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

Management of HHT with Mildly Elevated Red Blood Cell Count

The first priority is to screen for pulmonary arteriovenous malformations (PAVMs) using contrast echocardiography or chest CT, as these are the most common HHT-related cause of erythrocytosis through chronic hypoxemia and require immediate intervention regardless of feeding artery size to prevent stroke and cerebral abscess. 1

Initial Diagnostic Workup

The elevated RBC count in HHT patients most commonly results from chronic hypoxemia secondary to PAVMs creating right-to-left shunting. Your diagnostic algorithm should proceed as follows:

• Screen for PAVMs first using contrast echocardiography or chest CT as the initial imaging modality 1
• Evaluate hepatic AVMs with Doppler ultrasonography, as these can contribute to abnormal erythropoietin production 1
• Obtain brain MRI to assess for cerebral vascular malformations and complete the AVM screening 1
• Rule out coincidental polycythemia vera through hematology referral with JAK2 mutation testing and bone marrow evaluation if the clinical picture is atypical 1

Definitive Management Based on PAVM Findings

If PAVMs are identified, perform percutaneous transcatheter embolization immediately regardless of feeding artery size. 1 This intervention serves dual purposes:

• Corrects the hypoxemia driving erythrocytosis 1
• Prevents life-threatening paradoxical embolism leading to stroke or cerebral abscess 1

The embolization threshold has shifted—older guidelines used a 3mm feeding artery cutoff, but current evidence supports treating all PAVMs due to stroke risk even from smaller lesions.

Concurrent Bleeding Management Strategy

Despite the elevated RBC count, HHT patients typically have ongoing bleeding that requires management. Use this stepwise escalation:

First-Line: Nasal Moisturization

• Initiate air humidification and topical saline solution or gels immediately 1, 2
• Continue these measures throughout all subsequent treatment escalations 2

Second-Line: Oral Tranexamic Acid

• Start at 500 mg twice daily if moisturizing therapies fail 1, 2
• Titrate gradually up to 1000 mg four times daily or 1500 mg three times daily as needed 1, 2
• Contraindications: recent thrombosis (absolute); atrial fibrillation or known thrombophilia (relative) 1, 2
• Expected outcomes: 54% reduction in composite epistaxis endpoints and 17.3% reduction in epistaxis duration per month 2

Third-Line: Systemic Bevacizumab

Reserve for refractory cases failing conservative measures and tranexamic acid 1, 2:

• Induction: 5 mg/kg IV every 2 weeks for 4-6 doses 1, 2
• Maintenance: 5 mg/kg IV every 1-3 months (variable dosing) 1, 2
• Expected outcomes: 50% reduction in Epistaxis Severity Score (from 6.81 to 3.44), 85% epistaxis control rate, and 3-4 g/dL hemoglobin increase 2, 3
• Monitor for: hypertension, proteinuria, infection risk, and delayed wound healing 1, 2
• VTE rate is only 2% with no fatal adverse events in the 238-patient InHIBIT-Bleed study 1, 3

Critical Anticoagulation Considerations

A common pitfall is withholding indicated anticoagulation due to bleeding concerns. Bleeding in HHT is not an absolute contraindication for anticoagulation or antiplatelet therapy when there is a clear indication. 3, 1

• Prefer heparin agents and vitamin K antagonists over direct oral anticoagulants due to better tolerability and lower bleeding risk in HHT 3, 1
• Avoid dual antiplatelet therapy and combination antiplatelet/anticoagulation wherever possible 3, 4
• For atrial fibrillation patients who cannot tolerate anticoagulation, consider left atrial appendage closure 3, 4

Iron Status Management

Despite elevated RBC count, assess iron status as HHT patients often have concurrent iron deficiency from chronic bleeding:

• Screen all adults with HHT for iron deficiency regardless of symptoms 3
• Start with oral iron (35-65 mg elemental iron daily) if deficiency is identified 3
• Use IV iron if oral is ineffective, not absorbed, not tolerated, or if severe anemia is present 3
• Regularly-scheduled iron infusions may be needed unless chronic bleeding is halted through systemic therapies 3

Family Screening

Screen first-degree relatives given the autosomal dominant inheritance pattern with 50% transmission risk 1