Hereditary hemorrhagic telangiectasia associated with inherited thrombophilia
Abstract
Introduction. Hereditary hemorrhagic telangiectasia and inherited thrombophilia are genetic disorders with quite opposite clinical manifestation. The main characteristic for hereditary hemorrhagic telangiectasia is recurrent bleeding, while the main characteristic for hereditary thrombophilia is thrombosis. The association between hereditary hemorrhagic telangiectasia and inherited thrombophilia in the same patient is rare. Case report. We presented a 32-year-old female with recurrent gastrointestinal hemorrhage and epistaxes, during a 9-year period. Hereditary hemorrhagic telangiectasia was established according to “Curaçao” criteria. Three of four criteria have been present: spontaneous recurrent epistaxis, multiple telangiectasias (nose) and visceral lesions (gastric angiodysplasias, jejunal telangiectasias, arterio-venous jejunal fistula). Pulmonary thromboembolism was the first manifestation of thrombophilia; the diagnosis was confirmed by genetic testing. Therapy of hemorrhage with tranexamic acid (anti-fibrinolytic agent; its use increases risk of thrombosis) was unsuccessful. Remission was achieved by thalidomide. The initial therapy for pulmonary thromboembolism included aspirin (that have an increased risk of bleeding), but aspirin had to be discontinued because of massive hematemesis. Unfortunately, a year later, anticoagulant therapy combined with the proton pump inhibitors, were introduced, because of a new thrombosis. One month after, the patient was still on this therapy, without new episodes of bleeding and thromboembolic events. Conclusion. Hereditary hemorrhagic telangiectasia and inherited thrombophilia could be unrecognized for years, partly due to the lower degree of clinical suspicion. Early diagnosis and the appropriate choice of therapy are essential for reducing serious consequences and to improve quality of life.
References
Duffau P, Lazarro E, Viallard JF. Hereditary hemorrhagic telan-giectasia. Rev Med Interne 2014; 35(1): 21−7. (French)
Kapur KN, Morin JK, Letarte M. Endoglin: A critical mediator of cardiovascular health. Vasc Health Risk Manag 2013; 9:195−206.
Soubrier F, Chung WK, Machado R, Grunig E, Aldred M, Geraci M, et al. Genetics and genomics of pulmonary arterial hyperten-sion. J Am Coll Cardiol 2013; 62(25 Suppl): D13−21.
Grosse SD, Boulet SL, Grant AM, Hulihan MM, Faughnan ME. The use of US health insurance data for surveillance of rare disorders: Hereditary hemorrhagic telangiectasia. Genet Med 2014; 16(1): 33−9.
Shovlin CL, Guttmacher AE, Buscarini E, Faughnan ME, Hyland RH, Westermann CJ, et al. Diagnostic criteria for hereditary he-morrhagic telangiectasia (Rendu-Osler-Weber syndrome). Am J Med Genet 2000; 91(1): 66−7.
Govani FS, Shovlin CL. Hereditary haemorrhagic telangiectasia: A clinical and scientific review. Eur J Hum Gen 2009; 17(7): 860−71.
Botella LM, Albiñana V, Ojeda-Fernandez, L Recio-Poveda L, Ber-nabèu C. Research on potential biomarkers in hereditary he-morrhagic telangiectasia. Front Genet 2015; 6: 115.
Rambaldi MP, Mecacci F, Guaschino S, Paidas MJ. Inherited and acquired thrombophilias. Reprod Sci 2014; 21(2): 167−82.
Schellong SM. Importance of thrombophilia screening. Internist (Berl) 2014; 55(5): 529−30; 532−4, 536. (German)
Pomero F, Ageno W, Serraino C, Borretta V, Gianni M, Fenoglio L, et al. The role of inherited thrombophilia in patients with isolated pulmonary embolism: A systematic review and a meta-analysis of the literature. Thromb Res 2014; 134(1): 84−9.
Martinelli I, De Stefano V, Mannucci PM. Inherited risk factors for venous thromboembolism. Nat Rev Cardiol 2014; 11(3): 140−56.
