Pediatric Thrombocytosis Clinical Presentation

Updated: Aug 17, 2020
  • Author: Susumu Inoue, MD; Chief Editor: Hassan M Yaish, MD  more...
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The history of patients with thrombocytosis may include the following.

Reactive thrombocytosis

The history is that of a preceding illness (eg, pneumonia, upper respiratory tract infection, urinary tract infection, iron-deficiency anemia, surgery, hemorrhage, burn, and many others) that triggers thrombocytosis. In some instances, no clear etiology is found; in these cases, investigative efforts may be necessary to exclude asymptomatic asplenia/hyposplenia, primary thrombocytosis, and hereditary thrombocytosis.

In general, symptoms (thrombotic or hemorrhagic) caused by a high platelet count are absent in virtually all cases of reactive thrombocytosis. However, there are exceptions as described below.

In a review article, Sutor reported two children with severe iron-deficiency anemia and platelet counts of more than 1 million/μL who had cerebral infarction. [32] Other comorbid factors, such as vasculitis or hereditary thrombophilia, could not be excluded. An additional four cases of stroke were reported with iron-deficiency anemia, but only one of the four had thrombocytosis. [46] Thus, it is unclear to what degree thrombocytosis contributes to these rare vascular events.

Though extremely rare, children with congenital nephrotic syndrome have a high frequency of thrombosis due to persistent thrombocytosis, activated states of platelets, elevated level of coagulation factors such as von Willebrand factor and factors V and VIII, and a  reduced level of antithrombotic factors such as antithrombin, protein C, and protein S. [12]

Essential (primary) thrombocytosis (ET)

The history is that of mucocutaneous bleeding, such as GI, epistaxis, or postsurgical bleeding, and excessive bruising. Though rare, children also develop hemorrhagic and/or thrombotic complications, although the frequencies are unknown. Ten of 36 children that were reviewed by Dror et al had bleeding or thrombotic episodes before the diagnosis was established. [30]

Headache is the most common feature in the history.

The patient's family members may have the same disorder. To establish familial thrombocythemia, a careful family history and platelet counts should be obtained from the suspected family members when indicated. High levels of TPO assay in multiple family members indicate TPO mutation.



Reactive thrombocytosis

No specific physical findings are related to the increased platelet count.

Essential (primary) thrombocytosis (ET)

Splenomegaly is common but not always present; less commonly, hepatomegaly may be present. Splenomegaly is also common in familial thrombocythemia.

Other physical findings may be found, depending on the hemorrhagic (typically mucous membrane bleeding) or thrombotic complications.

Thrombosis may affect the cerebral, coronary, and/or mesenteric arteries; the portal vein; and/or the inferior vena cava. A thrombotic event may be the presenting symptom of ET.

Classic erythromelalgia (throbbing, aching burning of palms and soles) associated with ET and polycythemia rubra vera has not been described in children.



Reactive (secondary) thrombocytosis

Causes of reactive, or secondary, thrombocytosis include the following:

  • Infection - Meningitis, upper and lower respiratory tract infections, septic arthritis, osteomyelitis, urinary tract infection, gastroenteritis, sepsis, severe dermatitis, toxocariasis, HIV infection
  • Chronic inflammations and vasculitis -  Rheumatoid arthritis, Kawasaki syndrome, Henoch-Schönlein purpura, Caffey disease, TNF (tumor necrosis factor) receptor–associated periodic (TRAP) syndrome, inflammatory bowel disease, autoimmune disease, collagen vascular disease
  • Hemorrhage, iron-deficiency anemia
  • Tissue damage - Postsurgical, burns, trauma, fracture [47]
  • Rebound thrombocytosis - cancer chemotherapy, recovery phase of immune thrombocytopenic purpura (ITP)
  • Postsplenectomy - ITP, splenectomy for hereditary spherocytosis, traumatic asplenia, post splenic artery embolization, autosplenectomy in sickle cell disease
  • Congenital asplenia, or hyposplenia associated with immunodeficiency syndrome
  • Hemolytic anemia - Sickle cell disease, thalassemia, and other hemolytic anemia
  • Renal disorders - Nephrotic syndrome, nephritis
  • Malignancy - Soft tissue sarcoma, osteosarcoma, hepatoblastoma, hepatocellular carcinoma, malignant ovarian tumor [48]
  • Low birth weight/preterm infants
  • Miscellaneous causes - Use of low molecular–weight heparin, granulocyte-colony stimulating factor treatment in neonates, familial urticaria pigmentosa
  • PACAP deficiency

A retrospective, observational cohort study by Boucher et al indicated that in pediatric patients, splenectomy performed as a result of pancreatectomy with islet autotransplantation (IAT) is associated with more severe reactive thrombocytosis than is splenectomy for other indications. While 93.8% of the splenectomy patients in the study developed reactive thrombocytosis, those who underwent IAT had a risk ratio of 4.11 for extreme thrombocytosis (platelets 1000 K/μL or more). In addition, the platelet count rose significantly faster in the IAT patients. According to the investigators, these results strongly suggest that following IAT, it is unlikely that splenectomy alone contributes to reactive thrombocytosis. [49]

Essential (primary) thrombocytosis

Causes of essential, or primary, thrombocytosis include the following:

  • Myelofibrosis with myeloid metaplasia
  • Polycythemia vera -  PRV-1 overexpression may be present
  • Chronic myelocytic leukemia: BCR-ABL fusion gene is present
  • Familial essential thrombocytosis -  MPL or TPO gene mutation may be present; blood TPO assay may be helpful (high); this includes K39N substitution of MPL gene, MPLBaltimore (polymorphism is limited to African American population)
  • Essential thrombocytosis -  JAK2V617Fmutation or CALR gene mutation may be present; the frequency of JAK2V617F is lower in children (11-50%) than in adults (>50%); frequency of CALR mutation in children is not known; JAK2V617I mutation somatic cells described in one family; MPL gene mutations