What causes thrombocytosis?

Causes of Elevated Platelet Count (465 × 10⁹/L)

A platelet count of 465 × 10⁹/L most likely represents secondary (reactive) thrombocytosis, which accounts for approximately 83-88% of all thrombocytosis cases and is generally benign, requiring identification and treatment of the underlying cause rather than platelet-lowering therapy. 1, 2, 3

Primary vs Secondary Thrombocytosis: Key Distinction

The critical first step is distinguishing between primary (clonal) and secondary (reactive) thrombocytosis, as this determines both prognosis and management:

Primary Thrombocytosis (12-12.5% of cases)

• Essential thrombocythemia (most common primary cause): Myeloproliferative neoplasm with sustained platelet count ≥450 × 10⁹/L, bone marrow megakaryocyte proliferation, and presence of JAK2V617F mutation (found in ~86% of cases) or other clonal markers 1, 2
• Other myeloproliferative disorders: Polycythemia vera, primary myelofibrosis, chronic myeloid leukemia 1
• Median platelet count significantly higher in primary thrombocytosis with increased thrombotic risk (both arterial and venous) 2, 3

Secondary Thrombocytosis (83-88% of cases)

The most common causes in order of frequency are:

• Tissue damage/trauma (32-42%): Surgery, burns, fractures 1, 2, 3
• Infection (17-24%): Acute bacterial or viral infections 1, 2, 3
• Chronic inflammatory disorders (10-13%): Inflammatory bowel disease, rheumatoid arthritis 1, 2, 3
• Iron deficiency anemia (11%): Must be excluded before diagnosing essential thrombocythemia, as occult polycythemia vera may be masked 1, 2
• Malignancy (13%): Solid tumors, lymphoproliferative disorders producing inflammatory cytokines 1, 2, 3
• Post-splenectomy or hyposplenism: Loss of splenic platelet sequestration 1
• Drug-induced: Corticosteroids, epinephrine, erythropoiesis-stimulating agents 1

Diagnostic Approach

Laboratory Parameters to Distinguish Primary from Secondary

Obtain the following to differentiate:

• Complete blood count with differential: Elevated leukocyte count and hematocrit favor primary thrombocytosis 3
• Inflammatory markers: Elevated ESR and fibrinogen suggest secondary thrombocytosis 3
• Iron studies: Serum ferritin, iron, TIBC to exclude iron deficiency 1
• JAK2V617F mutation testing: If primary thrombocytosis suspected (present in 86% of essential thrombocythemia) 1, 2
• Peripheral blood smear: Evaluate for other cell line abnormalities 4

Clinical Context Matters

• Recent surgery, trauma, or infection: Strongly suggests secondary thrombocytosis 2, 3
• Known chronic inflammatory condition: Likely reactive 1, 3
• Isolated thrombocytosis without clear cause: Consider primary thrombocytosis and proceed with molecular testing 1

Clinical Significance and Thrombotic Risk

Primary Thrombocytosis

• Significantly increased risk of both arterial and venous thromboembolism 2, 3
• Thrombotic complications are the predominant clinical concern affecting prognosis and quality of life 5

Secondary Thrombocytosis

• Venous thrombosis only occurs when additional risk factors are present (immobility, malignancy, surgery) 3
• Generally benign and self-limited when underlying cause resolves 4, 1
• In children with empyema, platelet counts >500 × 10⁹/L occurred in 93% without thromboembolic complications 4

Management Based on Etiology

For Secondary Thrombocytosis (Most Likely at 465 × 10⁹/L)

• Treat the underlying condition—this is the primary approach 1
• Platelet-lowering therapy is NOT required 1
• Antiplatelet therapy is NOT necessary unless other cardiovascular indications exist 4
• Monitor platelet count to confirm resolution with treatment of underlying cause 4

For Primary Thrombocytosis (If Confirmed)

• Cytoreductive therapy (hydroxyurea or anagrelide) for high-risk patients (age ≥60 years or prior thrombosis) 1, 6
• Low-dose aspirin (81-100 mg/day) for thrombosis prevention if platelet count <1,500 × 10⁹/L 1, 6

Critical Pitfalls to Avoid

• Do not assume benign reactive thrombocytosis without investigating the cause—persistent unexplained elevation requires hematology consultation 7
• Exclude heparin-induced thrombocytopenia, DIC, and drug reactions before attributing to other causes 1
• Do not miss iron deficiency as a cause, as it may mask polycythemia vera 1
• In malignancy-associated DIC, a decreasing platelet trend from an initially elevated level may be the only sign, even if absolute count remains normal 1