Erythrocytosis in HHT: A Dangerous Misconception
No, patients with HHT should absolutely not aim for high red blood cell counts—this represents a fundamental misunderstanding of the disease. HHT is characterized by chronic bleeding leading to iron deficiency anemia in approximately 50% of patients, making elevated RBC counts exceedingly rare and pathological when present 1, 2.
The Reality of HHT Hematology
HHT patients overwhelmingly present with anemia, not erythrocytosis. The disease causes:
- Chronic bleeding from telangiectasias in the nose (>90% of adults), gastrointestinal tract, and other mucosal surfaces, resulting in iron deficiency anemia as the dominant hematologic manifestation 1, 3
- Iron deficiency anemia affects approximately 50% of HHT patients, causing fatigue, reduced exercise tolerance, and significant quality of life impairment 1
- Recurrent epistaxis and GI bleeding deplete iron stores, requiring aggressive iron replacement therapy rather than any strategy to increase RBC counts 1, 4
When Erythrocytosis Occurs: A Red Flag
Erythrocytosis in an HHT patient is exceedingly rare and demands immediate investigation for alternative causes 2. The American Society of Hematology emphasizes this is not a typical HHT presentation 2.
Mandatory Evaluation Protocol
If elevated RBC counts are discovered, immediately screen for:
- Pulmonary arteriovenous malformations (PAVMs) causing chronic hypoxemia using contrast echocardiography or chest CT—PAVMs create right-to-left shunts that may trigger compensatory erythrocytosis 1, 2
- Polycythemia vera or other primary myeloproliferative disorders that coincidentally coexist with HHT, requiring JAK2 mutation testing and hematology referral 2
- Hepatic AVMs via Doppler ultrasonography (never liver biopsy due to catastrophic hemorrhage risk) 1, 2
- Cerebral vascular malformations with brain MRI 1, 2
The Correct Management Paradigm
Treatment priorities in HHT focus on controlling bleeding and correcting anemia, not elevating RBC counts:
Stepwise Bleeding Management
- Nasal moisturization with air humidification and topical saline for epistaxis 1
- Oral tranexamic acid (antifibrinolytic) when moisturization fails—reduces epistaxis duration by 17.3% and composite endpoints by 54% 1, 4
- Local ablative therapies for refractory bleeding 1
- Systemic bevacizumab (anti-VEGF) for severe bleeding failing all other interventions—produces 50% reduction in epistaxis severity and mean hemoglobin improvement of 3.2 g/dL 1, 4, 5
Iron Replacement Strategy
- All adults with HHT require iron deficiency screening regardless of symptoms (hemoglobin, ferritin, transferrin saturation) 1
- Start with oral iron (35-65 mg elemental iron daily), escalating to intravenous iron for inadequate absorption, intolerance, or severe anemia 1
- Reassess at 1 month for adequate response (hemoglobin rise ≥1.0 g/dL, normalization of iron stores) 1
Critical Clinical Pitfalls
Never perform liver biopsy in HHT patients due to catastrophic hemorrhage risk from vascular malformations 1, 2. This applies even when investigating hepatic involvement or elevated RBC counts 1.
Treatment decisions should prioritize quality of life, not just hemoglobin levels alone—epistaxis causes significant psychosocial morbidity, social isolation, and difficulties with employment and daily activities 1, 4. Fatigue severity correlates with iron deficiency and anemia degree, requiring normalization of ferritin and transferrin saturation, not just hemoglobin 1.
If PAVMs are identified during erythrocytosis workup, perform percutaneous transcatheter embolization regardless of feeding artery size due to paradoxical embolism risk and potential for stroke or cerebral abscess 1, 2.
Monitoring Considerations
Even if erythrocytosis is present initially, establish baseline iron studies because HHT patients may transition to iron deficiency as bleeding worsens 2. Reassess hemoglobin and hematocrit at 1-month intervals to detect evolution toward anemia, which indicates progression of typical HHT bleeding manifestations 2.