What are the causes of thrombocytosis (elevated platelets)?

Causes of Elevated Platelets (Thrombocytosis)

Thrombocytosis is primarily caused by either primary (essential) thrombocythemia or secondary (reactive) causes, with secondary causes accounting for approximately 83% of cases. 1

Primary Thrombocytosis

Primary thrombocytosis refers to autonomous platelet production due to clonal disorders, primarily myeloproliferative neoplasms (MPNs):

1. Essential Thrombocythemia (ET)

   • Characterized by JAK2V617F mutation (in 50-60% of cases)
   • CALR or MPL mutations in JAK2-negative cases 2
   • Associated with higher risk of thrombosis and hemorrhage
   • Often presents with platelet counts >1,000 × 10^9/L
   • May have splenomegaly and qualitative platelet abnormalities

2. Other Myeloproliferative Neoplasms

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

Secondary (Reactive) Thrombocytosis

Secondary thrombocytosis accounts for the majority of elevated platelet cases (83.1%) 1. Major causes include:

1. Tissue Injury/Surgery (32.2% of secondary cases)

   • Post-surgical states
   • Trauma
   • Burns

2. Infections (17.1% of secondary cases)

   • Acute infections
   • Chronic infections (tuberculosis, osteomyelitis)

3. Chronic Inflammatory Disorders (11.7% of secondary cases)

   • Rheumatoid arthritis
   • Inflammatory bowel disease
   • Connective tissue diseases
   • Vasculitis

4. Iron Deficiency Anemia (11.1% of secondary cases)

   • Particularly common in women of reproductive age

5. Malignancy

   • Solid tumors (lung, gastrointestinal, brain, ovarian, pancreatic)
   • Lymphoproliferative disorders

6. Post-Splenectomy State

   • Due to removal of splenic platelet sequestration

7. Medications

   • Corticosteroids
   • Epinephrine
   • Vincristine
   • Erythropoietin
   • Granulocyte colony-stimulating factors 3

8. Rebound Thrombocytosis

   • Following treatment of severe thrombocytopenia
   • After chemotherapy

Distinguishing Features

Primary Thrombocytosis

• Higher median platelet counts
• Higher incidence of thrombosis
• Presence of JAK2, CALR, or MPL mutations (in 86% of primary cases) 1
• Higher hemoglobin, mean corpuscular volume (MCV), red cell distribution width (RDW), and mean platelet volume (MPV) 4
• History of arterial thrombosis 4

Secondary Thrombocytosis

• Associated with active malignancy, chronic inflammatory disease, splenectomy, or iron deficiency 4
• Higher white blood cell count and neutrophil count 4
• Rarely causes vascular complications 5
• Resolves when underlying condition is treated

Clinical Implications

• Primary thrombocytosis carries significantly higher risk of thrombotic complications
• Secondary thrombocytosis rarely requires specific treatment for the elevated platelets themselves
• In cancer patients, thrombocytosis may be associated with increased risk of venous thromboembolism 3
• In cyanotic congenital heart disease, thrombocytosis may occur as a compensatory mechanism to chronic hypoxia 3

Diagnostic Approach

1. Evaluate for secondary causes first:

   • Recent surgery or trauma
   • Active infection
   • Inflammatory markers (ESR, CRP)
   • Iron studies (ferritin, transferrin saturation)
   • Medication review
   • Spleen status (history of splenectomy)

2. If no clear secondary cause or persistent thrombocytosis:

   • Molecular testing for JAK2V617F, CALR, and MPL mutations
   • Bone marrow examination if molecular testing is negative but clinical suspicion for MPN remains high

3. Additional testing based on clinical presentation:

   • Complete blood count with peripheral smear
   • Coagulation studies if bleeding or thrombotic symptoms present

The most recent evidence suggests that a practical diagnostic approach focusing on clinical characteristics can accurately identify patients more likely to have secondary causes of thrombocytosis and reduce unnecessary molecular testing 4.