What causes thrombocytosis?

Causes of Thrombocytosis

Thrombocytosis is primarily caused by either primary (clonal) disorders or secondary (reactive) conditions, with secondary causes accounting for over 80% of cases. 1

Primary (Clonal) Thrombocytosis (12.5% of cases)

Primary thrombocytosis occurs due to clonal disorders, mainly myeloproliferative neoplasms (MPNs):

• Essential Thrombocythemia (ET)

  • Characterized by sustained platelet count ≥450×10⁹/L
  • Associated with JAK2 V617F mutation in ~50% of cases 2
  • CALR and MPL mutations may also be present

• Polycythemia Vera (PV)

  • JAK2 V617F mutation present in >90% of cases 2
  • Often presents with elevated red blood cells and platelets

• Primary Myelofibrosis (PMF)

  • JAK2 V617F mutation in ~50% of cases 2
  • Associated with bone marrow fibrosis

• Chronic Myeloid Leukemia

  • Associated with BCR-ABL1 fusion gene

Secondary (Reactive) Thrombocytosis (83.1% of cases)

Secondary thrombocytosis is much more common and occurs in response to various conditions:

1. Tissue Injury (32.2%) 1

   • Surgical procedures
   • Trauma
   • Burns

2. Infections (17.1%) 1

   • Bacterial, viral, or fungal infections
   • Particularly common in children

3. Chronic Inflammatory Disorders (11.7%) 1

   • Rheumatoid arthritis
   • Inflammatory bowel disease
   • Adult-onset Still's disease 3
   • Vasculitis

4. Iron Deficiency Anemia (11.1%) 1

   • Common cause, especially in children

5. Malignancy

   • Solid tumors (lung, gastrointestinal, breast)
   • Lymphomas

6. Post-Splenectomy or Hyposplenism

   • Due to loss of splenic platelet pooling

7. Medications

   • Corticosteroids
   • Epinephrine
   • Vincristine

8. Acute Blood Loss

   • Post-hemorrhagic response

9. Rebound from Myelosuppression

   • Following chemotherapy or bone marrow recovery

10. Pregnancy and Hormonal Factors

    • Pregnancy can increase thrombotic risk 3

Clinical Significance and Complications

The clinical significance of thrombocytosis varies based on etiology:

• Thrombotic Risk

  • Significantly higher in primary thrombocytosis compared to secondary causes 1
  • In primary thrombocytosis, arterial and venous thromboses can occur 3
  • Essential thrombocythemia can lead to both arterial and venous thromboses 3

• Bleeding Risk

  • Paradoxically, extreme thrombocytosis can sometimes cause bleeding due to acquired von Willebrand syndrome

Diagnostic Approach

When evaluating thrombocytosis:

1. Exclude secondary causes first

   • Active malignancy, chronic inflammatory disease, splenectomy, and iron deficiency are strongly associated with secondary thrombocytosis 4

2. Laboratory evaluation

   • Complete blood count with peripheral smear
   • Iron studies (ferritin, transferrin saturation)
   • Inflammatory markers (ESR, CRP)
   • Molecular testing for JAK2, CALR, and MPL mutations if primary thrombocytosis is suspected

3. Clinical factors suggesting primary thrombocytosis

   • History of arterial thrombosis
   • Higher hemoglobin, MCV, RDW, and MPV 4
   • Persistent unexplained thrombocytosis
   • Family history of myeloproliferative disorders

Common Pitfalls

• Overlooking secondary causes: Always rule out common reactive causes before pursuing extensive workup for primary thrombocytosis
• Misinterpreting platelet count thresholds: Mild thrombocytosis (450-700×10⁹/L) is most commonly reactive, while extreme thrombocytosis (>1,000×10⁹/L) may be seen in either primary or secondary causes
• Assuming thrombosis risk is proportional to platelet count: The risk of thrombosis in primary thrombocytosis is not directly proportional to the degree of thrombocytosis
• Failing to recognize that the presence of a condition associated with reactive thrombocytosis does not exclude the possibility of essential thrombocythemia if other diagnostic criteria are met 2

In pediatric populations, reactive thrombocytosis is particularly common (occurring in 3-13% of hospitalized children), with primary thrombocytosis being extremely rare (incidence of one per million children) 5.