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Huge Pulmonary Arteriovenous Malformation, Venous Thromboembolism and Anticoagulation Treatment in a Patient with Hereditary Hemorrhagic Telangiectasia

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Huge Pulmonary Arteriovenous Malformation, Venous Thromboembolism and Anticoagulation Treatment in a Patient with Hereditary Hemorrhagic Telangiectasia □ CASE REPORT □ Huge Pulmonary Arteriovenous Malformation, Venous Thromboembolism and Anticoagulation Treatment in a Patient with Hereditary Hemorrhagic Telangiectasia Marcelo M. Serra 1,2, Bruno L. Ferreyro 1, Oscar Peralta 2,3, Ezequiel Levy Yeyati 2,3, Natalia Causada Calo 4, Teresa Garcia-Botta 5, Diego Andresik 1, Martín Rabellino 3 and Ricardo Garcia-Mónaco 2,3 Abstract Hereditary hemorrhagic telangiectasia (HHT) usually presents in association with pulmonary arteriovenous malformations (PAVMs). In addition, the incidence of venous thromboembolism tends to be increased in these patients. A 74-year-old female with HHT presented with cyanosis and hypoxemia. Contrast-enhanced multislice computed tomography (MSCT) revealed two left PAVMs and one in the right upper lobe. Both left PAVMs were treated with embolotherapy. Follow-up MSCT revealed an incidental pulmonary embolism in the right pulmonary branches. Deep venous thrombosis was confirmed and anticoagulation was initiated. Follow-up MSCT revealed the resolution of thromboembolism. Finally, embolotherapy was performed. This case illustrates the chronic adaptation to hypoxemia and adds further evidence to the relative safety of antico- agulation treatment in these patients. Key words: hereditary hemorrhagic telangiectasia, pulmonary arteriovenous malformation, pulmonary embolism, anticoagulation, deep vein thrombosis, Osler Weber-Rendu disease (Intern Med 54: 2745-2748, 2015) (DOI: 10.2169/internalmedicine.54.4540) Pulmonary arteriovenous malformations (PAVMs) are ab- Introduction normal communications between the pulmonary veins and arteries, and are present in nearly half of all HHT pa- Hereditary hemorrhagic telangiectasia (HHT, former tients (3). Approximately 80-90% of PAVMs are due to Rendu-Osler-Weber syndrome) is an autosomal dominant HHT and up to one third of such patients have clinical disease affecting vascular regions. Its main clinical charac- symptoms such as dyspnea, hemoptysis and platypnea. Right teristics are epistaxis, mucocutaneous telangiectases and ar- to left shunts explain most of the distal complications of teriovenous malformations (AVMs) in organs such as the PAVMs, such as paradoxical emboli presenting as transient lung, liver and brain. The clinical diagnosis was established ischemic attacks, stroke, brain abscess or migraine (4). based on the Curaçao Criteria (1). Genetically, HHT is char- PAVMs can be simple, with one or more feeding arteries acterized by mutations in Endoglin (ENG), ACVRL (Activin arising from the same segmental artery, or complex, with receptor like kinase type I -ALK-1-) and MADH 4 (SMAD multiple feeders from different segmental arteries (5). Em- 4). These genes codify for proteins involved in the trans- bolization is regarded as the treatment of choice and it is forming growth factor (TGF)-β receptor-signaling pathway generally indicated when the diameter of the feeding artery which regulates angiogenesis (2). is 3 mm or larger. In this scenario, the occurrence of brain １Internal Medicine Department, Italian Hospital of Buenos Aires, Buenos Aires University, Argentina, ２Hereditary Hemorrhagic Telangiectasia Unit, Italian Hospital of Buenos Aires, Argentina, ３Radiology Department, Italian Hospital of Buenos Aires, Argentina, ４Gastroenterology De- partment, Italian Hospital of Buenos Aires, Argentina and ５Cardiology Department, Italian Hospital of Buenos Aires, Argentina Received for publication November 18, 2014; Accepted for publication March 10, 2015 Correspondence to Dr. Bruno L. Ferreyro, [email protected] 2745 Intern Med 54: 2745-2748, 2015 DOI: 10.2169/internalmedicine.54.4540 Figure 1. Multislice CT Angiography: a) A volume rendering reconstruction anterior view showing a bulky PAVM near the mediastinum. b) A lateral view of the same PAVM showing a large feeding artery on the top of the PAVM (white arrow). The black arrow shows the thrombus inside. c) An oblique view showing a PAVM in the upper right lobe (arrow). abscesses might be prevented by the prophylactic use of an- measured 90×88×74 mm with a thrombus inside. Successful tibiotics (6). embolotherapy using 10 and 18 mm Amplatzer vascular The incidence of thromboembolic disease is known to in- plugs of both left PAVMs was performed and thereafter crease in HHT patients and can be associated with thrombus pulse oximetry improved significantly (SaO2 94% at rest). formation inside the AVMs or deep veins. The underlying Three months later the patient was admitted for reevalu- mechanism of this association appears to be an augmented ation. A new MSCT scan showed