title: The Pathobiology of Chronic Thromboembolic Pulmonary Hypertension.
abstract: Chronic thromboembolic pulmonary hypertension (CTEPH) is a late sequel of venous thromboembolism that cannot be completely reproduced in animal models. The prevalence of CTEPH in humans is estimated at roughly 17-20 per million; however, partly because up to 50% of patients with CTEPH never experience symptomatic pulmonary embolism, precise numbers on the incidence and prevalence are not known. Because CTEPH is diagnosed at a median age of 63 years in patients who often have other concomitant cardiovascular disease or lung disease, assessment of pathophysiology in patients can be challenging, We do know that CTEPH is a dual vascular disorder. Stenoses, webs, and occlusions predominate in large and medium-sized pulmonary arteries at the sites of previous pulmonary emboli. A "secondary vasculopathy" resembling the pulmonary arteriopathy encountered in other forms of pulmonary hypertension predominates in low-resistance vessels. Anastomoses between bronchial artery branches and precapillary pulmonary arterioles appear during evolution of the disease. Other acquired vascular connections between bronchial arteries and pulmonary veins may trigger venous remodeling. Current concepts regarding the pathophysiology of CTEPH include contributions of hyperactive coagulation (e.g., high coagulation factor VIII, combined coagulation defects, dysfibrinogenemias), insufficient anticoagulation, non-O blood groups, and misguided thrombus resolution (e.g., infection, inflammation, dysfunctional innate immunity, abnormal circulating phospholipids). Current research focuses on the question as to whether a genetic predisposition leads to misguided vascular healing after pulmonary thromboembolism in susceptible individuals.
authors: 1 Division of Cardiology, Vienna General Hospital, Medical University of Vienna, Vienna, Austria.
authors: Irene M
authors: IM
authors: Lang
authors: 2 Department of Pathology and Institut National de la Santé et de la Recherche Médicale UMR-S 999, Paris-South University, Marie Lannelongue Hospital, Le Plessis-Robinson, France; and.
authors: Peter
authors: P
authors: Dorfmüller
authors: 3 Department of Pulmonology, Vrije Universiteit Medical Center, Amsterdam, the Netherlands.
authors: Anton
authors: A
authors: Vonk Noordegraaf
mesh_terms: D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D006801:Humans; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000473:pathology*; D007249:Inflammation / Q000473:pathology; D008168:Lung / Q000473:pathology*; D051379:Mice; D011651:Pulmonary Artery / Q000473:pathology; D011655:Pulmonary Embolism / Q000150:complications* / Q000473:pathology*; D011667:Pulmonary Veins / Q000473:pathology; D013927:Thrombosis / Q000150:complications*; D020257:Ventricular Remodeling
keywords: chronic thromboembolic pulmonary hypertension; coagulation; review; vascular biology