What causes thrombocytosis (high platelet count)?

Causes of High Platelets (Thrombocytosis)

Thrombocytosis is divided into two main categories: secondary (reactive) causes, which account for approximately 83% of cases, and primary (clonal) causes, which account for about 12.5% of cases. 1

Primary (Clonal) Thrombocytosis

Primary thrombocytosis results from myeloproliferative neoplasms and typically presents with higher platelet counts and greater thrombotic risk than secondary causes. 1

Essential Thrombocythemia

• Defined by sustained platelet count ≥450 × 10⁹/L with bone marrow showing proliferation of enlarged, mature megakaryocytes. 2
• Requires demonstration of JAK2V617F mutation or other clonal marker, or exclusion of reactive causes when no clonal marker is present. 3
• Must not meet WHO criteria for polycythemia vera, primary myelofibrosis, chronic myeloid leukemia, or myelodysplastic syndrome. 3
• Accounts for 86% of primary thrombocytosis cases with at least one molecular marker indicative of myeloproliferative neoplasms. 1

Other Myeloproliferative Disorders

• Polycythemia vera, primary myelofibrosis, and chronic myeloid leukemia can all present with thrombocytosis. 2
• These disorders are more likely to cause extreme thrombocytosis (>800 × 10⁹/L) and prolonged elevation (>1 month). 4

Secondary (Reactive) Thrombocytosis

Secondary thrombocytosis is far more common and results from underlying conditions that stimulate platelet production. The major causes include:

Tissue Damage and Trauma

• Surgery, burns, and tissue injury account for 32.2% of secondary thrombocytosis cases. 1
• Post-splenectomy or hyposplenism causes persistent thrombocytosis due to loss of platelet sequestration. 2

Infection

• Acute bacterial or viral infections account for 17.1% of secondary thrombocytosis and represent nearly half of all secondary cases in some series. 4, 1
• Demographic factors associated with infectious thrombocytosis include inpatient status, quadriplegia/paraplegia, indwelling prosthesis, dementia, and diabetes. 4
• Clinical features suggesting infection include fever, tachycardia, weight loss, hypoalbuminemia, neutrophilia, leukocytosis, and anemia. 4

Chronic Inflammatory Disorders

• Inflammatory bowel disease and rheumatoid arthritis account for 11.7% of secondary thrombocytosis. 2, 1
• Other chronic inflammatory conditions including connective tissue diseases can cause sustained elevation. 3

Iron Deficiency Anemia

• Iron deficiency accounts for 11.1% of secondary thrombocytosis cases. 1
• Must exclude occult polycythemia vera in iron-deficient patients by trial of iron replacement therapy before diagnosing essential thrombocythemia. 3

Malignancy

• Solid tumors and lymphoproliferative disorders cause thrombocytosis through inflammatory cytokine production. 3, 2
• Metastatic cancer is a recognized cause of reactive thrombocytosis. 3

Drug-Induced

• Corticosteroids and epinephrine can cause thrombocytosis. 2
• Erythropoiesis-stimulating agents are associated with thrombocytosis in cancer patients. 3

Key Distinguishing Features

Platelet Count Magnitude

• Extreme thrombocytosis (≥1,000 × 10⁹/L) is more commonly secondary (66.6%) than clonal (33.4%). 5
• Primary thrombocytosis has significantly higher median platelet counts than secondary causes. 1

Thrombotic Risk

• Primary thrombocytosis carries significantly higher thrombotic risk than secondary thrombocytosis. 1
• Increased platelet turnover (measured by reticulated platelet percentage >14%) is strongly associated with thrombotic complications in both primary and secondary thrombocytosis. 6
• Only 7.9% of secondary thrombocytosis cases experience bleeding or vaso-occlusive complications, compared to 17.1% of clonal cases. 5

Duration and Resolution

• Secondary thrombocytosis typically resolves more rapidly once the underlying condition is treated, whereas primary thrombocytosis is prolonged. 4
• Infection-related thrombocytosis normalizes faster but carries higher mortality risk than non-infectious secondary causes. 4

Critical Diagnostic Pitfalls

Always exclude heparin-induced thrombocytopenia, disseminated intravascular coagulation, infection, and drug reactions before attributing thrombocytosis to other causes. 3

In iron-deficient patients with thrombocytosis, trial iron replacement before diagnosing essential thrombocythemia, as occult polycythemia vera may be masked. 3

Careful bone marrow histologic assessment is necessary to exclude cellular phase/prefibrotic primary myelofibrosis or myelodysplastic syndrome. 3

A patient may have both a reactive cause and essential thrombocythemia simultaneously—diagnosis of essential thrombocythemia can still be made if the first three WHO criteria are met, even with a concurrent reactive condition. 3