complete occlusion of the activity of factor VIII due to iron deficiency anemia (7, 8). aneurysm sac and the adjacent PAVM. Surprisingly, the Moreover, polyglobulia due to hypoxemia might also in- study revealed segmental and subsegmental pulmonary em- crease the aforementioned risk. In this clinical setting, the bolism (PE) in the right lung. A thrombus was present in decision regarding whether to start anticoagulation treatment the feeding artery of the upper right lobe (Fig. 2). The pa- or not is a clinical dilemma which requires careful judg- tient did not complain of any shortness of breath. Lower ment (8-10). Even though hemorrhagic complications of limb ultrasound revealed deep vein thrombosis (DVT) and HHT can be life-threatening, anticoagulation is not usually the serum factor VIII levels were increased. Treatment with contraindicated (8-10). low molecular weight heparin was started and the factor anti-Xa levels were monitored. She remained in-hospital for Case Report a week so as to monitor any bleeding and/or embolic com- plications. After seven days of treatment, a new MSCT scan A 74-year-old female who was diagnosed to have HHT revealed the complete resolution of PE. Embolotherapy of after fulfilling the four Curaçao criteria was admitted to our the remaining right PAVM was then successfully performed. hospital for evaluation. The diagnosis was based on her fam- The patient was discharged thereafter was administerd oral ily history, mild epistaxis (Sadick Scale 1) (11), mucocuta- anticoagulation for six months. During this period she only neous telangiectases, and the presence of hepatic and pulmo- presented with mild episodes of epistaxis that were treated nary AVMs. A huge PAVM within the left upper lobe had with YAG laser cauterization. After six months, she under- been diagnosed 15 years before this presentation, but treat- went the last part of the required embolotherapy procedure. ment had been discouraged at that time due to the risk of At that time, the upper lobe PAVM was adequately closed complications. Physical evaluation revealed telangiectases and the anticoagulation medication was stopped. present in face, lips, tongue and fingers, distal cyanosis, tachycardia, a systo-diastolic murmur on left hemithorax and Discussion hypoxemia at rest [saturation level of oxygen in hemoglobin (SaO2) 74%]. Laboratory studies revealed polyglobulia (he- This case highlights some interesting features regarding matocrit 47%) and iron deficiency. Magnetic resonance im- the pathophysiology of HHT and the clinical decision- aging (MRI) of the central nervous system revealed old si- making process in the management of these patients. Our lent ischemic images, but no AVMs. patient presented with severe hypoxemia without any evi- Contrast-enhanced multislice computed tomography dent dyspnea, thus reflecting the chronic adaptation to hy- (MSCT) showed the presence of a huge PAVM within the poxemia in HHT subjects (12). Moreover, after successfully left upper lobe, a smaller PAVM close to the latter and a treating the left PAVM, she suffered a PE, which was fortu- third complex PAVM within the apical segment of the right nately asymptomatic. Paradoxically, HHT patients can some- lobe with two feeding arteries with a diameter of 6, 5 mm times demonstrate an improved oxygenation and exercise (Fig. 1). The main left PAVM had a single feeding artery tolerance after the auto-embolization of PAVM (13). This in- measuring at 12 mm in diameter and a huge aneurysm that teresting mechanism could partially explain why the patient 2746 Intern Med 54: 2745-2748, 2015 DOI: 10.2169/internalmedicine.54.4540 Figure 2. A control CT scan after embolization of the bulky PAVM with a type II amplatzer. a) Sagittal MIP reconstruction. b) Axial MIP reconstruction. c) Sagittal Volume Rendering color recon- struction shows the complete occlusion of the large feeding artery and total thrombosis of the sac. d) Coronal MIP reconstruction of the same CT exam shows pulmonary embolism in the feeding artery of the PAVM in the right superior pulmonary lobe as an incidental finding. did not present with any overt clinical symptoms. tient had only mild epistaxis, we were therefore encouraged This case also exhibits the complexity of thromboembolic to start anticoagulation. Furthermore, we decided to perform events that these patients may suffer. It is unclear whether laser photocoagulation in order to increase the safety and DVT and PE after embolotherapy might have been triggered comfort of our patient. by the intervention itself, but the patient did have increased In summary, valuable information regarding the chronic levels of Factor VIII due to iron deficiency, which is a well- adaptation to hypoxemia, diverse thromboembolic pathways recognized thromboembolic factor in HHT. As PE was an and evidence of anticoagulation safety among HHT patients asymptomatic finding after MSCT screening, we therefore was obtained
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