What causes elevated platelet counts (thrombocytosis)?

Causes of Elevated Platelet Counts (Thrombocytosis)

Thrombocytosis (elevated platelet count >450 × 10^9/L) is primarily caused by either reactive/secondary conditions (83.1%) or primary hematologic disorders (12.5%), with reactive causes being significantly more common. 1

Primary Thrombocytosis (Clonal)

Primary thrombocytosis occurs due to clonal hematologic disorders, most commonly:

1. Essential Thrombocythemia (ET)

   • Characterized by sustained platelet count ≥450 × 10^9/L 2
   • Bone marrow shows proliferation of megakaryocytic lineage with increased numbers of enlarged, mature megakaryocytes 2
   • Diagnosis requires:
     • JAK2V617F or other clonal marker (present in 86% of cases) 2, 1
     • Not meeting criteria for other myeloproliferative neoplasms 2

2. Other Myeloproliferative Neoplasms (MPNs)

   • Polycythemia Vera (PV)
   • Primary Myelofibrosis (PMF)
   • Chronic Myeloid Leukemia (CML)

Secondary/Reactive Thrombocytosis

Secondary thrombocytosis accounts for over 80% of cases and is caused by:

1. Tissue Injury (32.2%) 1

   • Surgery
   • Trauma
   • Recent procedures

2. Infection (17.1%) 1

   • Acute or chronic infections

3. Chronic Inflammatory Disorders (11.7%) 1

   • Inflammatory bowel disease
   • Rheumatoid arthritis
   • Connective tissue diseases

4. Iron Deficiency Anemia (11.1%) 1, 3

   • Iron deficiency stimulates platelet production
   • Can increase thromboembolic risk in both arterial and venous systems 3

5. Other Causes 2

   • Malignancy/metastatic cancer
   • Post-splenectomy
   • Hemolytic anemia
   • Medications
   • Rebound from thrombocytopenia

Distinguishing Primary from Secondary Thrombocytosis

Clinical Features

• Platelet Count: Significantly higher in primary thrombocytosis 1
• Thrombosis Risk: Higher in primary thrombocytosis 1
• Splenomegaly: More common in primary thrombocytosis 4
• Bleeding Complications: Paradoxical bleeding can occur in primary thrombocytosis 4

Laboratory Assessment

• Molecular Testing: JAK2V617F or other clonal markers present in 86% of primary cases 1
• Inflammatory Markers: Elevated C-reactive protein, fibrinogen, ESR, and IL-6 suggest secondary thrombocytosis 5
• Bone Marrow Examination: Shows characteristic findings in primary thrombocytosis 2
• Iron Studies: To identify iron deficiency as a cause 3

Special Considerations

Platelet Function in Primary Thrombocytosis

Despite elevated platelet counts, patients with primary thrombocytosis (especially PV) may have:

• Paradoxical platelet dysfunction 6
• Acquired von Willebrand syndrome (in >1/3 of PV patients) 6
• Increased risk of both thrombosis and bleeding 6

Risk Stratification in Primary Thrombocytosis

Risk factors for thrombotic complications in ET and PV include:

• Age >60 years 2
• Previous thrombosis 2
• Cardiovascular risk factors 2

Extreme Thrombocytosis

• Platelet counts >1,000 × 10^9/L can be associated with acquired von Willebrand syndrome and bleeding tendency 2, 6
• Paradoxically, extreme thrombocytosis (≥1,500 × 10^9/L) may be associated with lower thrombotic risk in ET 2

Management Implications

The cause of thrombocytosis determines management:

• Secondary Thrombocytosis: Treat underlying cause
• Primary Thrombocytosis: Risk-stratified approach with:
  • Low-dose aspirin (81-100 mg daily) unless contraindicated 6
  • Cytoreductive therapy for high-risk patients 6
  • Regular monitoring of complete blood count 6

Pitfalls to Avoid

1. Assuming all thrombocytosis is benign: While secondary thrombocytosis is generally less concerning, it can still contribute to thrombotic risk, especially in iron deficiency 3

2. Missing underlying malignancy: Thrombocytosis may be the presenting sign of solid tumors 7

3. Overlooking acquired von Willebrand syndrome: Can occur with extreme thrombocytosis, increasing bleeding risk 6

4. Relying solely on platelet count: The degree of elevation does not perfectly distinguish primary from secondary causes 5