Bianca S, Cutuli N, Bianca M, Barrano B, Cataliotti A, Barone C, et al. Hereditary haemorrhagic telangiectasia and genetic throm-bophilia. Eur J Hum Genet 2010; 18(4): 405−6.
Wechalekar A, Parapia L. Hereditary haemorrhagic telangiectasia with protein S deficiency in a family: A case report. Eur J Haematol 2000; 64(1): 59−60.
Zarrabeitia R, Albiñana V, Salcedo M, Señaris-Gonzalez B, Fernan-dez-Forcelledo J, Botella L. A review on clinical management and pharmacological therapy on hereditary haemorrhagic telangiec-tasia (HHT). Curr Vasc Pharmacol 2010; 8(4): 473−81.
Kjeldsen AD, Kjeldsen J. Gastrointestinal bleeding in patients with hereditary hemorrhagic telangiectasia. Am J Gastroenterol 2000; 95(2): 415−8.
Ha M, Kim YJ, Kwon KA, Hahm KB, Kim M, Kim DK, et al. Gas-tric angiodysplasia in a hereditary hemorrhagic telangiectasia type 2 patient. World J Gastroenterol 2012; 18(15): 1840−4.
Kamath N, Bhatia S, Singh H, Shetty A, Shetty S. Hereditary he-morrhagic telangiectasia. N Am J Med Sci 2015; 7(3): 125−8.
Amanzada A, Töppler GJ, Cameron S, Schwörer H, Ramadori G. A case report of a patient with hereditary hemorrhagic telangiec-tasia treated successively with thalidomide and bevacizumab. Case Rep Oncol 2010; 3(3): 463−70.
Pierucci P, Lenato GM, Suppressa P, Lastella P, Triggiani V, Valerio R, et al. A long diagnostic delay in patients with hereditary haemorrhagic telangiectasia: A questionnaire-based retrospec-tive study. Orphanet J Rare Dis 2012; 7: 33.
Sabbà C. A rare and misdiagnosed bleeding disorder: Heredita-ry hemorrhagic telangiectasia. J Thromb Haemost 2005; 3(10): 2201−10.
Shovlin CL. Hereditary haemorrhagic telangiectasia: Pathophy-siology, diagnosis and treatment. Blood Rev 2010; 24(6): 203−19.
Dittus C, Streeiff M, Ansell J. Bleeding and clotting in hereditary hemorrhagic telangiectasia. World J Clin Cases 2015; 3(4): 330−7.
Cruz-Amy M, Hunter-Mellado R. Factor V Leiden thrombophilia: presentation of three patients and a literature review. Bol Asoc Med P R 2006; 98(3): 213−21.
Martinelli I, Passamonti SM, Bucciarelli P. Thrombophilic states. Handb Clin Neurol 2014; 120: 1061−71.
Kupferminc MJ, Eldor A, Steinman N, Many A, Bar-Am A, Jaffa A, et al. Increased frequency of genetic thrombophilia in women with complications of pregnancy. N Engl J Med 1999; 340(1): 9−13.
Bleker SM, Coppens M, Middeldorp S. Sex, thrombosis and inhe-rited thrombophilia. Blood Rev 2014; 28(3): 123−33.
Zaffar N, Ravichakaravarthy T, Faughnan ME, Shebata N. The use of anti-fibrinolytic agents in patients with HHT: A retrospec-tive survey. Ann Hematol 2015; 94(1): 145−52.
Gaillard S, Dupuis-Girod S, Boutitie F, Rivière S, Morinière S, Hatron PY, et al. Tranexamic acid for epistaxis in hereditary he-morrhagic telangiectasia patients: a European cross-over con-trolled trial in a rare disease. J Thromb Haemost 2014; 12(9): 1494−502.
Edwards CP, Shehata N, Faughnan ME. Hereditary hemorrhagic telangiectasia patients can tolerate anticoagulation. Ann Hema-tol 2012; 91(12): 1959−68.