Can Hereditary Hemorrhagic Telangiectasia (HHT) cause abnormal uterine bleeding?

Can HHT Cause Abnormal Uterine Bleeding?

Yes, Hereditary Hemorrhagic Telangiectasia (HHT) can cause abnormal uterine bleeding through the development of uterine telangiectasias and vascular malformations, though this manifestation is not commonly emphasized in the primary HHT literature which focuses predominantly on epistaxis, gastrointestinal bleeding, and visceral arteriovenous malformations.

Understanding HHT as a Bleeding Disorder

HHT is an autosomal dominant vascular disorder affecting approximately 1 in 5,000 to 18,000 individuals, characterized by telangiectasias and arteriovenous malformations throughout the body 1. The fundamental pathology involves enlarged vessels with thin walls that are prone to rupture and bleeding 1.

Primary Bleeding Manifestations

The most common bleeding sites in HHT include:

• Epistaxis (nosebleeds): Occurs in more than 90% of adults with HHT, typically starting around age 11 years 1, 2
• Gastrointestinal bleeding: From telangiectasias in the GI tract, leading to chronic anemia 1, 2
• Mucocutaneous telangiectasias: Present on lips, oral cavity, fingers, and nose 2, 3

Uterine Involvement in HHT

While the provided guidelines do not explicitly detail uterine bleeding as a primary manifestation of HHT, the pathophysiology strongly supports this possibility:

Mechanism of Uterine Bleeding

Telangiectasias can develop in any mucosal surface, including the uterine endometrium, following the same vascular pathology seen in nasal, oral, and gastrointestinal mucosa 1, 2. These fragile, dilated vessels with thin walls are susceptible to spontaneous rupture and bleeding 1.

Clinical Considerations

When evaluating abnormal uterine bleeding in a patient with known or suspected HHT:

• Consider HHT as a potential coagulopathy: Women with high-risk bleeding factors, including those with family history of bleeding disorders, should be screened for coagulopathies 4
• Assess for systemic bleeding manifestations: Look for epistaxis history, mucocutaneous telangiectasias on lips/tongue/fingers, family history of HHT, and anemia disproportionate to menstrual blood loss 2
• Apply Curaçao diagnostic criteria: Diagnosis requires 3 of 4 criteria (spontaneous recurrent epistaxis, multiple telangiectasias, visceral lesions, first-degree relative with HHT) 2

Diagnostic Approach for Abnormal Uterine Bleeding in HHT Context

Initial Assessment

• Transvaginal ultrasound remains the first-line imaging for structural uterine abnormalities 1
• Complete blood count to assess for anemia severity 1
• Iron studies given the chronic bleeding nature of HHT 2

When to Suspect HHT

Consider HHT in patients with abnormal uterine bleeding who have:

• Recurrent bilateral epistaxis 1
• Visible telangiectasias on examination 2, 3
• Family history of similar bleeding patterns 2
• Anemia disproportionate to apparent menstrual blood loss 2

Genetic Testing Indications

Genetic testing for ENG, ACVRL1, and SMAD4 mutations should be performed in asymptomatic persons from families with known HHT or when clinical suspicion is high, as this identifies causative mutations in 97% of definite HHT cases 2, 5.

Management Implications

Stepwise Treatment Approach

For patients with confirmed HHT and abnormal uterine bleeding:

1. Iron replacement therapy for anemia management 2
2. Oral tranexamic acid as first-line systemic therapy, which reduces bleeding duration by 17.3% and composite endpoints by 54% 2
3. Hormonal therapies may be considered, though data are limited and thromboembolic risks must be weighed 1
4. Systemic bevacizumab for refractory cases failing other interventions, producing 50% reduction in bleeding severity 2

Critical Precautions

• Avoid endometrial biopsy or any invasive uterine procedures when possible due to increased hemorrhage risk, similar to the absolute contraindication for liver biopsy in HHT 2
• Multidisciplinary management with HHT specialists is recommended for complex cases 2

Important Caveats

The absence of explicit mention of uterine bleeding in HHT guidelines does not exclude it as a manifestation—the vascular pathology affecting nasal, oral, and GI mucosa can logically affect endometrial tissue. However, uterine bleeding appears less commonly reported than other bleeding sites, possibly due to:

• Overlap with common gynecologic causes of abnormal uterine bleeding 1, 4
• Underrecognition of HHT in women presenting primarily with menstrual complaints 1
• Later age of onset compared to epistaxis 2, 3

Quality of life should drive treatment decisions, not just hemoglobin levels, as chronic bleeding causes significant psychosocial morbidity and impacts daily functioning 1, 2.