What is the management approach for patients with Hereditary Hemorrhagic Telangiectasia (HHT) and erythrocytosis?

Management of Erythrocytosis in HHT Patients

Erythrocytosis in HHT patients is exceedingly rare and should prompt immediate investigation for alternative causes, as the overwhelming majority of HHT patients present with anemia from chronic bleeding rather than elevated red blood cell counts. 1

Understanding the Paradox

The typical HHT patient has anemia, not erythrocytosis, with approximately 50% of HHT patients experiencing iron deficiency anemia from chronic bleeding. 1 When an HHT patient presents with elevated red blood cell counts, this represents a significant deviation from expected disease manifestations and requires systematic evaluation.

Immediate Diagnostic Workup

Screen for secondary causes of erythrocytosis that may coexist with HHT:

• Pulmonary arteriovenous malformations (PAVMs) causing chronic hypoxemia can trigger compensatory erythrocytosis through right-to-left shunting 2, 3
• Hepatic AVMs with significant shunting may contribute to altered oxygen sensing 2
• Evaluate for polycythemia vera or other primary myeloproliferative disorders that are coincidentally present 1
• Assess for obstructive sleep apnea, smoking, or high-altitude exposure as contributing factors 3

Screening Protocol for Visceral AVMs

All HHT patients with erythrocytosis require comprehensive AVM screening:

• Contrast echocardiography or chest CT to detect pulmonary AVMs that may be causing hypoxemia-driven erythrocytosis 2
• Doppler ultrasonography as first-line imaging for hepatic AVM assessment 1, 2
• MRI of the brain to evaluate for cerebral vascular malformations 2
• Never perform liver biopsy due to catastrophic hemorrhage risk 1, 2

Management Algorithm

If Pulmonary AVMs Are Identified:

Percutaneous transcatheter embolization should be performed regardless of feeding artery size due to paradoxical embolism risk and potential for stroke or cerebral abscess. 2 Successful treatment of PAVMs may normalize oxygen saturation and resolve secondary erythrocytosis.

If No Secondary Cause Is Found:

Refer to hematology for evaluation of primary polycythemia including JAK2 mutation testing and bone marrow evaluation if indicated. 1 This represents a separate disease process requiring standard polycythemia vera management protocols.

Critical Anticoagulation Considerations:

If therapeutic anticoagulation becomes necessary (e.g., for polycythemia vera-associated thrombosis):

• Anticoagulation is NOT an absolute contraindication in HHT despite bleeding risks 1
• Heparin agents and vitamin K antagonists are preferred 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

Monitoring and Follow-Up

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

Common Pitfalls to Avoid

• Do not assume erythrocytosis is "normal" for HHT—it is not and requires investigation 1
• Do not withhold indicated anticoagulation solely due to HHT diagnosis—bleeding can be managed with hemostatic treatments while maintaining necessary anticoagulation 1
• Do not perform phlebotomy without first ruling out occult bleeding—HHT patients may have concurrent GI bleeding that is masked by erythrocytosis 1
• Do not delay PAVM screening—untreated pulmonary AVMs carry risk of stroke, cerebral abscess, and hemorrhage regardless of red blood cell count 2