How to manage mildly elevated hematocrit (Hct) and hemoglobin (Hb) in a patient with Hereditary Hemorrhagic Telangiectasia (HHT)?

Management of Mildly Elevated Hematocrit and Hemoglobin in HHT Patients

Erythrocytosis in HHT is exceedingly rare and demands 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

Initial Diagnostic Imperative

The presence of elevated hematocrit and hemoglobin in an HHT patient is paradoxical and requires urgent workup, as approximately 50% of HHT patients experience iron deficiency anemia from chronic bleeding. 1 This presentation should trigger a systematic search for secondary causes:

Screen for Pulmonary Arteriovenous Malformations (PAVMs)

• Obtain contrast echocardiography or chest CT as the first-line investigation, as PAVMs are the most likely HHT-related cause of erythrocytosis through chronic hypoxemia-driven erythropoietin production. 1, 2
• PAVMs occur in 15-50% of HHT patients and can cause right-to-left shunting with resultant hypoxemia. 1

Evaluate for Hepatic AVMs

• Perform Doppler ultrasonography as first-line imaging to detect hepatic vascular malformations that may contribute to abnormal erythropoietin production. 1, 2
• Hepatic AVMs can alter hepatic metabolism and hormone production. 1

Assess for Cerebral Vascular Malformations

• Obtain brain MRI to complete the comprehensive AVM screening protocol. 1, 2
• This is critical for risk stratification before any interventions. 1

Rule Out Coincidental Primary Polycythemia

• Refer to hematology for JAK2 mutation testing and bone marrow evaluation if indicated to exclude polycythemia vera or other primary myeloproliferative disorders that are coincidentally present. 1, 2
• These conditions can coexist with HHT independent of the genetic mutation. 1

Management Based on Findings

If PAVMs Are Identified

Perform percutaneous transcatheter embolization regardless of feeding artery size. 1, 2 This intervention is critical because:

• It addresses the erythrocytosis by correcting hypoxemia. 2
• It prevents life-threatening paradoxical embolism, stroke, or cerebral abscess. 1, 2
• The risk of neurological complications outweighs procedural risks. 1

If No Secondary Cause Is Found

• Complete hematology evaluation for primary polycythemia with comprehensive testing including JAK2, CALR, and MPL mutations. 1
• Consider bone marrow biopsy if mutation testing suggests myeloproliferative neoplasm. 1

Critical Monitoring Considerations

Establish Baseline Iron Studies

Obtain ferritin and transferrin saturation even in the presence of erythrocytosis, as HHT patients may transition to iron deficiency if bleeding worsens. 1 This is essential because:

• The natural history of HHT involves progressive bleeding manifestations. 3
• Iron deficiency can develop rapidly with increased epistaxis or gastrointestinal bleeding. 3

Serial Hemoglobin Monitoring

• Reassess hemoglobin and hematocrit at 1-month intervals to detect evolution toward anemia, which would indicate progression of typical HHT bleeding manifestations. 1
• This monitoring helps distinguish transient from persistent erythrocytosis. 1

Anticoagulation Management in This Context

If the patient requires anticoagulation for comorbid conditions (atrial fibrillation, venous thromboembolism), anticoagulation is not an absolute contraindication in HHT despite bleeding risks. 3, 1, 2

Preferred Anticoagulation Strategies

• Use heparin agents and vitamin K antagonists rather than direct oral anticoagulants due to better tolerability and lower bleeding risk in HHT. 3, 1, 2
• Avoid dual antiplatelet therapy and combination antiplatelet/anticoagulation therapy wherever possible. 3, 1
• Consider left atrial appendage closure for atrial fibrillation in patients who cannot tolerate anticoagulation. 1

Common Pitfalls to Avoid

Do Not Assume Erythrocytosis Is Benign

The rarity of erythrocytosis in HHT (versus the typical anemia) means this finding cannot be dismissed as a variant presentation. 1 Missing a PAVM can result in catastrophic stroke or brain abscess. 1, 2

Do Not Delay PAVM Screening

Contrast echocardiography or chest CT should be obtained urgently, not scheduled routinely. 1, 2 The risk of paradoxical embolism exists regardless of symptom severity. 1

Do Not Perform Liver Biopsy

Liver biopsy carries catastrophic hemorrhage risk in HHT patients and should be avoided. 1 Use non-invasive imaging instead. 1

Do Not Withhold Necessary Anticoagulation

While bleeding is a concern, HHT patients can tolerate anticoagulation with close monitoring. 3, 4 The thrombotic risk from untreated conditions may exceed bleeding risk. 3

Concurrent Bleeding Management

Even with erythrocytosis, HHT patients may have concurrent bleeding symptoms requiring management:

For Epistaxis

• Start with nasal moisturization through air humidification and topical saline solution or gels. 5, 2
• Add oral tranexamic acid (500 mg twice daily, titrating up to 1000 mg four times daily) if moisturizing therapies fail. 3, 5, 2
• Contraindications to tranexamic acid include recent thrombosis; relative contraindications include atrial fibrillation or known thrombophilia. 3, 5
• Reserve systemic bevacizumab (5 mg/kg IV every 2 weeks for 4-6 doses, then maintenance every 1-3 months) for refractory cases. 3, 5, 2

Safety Profile of Systemic Therapies

The venous thromboembolism rate is only 2% in HHT patients treated with bevacizumab, with no fatal adverse events in the InHIBIT-Bleed study of 238 patients. 3, 2 Monitor for hypertension, proteinuria, infection risk, and delayed wound healing. 3, 2

Family Screening

Screen family members given the autosomal dominant inheritance pattern of HHT. 5, 2 This includes screening for PAVMs, hepatic AVMs, and cerebral vascular malformations even in asymptomatic relatives. 2