What is the initial workup and treatment for a patient presenting with thrombocytosis (elevated platelet count)?

From the Guidelines

The initial workup for thrombocytosis should begin with determining whether it is reactive or primary, and treatment depends on the underlying cause, with low-risk patients potentially receiving low-dose aspirin alone and high-risk patients requiring cytoreductive therapy such as hydroxyurea in addition to aspirin, as recommended by the most recent guidelines 1. To approach a patient with thrombocytosis, the following steps should be taken:

• Obtain a complete blood count with peripheral smear, comprehensive metabolic panel, inflammatory markers (ESR, CRP), iron studies, and JAK2, CALR, and MPL mutation testing to differentiate between reactive and primary thrombocytosis.
• Review the patient's medication list and recent medical history for potential causes of reactive thrombocytosis, such as infection, inflammation, iron deficiency, or post-splenectomy state.
• If primary thrombocytosis is suspected, particularly essential thrombocythemia, bone marrow biopsy with cytogenetic studies should be performed.
• Risk stratification based on age, prior thrombotic events, cardiovascular risk factors, and platelet count guides therapy, with low-risk patients potentially receiving low-dose aspirin (81-100 mg daily) alone, as suggested by the NCCN guidelines 1.
• High-risk patients typically require cytoreductive therapy, with hydroxyurea being the first-line treatment, starting at 500-1000 mg daily, adjusted to maintain platelets <400,000/μL, in addition to aspirin, as recommended by European LeukemiaNet 1.
• Alternative cytoreductive agents include anagrelide or interferon-alpha, particularly in younger patients, as indicated by the revised management recommendations from European LeukemiaNet 1. The goal of treatment is to prevent thrombotic and hemorrhagic complications by reducing the platelet count and platelet activation, as elevated platelets can lead to both arterial and venous thrombosis as well as paradoxical bleeding in some cases, highlighting the importance of careful management and monitoring of patients with thrombocytosis 1.

From the FDA Drug Label

INDICATIONS AND USAGE Anagrelide hydrochloride capsules are indicated for the treatment of patients with thrombocythemia, secondary to myeloproliferative disorders, to reduce the elevated platelet count and the risk of thrombosis and to ameliorate associated symptoms including thrombo-hemorrhagic events

The initial workup for a patient presenting with thrombocytosis (elevated platelet count) is not directly addressed in the provided drug label. However, the label does indicate that anagrelide is used to treat thrombocythemia secondary to myeloproliferative disorders, which is a condition characterized by an elevated platelet count.

• The treatment for thrombocytosis, in the context of myeloproliferative disorders, includes the use of anagrelide to reduce the elevated platelet count and the risk of thrombosis 2. The FDA label does not provide information on the initial workup for thrombocytosis.

From the Research

Initial Workup for Thrombocytosis

The initial workup for a patient presenting with thrombocytosis (elevated platelet count) involves distinguishing between reactive or secondary thrombocytosis and thrombocytosis associated with an underlying myeloproliferative neoplasm 3. This can be achieved through a combination of clinical assessment, laboratory tests, and bone marrow histology.

Laboratory Tests

Laboratory tests for thrombocytosis may include:

• Complete blood count (CBC) to confirm elevated platelet count
• Blood smear to evaluate platelet morphology
• Iron studies to rule out iron deficiency anemia
• Erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) to assess for inflammation
• Testing for JAK2, CALR, and MPL mutations to diagnose myeloproliferative neoplasms 4, 5

Risk Stratification

Patients with essential thrombocythemia can be stratified into low-risk, intermediate-risk, and high-risk categories based on factors such as age, prior thrombosis, and cardiovascular risk factors 6, 7. This risk stratification guides treatment decisions.

Treatment Options

Treatment options for thrombocytosis depend on the underlying cause and risk category:

• Low-risk patients: observation or low-dose aspirin (81-100 mg/d) 5, 7
• High-risk patients: cytoreductive therapy with hydroxyurea, interferon-alpha (IFN-α), or anagrelide, in addition to low-dose aspirin 6, 7
• Patients with cardiovascular risk factors: strict control of coexistent risk factors is mandatory 7

Special Considerations

Special considerations in the management of thrombocytosis include:

• Pregnancy: IFN-α may be used in high-risk pregnant women who need treatment 6
• Resistance or intolerance to hydroxyurea: anagrelide is recommended as second-line therapy 7