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HHT for the hematologist
AVMs can involve the large and small intestines as well as the stomach.
Central nervous system manifestations
Central nervous system manifestations may affect up to 10% of patients with HHT. Cerebral AVMs can be symptomatic and multiple in number,50 and are often present at birth.51 Neurological involvement may result in epilepsy, transient ischemic attack, stroke, or spinal hem- orrhage. In addition to embolic strokes and hemorrhage, CNS infections such as brain abscesses may occur in 1% or more of patients, ranging in severity from mild to life- threatening. They are likely a result of bacterial seeding or septic emboli from ischemic brain matter or pulmonary AVMs.52,53
Skin telangiectasias
Skin telangiectasias can be seen on the fingertips, tongue, face, lip, mucosa, and arms in up to 90% of patients (Figure 2).45 These sites can bleed and can be treated with laser ablation.
Iron deficiency/iron deficiency anemia
Iron deficiency/iron deficiency anemia is common in HHT. The underlying cause of iron deficiency in this patient population is the chronic blood loss from telang- iectasias (e.g. nasal mucosa or intestinal tract) leading to iron store depletion. Approximately 5% of patients with HHT may have severe hemorrhages from epistaxis and/or intestinal AVMs. This consequently leads to a microcytic or normocytic anemia and symptoms of fatigue. Cardiopulmonary complications as described above can develop.
Other events
Though other events are not frequently reported, they include thromboembolic disease, pulmonary hyperten- sion, liver disease, high-risk pregnancies, and spinal events. There is a 1% risk of mortality during pregnancy due to hemorrhage from cerebral or pulmonary AVMs.44 Patients are also affected socially and psychologically due to uncontrolled bleeding episodes. They commonly face difficulties with work, travel, social phobias, isolation, anxiety, and depressive disorders.
Figure 2. Clinical manifestations of telangiectasias. (A) Small red telangiec- tasias are often seen on the skin of hereditary hemorrhagic telangiectasia patients. (B) Similar lesions may be present on the tongue, lips, or palate.
Juvenile polyposis
Juvenile polyposis is a rare association with HHT and results from a germline mutation in MADH4.54 This con- dition is also an autosomal dominant disorder. Mutations in MADH4 may manifest phenotypically as juvenile poly- posis alone, HHT alone, or the combined syndrome of JP- HHT.55 The polyposis is best characterized by numerous hamartomatous polyps (i.e. 5-100) that are typically benign, but some patients may develop gastric or colorec- tal cancer, and so screening is encouraged. Patients with JP-HHT associated with MADH4 mutations are at an increased risk for early colorectal cancer.44 These patients may also have thoracic aorta dilation.
Diagnosis
Hereditary hemorrhagic telangiectasia is primarily a clin- ical diagnosis based on the following Curaçao criteria:44
• spontaneous and recurrent epistaxis
Table 2. Screening and management of hereditary human telangiecta- sia patients.
Anemia
• Evaluate for blood transfusion and iron requirements
• Monitor ferritin, reticulocytes, hemoglobin
• Start oral iron to maintain transferrin saturation >20% and ferritin
>50 ng/mL
• IV iron: 1 g over multiple infusions
Epistaxis
• Otolaryngology evaluation
• Humidification
• Nasal moisture with spray/ointment
• Electrocautery or laser therapy
• Antifibrinolytics, estrogen or progesterone therapy, surgery,
and embolization
Gastrointestinal bleeding
• Evaluation for telangiectasias and AVMs with upper endoscopy, colonoscopy, capsule endoscopy
• Antifibrinolytics, estrogen or progesterone therapy, laser therapy, surgery, and embolization
CNS AVM
• MRI/MRA brain
• >1 cm in diameter: neurosurgical evaluation, embolotherapy,
+/- stereotactic radiosurgery
Pulmonary AVM
• Pulmonary evaluation
• Transthoracic echocardiogram with bubble study for screening
+/- CT/CTA
• If 1+ bubbles on echocardiogram: avoid scuba diving, use IV with filters,
antibiotic prophylaxis for procedures (amoxicillin or clindamycin if PCN
allergic)
• Consider embolization
Hepatic AVM
• Abdominal ultrasound screening +/- CT/MRI
• Consider embolization/ligation, liver transplantation
Other
• Genetic consultation
• Evaluation for other bleeding disorders
• Discussion regarding anticoagulation, antiplatelet agents • Pregnancy is considered high risk
• Consider assessment for hypercoagulability
IV: intravenous; CNS: central nervous system; AVM: arteriovenous malformation; CT: computed tomography; MRI: magnetic resonance imaging; MRA: magentic resonance angiography; CTA: CT angiography; PCN: penicillin.
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