How is anemia due to chronic bleeding managed in patients with Hereditary Hemorrhagic Telangiectasia (HHT) with low hematocrit levels?

Management of Anemia Due to Chronic Bleeding in HHT with Low Hematocrit

Start with oral iron replacement (35-65 mg elemental iron daily) as initial therapy, but immediately escalate to intravenous iron for patients presenting with severe anemia or when oral replacement is expected to be inadequate or ineffective. 1

Screening and Diagnosis

• Screen all adults with HHT for iron deficiency and anemia regardless of symptoms (high quality evidence, strong recommendation). 1
• Screen all children with recurrent bleeding and/or symptoms of anemia. 1
• Assess complete iron studies including hemoglobin, ferritin, and transferrin saturation—not just hemoglobin alone. 1
• Evaluate for additional causes of anemia if response to iron replacement is inadequate (hemoglobin rise <1.0 g/dL at 1 month), as concomitant hemolysis may contribute in a subset of patients. 1

Iron Replacement Strategy

Oral Iron Therapy

• Start with 35-65 mg of elemental iron daily. 1
• If inadequate response, increase to twice daily dosing or higher daily dose. 1
• If not tolerated, attempt alternate oral iron preparation. 1
• Reassess at 1 month for adequate response (hemoglobin rise ≥1.0 g/dL, normalization of ferritin and transferrin saturation). 1

Intravenous Iron Therapy

Use IV iron as first-line therapy in patients with:

• Severe anemia at presentation 1
• Oral iron not effective, not absorbed, or not tolerated 1
• Expected inadequacy of oral replacement 1

Dosing approach:

• Calculate total iron deficit using Ganzoni formula, or 1
• Provide empiric total dose of 1 gram with interval reassessment 1
• Expect need for regularly-scheduled iron infusions unless chronic bleeding is halted through systemic therapies and/or procedural interventions. 1

Severity Classification and Treatment Escalation

The Second International HHT Guidelines classify bleeding severity based on hemoglobin goals (normal for age and gender) and iron requirements: 1

Mild HHT-Related Bleeding

• Patient meets hemoglobin goals with oral iron replacement alone 1
• Consider oral tranexamic acid (500 mg twice daily, titrating up to 1000 mg four times daily or 1500 mg three times daily) 1

Moderate HHT-Related Bleeding

• Patient meets hemoglobin goals with IV iron treatment 1
• Consider intravenous bevacizumab or other systemic antiangiogenic therapy (moderate quality evidence, strong recommendation) 1

Severe HHT-Related Bleeding

• Patient does not meet hemoglobin goals despite adequate iron replacement or requires blood transfusions 1
• Strongly consider intravenous bevacizumab (moderate quality evidence, strong recommendation) 1

Systemic Antiangiogenic Therapy

Bevacizumab dosing protocol:

• Induction: 5 mg/kg IV every 2 weeks for 4-6 doses 1
• Maintenance: 5 mg/kg IV every 1-3 months (variable dosing) 1

Expected outcomes:

• Mean hemoglobin improvement of 3.2 g/dL 1
• 82% reduction in red blood cell transfusions 1
• 70% reduction in iron infusions 1

Monitoring requirements:

• Hypertension 1
• Proteinuria 1
• Infection risk 1
• Delayed wound healing 1
• Venous thromboembolism 1

Red Blood Cell Transfusion Indications

Transfuse RBCs in the following settings:

• Hemodynamic instability/shock 1
• Comorbidities requiring higher hemoglobin target 1
• Need to increase hemoglobin acutely (prior to surgery or during pregnancy) 1
• Inability to maintain adequate hemoglobin despite frequent iron infusions 1

Critical Pitfalls to Avoid

• Never perform liver biopsy in patients with proven or suspected HHT due to catastrophic hemorrhage risk from vascular malformations. 1
• Do not rely solely on hemoglobin levels—treatment decisions should prioritize quality of life, as chronic bleeding causes significant psychosocial morbidity, social isolation, and difficulties with employment and daily activities. 1
• Recognize that fatigue may persist despite hemoglobin normalization if iron stores (ferritin, transferrin saturation) remain depleted. 1
• Avoid dual antiplatelet therapy and/or combination of antiplatelet therapy with anticoagulation where possible. 1

Antifibrinolytic Therapy Considerations

Tranexamic acid contraindications and precautions:

• Absolute contraindication: recent thrombosis 1
• Relative contraindications: atrial fibrillation or known thrombophilia 1
• Can be coadministered with systemic antiangiogenic therapy 1