What is the recommended management approach for abnormal uterine bleeding (AUB) in patients with Hereditary Hemorrhagic Telangiectasia (HHT)?

Management of Abnormal Uterine Bleeding in HHT Patients

For women with HHT experiencing abnormal uterine bleeding, begin with oral tranexamic acid as first-line therapy, escalating to systemic bevacizumab if bleeding remains refractory to antifibrinolytics, while simultaneously addressing iron deficiency anemia with oral or intravenous iron replacement. 1, 2

Initial Diagnostic Evaluation

• Obtain complete blood count with iron studies (hemoglobin, ferritin, transferrin saturation) to assess severity of iron deficiency anemia, which occurs in approximately 50% of HHT patients due to chronic bleeding 3, 4
• Perform transvaginal ultrasound as first-line imaging to exclude structural uterine abnormalities, though recognize that uterine endometrial telangiectasias follow the same vascular pathology seen in nasal, oral, and gastrointestinal mucosa 3
• Apply Curaçao diagnostic criteria if HHT diagnosis not yet established: spontaneous/recurrent epistaxis, multiple telangiectasias, visceral lesions, or first-degree relative with HHT (definite diagnosis requires 3 of 4 criteria) 3, 5

Critical pitfall: Iron deficiency anemia is equally common in HHT patients with or without active bleeding (15.7% vs 16.0%), suggesting ongoing occult blood loss, making universal iron screening mandatory regardless of bleeding symptoms 4

Stepwise Treatment Algorithm

First-Line: Antifibrinolytic Therapy

• Prescribe oral tranexamic acid (35-65 mg elemental iron daily equivalent dosing) for mild-to-moderate abnormal uterine bleeding, which reduces bleeding duration by 17.3% and composite bleeding endpoints by 54% in HHT patients 1, 6
• Tranexamic acid is now recommended as standard treatment in the Second International HHT Guidelines for bleeding that does not respond to moisturizing therapies alone 1
• Reassess response at 1 month, looking for hemoglobin rise ≥1.0 g/dL and normalization of ferritin and transferrin saturation 3

Second-Line: Systemic Antiangiogenic Therapy

• Initiate systemic bevacizumab (5 mg/kg IV every 2 weeks for 4-6 doses) for moderate-to-severe bleeding failing tranexamic acid, followed by maintenance dosing every 1-3 months 2, 7
• The InHIBIT-Bleed study of 238 patients demonstrated 50% reduction in bleeding severity scores, 82% reduction in red cell transfusion requirements, and mean hemoglobin improvement of 3.2 g/dL 2, 6
• Bevacizumab is explicitly recommended by the Second International HHT Guidelines for bleeding that has failed moisturizing therapies, tranexamic acid, and/or local ablative therapies 1, 2

Safety consideration: Despite theoretical thrombotic risks, bevacizumab shows reassuring safety with only 2% venous thromboembolism rate in the InHIBIT-Bleed study, and a single arterial thrombotic event in 69 patients treated for mean 11 months 2

Alternative Antiangiogenic Options

• Consider oral pazopanib or pomalidomide as alternative systemic antiangiogenic agents if bevacizumab is unavailable or not tolerated 7, 6
• Thalidomide has documented effectiveness in 67 patients but carries significant risk of persistent neuropathy, limiting enthusiasm for long-term use 1

Iron Deficiency Management

• Start oral iron supplementation (35-65 mg elemental iron daily) for all HHT patients with abnormal uterine bleeding, escalating dose or frequency if inadequate response 3
• Switch to intravenous iron for patients with inadequate absorption, intolerance, or severe anemia requiring more rapid repletion 3, 6
• Monitor complete iron panel (not just hemoglobin) as fatigue may persist despite hemoglobin normalization if iron stores remain depleted 3

Critical pitfall: Assess ferritin and transferrin saturation in addition to hemoglobin, as iron deficiency without anemia still causes significant fatigue and reduced quality of life 3

Hormonal Therapy Considerations

• Hormonal therapies may be considered for confirmed HHT with abnormal uterine bleeding, though data are limited and thromboembolic risks must be carefully weighed against bleeding benefits 3
• The evidence base for hormonal management specifically in HHT-related uterine bleeding is sparse compared to antifibrinolytic and antiangiogenic approaches 3, 5

Quality of Life Priority

• Treatment decisions should prioritize quality of life over hemoglobin levels alone, as chronic bleeding causes significant psychosocial morbidity, social isolation, and difficulties with employment and daily activities 1, 3, 6
• Recognize that abnormal uterine bleeding in HHT represents part of a systemic vascular disorder requiring multidisciplinary management through specialized HHT centers 3, 5

Important caveat: Discontinuation of bevacizumab leads to eventual rebleeding in most HHT patients, necessitating either scheduled continuous maintenance or as-needed intermittent maintenance strategies based on individual response 2