Sickle cell disease (SCD) refers to the different genotypes that cause characteristic clinical syndromes. It is an autosomal recessive genetic blood disorder consisting of a valine substitution for glutamic acid at the sixth position of the B-globin chain. Sickle-cell anemia (HbSS) is the most common form accounting for 70% of cases and consists of homozygosity of the B-globin chains with hemoglobin S. The other types of SCD are heterozygotes, having one hemoglobin S chain and a copy of another β-globin mutation, such as hemoglobin C or β-thalassemia. De-oxygenation of hemoglobin S causes polymerization leading to decreased flexibility of the erythrocyte which obstructs the microvasculature. This also leads to a decrease in the life of the hemoglobin causing a chronic hemolytic anemia.
Acute chest syndrome (ACS) is characterized by a new pulmonary infiltrate, which is associated with fever, chest pain, wheezing, or cough. It is the second most common cause of ICU admission and mortality in sickle cell disease. Children commonly present with symptoms of reactive airways disease, whereas adults present with chest or extremity pain. Signs of systemic inflammation, fever and elevated white blood cell count, are common. The pathophysiology consists of three main mechanisms:
- The most common trigger for ACS is a pulmonary infection, particulary in children. Chlamydia pneumoniae and Mycoplasma pneumoniae are the most common organisms. Streptococcus pneumoniae is an uncommon cause, occurring in only 1%-3%. Respiratory syncytial virus is the most common virus.
- Fat embolization is the second most common cause, which occurs during severe vasoocclusive crises.
- The third cause of ACS is direct lung infarction or vasoocclusion.
Emergency department treatment consists of good supportive care with supplemental oxygen, analgesia (ketorolac and opioids) and incentive spirometry (10 puffs every 2 hours while awake). Bronchodilators should be started if there is a reactive airway component. Steroids are usually given for reactive airway, although they increase the risk of readmission usually secondary to pain crisis. Empiric antibiotics should be administered to all patients and should include a macrolide with possible pneumococcal coverage for high risk patients. Do not forget to obtain a CBC, reticulocyte count, type and screen or cross, blood cultures and seasonal virus screens (ie RSV, influenza).
Transfusion remains the cornerstone of treatment in ACS and is given in severe disease or if the hemoglobin is > 2g/dL below baseline. 1-3 units of packed RBCs are transfused keeping the hemoglobin level < 10 g/dL. Increasing the hemoglobin level to > 11 g/dL is not recommended due to the risk of increased viscosity and vasoocclusion. For severe disease erythrocytapheresis, targeting a hemoglobin S level < 30% may be needed. Blood transfusions are complicated in sickle cell patients because of incompatibility with antigens C, E, and Kell, a thorough cross match must be preformed. After a single episode of ACS many patients are started on hydroxyurea or chronic transfusion therapy to decrease the risk of future occurrence.
Vij R, Machado RF. Pulmonary complications of hemoglobinopathies. Chest. 2010 Oct;138(4):973-83.
Miller ST. How I treat acute chest syndrome in children with sickle cell disease. Blood. 2011 May 19;117(20):5297-305. Epub 2011 Mar 15.