What causes elevated platelets (thrombocytosis)?

Causes of Elevated Platelets (Thrombocytosis)

Thrombocytosis (elevated platelet count) can be categorized as either primary (clonal) or secondary (reactive), with secondary causes being significantly more common in clinical practice.

Primary (Clonal) Thrombocytosis

Primary thrombocytosis occurs due to intrinsic abnormalities in bone marrow megakaryocyte production:

• Essential thrombocythemia (ET): A myeloproliferative neoplasm characterized by sustained platelet count ≥450 × 10^9/L, bone marrow showing proliferation of megakaryocytes, and not meeting criteria for other myeloproliferative disorders 1
• Other myeloproliferative disorders:
  • Polycythemia vera 1
  • Primary myelofibrosis 1
  • Chronic myeloid leukemia 1

Secondary (Reactive) Thrombocytosis

Secondary thrombocytosis is much more common (87.7% of cases) and occurs in response to various underlying conditions 2:

• Tissue damage/trauma (42% of secondary cases) 2

  • Surgery
  • Burns
  • Major trauma 1

• Infections (24% of secondary cases) 2

  • Acute bacterial or viral infections
  • Chronic infections

• Malignancy (13% of secondary cases) 2

  • Solid tumors, particularly breast, lung, gastrointestinal cancers 3
  • Lymphoproliferative disorders

• Chronic inflammation (10% of secondary cases) 2

  • Inflammatory bowel disease
  • Rheumatoid arthritis
  • Connective tissue disorders

• Iron deficiency anemia 1

• Post-splenectomy or hyposplenism 1

• Drug-induced:

  • Corticosteroids
  • Epinephrine
  • Vincristine

Clinical Significance and Complications

The clinical significance of thrombocytosis varies based on etiology:

• Primary thrombocytosis:

  • Higher risk of both arterial and venous thromboembolic complications 2
  • Paradoxically may have increased bleeding risk with extreme thrombocytosis (>1000 × 10^9/L) due to acquired von Willebrand disease 3
  • Increased platelet turnover correlates with thrombotic risk 4

• Secondary thrombocytosis:

  • Generally lower thrombotic risk than primary thrombocytosis 2
  • Thromboembolic events typically restricted to venous system and occur only with additional risk factors 2
  • Usually resolves when underlying condition is treated 5

Laboratory Differentiation

Several laboratory parameters can help distinguish primary from secondary thrombocytosis:

• Primary thrombocytosis typically has:

  • Higher platelet counts 2
  • Normal or lower ESR and fibrinogen 2
  • Presence of JAK2V617F or other clonal markers in ET 1
  • Abnormal megakaryocyte morphology on bone marrow examination 1

• Secondary thrombocytosis typically has:

  • Elevated inflammatory markers (ESR, CRP, fibrinogen) 2
  • Abnormalities in other laboratory values related to the underlying condition 2
  • Absence of clonal markers 1

Management Considerations

Management depends on the underlying cause:

• For primary thrombocytosis:

  • Cytoreductive therapy (anagrelide, hydroxyurea) may be indicated 3
  • Low-dose aspirin (81-100 mg/day) for thrombosis prevention 3
  • Regular monitoring of platelet counts 3

• For secondary thrombocytosis:

  • Treatment of the underlying condition is the primary approach 5
  • Platelet-lowering therapy is generally not required 6
  • In trauma patients with bleeding risk, platelets should be maintained above 50 × 10^9/L (or above 100 × 10^9/L in multiple trauma or traumatic brain injury) 1

Clinical Pearls and Pitfalls

• Extreme thrombocytosis (>1000 × 10^9/L) may paradoxically increase bleeding risk due to acquired von Willebrand disease, especially in primary thrombocytosis 3

• Reticulated platelet percentage (RP%) can help assess thrombotic risk in thrombocytosis - elevated values correlate with increased risk of thrombotic complications 4

• The finding of an elevated platelet count should always prompt investigation for underlying causes, as the majority of cases are secondary (reactive) 2

• In cancer patients, thrombocytosis may be both a paraneoplastic phenomenon and a risk factor for thrombosis 3