Risk factors and basic mechanisms of chronic thromboembolic pulmonary hypertension: a current understanding

• Published in: The European respiratory journal Vol. 41; no. 2; pp. 462 - 468
• Main Authors: Lang, Irene M., Pesavento, Raffaele, Bonderman, Diana, Yuan, Jason X-J.
• Format: Journal Article
• Language: English
• Published: Leeds Maney 01.02.2013
• Subjects: Animals; Biological and medical sciences; Biopsy; Blood and lymphatic vessels; Blood Coagulation; Cardiology. Vascular system; Disease Models, Animal; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Fibrinogen - metabolism; Fibrinolysis; Humans; Hypertension, Pulmonary - diagnosis; Hypertension, Pulmonary - physiopathology; Inflammation; Medical sciences; Pneumology; Pulmonary Artery - pathology; Pulmonary Embolism - diagnosis; Pulmonary Embolism - physiopathology; Pulmonary hypertension. Acute cor pulmonale. Pulmonary embolism. Pulmonary vascular diseases; Risk Factors; Thromboembolism - epidemiology; Thromboembolism - physiopathology; Respiratory disease; Coagulation; Cardiovascular disease; Biology; vascular biology; Review; Thrombosis; Embolism; Pulmonary hypertension; Vascular disease; Chronic; Blood vessel; Risk factor; Chronic thromboembolic pulmonary hypertension; Thromboembolism; Bibliographic review; Pneumology
• ISSN: 0903-1936; 1399-3003; 1399-3003
• DOI: 10.1183/09031936.00049312

All available evidence today indicates that chronic thromboembolic pulmonary hypertension (CTEPH) is primarily caused by venous thromboembolism, as opposed to primary pulmonary vascular in situ thrombosis. Both the initial magnitude of clot and pulmonary embolism (PE) recurrence may contribute to the development of CTEPH. Only few specific thrombophilic factors, such as phospholipid antibodies, lupus anticoagulant and elevated factor VIII, are statistically associated with CTEPH. A mechanistic view of CTEPH as a disease caused by obliteration of central pulmonary arteries by pulmonary emboli is too simplistic. Based on available data one may speculate that PE may be followed by a pulmonary vascular remodelling process modified by infection, immune phenomena, inflammation, circulating and vascular-resident progenitor cells, thyroid hormone replacement or malignancy. Both plasmatic factors (hypercoagulation, “sticky” red blood cells, high platelet counts and uncleavable fibrinogens) and a misguided vascular remodelling process contribute to major vessel and small vessel obliteration. Endothelial dysfunction and endothelial–mesenchymal transition may be important, but their precise roles remain obscure. There exists no animal model for CTEPH; therefore, experimentation in the future must include human tissues and clinical data in parallel.