Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Pediatric Thrombocytosis

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

Background

The physiologic reference range of platelet counts is 150-400 X 109/L. A platelet count exceeding the upper limit is called thrombocytosis or thrombocythemia. Thrombocytosis is classified as either primary or secondary.

Primary thrombocytosis

Primary thrombocytosis (also called essential thrombocytosis or essential thrombocythemia) consists of 2 types. The first is classical primary thrombocytosis and is caused by autonomous production of platelets unregulated by the physiologic feedback mechanism to keep the count within the reference range. It is a subset of myeloproliferative disorder (eg, essential thrombocythemia, myelofibrosis with myeloid metaplasia, polycythemia vera, chronic myelocytic leukemia [rare]) or, in rare cases, of acute myelocytic leukemia.

Hematopoiesis in these patients is monoclonal and is caused by JAK2V617Fmutation[1] or calreticulin gene (CALR) mutation.[2, 3] JAK2 mutation and CALR mutation are mutually exclusive, and there is a distinct phenotypic difference between these 2.[4]

The second type of primary thrombocytosis is, in most cases, familial and is caused by a mutation of either the thrombopoietin (TPO) gene or thrombopoietin receptor gene (MPL). Hematopoiesis in this type of mutation is polyclonal.

Secondary thrombocytosis

In contrast to primary thrombocytosis, secondary thrombocytosis is an exaggerated physiologic response to a primary event, such as an infection. In pediatrics, primary thrombocytosis is exceedingly rare, whereas secondary, or reactive, thrombocytosis is exceedingly common, particularly in infants.

Secondary thrombocytosis (the term reactive thrombocytosis is used in all subsequent discussions) is usually transient and subsides when the primary stimulus ceases. Despite the strikingly high platelet count (on occasions exceeding 1000 X 109/L, or 1 million/mcL), thrombotic and/or hemorrhagic complications are highly exceptional. This is in contrast to thrombosis and bleeding that are more common complications of primary thrombocythemia.

Next

Pathophysiology

Reactive thrombocytosis is usually mediated by increased release of numerous cytokines in response to infections, inflammation, vasculitis, tissue trauma, and other factors. Thrombopoietin (TPO), the primary cytokine for platelet production and maturation, and interleukin (IL)-6 levels are usually initially elevated in response to the primary events mentioned earlier; they stimulate an increase in platelet production. However, serum or plasma levels of these cytokines do not seem to be correlated with degree of thrombocytosis.

Other cytokines may participate in the stimulation of platelet production. They include IL-3, IL-11, granulocyte-macrophage colony-stimulating factor (GM-CSF), and erythropoietin. These cytokines are directly or indirectly released during the primary events. When the original stimulation stops, the platelet count then returns to the reference range.

In severe infections, such as bacterial meningitis, one of the causes may be a rebound phenomenon after initial thrombocytopenia due to rapid consumption of platelets. This most commonly occurs in neonates and infants, indicating the labile nature of platelet count control in these subjects.

The most common infection associated with thrombocytosis is pneumonia. Vlacha and Feketea described 102 children admitted with a diagnosis of lower respiratory tract infection; 49 of these children (median age 31 mo) developed platelet counts over 500,000.[5] Rebound thrombocytosis is also observed in the recovery phase of chemotherapy-induced thrombocytopenia and during the recovery phase of immune thrombocytopenic purpura (ITP). None of the patients developed thrombotic episodes.

