How to manage Hereditary Hemorrhagic Telangiectasia (HHT) with chronic mildly elevated erythrocytosis (elevated red blood cell count)?

Management of HHT with Chronic Mildly Elevated Erythrocytosis

Chronic mildly elevated red blood cell counts in HHT patients is exceedingly rare and should immediately trigger investigation for secondary causes, as approximately 50% of HHT patients typically present with iron deficiency anemia from chronic bleeding rather than erythrocytosis. 1

Initial Diagnostic Workup

The presence of erythrocytosis in an HHT patient represents an atypical presentation that demands systematic evaluation:

• Screen for pulmonary arteriovenous malformations (PAVMs) causing chronic hypoxemia using contrast echocardiography or chest CT as first-line imaging, since PAVMs can drive hypoxemia-induced erythrocytosis 1

• Perform Doppler ultrasonography to assess for hepatic AVMs, as this is the recommended first-line imaging modality for detecting liver involvement 1, 2

• Evaluate for primary polycythemia vera or other myeloproliferative disorders that may coincidentally coexist with HHT through hematology referral for JAK2 mutation testing and bone marrow evaluation if indicated 1

• Never perform liver biopsy in any patient with proven or suspected HHT due to catastrophic hemorrhage risk from the high prevalence of liver vascular malformations 2, 3

Management Algorithm Based on Findings

If Pulmonary AVMs Are Identified:

• Proceed with percutaneous transcatheter embolization regardless of feeding artery size due to the risk of paradoxical embolism, stroke, or cerebral abscess 1

• This intervention addresses both the hypoxemia driving erythrocytosis and prevents life-threatening embolic complications

If No Secondary Cause Is Found:

• Refer to hematology for comprehensive evaluation of primary polycythemia, including JAK2 V617F mutation testing, exon 12 mutations, and consideration of bone marrow biopsy 1

• The coexistence of HHT and polycythemia vera, while rare, requires standard polycythemia management with careful attention to bleeding risks

Critical Monitoring Considerations

Establish baseline iron studies, ferritin, and transferrin saturation even in the presence of erythrocytosis, as HHT patients may transition to iron deficiency if bleeding manifestations worsen over time 1

• Reassess hemoglobin and hematocrit at 1-month intervals to detect evolution toward anemia, which would indicate progression of typical HHT bleeding manifestations 1

• This monitoring is essential because the natural history of HHT involves progressive telangiectasia formation and increasing bleeding burden with age 4

Anticoagulation Management If Required

Should this patient develop an indication for anticoagulation (such as atrial fibrillation or venous thromboembolism):

• Bleeding in HHT is not an absolute contraindication for anticoagulation or antiplatelet therapy when there is a clear indication 4, 1

• Prefer heparin agents or vitamin K antagonists over direct oral anticoagulants (DOACs), as DOACs may be less well tolerated due to increased bleeding risk in HHT patients 4, 5

• Avoid dual antiplatelet therapy and combination antiplatelet/anticoagulation therapy wherever possible 4, 1

• Consider left atrial appendage closure for atrial fibrillation in patients who cannot tolerate anticoagulation 4, 1

Common Pitfalls to Avoid

The most critical error would be assuming the erythrocytosis is benign or unrelated to HHT without thorough investigation. The typical HHT patient presents with anemia, not erythrocytosis, making this finding a red flag for either:

1. Significant pulmonary AVMs with chronic hypoxemia requiring urgent intervention to prevent stroke 1
2. Coincidental primary polycythemia requiring standard hematologic management 1
3. Hepatic AVMs causing complex hemodynamic alterations 2

Additionally, never delay screening for other visceral AVMs (cerebral, gastrointestinal) as part of comprehensive HHT management, regardless of the hematologic presentation 2, 3.