What are the causes and management of thrombocytosis (high platelet count)?

Thrombocytosis: Causes and Management

Thrombocytosis is most commonly secondary (reactive) and benign, requiring no specific treatment beyond addressing the underlying cause, while primary thrombocytosis from myeloproliferative neoplasms requires platelet-reducing therapy to prevent thrombotic complications.

Classification and Causes

Primary (Clonal) Thrombocytosis

• Essential thrombocythemia is the most common primary cause, characterized by extreme platelet counts (>800 × 10⁹/L) and prolonged duration (>1 month) 1
• Associated with myeloproliferative neoplasms including polycythemia vera and primary myelofibrosis 2
• Caused by mutations in JAK2V617F or MPLW515L/K genes that regulate thrombopoiesis 3, 4
• These patients have hyperreactive platelets with increased thrombotic risk requiring treatment 5

Secondary (Reactive) Thrombocytosis

Secondary causes account for the majority of thrombocytosis cases and include 5, 1:

• Infection (accounts for nearly half of secondary cases) 1
• Chronic inflammation and inflammatory conditions 5, 1
• Malignancy 5, 1
• Iron deficiency 5
• Asplenia 5

Clinical clues to infectious etiology include fever, tachycardia, weight loss, hypoalbuminemia, neutrophilia, leukocytosis, and anemia 1. Risk factors include inpatient status, quadriplegia/paraplegia, indwelling prosthesis, dementia, and diabetes 1.

Diagnostic Approach

Initial Evaluation

• Review complete blood count and peripheral blood smear to determine if thrombocytosis is primary or secondary 6
• Exclude spurious thrombocytosis from microspherocytes, schistocytes, cryoglobulins, or bacteria 5

Distinguishing Primary from Secondary

Primary thrombocytosis characteristics 1:

• Platelet count typically >800 × 10⁹/L
• Duration >1 month
• Absence of inflammatory markers or underlying conditions

Secondary thrombocytosis characteristics 1:

• More rapid normalization of platelet count once underlying cause is treated
• Associated with identifiable inflammatory, infectious, or malignant conditions

Bone Marrow Evaluation

• Accurate bone marrow histology evaluation is a key diagnostic step for distinguishing among different myeloproliferative disorders 4
• JAK2V617F and MPLW515L/K mutation testing can support diagnosis but are neither disease-specific nor universally present 4

Management

Secondary Thrombocytosis

In children:

• No antiplatelet therapy is necessary for secondary thrombocytosis, as platelet function remains normal 6
• Thromboembolic complications are extremely rare in children with secondary thrombocytosis, with no reports in over 1,000 children studied 6
• Treat the underlying condition only; no specific platelet-directed therapy required 6
• Consider hematology consultation only if the patient becomes symptomatic 6

In adults:

• No specific platelet-directed treatment is necessary for secondary thrombocytosis 6
• Focus on treating the underlying cause (infection, inflammation, malignancy, iron deficiency) 5, 1
• Consider antiplatelet therapy in select cases with chronic inflammation, malignancy, or high-altitude exposure where thrombotic risk may be elevated 5

Primary Thrombocytosis (Myeloproliferative Neoplasms)

Anagrelide is FDA-approved for treatment of thrombocythemia secondary to myeloproliferative neoplasms to reduce elevated platelet count and thrombosis risk 2:

Dosing 2:

• Adults: Start 0.5 mg four times daily or 1 mg twice daily
• Pediatrics: Start 0.5 mg per day
• Maintain starting dose for at least one week, then titrate to target platelet count
• Maximum: 10 mg/day or 2.5 mg single dose
• Do not exceed dose increments of 0.5 mg/day in any one week

Monitoring requirements 2:

• Obtain pre-treatment cardiovascular examination including ECG (risk of QT prolongation and ventricular tachycardia)
• Assess for underlying cardiopulmonary disease before initiating
• Monitor for bleeding, especially with concomitant anticoagulants or antiplatelet agents

Aspirin therapy:

• One prospective randomized trial demonstrates benefit of acetylsalicylic acid in polycythemia vera 5
• For other primary thrombocytosis types, decisions must weigh individual thrombotic versus bleeding risk 5

Special Considerations

Thrombocytosis with Thrombocytopenia Risk

In cancer patients receiving chemotherapy, thrombocytopenia may develop requiring dose adjustments of anticoagulation 7:

• Platelet count >50 × 10⁹/L: Full-dose anticoagulation acceptable
• Platelet count 20-50 × 10⁹/L: Half-dose anticoagulation with close monitoring
• Platelet count <20 × 10⁹/L: Hold therapeutic anticoagulation

Cyanotic Congenital Heart Disease

• Thrombocytopenia and platelet dysfunction occur with polycythemia and hyperviscosity 7
• Platelet counts inversely related to hematocrit levels 7
• Increased fibrinolysis with elevated d-dimers suggests consumptive process 7

Key Pitfalls to Avoid

• Do not use antiplatelet therapy for secondary thrombocytosis in children or most adults—it provides no benefit and increases bleeding risk 6
• Do not assume all thrombocytosis requires treatment—secondary forms resolve with treatment of underlying condition 6, 1
• Do not overlook infection as a common cause of thrombocytosis, particularly in hospitalized or immunocompromised patients 1
• Do not start anagrelide without cardiovascular assessment due to risk of QT prolongation and cardiac toxicity 2