It is an autosomal dominant inherited disorder where haemoglobin production is abnormal. Normal haemoglobin has two α globin chains and two β globin genes. A single base mutation of exon-1 (codon-6) on β globin chain results in HbS (sickle haemoglobin). This haemoglobin polymerises in states of low oxygen making red blood cells rigid and causing obstruction to the circulation. The red cells become dehydrated and adhere to vascular endothelium. Inflammatory factors are released which leads to tissue damage. All these factors presents as painful vaso-occlusive crisis. It most commonly involves bones and joints. The pain is severe which may last for few hours to few weeks. Infection, stress and emotional upheaval may precipitate acute attack. Painful crisis is accompanied by fever, increased white cell count and effusions. Pain is most commonly seen in the low back, legs, chest and arms.

Involvement of chest usually involves fever and infiltrates on chest X-ray. Patients present with chest pain, dyspnoea and fever. Opioids should be given cautiously as this may precipitate further respiratory depression. Increased levels of phospholipase A2 is both a marker and predictor of acute chest syndrome.

The crisis may involve the liver, and patients may present with right upper quadrant pain, increase in liver size, hyperbilirubinaemia, increased prothrombin time and activated prothrombin times. Exchange transfusion often helps.