What is the management approach for a patient with myeloproliferative disorder (MPD) and essential thrombocythemia (ET) at risk of developing deep vein thrombosis (DVT) and pulmonary embolism (PE)?

Management of DVT/PE Risk in Essential Thrombocythemia

Patients with essential thrombocythemia (ET) require risk stratification to determine whether low-dose aspirin alone or combination therapy with cytoreductive agents is needed to prevent venous thromboembolism. 1, 2

Risk Stratification Framework

The management approach depends on identifying high-risk versus low-risk features:

High-Risk Features (Requiring Cytoreductive Therapy + Aspirin)

• Age >60 years 1, 2
• Prior thrombotic event (arterial or venous) 1, 2
• JAK2V617F mutation presence is associated with increased venous thrombosis risk (incidence rate ratio 4.0; 95% CI, 1.2-12.9) 2, 3
• Cardiovascular risk factors (hypertension, diabetes, hyperlipidemia, smoking) increase arterial thrombosis risk (incidence rate ratio 2.5; 95% CI, 1.02-6.1) 2, 4

Low-Risk Features (Aspirin Monotherapy)

• Age <60 years with no prior thrombosis 1, 2
• Absence of JAK2V617F mutation 2
• No cardiovascular risk factors 2

Primary Prevention Strategy

For Low-Risk Patients

Aspirin 81-100 mg daily is the cornerstone of thromboprophylaxis 1, 2. In low-risk patients not taking aspirin, the baseline thrombosis rates are arterial thrombosis 9.4/1000 patient-years and venous thrombosis 8.2/1000 patient-years 2.

For High-Risk Patients

Hydroxyurea plus low-dose aspirin (81-100 mg daily) is the preferred regimen 1, 2. In a randomized trial of 114 high-risk patients, cytoreduction with hydroxyurea significantly reduced thrombotic events compared to no cytoreductive therapy (3.6% vs 24%; P < .01) 2.

Target platelet count normalization (maintaining platelets <450 × 10⁹/L) reduces thrombosis frequency, though the platelet count itself does not directly correlate with thrombotic incidence 5. The goal is complete normalization of blood counts, as patients with adequate myelosuppression have the lowest thrombotic incidence 5.

Alternative Cytoreductive Agents

• Anagrelide is reserved for young patients or pregnant women 4
• Interferon is an alternative for young patients or during pregnancy 4
• Anagrelide plus aspirin showed better prevention of venous thrombosis (P=.006) but higher rates of arterial thrombosis (P=.004), serious hemorrhage (P=.008), and transformation to myelofibrosis (P=.01) compared to hydroxyurea plus aspirin 1

Management of Acute DVT/PE in ET Patients

Anticoagulation Duration

There are no specific data guiding anticoagulation duration in ET patients 1. Duration depends on:

• Severity of thrombotic event (abdominal vein thrombosis requires longer duration than lower extremity DVT) 1
• Degree of disease control with cytoreductive therapy 1
• Assessment of recurrence likelihood after anticoagulation cessation 1

Standard anticoagulation principles apply: 3-6 months for provoked DVT/PE, with consideration for extended therapy based on recurrence risk 1.

Cytoreductive Therapy Initiation

Assess need for cytoreductive therapy if not already initiated and start treatment to normalize blood counts if necessary 1. If inadequate response occurs, consider intensification or switching to an alternate agent 1.

Plateletpheresis

Plateletpheresis may be indicated in ET patients presenting with acute life-threatening thrombosis or severe bleeding 1.

Special Considerations

Leukocytosis as Risk Factor

Leukocytosis, not thrombocytosis per se, is an independent risk factor for thrombosis in ET 6. This is consistent with laboratory findings of increased activated granulocytes, granulocyte-platelet aggregates, upregulated platelet P-selectin, and tissue factor expression by granulocytes 6.

Surgical Patients

Multi-disciplinary management is essential for ET patients undergoing surgery 1. For high-risk procedures (orthopedic, cardiovascular, cancer surgery, splenectomy):

• Normalize blood counts prior to elective surgery without causing prohibitive cytopenias 1
• Extended prophylaxis with LMWH should be considered for procedures associated with high VTE risk 1
• Aspirin prophylaxis may be considered following vascular surgery 1

Bleeding Management

Withhold aspirin until bleeding is controlled 1. Use appropriate cytoreductive therapy to normalize platelet counts 1. Coagulation tests to evaluate for acquired von Willebrand disease are recommended for patients with elevated platelet counts, splenomegaly, or unexplained bleeding 1.

Concomitant Prothrombotic Conditions

ET patients presenting with thrombosis should be investigated for other congenital or acquired prothrombotic conditions, as their presence may alter long-term management with additional aspirin or anticoagulation beyond cytoreduction 5.

Critical Pitfalls

• Do not rely on platelet count alone to assess thrombotic risk; age, prior thrombosis, JAK2 mutation status, and cardiovascular risk factors are more predictive 2, 5
• Do not withhold cytoreductive therapy in high-risk patients based solely on platelet count, as complete blood count normalization provides the greatest thrombosis reduction 5
• Do not use anagrelide as first-line therapy in high-risk patients due to increased arterial thrombosis, hemorrhage, and myelofibrosis transformation risk compared to hydroxyurea 1
• Monitor for disease progression to myelofibrosis (10% at 8.5 years) and acute myeloid leukemia (3% at 8.5 years) 2