Sickle cell disease (SCD) is a common genetic disease concerning millions of individuals worldwide, characterized by production of an abnormal hemoglobin. It is a chronic disease whose first signs can appear early in life and can affect every organ.
Pulmonary complications are common and potentially life-threatening. They can be both acute (acute chest syndrome) or chronic (loss of lung function, pulmonary hypertension).
Acute chest syndrome (ACS) is a potentially fatal event presenting with chest pain, fever, with or without acute respiratory symptoms, associated with radiological abnormalities.
Recurrent episodes of ACS can result in chronic lung disease and are linked to premature mortality.
In order to prevent ACS and improve management of pulmonary complications, specific markers are needed. Currently the known clinical and hematological factors that can increase the risk of ACS such as infections, associated asthma and hemolysis, cannot be used for screening of cardiopulmonary complications.
Recently, there have been reports of the role of circulating biological markers that could indicate an impending ACS or future cardiopulmonary complications. For example, inflammatory markers such as C-reactive protein (CRP), phospholipase A2 (sPLA2) and pentraxin-3 (PTX3), though non-specific for ACS, are elevated prior to such an acute event. Likewise, inflammatory markers such as interleukin-6, angiogenic markers such as platelet derived growth factor (PDGF-BB) and vascular endothelial growth factor (VEGF) are strongly correlated with cardiac dysfunction. Nitric oxide, an important pathway of vasodilatation, is significantly reduced in SCD patients whereas Fas and its ligand FasL, members of the tumor necrosis factor receptor superfamily, are significantly higher in SCD patients compared to healthy controls and SCD patients treated with hydroxyurea. NO and Fas-FasL could thus be potential markers for vascular dysfunction.
More recently, low levels of serum Apelin, a peptide involved in cardiovascular function, seem to be present in early stage subclinical cardiac disease and could enable the early recognition of high risk patients. Apelin is also an independent risk factor for pulmonary hypertension, being a potential preclinical marker for pulmonary vascular damage.
The aim of this review is to describe potentially useful biological biomarkers of cardiopulmonary complications in SCD in order to develop strategies for their early detection at the subclinical stage and propose new guidelines for follow-up.