A study from Taiwan on pediatric reactive thrombocytosis (platelet count >500,000/μL) showed a positive correlation between platelet count and WBC count and an inverse relation between platelet count and blood hemoglobin level. The same study reported that thrombocytosis is a significant independent risk factor for the length of hospital stay. A study done on an adult population in Israel showed that thrombocytosis is a risk factor for prolonged hospitalization in adults as well; the mortality rate of patients with thrombocytosis was significantly higher than that of nonthrombocytosis patients.[6]

In some instances, such as chronic hemolytic anemia, the stimulus (hypoxia) to produce cytokines persists, causing long-term elevation of platelet counts. Although thrombocytosis in association with iron-deficiency anemia is well documented, the mechanism remains unclear. Although elevated erythropoietin levels are observed in patients with thrombocytosis who have iron-deficiency anemia, one study showed that these elevated levels had no correlation with platelet count. levels of other cytokines potentially responsible for thrombocytosis, such as IL-6 and TPO, were not elevated. In some cases, an increased number of bone marrow megakaryocytes is observed.[7, 8]

In this context, a study on patients with chemotherapy-induced anemia shed some light on this subject. Patients randomly received intravenous (IV) iron, oral iron, or no iron in addition to erythroid-stimulating agents (ESA). The patients who received IV iron developed the least degree of thrombocytosis, and patients who received no iron developed the greatest degree of thrombocytosis, whereas the patients who received oral iron developed an intermediate degree of thrombocytosis. This observation suggested that although ESA causes thrombocytosis, iron deficiency itself was an additional factor to contribute to thrombocytosis.[9]

A rare disorder of unknown etiology, idiopathic cyclic thrombocytopenia is characterized by female predominance, fluctuation of platelet count with rebound thrombocytosis (with peak >1 million/μL), and median age of onset at age 35 years, although the youngest child described was aged 1 year.[10] If a patient with this diagnosis were to be evaluated during the rebound thrombocytosis, one may erroneously conclude that the patient developed acquired thrombocytosis.

Sporadic (nonfamilial) primary thrombocytosis is usually a clonal disorder, although nonclonal essential thrombocythemia has also been well documented. The recently described MPL polymorphism gene, MPLBaltimore, belongs to this polyclonal thrombocytosis (see below). The most common diagnosis in the pediatric age group is chronic myelogenous leukemia (CML). Polycythemia vera, essential thrombocytosis (ET), and myelofibrosis (MF) with myeloid metaplasia are other diagnoses associated with primary thrombocytosis; however, these are rare in children.

In primary thrombocytosis, primary and secondary hypercoagulable states frequently lead to thrombotic episodes and to a hemorrhagic tendency. In about 30% of pediatric cases, JAK2V617Fmutation has been documented. More recently another mutation involving the CALR gene was independently documented by 2 groups of investigators[2, 3] in patients with myeloproliferative disorders. Though JAK2V617mutation has been found in both polycythemia vera and essential thrombocytosis patients, CALR mutation was found only in patients with essential thrombocytosis.[4]

Familial or hereditary primary ET in children are heterogeneous disorders of different molecular abnormalities. Inheritance patterns vary; most familial thrombocythemia cases due to TPO gene mutations are transmitted in autosomal dominant manner. However, some are autosomal recessive. In one family, transmission appears to be X-linked recessive.[11]

At least 2 classes of molecular mutations that lead to familial thrombocytosis are known. One involves mutations of the TPO gene that result in increased TPO production by various mechanisms. The other involves mutations of the C-MPL (TPO) receptor gene that somehow constitutively maintains activated signal transduction, leading to continuous signaling for megakaryocytic proliferation. In some families, no specific molecular abnormalities have been found. Reported cases in which molecular abnormalities were investigated include the following:

Additional new mutations are likely to be reported in future. Readers may consult the recent comprehensive review of all reported mutations that cause hereditary thrombocytosis.[12] Familial (hereditary) thrombocytosis reports are as follows:

