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

Management of HHT with Mildly Elevated Red Blood Cell Count

A mildly elevated red blood cell count in an HHT patient is exceedingly rare and demands immediate investigation for pulmonary arteriovenous malformations (PAVMs) causing chronic hypoxemia or coincidental polycythemia vera, as the overwhelming majority of HHT patients present with anemia from chronic bleeding rather than erythrocytosis. 1

Critical First Step: Rule Out Life-Threatening Causes

The presence of erythrocytosis in HHT is paradoxical and should trigger urgent evaluation for:

• Pulmonary AVMs causing chronic hypoxemia-driven erythrocytosis using contrast echocardiography or chest CT as first-line screening 2, 1
• Hepatic AVMs that may contribute to abnormal erythropoietin production, assessed with Doppler ultrasonography 2, 1
• Cerebral vascular malformations evaluated with brain MRI to complete comprehensive AVM screening 2, 1
• Coincidental polycythemia vera or other primary myeloproliferative disorders through hematology referral with JAK2 mutation testing and bone marrow evaluation if indicated 2, 1

Common pitfall: Approximately 50% of HHT patients experience iron deficiency anemia from chronic bleeding, making anemia the typical presentation—erythrocytosis should never be dismissed as a normal variant in HHT. 1

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. 2, 1 This intervention simultaneously:

• Corrects the hypoxemia driving erythrocytosis 2
• Prevents life-threatening neurological complications from paradoxical emboli 2

If No Secondary Cause Is Found:

Proceed with hematology evaluation for primary polycythemia including JAK2 mutation testing and bone marrow biopsy if clinically indicated. 1

Concurrent Management of HHT Bleeding Manifestations

Even with erythrocytosis, HHT patients require proactive bleeding management as they may transition to anemia if bleeding worsens:

Epistaxis Management (Stepwise Escalation):

1. Start with nasal moisturization through air humidification and topical saline solution or gels 2, 3

2. Add oral tranexamic acid if moisturizing therapies fail:

   • Start at 500 mg twice daily 4, 2, 3
   • Gradually increase to 1000 mg four times daily or 1500 mg three times daily 4, 2, 3
   • Contraindications: Recent thrombosis (absolute); atrial fibrillation or known thrombophilia (relative) 4, 2, 3

3. Reserve systemic bevacizumab for refractory cases failing conservative measures and ablative therapies:

   • Induction: 5 mg/kg IV every 2 weeks for 4-6 doses 4, 2, 3
   • Maintenance: 5 mg/kg IV every 1-3 months (variable dosing) 4, 2, 3
   • Monitor for hypertension, proteinuria, infection, delayed wound healing, and venous thromboembolism 4, 2, 3
   • Safety data: Only 2% VTE rate with no fatal adverse events in 238 patients from the InHIBIT-Bleed study 2

GI Bleeding Management:

Grade severity based on iron/transfusion requirements 4:

• Mild: Meets hemoglobin goals with oral iron replacement—consider oral tranexamic acid 4
• Moderate: Requires IV iron to meet hemoglobin goals—consider systemic bevacizumab 4
• Severe: Fails to meet hemoglobin goals despite adequate iron or requires transfusions—strongly consider systemic bevacizumab 4

Anticoagulation Considerations in Erythrocytosis

Anticoagulation is not an absolute contraindication in HHT despite bleeding risks. 2, 1, 5

• Prefer heparin agents and vitamin K antagonists over direct oral anticoagulants due to better tolerability and lower bleeding risk in HHT 2, 1
• Avoid dual antiplatelet therapy and combination antiplatelet/anticoagulation wherever possible 1
• Consider left atrial appendage closure for atrial fibrillation in patients who cannot tolerate anticoagulation 1
• Key data: In a retrospective study of 64 HHT patients on anticoagulation, 23% reported severe complications but no pulmonary or cerebral hemorrhage occurred 5

Monitoring Strategy

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 1
• Hemoglobin goals should reflect normal values for age and gender 4
• This monitoring is crucial for patients post-initial iron repletion (≥3 months after diagnosis) to represent chronic hematologic support requirements 4

Family Screening

Screen first-degree relatives given the autosomal dominant inheritance pattern of HHT. 2