In what medical situations would a patient with Hereditary Hemorrhagic Telangiectasia (HHT) have elevated red blood cell counts, hematocrit, and hemoglobin levels?

Erythrocytosis in HHT Patients

Primary Mechanism: Pulmonary Arteriovenous Malformations

HHT patients develop elevated red blood cell counts, hematocrit, and hemoglobin primarily due to chronic hypoxemia from pulmonary arteriovenous malformations (PAVMs), which create right-to-left shunts that bypass normal gas exchange and trigger compensatory erythropoietin production. 1

Pathophysiology of PAVM-Induced Erythrocytosis

• PAVMs create direct artery-to-vein connections that bypass capillaries, resulting in deoxygenated blood entering systemic circulation without undergoing gas exchange 1, 2
• This chronic hypoxemia stimulates the kidneys to produce erythropoietin, driving increased red blood cell production as a compensatory mechanism 1
• Pulmonary AVMs are more frequent and larger in HHT type 1 (ENG mutations) compared to HHT type 2 (ACVRL1 mutations), making erythrocytosis more common in HHT1 patients 3

Secondary Mechanism: Hepatic Arteriovenous Malformations

• Hepatic AVMs can contribute to abnormal erythropoietin production through altered hepatic hemodynamics and potential ischemic stimulation 1
• Hepatic involvement occurs in 44-74% of HHT patients but is symptomatic in only 5-8%, making it a less common cause of erythrocytosis than PAVMs 3
• HHT type 2 patients show substantially higher prevalence of hepatic vascular malformations with marked female predominance 3, 4

Critical Diagnostic Algorithm

Step 1: Screen for Pulmonary AVMs First

• Perform contrast echocardiography or chest CT as the initial screening test, as PAVMs are the most likely HHT-related cause of erythrocytosis 1
• Assess transcutaneous oxygen saturation, and if pathologic, proceed with transthoracic contrast cardiac echocardiography with agitated saline 3

Step 2: Evaluate Hepatic Involvement

• Perform Doppler ultrasonography as first-line imaging for liver involvement, looking for enlarged hepatic artery (>6 mm), peak flow velocity >80 cm/sec, and resistivity index <0.55 1, 3
• Never perform liver biopsy in HHT patients due to catastrophic hemorrhage risk from vascular malformations 1, 3, 5

Step 3: Rule Out Primary Polycythemia

• Obtain hematology referral with JAK2 mutation testing and bone marrow evaluation if indicated to exclude coincidental polycythemia vera or other primary myeloproliferative disorders 1
• This is critical because erythrocytosis in HHT is secondary (reactive) rather than primary, and treatment approaches differ fundamentally 1

Step 4: Complete AVM Screening

• Perform brain MRI to assess for cerebral vascular malformations, as cerebral AVMs occur more commonly in HHT1 and can contribute to overall disease burden 1, 3

Management 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 1, 3
• This intervention addresses both the erythrocytosis (by correcting hypoxemia) and prevents life-threatening neurological complications including stroke and brain abscess 1, 2
• Nearly one in five HHT patients develop stroke or cerebral abscess from untreated PAVMs 3

If Hepatic AVMs Are Symptomatic

• Large hepatic arteriovenous malformations can lead to high-output congestive heart failure, portal hypertension, hepatic encephalopathy, and biliary ischemia 4
• Invasive therapies including liver transplantation should only be considered after failure of intensive medical therapy 1, 4

Critical Pitfall to Avoid

The most dangerous error is assuming erythrocytosis in HHT is benign or treating it as primary polycythemia with phlebotomy alone, when the underlying PAVMs require urgent embolization to prevent stroke and cerebral abscess. 1, 3

• Erythrocytosis is a marker of significant underlying pathology (PAVMs) that requires definitive treatment, not just symptom management 1
• Treating only the elevated blood counts without addressing the underlying PAVMs leaves patients at ongoing risk for paradoxical emboli causing stroke or brain abscess 1, 2

Genotype-Phenotype Considerations

• HHT1 (ENG mutations) patients have more frequent and larger pulmonary AVMs, making them more likely to develop erythrocytosis from chronic hypoxemia 3
• HHT2 (ACVRL1 mutations) patients have higher rates of hepatic involvement, which may contribute to erythrocytosis through hepatic AVM-mediated mechanisms 3, 4
• SMAD4 mutation carriers develop combined HHT and juvenile polyposis syndrome with up to 76% manifesting life-threatening AVMs requiring immediate evaluation 3