  • MPL mutation
    • A large Arab family with a p.Pro106Leu mutation and no thrombosis was reported by El-Harith et al.[13]
    • Abe et al reported an amino acid substitution of Trp(508) to Ser(508) in the intracellular domain of MPL.[14]
    • Ding et al reported 8 members of a Japanese family with a mutation in the transmembrane domain of MPL.[15]
    • An MPL gene polymorphism, designated as MPOBaltimore(K39N substitution) causes little-to-moderate thrombocytosis (median of about 400,000) in heterozygous individuals and marked thrombocytosis (800,000-900,000) in homozygous persons. The frequency of MPLBalitmorewas found to be 7% in African American population.[16] Thus, some African Americans who were previously diagnosed to have essential thrombocytosis without detectable JAK2 or CALR mutation may have this polymorphism.
  • TPO gene mutation or increased blood TPO level
    • Fujiwara et al reported on 3 members in a Japanese family with increased serum TPO levels and no mutation found in the TPO or MPL gene.[17]
    • Ghilardi et al and Kikuchi et al reported 4 members in 3 generations in a Japanese family who had a novel point mutation in the TPO gene.[18, 19]
    • Graziano et al reported on 3 members in a family who had a TPO mutation (G185T) and associated limb defects.[20]
    • Kondo et al reported on 5 members in 3 generations of a Japanese family who had a base deletion in the TPO gene (5'UTR).[21]
    • Liu et al reported on 11 members in a Polish family with a G→C transversion in the splice donor of intron 3 of the TPO gene.[22]
    • Robins et al reported a mother and child with elevated TPO levels. The mutation was not studied. The child had a limb defect.[23]
    • Wiestner et al and Schlemper et al reported 11 members of a Dutch family with a G→C transversion in the splice donor of intron 3 of the TPO gene.[24, 25] Thrombosis and hemorrhage were noted.
    • Stockklausner et al in Germany reported 2 families due to TPO gene c. 13+1 G/C mutation in the splice donor of intron 3. Two members of 1 family had upper limb defects.[26] One of the family was previously described by Wiestner et al as above.
  • Mutation of other genes
    • Homozygous mutations of interleukin 1 receptor antagonist (IL1RN) reported by Aksentijevich I et al[27] and homozygous mutations of interleukin 36 receptor antagonist (IL36RN) reported by Rossi-Semerano L et al[28] caused significant thrombocytosis and leukocytosis in affected individuals. Treatment with anakinra normalized these counts.
    • In addition to blood count abnormalities, patients with IL1RN mutation showed skin pustulosis, skeletal abnormalities, hepatosplenomegaly, and pulmonary disease, whereas patients with latter mutations showed only dermatological manifestations (ie, systemic pustular psoriasis).
  • Neither MPL gene nor TPO gene mutation found or studied
    • Stuhrmann et al reported on 4 Arab siblings with familial thrombocytosis.[11]
    • Tecuceanu et al reported on an Israeli-Jewish family with mild thrombocytosis (highest platelet count was 506 X 109/L).[29]
    • Patients with microcephalic osteodystrophic primordial dwarfism (MOPD) type II have been described to have a moderate degree of thrombocytosis and leukocytosis. MOPD type 2 is caused by loss of function mutation of pericentrin gene.[30]

Causes of secondary noninfectious thrombocytosis reported in the literature are listed below:

  • Caffey disease [31]
  • Granulocyte-colony stimulating factor treatment in neonates [32]
  • Hepatocellular carcinoma [33]
  • Low molecular–weight heparain [34]
  • Malignant ovarian tumors [35]
  • Trauma [36]

Acquired ET in children is similar to that found in adults. JAK2V617Fmutation and PRV-1 RNA positivity are less frequent than in adults, but frequency of JAK2 mutation increases with age. Although the role of JAK2 mutation in myeloproliferation is clear, many pediatric patients do not exhibit this mutation; CALR, mutation has been recently described. This mutation causes features of essential thrombocytosis and does not cause other clinical features characteristic of myeloproliferative disorder. The incidence of this somatic gene mutation in children is currently not published.

The spleen is the major organ for the destruction of platelets; therefore, after splenectomy, a sharp rise in the platelet count is routinely observed, although the count subsequently slowly decreases to the reference range. Similarly, functional asplenia that may occur after splenic artery embolization results in thrombocytosis.

