What are the causes and management of reactive thrombocytosis?

Causes of Reactive Thrombocytosis

Reactive thrombocytosis is most commonly caused by iron deficiency, inflammation, infection, malignancy, surgery (especially splenectomy), and certain medications. 1

Definition and Distinction

Reactive (or secondary) thrombocytosis is defined as an elevated platelet count that occurs in response to an underlying medical condition, as opposed to essential thrombocytosis which is a clonal myeloproliferative disorder. The key distinction is:

• Reactive thrombocytosis: Platelet elevation secondary to another condition
• Essential thrombocytosis: Primary clonal disorder with JAK2 V617F or other mutations

Common Causes of Reactive Thrombocytosis

Inflammatory Conditions

• Infections (acute or chronic)
• Autoimmune disorders (rheumatoid arthritis, SLE)
• Connective tissue diseases
• Inflammatory bowel disease
• Adult-onset Still's disease 1

Tissue Damage

• Surgery (particularly splenectomy, with incidence of 75-82%) 2
• Trauma
• Burns
• Pancreatitis

Hematologic Causes

• Iron deficiency anemia (can cause extreme thrombocytosis >1000×10^9/L) 3
• Hemolytic anemia
• Acute blood loss
• Post-splenectomy (most common surgical cause) 2

Malignancy

• Solid tumors (lung, breast, gastrointestinal, ovarian)
• Lymphoproliferative disorders
• Paraneoplastic syndrome (found in approximately 34% of patients with malignancy) 4

Medications

• Vincristine
• Epinephrine
• All-trans retinoic acid
• Cytokines (GM-CSF, G-CSF)
• Corticosteroids

Other Causes

• Rebound thrombocytosis after myelosuppressive therapy
• Post-partum state
• Renal disorders (nephrotic syndrome)
• Nutritional deficiencies (iron, vitamin B12, folate)

Diagnostic Approach

When evaluating thrombocytosis, the following approach should be taken:

1. Complete blood count with differential to assess for other cytopenias or abnormalities 5
2. Peripheral blood smear examination to evaluate platelet morphology 5
3. Iron studies (serum ferritin, iron, TIBC, transferrin saturation) to rule out iron deficiency 5
4. Inflammatory markers (ESR, CRP) to assess for inflammatory conditions
5. JAK2 V617F mutation testing to rule out essential thrombocytosis 1
6. Bone marrow examination if primary thrombocytosis is suspected 5

Management of Reactive Thrombocytosis

The management of reactive thrombocytosis focuses on treating the underlying cause:

• Treat the underlying condition: Address infection, inflammation, or malignancy
• Iron replacement for iron deficiency-related thrombocytosis 3
• Observation is appropriate for most cases as reactive thrombocytosis rarely causes thrombotic complications 6
• Antiplatelet therapy is generally not required for reactive thrombocytosis unless there are additional risk factors for thrombosis 7
• Cytoreductive therapy (hydroxyurea) is rarely needed in reactive thrombocytosis and should be reserved for extreme cases with thrombotic events 7

Clinical Pearls and Pitfalls

• Reactive thrombocytosis is much more common than essential thrombocytosis (88% vs 12% of thrombocytosis cases) 7
• The degree of thrombocytosis does not reliably distinguish between reactive and essential causes
• Extreme thrombocytosis (>1000×10^9/L) can occur in reactive conditions, particularly severe iron deficiency 3
• The risk of thrombotic complications is much lower in reactive compared to essential thrombocytosis
• Post-splenectomy thrombocytosis has a 5% risk of thrombotic complications 2
• Always consider malignancy as a potential cause of unexplained thrombocytosis, especially in older adults
• Reactive thrombocytosis typically resolves when the underlying condition is treated

By systematically evaluating the potential causes and following a structured diagnostic approach, the etiology of reactive thrombocytosis can be identified and appropriately managed.