Acute chest syndrome (ACS) is a common complication of sickle cell disease. In fact, around 10% sickle cell patients develop ACS every year. Though it is usually more common in children, it tends to be more severe in adults and can lead to other complications such as pneumonia. It’s therefore important to understand the symptoms and seek diagnosis if you suspect you have ACS.
Acute chest syndrome is an umbrella term used to define several conditions that affect the respiratory system. ACS is defined as:
People with ACS are at higher risk of respiratory failure and lung disease. As sickle cell patients get older, they are at increased risk of acute chest syndrome leading to restrictive lung disease in adults. It is thought that about half of children with sickle cell disease will develop ACS at least once. Children who have had an episode of ACS also are at a higher risk of repeated episodes. Asthma is also associated with increased risk.
Though little is known about how ACS occurs, there are several hypotheses. One of them states that ACS can be caused by sickle cells sticking to the walls of blood vessels in the lungs.
ACS can show as a single event or during a pain crisis, but it is characterized by…
Symptoms for acute chest syndrome can be different for children and adults.
Children have a lot of respiratory infections compared to adults, so the primary cause of ACS in children is a pulmonary infection. The disease is typically less severe in children and there is less chance of a child needing a red cell transfusion.
The primary symptoms for children 10 years of age or youngerinclude:
In adults ACS is generally more severe. It’s more likely to be due to a blood clot in the lungs / in the main arteries connected to the lungs (pulmonary embolism) or due to a fat embolism (see causes). Adults are much sicker and more often require transfusion.
Common symptoms for adults include:
In the event of ACS being caused by a fat embolism, symptoms can be much more severe and can be accompanied by other serious symptoms relating to multiple organ failure.
There haven’t been that many studies into the causes of acute chest syndrome. There are also multiple causes, which is why it is difficult to diagnose ACS.
Correct diagnosis is vital as in adults pulmonary emboli are more common and present two of the same symptoms: chest pain and infiltrate. Further investigations should be made to rule out a pulmonary embolism.
One study by Elliott P. Vichinsky, M.D showed that patients with sickle cell disease who developed acute chest syndrome often also had either an infection or a fat embolism.
In the study 56% of the patients who died from ACS also had infections. The specific infections that led to ACS in the patients in the study were chlamydia, mycoplasma and viral pneumonia, parvovirus, M. hominis, and legionella. This showed that the infections leading to ACS can be either viral or bacterial.
A fat embolism happens when particles of fat enter the blood and clog up and damage blood vessels. Fat embolisms are usually a result of bone infarcts. A bone infarct is when part of the bone dies as a result of lack of blood supply.
The most severe manifestation of fat emboli is multiorgan failure and can be rapidly fatal. Rib infarcts cause a decrease in the ability to take a breath which leads to alveolar collapse, decreased oxygenation, shunting and ACS.
Previously, bacterial pneumonia (S. pneumoniae) was commonly associated with ACS. However, more recent studies have found that it’s not as strongly linked as it once was. In the 1990s, studies found that pneumonia was only associated with a quarter of the incidences of ACS compared with a study from the 1970s. Thanks to the introduction of immunization for pneumococcus and H. influenza there are fewer incidences of these bacteria as a cause of ACS and infection. Current reports have found that other infections H. Influenza, S. aureus, and Chlamydiae pneumoniae have increased as causes of ACS, whereas S. pneumoniae has decreased.
Risk factors in children include:
Risk factors in adults include:
ACS might lead to cor pulmonale in adults. Cor pulmonale is commonly known as right-sided heart failure. It is usually caused by high blood pressure building up in the pulmonary arteries (or pulmonary hypertension). In a study conducted by Armand Dessap in 2007, 13% of sickle cell patients experiencing acute chest syndrome also experienced cor pulmonale. Though, since this study did not include CT scans, it could be due to pulmonary emboli (see below). Another possibility is that patients had pulmonary hypertension before an ACS episode, which exacerbated the hypertension and triggered worse right heart failure. Therefore a direct link between ACS and cor pulmonale is disputed.
