Can a patient with Hereditary Hemorrhagic Telangiectasia (HHT) have elevated red blood cell counts?

Can HHT Patients Have Elevated Red Blood Cell Counts?

Yes, HHT patients can have elevated red blood cell counts, but this is exceedingly rare and should immediately trigger investigation for secondary causes, as the overwhelming majority of HHT patients present with anemia from chronic bleeding rather than erythrocytosis. 1

Understanding the Typical Presentation

• Approximately 50% of HHT patients experience iron deficiency anemia from chronic bleeding, making anemia the expected hematologic finding rather than erythrocytosis 2, 1
• Recurrent epistaxis and gastrointestinal bleeding are the dominant bleeding sources that lead to chronic iron depletion and anemia 2, 3
• The presence of erythrocytosis in an HHT patient represents a paradoxical finding that demands explanation 1

Immediate Diagnostic Workup When Erythrocytosis Is Found

Screen for pulmonary arteriovenous malformations (PAVMs) first, as these are the most likely HHT-related cause of erythrocytosis through chronic hypoxemia: 1, 4

• Perform contrast echocardiography or chest CT as the initial screening test 1, 4
• PAVMs create right-to-left shunts that cause chronic hypoxemia, which stimulates erythropoietin production and drives secondary erythrocytosis 5
• Pulmonary AVMs are more frequent and larger in HHT type 1 (ENG mutations) 5

Evaluate for hepatic AVMs as a secondary contributor: 1, 4

• Use Doppler ultrasonography as first-line imaging for liver involvement 2, 1, 4
• Hepatic AVMs can contribute to abnormal erythropoietin production 4
• Never perform liver biopsy in HHT patients due to catastrophic hemorrhage risk 2, 1, 4, 5

Rule out coincidental polycythemia vera or other primary myeloproliferative disorders: 1, 4

• Refer to hematology for JAK2 mutation testing and bone marrow evaluation if indicated 1, 4
• These conditions can coexist with HHT independently and require distinct management 1

Management Algorithm Based on Findings

If PAVMs are identified, proceed with percutaneous transcatheter embolization regardless of feeding artery size: 1, 4, 5

• This intervention addresses both the erythrocytosis (by correcting hypoxemia) and prevents life-threatening neurological complications 1, 4
• PAVMs carry risk of paradoxical embolism leading to stroke or cerebral abscess 1, 5, 3
• Nearly one in five HHT patients develop stroke or cerebral abscess, making PAVM treatment critical 4

If no secondary cause is identified, manage as primary polycythemia with hematology guidance 1, 4

Critical Monitoring Considerations

Establish baseline iron studies even in the presence of erythrocytosis: 1

• Measure ferritin and transferrin saturation at baseline 1
• HHT patients may transition from erythrocytosis to iron deficiency if bleeding worsens over time 1
• Reassess hemoglobin and hematocrit at 1-month intervals to detect evolution toward anemia 1

Screen all adults with HHT for iron deficiency regardless of current hemoglobin levels: 2

• This recommendation applies even when erythrocytosis is present, as bleeding patterns can change 2
• Iron replacement should be initiated if deficiency develops: start with oral iron (35-65 mg elemental iron daily) 2, 4
• Escalate to intravenous iron for inadequate response, intolerance, or severe anemia 2

Anticoagulation Considerations in Erythrocytosis

Bleeding in HHT is not an absolute contraindication for anticoagulation when there is a clear indication: 2, 1, 6, 7

• Prefer heparin agents and vitamin K antagonists over direct oral anticoagulants due to better tolerability and lower bleeding risk in HHT 1, 4
• Avoid dual antiplatelet therapy and combination antiplatelet/anticoagulation therapy wherever possible 2, 1, 4
• Consider left atrial appendage closure for atrial fibrillation in patients who cannot tolerate anticoagulation 1, 4
• In one retrospective study, 23% of HHT patients on anticoagulation reported severe complications (transfusion, ER visit, or hospitalization), while 58% reported minor complications (increased epistaxis or GI bleeding) 6

Common Pitfalls to Avoid

Do not assume erythrocytosis excludes HHT or represents a benign finding: 1

• The rarity of erythrocytosis in HHT makes it a red flag for life-threatening complications like PAVMs 1
• Failure to screen for PAVMs can result in preventable stroke or cerebral abscess 4, 5

Do not delay PAVM screening while pursuing other diagnostic workup: 1, 4

• PAVMs can be treated presymptomatically to prevent catastrophic complications 4, 5
• Contrast echocardiography or chest CT should be performed immediately upon recognition of erythrocytosis in HHT 1, 4

Do not overlook the possibility of transitioning from erythrocytosis to anemia: 1

• HHT is a progressive bleeding disorder, and hematologic parameters can shift over time 2, 3
• Regular monitoring is essential to detect this transition and initiate iron replacement promptly 1