Clinical relevance of pulmonary vasculature involvement in sickle cell disease

Abstract

Summary Pulmonary complications are frequent in patients with sickle cell disease (SCD), but few studies have described lung pathology in SCD. We studied the lung tissue of 30 deceased SCD patients (1994–2012). Demographics, genotype, clinical characteristics, cause of death and associated conditions are presented. We quantified the presence of pulmonary arterial changes, thrombosis and venous thickening. Alveolar capillary abnormalities were demonstrated using CD34 expression and confocal microscopy. Autopsy and echocardiography reports were reviewed to classify heart abnormalities. Tissue expression of markers of endothelial activation (vascular cell adhesion molecule 1, intercellular adhesion molecule 1 and vascular endothelial growth factor) was quantified in pulmonary vessels. Median age was 33 years; genotype was SS in 19, SC in 7 and Sβ in 4, and there were 18 males. Hypertensive arterial changes were present in 76% of the patients, recent thrombosis in 80% and old thrombosis in 43%. Venous thickening was present in 23% and pulmonary capillary haemangiomatosis foci in 87%. Ten percent of the patients presented right ventricular hypertrophy. There was no increased expression of endothelial activation markers when compared to controls. SCD affects the whole pulmonary vascular tree and reflects the multiple burden on lung vasculature imposed by the disease upon time.

Epidemiology, Pathogenesis, and Clinical Approach in Group 5 Pulmonary Hypertension

“…A hypercoagulable state results from reduced NO, asplenia (functional or surgical), and activation of thrombotic factors (tissue factor, platelets, and thrombin) in SCD (22,23). This is supported by findings of pulmonary thromboemboli in 38-80% of postmortem lung examinations of deceased SCD patients (24,25).…”

Point of care ultrasound detection of thrombus straddling a patent foramen ovale in a patient with acute chest syndrome

“…Additionally, the patient had thrombolytics administered hours prior to autopsy, potentially leading to dissolution of the thrombi. On autopsy studies, filling defects on CT angiogram can be derived from (1) propagation from distal thrombus, (2) in situ thrombosis, and/or (3) embolism of bone marrow/fat [ 10 , 11 ]. Clinically distinguishing fat/marrow embolism from in situ thrombosis or distal propagation is not possible, thus treatment with anticoagulation and possibly thrombolytics is recommended [ 1 , 12 ].…”

Pulmonary capillary haemangiomatosis: a distinct entity?

“…The extent of bronchial artery hypertrophy and increased bronchial microvessel density are highly related to the degree of muscular hypertrophy and intimal fibrosis in pulmonary veins [76]. Furthermore, substantial PCH-like changes were demonstrated in 86% of patients with sickle-cell disease along with bronchial hypervascularisation and venous thickening in the majority patients [77]. Therefore, exposure of the pulmonary venous circulation to higher bronchial circulation pressure and flow likely precipitate venous remodelling and secondary PCH-like changes [67].…”