The Battle of Bleeding and Clotting: Novel Use of Intranasal Bevacizumab in a Patient With Hereditary Hemorrhagic Telangiectasia and Chronic Thromboembolic Pulmonary Hypertension

Abstract

INTRODUCTION: Hereditary Hemorrhagic Telangiectasia (HHT) frequently manifests as epistaxis, gastrointestinal bleeding and iron deficiency anemia with telangiectasias. Epistaxis is most common. Therapy can include intranasal bevacizumab, a recombinant, humanized monoclonal antibody that prevents angiogenesis. We present a case of HHT and antithrombin III deficiency (ATIII) with chronic thromboembolic pulmonary hypertension (CTEPH). Definitive therapy was intolerable until bevacizumab therapy controlled epistaxis. CASE PRESENTATION: 48 year old male smoker with HHT manifesting as epistaxis, DVT and PE with IVC filter in 2010 and known ATIII presented to pulmonary clinic after recurrent PE. Due to transfusion dependence from epistaxis, he was not on anticoagulation. He only reported months of dyspnea with showering and limitations of his work as a tree trimmer. History included hospitalizations for epistaxis, frequent blood transfusions, iron infusions, gastrointestinal arteriovenous malformations and nasal arterial cauterizations. Mother and sister had HHT and PE. Exam showed normal vitals, oxygen saturation 97%. He had a palpable right ventricular heave, prominent P2 and telangiectasias of the oral mucosa and hands. Imaging findings in Table 1. Echocardiogram suggested moderate pulmonary hypertension (Table 2). He received submucosal bevacizumab for severe epistaxis. Anticoagulation was initiated and topical bevacizumab used for residual bleeding. He had no further hospitalizations. Repeat VQ scan was unchanged. Echocardiogram showed an enlarged RV impinging on LV function. Improved epistaxis allowed for thromboendarterectomy. Extensive proximal obstructive clot was removed pulmonary hemodynamics and functional status improving rapidly. DISCUSSION: Controlling his epistaxis with bevacizumab allowed the patient to undergo thromboendarterectomy and anticoagulation, definitive therapy for CTEPH. HHT can cause pulmonary hypertension, however this is the first reported case of CTEPH in a patient with HHT. The combination is a therapeutic challenge in balancing the risk of bleeding with need for anticoagulation. CONCLUSIONS: This case demonstrates novel use of intranasal Bevacizumab in temporizing transfusion-dependent epistaxis in a hypercoagulable male with HHT and CTEPH, previously unable to attempt definitive therapy.