Previous
Next

Epidemiology

Frequency

United States

Dame and Sutor stated that the annual incidence of newly diagnosed primary thrombocytosis in childhood is 1 case per 10 million population.[37] According to these authors, about 75 children with primary thrombocytosis were reported from 1966-2000.

Dror et al published the results of an analysis of 36 children with essential thrombocytosis, but not the incidence of essential thrombocytosis.[38]

The frequency of reactive thrombocytosis is far more common than essential thrombocytosis and depends on age. Rates are highest during the first 3 months of life. Preterm infants have higher frequencies than those of term infants. According to Sutor's summary of several studies, 3-13% of hospitalized pediatric patients had a thrombocyte count of more than 500 X 109/L. In one study, 0.5% of hospitalized children had a platelet count more than 800 X 109/L.[39]

No evidence suggests that the incidences of either primary or reactive thrombocytosis vary significantly from one country to another or from one ethnic group to another. A Taiwanese study done at a general hospital indicated the incidence of reactive thrombocytosis to be 6.3% of all hospitalized children (birth to age 18 y).[40]

International

See above. The incidence of essential thrombocytosis is estimated to range from 1-4 cases per 10 million people younger than 20 years.[1]

Mortality/Morbidity

Thrombotic or hemorrhagic complications caused by reactive or secondary thrombocytosis are described only anecdotally and must be regarded as extremely rare. However, in children with autoimmune disease or vasculitis, such as Kawasaki syndrome, thromboses do develop. In Kawasaki syndrome, this occurs particularly in the coronary arteries.

In patients with primary nonfamilial thrombocytosis, which is a myeloproliferative disorder, the frequency of thrombosis and/or hemorrhage widely varies among various reports (20-84% for thrombotic complications and 4-41% for bleeding complications). However, these statistics are for adult patients, and incidences of hemorrhagic and thrombotic complications in primary thrombocytosis of children are not known.

On the basis of experiences in young adults with primary thrombocytosis, these complications may occur less often in children than in adults.[41] Teofili et al reported a 0% rate of thrombosis in children with essential thrombocytosis, as opposed to 10 of 32 patients in a study of adults. On the other hand, Dame and Sutor reported that about 30% of children with essential thrombocytosis had thromboembolic or hemorrhagic complications at the time of diagnosis or later, and that about 20% of initially asymptomatic children had these complications later.[37] These figures are similar to those of adults. Bleeding mainly involves the mucous membranes and skin (eg, GI hemorrhage, hemoptysis, post surgical bleeding, bruises, epistaxis). Thrombosis involves the veins and arteries. The complication rates in familial thrombocythemia are not well described due to its rarity, but both thrombosis and hemorrhage occur.[38, 41]

Race

Essential thrombocytosis has no reported racial predisposition.

Sex

No sex difference is reported in the frequency of essential or reactive thrombocytosis.

Age

Preterm infants and young infants do not maintain a platelet count in a range that is defined as normal for adults.

The frequency of reactive thrombocytosis is higher in infants and young children (see Frequency) than in older children. Preterm healthy infants have platelet counts higher than those of nonpreterm children. Lundstrom reported that the 95% limit for platelet counts in infants with a birth weight of less than 2000 g was 160-675 X 109/L, with a median value of 375 X 109/L.[42]

Matsubara et al reported an age-related shift in mean platelet counts.[43] According to the authors, 12.5% of infants younger than 1 month, 35.9% of infants aged 1 month, and 29.2% of those aged 2 months had platelet counts of 500 X 109/L or more, whereas only 0.6% of children aged 11-15 years had such counts.

An age-related reference range of platelet counts in preterm infants (22-42 weeks' gestation) is available.[44] According to this article, the 95th percentile line exceeds 700,000 at 35-49 postnatal days in this cohort of patients.

Previous
 
 
Contributor Information and Disclosures
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, 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.

References
  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].

 
Previous
Next
 
Algorithm for thrombocytosis workup and potential need for medication.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.