A common complication of ACS in adults is a pulmonary embolism. A pulmonary embolism is when a blood clot cuts off blood flow to a part of the lung. This often happens when a blood clot from the leg gets dislodged and travels into the lungs.
Pneumonia and infections:
Pneumonia is an infection that causes the air sacs in the lungs to fill with fluid. Pneumonia and ACS appear at the same time on x-ray and the symptoms present the same in many patients, particularly children. The symptoms include a wet cough, fever, and difficulty breathing. In infants, ACS leads more commonly to pneumonia. Bacteremia and meningitis also occur in children.
There is a strong relationship between acute chest syndrome and neurological complications including stroke. This is because acute chest syndrome can lead the brain to be starved of oxygen, and this can lead to tissue death in the brain.
If you are experiencing symptoms of acute chest syndrome this could be a medical emergency and you should contact your hematologist and seek emergent care at a hospital familiar with sickle cell disease or with the ability to transfer you to such a hospital.
A chest X-ray will test to see if you have any new pulmonary infiltrate on your lungs. If you are experiencing any of the below symptoms which are consistent with ACS you should call your hematologist:
Patients with suspected acute chest syndrome should be admitted to hospital for intravenous antibiotics, oxygen if needed and depending on the course and level of anemia either a simple transfusion or (in severe cases) an automated red cell exchange.
Adults with severe sickle cell disease are often prescribed hydroxyurea (HU) to manage pain episodes. Hydroxyurea can also help prevent acute chest syndrome. A large study on hydroxyurea found that HU reduced the incidence of ACS by 50% in adults. It was also effective in children, reducing the incidence in ACS by 73%.
Hydroxyurea is a Food and Drug Administration (FDA)-approved drug proven to prevent pain in sickle cell disease by increasing fetal hemoglobin levels, which increase the amount of healthy red blood cells in the body.
Research on hydroxyurea shows that it reduces the following:
One of the things that hydroxyurea does is to increase fetal hemoglobin production. Fetal hemoglobin (HbF) helps red blood cells retain their normal shape (round and flexible) by stopping sickle cell hemoglobin molecules from sticking to each other and forming sickle cells. This is all to do with the different structure of the subunits in fetal hemoglobin. We are all born with fetal hemoglobin, which is then replaced with adult hemoglobin. Since fetal hemoglobin is effective at preventing hemoglobin polymerization and changes in sickle cells from forming, babies often don’t show symptoms of sickle cell disease.
According to a study on treatments for ACS, the preferred initial treatment is a simple transfusion of red blood cells. This is because a transfusion gives the patient healthy blood delivered usually through an IV infusion. These healthy red blood cells help prevent complications such as ACS.
The two kinds of transfusions are simple transfusions and exchange transfusions. Simple transfusions deliver healthy red blood cells but don’t take blood away from the patient. Exchange transfusions replace the patient’s sickle-shaped blood cells with healthy red blood cells.
Simple red cell transfusions increase the total hemoglobin which can be very low in ACS. In addition, it will decrease the percentage of hemoglobin S depending on the level of anemia prior to the simple transfusion.
In some patients who have acute chest syndrome (in particular those who have SC or other sickle cell disease with a relatively high hemoglobin) the hemoglobin is so high that a simple transfusion will not decrease the percent hemoglobin S enough to be helpful. These patients will benefit from an automated exchange transfusion where equal amounts of the patients’ blood are exchanged for donated AA blood.
If a patient does not respond to a simple transfusion then an exchange is indicated.
“Acute Chest Syndrome.” Indiana Hemophilia & Thrombosis Center, Inc., https://www.ihtc.org/acute-chest-syndrome/ (accessed July 19, 2019).
“Acute chest syndrome in children with sickle cell disease.” Texas Children’s Hospital,
(accessed July 21, 2019).
