What is the recommended management for patients with Hereditary Hemorrhagic Telangiectasia (HHT) and uterine hyperplasia?

Management of HHT with Uterine Hyperplasia

For patients with HHT and uterine hyperplasia causing menorrhagia, endometrial ablation is the preferred definitive treatment when hormonal therapy fails, as it provides effective bleeding control while avoiding the high surgical risks of hysterectomy in this population. 1

Stepwise Management Algorithm

First-Line: Hormonal Therapy

• Initiate hormonal suppression as the initial approach for menorrhagia in HHT patients with uterine hyperplasia, though effectiveness may be limited 1
• Consider progestins or combined hormonal contraceptives, recognizing that these agents carry theoretical thromboembolic risks that must be weighed against bleeding severity 2

Second-Line: Endometrial Ablation

• Proceed to hysteroscopic endometrial ablation (rollerball electrocoagulation or equivalent technique) when hormonal therapy fails to control bleeding 1
• This approach is particularly critical in HHT patients who have contraindications to major surgery, including:
  • Profound anemia requiring transfusion support
  • History of stroke or cerebral arteriovenous malformations
  • Cardiac complications from hepatic shunting
  • Multiple comorbidities from visceral vascular malformations 1

Adjunctive Medical Management

• Administer oral tranexamic acid (500 mg twice daily, titrating up to 1000 mg four times daily) for menorrhagia not responding to hormonal therapy alone 2, 3
• Tranexamic acid reduces bleeding duration by 17.3% and composite bleeding endpoints by 54% in HHT patients 2, 3
• Monitor for thrombotic complications, though randomized trials showed no increased VTE risk with up to 3 months of therapy 2

Systemic Antiangiogenic Therapy for Severe Cases

• For severe menorrhagia with transfusion-dependent anemia failing hormonal therapy and tranexamic acid, consider systemic bevacizumab (5 mg/kg IV every 2 weeks for 4-6 doses as induction, followed by maintenance dosing every 1-3 months) 2, 4, 5
• Bevacizumab produces substantial hemoglobin improvements (3-4 g/dL increase) and reduces transfusion requirements with only 2% VTE rate 2, 5
• This represents disease-modifying therapy that induces telangiectasia regression rather than temporary hemostasis 4, 5

Critical Contraindications and Pitfalls

Avoid Major Surgery

• Never perform hysterectomy as first-line therapy in HHT patients due to excessive surgical bleeding risk and high comorbidity burden from visceral vascular malformations 1
• Major surgery is contraindicated in patients with hepatic arteriovenous malformations, pulmonary AVMs, or cerebrovascular involvement 1

Avoid Liver Biopsy

• Strictly avoid liver biopsy in any HHT patient due to catastrophic hemorrhage risk, even when evaluating for concurrent hepatic pathology 6

Anticoagulation Considerations

• If anticoagulation becomes necessary for thrombotic complications, prefer heparin agents or vitamin K antagonists over direct oral anticoagulants, as the latter may be less well tolerated due to increased bleeding risk 2
• Recent evidence suggests HHT patients can be safely anticoagulated with careful monitoring, though worsened epistaxis is the most frequent complication 7

Quality of Life Impact

• Menorrhagia in HHT patients compounds the psychosocial morbidity from epistaxis and gastrointestinal bleeding, causing social isolation and employment difficulties 3
• Treatment decisions should prioritize reducing bleeding burden to improve quality of life, not just correcting hemoglobin levels 6, 3

Iron Replacement

• Implement aggressive iron replacement therapy for all HHT patients with menorrhagia, as chronic blood loss leads to severe iron deficiency anemia 6, 5
• Intravenous iron is often required due to inadequate oral absorption and ongoing losses 2, 5