About the Condition


Thrombocytosis is defined as a platelet count > 450 x 109/L (some labs consider a threshold platelet count of > 400 x 109/L as qualifying for thrombocytosis).

Classification of thrombocytosis:

Spurious – Counting of nonplatelet structures in the peripheral blood by automated counters resulting in high platelet count.

Primary – 15% of cases:

  • Familial:
    • Intrinsic – mutations of genes within the megakaryocytic lineage (e.g., thrombopoietin receptor).
    • Extrinsic – mutations of genes outside the megakaryocytic lineage (e.g. thrombopoietin).
  • Acquired:
    • Essential thrombocythemia
    • Other myeloproliferative neoplasms
    • Myelodysplastic syndrome:
      • MDS/MPN-RS-T
      • del (5q-)

Secondary – 85% of cases:

  • Bleeding
  • Hemolysis
  • Cancer
  • Infections
  • Inflammatory disorders
  • Iron deficiency
  • Asplenia
  • Drugs
  • Tissue injury:
    • Trauma
    • Surgery


CauseGriesshammer et al, 1999Bess et al, 1994Hsieh et al, 2019
732 adult in-patients and outpatients; platelet count > 500 x 109/L280 adult patients with platelet count > 1,000 x 109/L305 adult patients with platelet count > 1,000 x 109/L*
Secondary 88%86%69%**
Tissue damage37%14%NM
Cancer11.6%14%28% (heme malignancy); 1.6% had newly diagnosed non-heme malignancy
Chronic inflammation9%9%NM
Renal disorders2%NM NM
Iron deficiencyNM NM 0.3%
MedicationsNM NM 6.2%
Blood lossNM 6%NM
Surgical complicationsNM NM54%
MultifactorialNM NM 79.3%
NM, not mentioned; *most were causes were multifactorial, prevalence of dominant causes shown; **11% had primary and secondary causes.
  • The patient in this case developed thrombocytosis following cardiac bypass surgery. How common is this occurrence?
    • In a cohort of 297 patients undergoing cardiac bypass surgery:
      • 20% reported to develop thrombocytosis
      • Typically occurred one week after operation
    • In another study of 30 patients undergoing cardiac bypass surgery who developed thrombocytosis (platelet count >500 x 109/L), thrombocytosis developed at mean day 6 and peaked on day 14 (see figure).


Cause of thrombocytosisPathophysiology
Primary thrombocytosis Mutations in driver genes such as Jak2, MPL (thrombopoietin receptor) and CALR.
Secondary thrombocytosis
Iron deficiencyIncreased commitment of mixed lineage progenitor cells to megakaryocytes.
AspleniaLoss of platelet sequestration, reduced platelet destruction (increased platelet lifespan).
SurgeryOvershoot from thrombopoietin response to platelet dilution and consumption (learn more here).
InfectionsMacrophage-derived cytokines, especially interleukin-6, increase thrombopoietin levels, which in turn increase platelet numbers.
Inflammatory disordersMacrophage-derived cytokines, especially interleukin-6, increase thrombopoietin levels, which in turn increase platelet numbers.
Cancer (highest prevalence in colorectal and mesothelioma)Macrophage-derived cytokines, especially interleukin-6, increase thrombopoietin levels, which in turn increase platelet numbers.

Clinical presentation:

Thrombocytosis may be found while evaluating other clinical findings or as an incidental finding on a complete blood count. Primary thrombocytosis is more likely if:

  • Unexplained vasomotor symptoms (eg, erythromelalgia, flushing, pruritus).
  • Constitutional symptoms (eg, unexplained fever, sweats, or weight loss) and/or splenomegaly.
  • Thrombosis at unusual sites or unprovoked or recurrent thrombosis without other explanation.
  • Blood smear that reveals leukemic blasts, leukoerythroblastic features, or other evidence of leukemia or related hematologic malignancy.
  • Family history of unexplained thrombocytosis.


Primary diagnostic goal is to differentiate between primary and secondary thrombocytosis because only primary types have established increased risk of thrombosis and bleeding.

Cause of thrombocytosisLab tests
Primary thrombocytosis If no secondary cause is found, genetic testing for driver mutations such as JAK2, MPL, CALR found in essential thrombocythemia.
Secondary thrombocytosis
BleedingCBC and reticulocyte count, investigation of underlying bleeding source, for example with upper and lower endoscopy.
HemolysisCBC, reticulocyte count, LDH, haptoglobin, bilirubin, AST.
Iron deficiencyCBC, serum iron, TIBC, ferritin.
AspleniaPeripheral smear for Howell-Jolly bodies.
InfectionsCXR, CT scan as indicated, blood cultures.
Inflammatory disordersCRP, erythrocyte sedimentation rate, additional evaluation for inflammatory conditions as indicated.
DrugsStop medication(s) and repeat platelet count.
Cancer (highest prevalence in colorectal and mesothelioma)Cancer screening, imaging as indicated (thrombocytosis may precede diagnosis of cancer by months or years).
CBC, complete blood count; TIBC, total iron binding capacity; CRP, C-reactive protein; CXR, chest X-ray.
Diagnostic pathway for the investigation of thrombocytosis. *BCR-ABL1 testing is only recommended if there are atypical features on the blood count and/or film (e.g. basophilia). Bone marrow examination is recommended to confirm the diagnosis, as per the WHO Classification. In some circumstances this may not be clinically indicated. The need for Cytogenetics on the bone marrow should be guided by the blood and bone marrow morphology. From BCSH guidelines for patients with thrombocytosis.


Primary thrombocytosis Secondary thrombocytosis
Antiplatelet agentYesNo
Cytoreductive therapyYesNo
Treat underlying causeNoYes
*May be considered rarely to reduce platelet counts in patients with extreme thrombocytosis of unknown cause and active bleeding or critical thrombosis.

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