“Acute chest syndrome and sickle cell disease.” St. Jude Children’s Research Hospital,
https://www.stjude.org/treatment/patient-resources/caregiver-resources/patient-family-educationsheets/hematology/acute-chest-syndrome-and-sickle-cell-disease.html (accessed July 20, 2019).
“Blood Transfusion.” Sickle Cell Anemia News. https://sicklecellanemianews.com/blood-transfusion/
(accessed July 20, 2019).
Bykersma, Alexander. “Sickle Cell Disease and Hydroxyurea Treatment.” AMSJ, April 16, 2018,
http://www.amsj.org/archives/6388 (accessed July 20, 2019).
Charache, S. “Mechanism of action of hydroxyurea in the management of sickle cell anemia in adults.”
Semin Hematol, 1997 Jul; 24(3 Suppl 3): 15-21.
“Cor pulmonale.” MedlinePlus, https://medlineplus.gov/ency/article/000129.htm (accessed July 19,
Dessap, Armand Mekontso et al. “Pulmonary Hypertension and Cor Pulmonale during Severe Acute
Chest Syndrome in Sickle Cell Disease.” AJRCCM 2008 Mar; 177(6): doi:10.1164/rccm.200710-1606OC.
Howard, Jo et al. “Guideline on the management of acute chest syndrome in sickle cell disease.” Brit J
Haematology 2015 Mar; 169(4): doi: https://doi.org/10.1111/bjh.13348.
“Hydroxyurea Treatment for Sickle Cell Disease.” St. Jude Children’s Research Hospital, 2008.
https://www.stjude.org/content/dam/en_US/shared/www/patient-support/hematology-literature/hdroxyurea-treatment-for-sickle-cell-disease.pdf (accessed July 20, 2019).
Jain, Shilpa et al. “Acute Chest Syndrome in Children with Sickle Cell Disease.” Pediatr Allergy
Immunol Pulmonol. 2017 Dec; 30(4): doi: 10.1089/ped.2017.0814.
Johnson, Cage S.. “Sickle Cell Disease: The Acute Chest Syndrome, 1995.” Sickle BWH Harvard, http://sickle.bwh.harvard.edu/acutechest.html (accessed July 19, 2019).
Kwaitt, Michael E. and Seamon, Mark J. “Fat embolism syndrome.” Int J Crit Illn Inj Sci 2013 Jan-Mar;
3(1): doi: 10.4103/2229-5151.109426.
Miller, Scott T. “How I treat acute chest syndrome in children with sickle cell disease.” Blood 2011; 117: doi: https://doi.org/10.1182/blood-2010-11-261834.
“Pneumonia.” Mayo Clinic, March 13, 2018. https://www.mayoclinic.org/diseases-conditions/pneumonia/symptoms-causes/syc-20354204 (accessed July 14, 2019).
“Pulmonary Embolism.” Mayo Clinic, March 7. 2018. https://www.mayoclinic.org/diseases-conditions/pulmonary-embolism/symptoms-causes/syc-20354647 (accessed July 14, 2019).
Sickle Cell Disease: Complications and Treatment.” CDC, https://www.cdc.gov/ncbddd/sicklecell/treatments.html#Acute (accessed July 20, 2019).
van Agtmael, MA, Cheng, JD, Nossent, HD. “Acute chest syndrome in adult Afro-Caribbean patients
with sickle cell disease: analysis of 81 episodes among 53 patients.” Archives of Internal
Medicine 1994; 154:557-61.
Vichinsky, Elliot P., M.D. et al. “Causes and Outcomes of the Acute Chest Syndrome in Sickle Cell
Disease.” N Engl J Med 2000; 342: doi: 10.1056/NEJM200006223422502.
Young, Roscoe C. Jr. et al. “The Lung in Sickle Cell Disease: A Clinical Overview of Common Vascular,
Infectious, and Other Problems.” J Natl Med Assoc. 1981 Jan; 73(1): PMC2552608.