Thrombocytosis

Background

Thrombocytosis is generally defined as a platelet count >450,000/microL. Thrombocytosis can be reactive or autonomous.

Reactive thrombocytosis (RT) is the most common cause of thrombocytosis, accounting for 85% of cases. RT is a reaction to another process, such as inflammation, infection, cancer, or iron deficiency. RT rarely causes complications even with extremely elevated platelet counts (>1,000,000/microL).

Autonomous thrombocytosis (AT) accounts for 15% of cases. AT is a primary problem that results from a myeloproliferative or myelodysplastic disorder, 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.

Physiology

Platelets are produced by megakaryocytes. Thrombopoietin (THPO) is the key hormone that regulates platelet production. THPO binds to receptors on megakaryocytes, leading to differentiation and proliferation. In disorders that cause AT, there is a dysregulation of THPO, or the THPO-receptor uptake mechanism, leading to increased production of platelets.

Thrombopoietin can be elevated in states of acute inflammation or neoplastic disorders, leading to the elevated platelet count seen in RT. This mechanism is most likely regulated by the acute phase reactant IL-6.

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 reactions
• Medication reactions: vincristine, epinephrine, glucocorticoids, IL-1B, ATRA, thrombopoietin, LMWH (uptodate)

Autonomous thrombocytosis:

• Essential Thrombocytopenia
• Polycythemia Vera
• Mixed myelodysplastic and/or myeloproliferative syndrome

Spurious (false) thrombocytosis:

• Mixed cryoglobulinemia
• Cytoplasmic fragments
• Bacteremia

Clinical Features

Thrombocytosis is generally asymptomatic and found on routine lab testing.

Complications are seen in AT disorders and include thrombosis, bleeding, or vasomotor symptoms. Thrombotic complications are the leading cause of morbidity and mortality. Thrombosis commonly occurs in arteries (stroke, TIA, MI, unstable angina), but can also occur in the venous system (DVT, PE, Budd-Chiari syndrome). Serious bleeding is a less common complication and is generally seen in the nasal and bucchal mucosa and the GI tract.

Vasomotor symptoms are due to microvascular disturbances and include: headache, lightheadedness, syncope, acral paresthesia, atypical chest pain, livedo reticularis, erythromelalgia, and transient visual disturbances.

Evaluation

General approach:

Is this reactive thrombocytosis (RT) or autonomous thrombocytosis (AT)?

Is this patient at risk for thrombotic events due to the thrombocytosis?

1. CBC. Compare to previous if possible.
2. H&P looking for causes of RT.
3. Labs looking for causes of RT: ESR, CRP, iron studies, blood cultures, LDH.
4. Testing looking for causes of RT: CXR, FOBT.
5. Consider spurious thrombocytosis.
6. If no signs of RT cause, consider AT: blood smear.

Management

Reactive thrombocytosis: treat underlying disease.

Asymptomatic AT:

1. 81mg ASA PO daily.
2. If high risk for thrombotic event (>60 yrs, history of thrombosis, or known JAK2 mutation), consider 15mg/kg hydroxyurea PO daily. Consult if available.
3. Second line agents include IFN-alpha, anagrelide, and pipobroman.

Thrombosis due to AT:

1. Anticoagulation with LMWH.
2. 81mg ASA PO daily.
3. Consult.
4. Consider 3-5 million U IFN alpha SQ daily if <40 years old. 15mg/kg hydroxyurea PO daily if >40 years old. Goal platelet count <400,000/microL.
5. Platelet apheresis if platelet count >800,000/microL.

Bleeding due to AT:

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

Disposition

If RT, disposition is based on underlying disorder.

If asymptomatic AT, consider outpatient treatment with close follow up.

AT thrombosis or bleeding complications should be admitted for stabilization and further work up.

External Links

FOAM: EMDocs, "Thrombocytosis in the ED." [1]