary thrombocytosis is strongly suspected, laboratory studies mentioned in the previous section and evaluation of family members are needed to confirm the diagnosis. Morphologic and cytogenetic examination of bone-marrow cells and marrow reticulin stains should be repeated in patients with a changing hematologic picture (refer patients to a hematologist).

Evolution of primary thrombocytosis to frank acute myeloblastic leukemia (AML), myelofibrosis/agnogenic myeloid metaplasia (AMM), or myelodysplastic syndrome (MDS) has been documented in adults and represents a progression of disease. The prognosis after this progression is poor. However, successful allogeneic bone-marrow or stem-cell transplantation has been reported in patients who developed AML/MDS and/or myelofibrosis. Therefore, keep this modality in mind when treating primary thrombocytosis. More detailed discussion of pediatric primary thrombocytosis is found in an article by Kucine et al.^[1]

Consultations

A persistent increase in neutrophil counts with immature forms (eg, metamyelocytes, myelocytes), persistent increase in basophils and eosinophils, and splenomegaly suggest a chronic myelocytic leukemia (CML). Kastan et al described two children whose clinical findings and blood counts best fit essential thrombocytosis (ET) but whose bone-marrow cytogenetic analyses showed the presence of the Philadelphia (Ph1) chromosome. Both of these patients presented with platelet counts in excess of 2 million/μL.^[50]Another child with CML presented with the initial platelet count of 2.8 million/μL.^[5]

A persistent increase in the hematocrit (with or without a change in the WBC count) with thrombocytosis suggests polycythemia vera. The image below shows suggested workup algorithm for thrombocytosis.

Algorithm for thrombocytosis workup and potential need for medication.

One should consult a hematologist if a workup for ET is needed. Older children with thrombocytosis with thrombosis (suspected or demonstrated) or a history of thrombosis, increased bleeding tendency despite thrombocytosis, or splenomegaly must promptly be referred to a hematologist. Also, a family history of thrombocytosis requires consultation with a hematologist and geneticist because a genetic work-up is necessary.

Activity

No medical reason warrants the limitation or encouragement of activity in a child with thrombocytosis. A child with a substantially enlarged spleen (usually caused by essential or familial thrombocythemia) requires necessary precautions regarding their activity to prevent splenic rupture.

Medication

Kucine N, Chastain KM, Mahler MB, Bussel JB. Primary thrombocytosis in children. Haematologica. 2014 Apr. 99 (4):620-8. [QxMD MEDLINE Link]. [Full Text].
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].
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.
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.
Verma SP, Subbiah A, Jacob SE, Basu D. Chronic myeloid leukaemia with extreme thrombocytosis. BMJ Case Rep. 2015 Aug 19. 2015:[QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Zheng SY, Xiao QY, Xie XH, et al. Association between secondary thrombocytosis and viral respiratory tract infections in children. Sci Rep. 2016 Mar 11. 6:22964. [QxMD MEDLINE Link]. [Full Text].
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. [QxMD MEDLINE Link].
Go RS. Idiopathic cyclic thrombocytopenia. Blood Rev. 2005 Jan. 19(1):53-9. [QxMD MEDLINE Link].
Teofili L, Larocca LM. Advances in understanding the pathogenesis of familial thrombocythaemia. Br J Haematol. 2011 Mar. 152(6):701-12. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Eneman B, Freson K, van den Heuvel L, et al. Pituitary adenylate cyclase-activating polypeptide deficiency associated with increased platelet count and aggregability in nephrotic syndrome. J Thromb Haemost. 2015 May. 13 (5):755-67. [QxMD MEDLINE Link].
Freson K, Hashimoto H, Thys C, et al. The pituitary adenylate cyclase-activating polypeptide is a physiological inhibitor of platelet activation. J Clin Invest. 2004 Mar. 113 (6):905-12. [QxMD MEDLINE Link]. [Full Text].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Kikuchi M, Tayama T, Hayakawa H, et al. Familial thrombocytosis. Br J Haematol. 1995 Apr. 89(4):900-2. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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.
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. [QxMD MEDLINE Link].
Dror Y, Zipursky A, Blanchette VS. Essential thrombocythemia in children. J Pediatr Hematol Oncol. Sep-Oct 1999. 21(5):356-63. [QxMD MEDLINE Link].
Zeng K, Li L, Huang L, Liang YH. Newly identified phenotypes in a FIP1L1/PDGFRA-associated paediatric HES patient: thrombocytosis, mHPA, young stroke and blindness. J Eur Acad Dermatol Venereol. 2015 Mar. 29 (3):614-6. [QxMD MEDLINE Link].
Sutor AH. Thrombocytosis in childhood. Semin Thromb Hemost. 1995. 21(3):330-9. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Eyster ME, Saletan SL, Rabellino EM, et al. Familial essential thrombocythemia. Am J Med. 1986 Mar. 80(3):497-502. [QxMD MEDLINE Link].
Lundstrom U. Thrombocytosis in low birthweight infants: a physiological phenomenon in infancy. Arch Dis Child. 1979 Sep. 54(9):715-7. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Kagialis-Girard S, Mialou V, Ffrench M, Dupuis-Girod S, Pages MP, Bertrand Y. Thrombocytosis and toxocariasis: report of two pediatric cases. Pediatr Blood Cancer. 2005 Feb. 44 (2):190-2. [QxMD MEDLINE Link].
Scheuerman O, Bar-Sever Z, Hoffer V, Gilad O, Marcus N, Garty BZ. Functional hyposplenism is an important and underdiagnosed immunodeficiency condition in children. Acta Paediatr. 2014 Sep. 103 (9):e399-403. [QxMD MEDLINE Link].
Dame C, Sutor AH. Primary and secondary thrombocytosis in childhood. Br J Haematol. Apr 2005. 129(2):165-77. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Szuber N, Vallapureddy RR, Penna D, et al. Myeloproliferative neoplasms in the young: Mayo Clinic experience with 361 patients age 40 years or younger. Am J Hematol. 2018 Aug 29. [QxMD MEDLINE Link].
[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].
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. [QxMD MEDLINE Link].
[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. [QxMD MEDLINE Link].
Tefferi A, Silverstein MN, Hoagland HC. Primary thrombocythemia. Semin Oncol. 1995 Aug. 22(4):334-40. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Boucher AA, Luchtman-Jones L, Palumbo JS, et al. Extreme Thrombocytosis after Pediatric Pancreatectomy with Islet Autotransplantation Is Unique Compared to Other Postsplenectomy States. J Pediatr Surg. 2019 Oct 25. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].

Media Gallery

Algorithm for thrombocytosis workup and potential need for medication.

of 1

Author

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, Hurley Medical Center

Susumu Inoue, 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, 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

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.

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.

Sections Pediatric Thrombocytosis
Overview
Presentation
- History
- Physical
- Causes
- Show All
DDx
Workup
Treatment
Medication
Follow-up
References

Pediatric Thrombocytosis Treatment & Management

Medical Care

Consultations

Activity

References

Tables

Contributor Information and Disclosures

What would you like to print?