Thrombocytosis

Background

• Defined as a platelet count >450,000/microL.

Reactive thrombocytosis (RT)

• Most common cause of thrombocytosis, accounting for 85% of cases.
• A reaction to another process, such as inflammation, infection, cancer, or iron deficiency.
• Rarely causes complications even with extremely elevated platelet counts (>1,000,000/microL).

Autonomous thrombocytosis (AT)

• Accounts for 15% of cases
• A primary problem that results from myeloproliferative disorders or myelodysplastic syndromes, such as essential thrombocytopenia or polycythemia vera.
• Complications, such as bleeding and/or thrombosis, are more likely with AT than with RT so it is clinically important to differentiate reactive thrombocytosis versus autonomous thrombocytosis.
• There are no diagnostic studies to differentiate RT versus AT.

Clinical Features

Generally asymptomatic and found on routine lab testing; complications are typically from AT disorders

• Thrombosis (leading cause of morbidity and mortality)
  • Arteries (more common)
    • Stroke, TIA, MI, unstable angina
  • Venous system
    • DVT, PE, Budd-Chiari syndrome
• Serious bleeding (less common)
  • Generally in the nasal and bucchal mucosa and the GI tract
• Vasomotor symptoms (due to microvascular disturbances)
  • Headache, lightheadedness, syncope, acral paresthesia, atypical chest pain, livedo reticularis, erythromelalgia, and transient visual disturbances

Differential Diagnosis

Reactive thrombocytosis

• Acute blood loss
• Acute hemolytic anemia
• Iron deficiency anemia
• Treatment of vitamin B12 deficiency
• Rebound effect after thrombocytopenia treatment
• Metastatic cancer
• Lymphoma
• Rheumatologic disorders
• IBD
• Celiac disease
• Kawasaki disease
• Nephrotic syndrome
• POEMS syndrome
• Thermal burn
• MI
• Severe trauma
• Acute pancreatitis
• Post-surgery, especially splenectomy
• CABG
• TB
• Acute bacterial/viral infections
• Asplenia
• Allergic reaction
• Medication reactions: vincristine, epinephrine, glucocorticoids, IL-1B, ATRA, thrombopoietin, LMWH

Autonomous thrombocytosis

• Essential thrombocytosis
• Polycythemia vera
• Mixed myelodysplastic and/or myeloproliferative syndrome

Spurious (false) thrombocytosis

• Mixed cryoglobulinemia
• Cytoplasmic fragments
• Bacteremia

Evaluation

Workup

• Labs
  • CBC, ESR, CRP, iron studies, LDH
• CXR
• Fecal occult blood test

Diagnosis

• platelet count >450,000/microL.

Management

Reactive thrombocytosis

• Treat underlying disease.

Autonomous thrombocytosis

Asymptomatic

• 81mg ASA PO daily.
• If high risk for thrombotic event (>60 yrs, history of thrombosis, or known JAK2 mutation), consider 15mg/kg hydroxyurea PO daily. Consult if available.
• Second line agents include interferon-α, anagrelide, and pipobroman.

Thrombosis due to AT

• Anticoagulation with LMWH.
• 81mg ASA PO daily.
• Consult heme/onc
• Consider 3-5 million U interferon-α SQ daily if <40 years old. 15mg/kg hydroxyurea PO daily if >40 years old. Goal platelet count <400,000/microL.
• Platelet apheresis if platelet count >800,000/microL.

Bleeding due to AT

• Discontinue antiplatelet medications.
• Consult.
• Consider 3-5 million U interferon-α SQ daily if <40 years old. 15mg/kg hydroxyurea PO daily if >40 years old. Goal platelet count <400,000/microL.

Disposition

Reactive thrombocytosis

• Disposition is based on underlying disorder.

Autonomous thrombocytosis

• If asymptomatic, consider outpatient treatment with close follow up.
• If thrombosis or bleeding complications, should be admitted for stabilization and further work up.

External Links

• EMDocs, "Thrombocytosis in the ED."