ENG Mutation Does Not Indicate Myeloproliferative Neoplasm
The presence of an Endoglin (ENG) mutation is not associated with polycythemia vera, essential thrombocythemia, or other myeloproliferative neoplasms, and should prompt evaluation for hereditary hemorrhagic telangiectasia (HHT) rather than MPN-directed therapy.
Critical Distinction: ENG vs. Driver Mutations
The molecular landscape of myeloproliferative neoplasms is well-defined and does not include ENG mutations:
- JAK2 mutations are present in >95% of polycythemia vera cases and approximately 55-60% of essential thrombocythemia cases 1, 2, 3
- CALR mutations occur in approximately 25% of ET patients 3
- MPL mutations are found in approximately 3% of ET patients 3
- These three mutations are mutually exclusive "driver" mutations in myeloproliferative neoplasms 3, 4
ENG mutations cause hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome), not myeloproliferative disease. This is a vascular disorder characterized by arteriovenous malformations and telangiectasias.
Recommended Approach for This Patient
If Polycythemia Vera is Confirmed (JAK2-positive):
All patients require phlebotomy to maintain hematocrit <45% plus low-dose aspirin (81 mg daily) 5, 6, 4
Risk Stratification Determines Cytoreductive Therapy:
High-risk (age >60 years OR history of thrombosis): Requires cytoreductive therapy 5, 4
Low-risk (age ≤60 years AND no thrombosis history): Phlebotomy plus aspirin alone until age 60 or thrombotic event occurs 5
Additional Indications for Cytoreductive Therapy:
Beyond age and thrombosis history, cytoreduction is indicated for 5:
- Poor phlebotomy tolerance or frequent phlebotomy requirements
- Symptomatic or progressive splenomegaly
- Severe disease-related symptoms
- Platelet count >1,500 × 10⁹/L
- Progressive leukocytosis
Critical Pitfall to Avoid
Do not confuse ENG mutations with myeloproliferative neoplasm driver mutations. If this patient has polycythemia with an ENG mutation, the polycythemia is either:
- Secondary polycythemia from another cause (requiring evaluation for hypoxia, renal disease, or other etiologies) 6
- Polycythemia vera with a JAK2 mutation (which should be tested separately) 1, 2
The ENG mutation is a separate genetic finding indicating HHT risk, which may actually increase bleeding risk and requires careful consideration before initiating aspirin therapy, particularly if extreme thrombocytosis is present 1, 2, 3.
Cardiovascular Risk Factor Management
All patients must have aggressive management of cardiovascular risk factors and smoking cessation counseling 5. Recent data suggests JAK2V617F mutation status and cardiovascular risk factors are additional thrombotic risk factors beyond the traditional age and thrombosis history criteria 1, 3.