What is the management approach for a patient with Hereditary Hemorrhagic Telangiectasia (HHT) and mildly elevated red blood cell counts?

Management of HHT with Mildly Elevated Red Blood Cell Counts

Erythrocytosis in HHT is exceedingly rare and should immediately trigger investigation for pulmonary arteriovenous malformations (PAVMs) causing hypoxemia-driven polycythemia, as the overwhelming majority of HHT patients present with anemia from chronic bleeding rather than elevated red blood cell counts. 1

Initial Diagnostic Workup

The presence of elevated red blood cells in an HHT patient represents an atypical presentation that demands systematic evaluation:

• Screen for PAVMs first using contrast echocardiography or chest CT, as these are the most likely HHT-related cause of erythrocytosis through chronic hypoxemia 1
• Evaluate for hepatic AVMs with Doppler ultrasonography as first-line imaging, since these can also contribute to abnormal erythropoietin production 1
• Assess for cerebral vascular malformations with brain MRI to complete the AVM screening 1
• Rule out coincidental polycythemia vera or other primary myeloproliferative disorders through hematology referral with JAK2 mutation testing and bone marrow evaluation if indicated 1

Critical Pitfall to Avoid

Approximately 50% of HHT patients experience iron deficiency anemia from chronic bleeding, making anemia the typical presentation 1. Do not assume the elevated red blood cell count is benign or unrelated to HHT—it may represent a treatable complication like PAVMs that carries significant stroke and cerebral abscess risk.

Management Algorithm Based on Findings

If PAVMs Are Identified

• Perform percutaneous transcatheter embolization regardless of feeding artery size due to paradoxical embolism risk and potential for stroke or cerebral abscess 1
• This intervention addresses both the erythrocytosis (by correcting hypoxemia) and prevents life-threatening neurological complications 1

If No Secondary Cause Is Found

• Complete hematology evaluation for primary polycythemia including JAK2 mutation testing 1
• Establish baseline iron studies (ferritin and transferrin saturation) even in the presence of erythrocytosis, as HHT patients may transition to iron deficiency if bleeding worsens 1
• Reassess hemoglobin and hematocrit at 1-month intervals to detect evolution toward anemia, which would indicate progression of typical HHT bleeding manifestations 1

Concurrent HHT Bleeding Management

Even with elevated red blood cell counts, these patients still have HHT and require standard screening and management:

Epistaxis Management (if present)

• Start with nasal moisturization through air humidification and topical saline solution or gels 2, 3
• Add oral tranexamic acid (500 mg twice daily, titrating up to 1000 mg four times daily) if moisturizing therapies fail 2, 3
• Reserve systemic bevacizumab (5 mg/kg IV every 2 weeks for 4-6 doses, then maintenance every 1-3 months) for refractory cases that fail conservative measures 2, 4, 3

Gastrointestinal Bleeding Screening

• Screen for GI telangiectasias as approximately 30% of HHT patients develop GI bleeding with age 2
• Systemic antiangiogenic therapy (bevacizumab or pomalidomide) is recommended as primary treatment for significant GI bleeding rather than repetitive endoscopic procedures 2

Anticoagulation Considerations (if needed)

Should this patient require anticoagulation for any indication:

• Anticoagulation is not an absolute contraindication in HHT despite bleeding risks 1
• Prefer heparin agents and vitamin K antagonists over direct oral anticoagulants due to better tolerability and lower bleeding risk in HHT 1
• Avoid dual antiplatelet therapy and combination antiplatelet/anticoagulation therapy wherever possible 1
• Consider left atrial appendage closure for atrial fibrillation in patients who cannot tolerate anticoagulation 1

Safety Profile of Systemic Therapies

If systemic bevacizumab becomes necessary for bleeding management:

• Venous thromboembolism rate is only 2% in HHT patients treated with bevacizumab, with no fatal adverse events in the InHIBIT-Bleed study of 238 patients 2, 4
• Monitor for hypertension, proteinuria, infection risk, and delayed wound healing 3
• A study of 69 HHT patients treated with bevacizumab for a mean of 11 months reported no VTE events and only a single arterial thrombotic event 4

Family Screening

• Screen family members given the autosomal dominant inheritance pattern of HHT 3
• This is particularly important as families with the same mutation exhibit considerable phenotypic variation 5