How should patients with Hereditary Hemorrhagic Telangiectasia (HHT) manage their red blood cell counts?

Managing Red Blood Cell Counts in Hereditary Hemorrhagic Telangiectasia

All adults with HHT should be screened for iron deficiency and anemia regardless of symptoms, and children with recurrent bleeding should also be screened, because chronic blood loss from telangiectasias causes iron deficiency anemia in approximately 50% of patients, profoundly impacting quality of life. 1, 2

Screening Protocol

• Screen all adults with HHT for iron deficiency and anemia even without bleeding symptoms or anemia complaints 1, 2
• Screen children only if they have recurrent bleeding and/or symptoms of anemia 1, 2
• Obtain complete iron studies including hemoglobin, ferritin, and transferrin saturation—not just hemoglobin alone 2
• Screening intervals should be determined by the severity and frequency of bleeding episodes, as HHT bleeding is chronic and progressive 1

Iron Replacement Strategy

Start with oral iron at 35-65 mg of elemental iron daily, but use intravenous iron as first-line therapy in patients presenting with severe anemia or when oral replacement is expected to be inadequate. 1, 2

Oral Iron Approach

• Begin with 35-65 mg elemental iron daily 1, 2
• If inadequate response after 1 month, increase to twice daily dosing or higher daily dose 1, 2
• If not tolerated, switch to an alternate oral iron preparation 1, 2
• Assess response at 1 month: adequate response is hemoglobin rise ≥1.0 g/dL with normalization of ferritin and transferrin saturation 1, 2

Intravenous Iron Indications

• Severe anemia at presentation 1, 2
• Oral iron not effective, not absorbed, or not tolerated 1, 2
• Expected inadequacy of oral replacement based on severity of ongoing bleeding 1
• Calculate dose using the Ganzoni formula or provide empiric total dose of 1 gram, then reassess 1
• Regularly-scheduled iron infusions should be expected unless chronic bleeding is halted through systemic therapies 1

Red Blood Cell Transfusion Indications

Transfuse red blood cells only in specific high-risk situations, not as routine management of chronic anemia. 1, 2

Transfuse when:

• Hemodynamic instability or shock is present 1, 2
• Comorbidities require a higher hemoglobin target 1, 2
• Need to increase hemoglobin acutely (prior to surgery or during pregnancy) 1, 2
• Inability to maintain adequate hemoglobin despite frequent iron infusions 1, 2

Systemic Therapy to Control Bleeding and Improve Hemoglobin

For patients requiring intravenous iron or red cell transfusions (moderate-to-severe bleeding), systemic bevacizumab produces substantial improvements with mean hemoglobin increases of 3-4 g/dL, 82% reduction in transfusions, and 70% reduction in iron infusion needs. 1, 2

Bevacizumab Dosing Protocol

• Induction: 5 mg/kg IV every 2 weeks for 4-6 doses 1, 2
• Maintenance: 5 mg/kg IV every 1-3 months (variable dosing) 1, 2
• Monitor for hypertension, proteinuria, infection risk, delayed wound healing, and venous thromboembolism (VTE rate is only 2% with no fatal adverse events) 1, 2

Tranexamic Acid for Milder Bleeding

• Start at 500 mg twice daily, gradually increasing up to 1000 mg four times daily or 1500 mg three times daily 1, 2
• Absolute contraindication: recent thrombosis 1, 2
• Relative contraindications: atrial fibrillation or known thrombophilia 1, 2
• Can be coadministered with systemic antiangiogenic therapy 1, 2

Evaluation for Inadequate Response

If hemoglobin rises less than 1.0 g/dL at 1 month despite adequate iron replacement, evaluate for additional causes of anemia including hemolysis or other complicating etiologies. 1, 2

• Consider hematology consultation for patients with anemia but without reduced ferritin 1
• Recognize that fatigue may persist despite hemoglobin normalization if iron stores (ferritin, transferrin saturation) remain depleted 2

Critical Safety Considerations

• Never perform liver biopsy in patients with proven or suspected HHT due to catastrophic hemorrhage risk from vascular malformations 2, 3
• Avoid dual antiplatelet therapy and/or combination of antiplatelet therapy with anticoagulation wherever possible 1, 2
• Anticoagulation is not an absolute contraindication in HHT when there is a clear indication, but prefer heparin agents and vitamin K antagonists over direct oral anticoagulants due to better tolerability 1, 4