Pulmonary thrombotic arteriopathy in patients with sickle cell disease

Background. - Shortened life expectancy due to pulmonary hypertension (PH) is seen in 5% to 10% of patients with sickle cell disease. The principal factors suspected of causing PH are pulmonary thromboemboli (PE) and in situ arterial thrombosis. Objective. - To investigate the possible role that PE or in situ arterial thrombosis play in the development of PH in sickle cell disease. Methods. - Autopsies of 12 patients with sickle cell disease were correlated with clinical data from medical records. Results. - Right ventricular hypertrophy was present in 9 of 12 patients. Six patients with right ventricular hypertrophy had thrombi in large elastic pulmonary arteries. All patients with elastic artery thrombi had fresh or organized thrombi in small muscular pulmonary arteries. Hypertensive small arterial changes were present in 5 of these 6 patients. Six patients showed no thrombi in elastic arteries. Among these 6 patients, 3 had right ventricular hypertrophy and recent and organized thrombi, as well as hypertensive changes in small arteries. One of these 3 patients demonstrated plexiform-like lesions and fibrinoid necrosis of small arteries. Three patients without right ventricular hypertrophy had pneumonia or pulmonary edema with no identifiable pulmonary artery pathology. Conclusions. - Arterial thrombosis with PH and cor pulmonale was regarded as the cause of death among most of these patients. Elastic artery thrombi are pulmonary thromboemboli, but pulmonary thromboemboli are always associated with widespread thrombosis of small arteries. Widespread thrombosis of small arteries alone was associated with PH in some cases. This finding suggests that pulmonary thromboemboli may be a late complication of PH and cor pulmonale and that an in situ thrombotic arteriopathy underlies the development of PH in most patients with sickle cell disease.