How to manage acute chest syndrome (ACS)

In clinical practice, the appearance of radiographic abnormalities may lag behind onset of ACS. Because of the potentially fatal consequences of delay in recognition and management of ACS, clinical judgment should err on the side of overtreating rather than undertreating. A patient with SCD presenting with evolving respiratory symptoms should be considered as having ACS unless proven otherwise, with a low threshold for transfusions.

How quickly should you expect ACS to stabilize after initiation of red cell exchange?
Anecdotally, red cell exchange is expected to quickly stabilize the hemodynamics of a patient within the first 24-48 hours, although not much literature is available to support this claim rigorously. Progressive decompensation beyond the initiation of RCE past this timeframe should prompt ongoing investigation for alternative triggers or causes. Also anecdotally, the occasional puzzling presentation of progressive ACS and laboratory evidence of severe inflammation have been sometimes explained by parvovirus infection. Such a phenotype has been reported in the literature [1].

How does one differentiate between ACS and fat embolism syndrome?
This is extremely challenging given the absence of biomarkers for either condition. Fat embolism syndrome (FES) is postulated to result from acute necrosis of bone and release of marrow fat into circulation, and is commonly associated with a hyperinflammatory presentation (occasionally reminiscent of HLH). The definitive diagnosis for FES is generally achieved upon autopsy; like ACS, we would favor low threshold to initiate directed therapy rather than strict adherence to diagnostic criteria, of which there are none which are robust. Directed therapy would generally include RCE; refractory cases would warrant discussion of plasma exchange, which may remove circulating lipids. Overall, the difference between ACS and FES may not be an important distinction to make; suspicion of either condition would favor initiation of aggressive therapy.

Is there a role for empiric therapeutic anticoagulation in ACS?
See below for a recent 2025 randomized controlled trial comparing outcomes between prophylactic and therapeutic anticoagulation in adult patients with SCD and ACS deemed low risk for bleeding [2]. Long story short - maybe. There appeared to be a statistically significant improvement in time to resolution of ACS. Limitations include lack of generalizability of the population studied. Also, the primary outcome seems vulnerable to subjectivity (e.g., how does one objectively assess improvement in dyspnea?). More data is needed. At least at our institution, therapeutic anticoagulation is generally not front of mind when managing acute chest syndrome.

Literature

1. Ségolène Gendreau, Louis-Marie Coupry, Pierre Cappy, Alexandra Beurton, Nicolas Verger, Anoosha Habibi, Maïté Agbakou, Sylvain Le Jeune, Laurent Argaud, Serge Barmo, Gauthier Blonz, Pierre Cougoul, Stéphanie Houcke, Antoine Lafarge, Arnaud Ly, Andréa Pastissier, Armand Mekontso Dessap, Slim Fourati, Nicolas de Prost; Severe parvovirus B19 infection in patients with sickle cell disease hospitalized in intensive care units. Blood Adv 2025; 9 (22): 5695–5707. doi: https://doi.org/10.1182/bloodadvances.2025015947
   • This French retrospective study describes critically ill patients with SCD who have severe parvovirus infections, and examines the phenotypes associated with such a syndrome.
2. Mekontso Dessap A, Habibi A, Arlet JB, Fartoukh M, Guerin L, Guillaud C, Roux D, Oziel J, Ngo S, Carpentier B, Lopez-Sublet M, Affo L, Melica G, Etienne-Julan M, Delacroix I, Lionnet F, Loko G, Da Silva D, Michel M, Razazi K, Charles-Nelson A, Bartolucci P, Gendreau S, Katsahian S, Maitre B. Comparison of Prophylactic and Therapeutic Doses of Anticoagulation for Acute Chest Syndrome in Sickle Cell Disease: The TASC Double-Blind Controlled Randomized Clinical Trial. Am J Respir Crit Care Med. 2025 May;211(5):832-841. doi: 10.1164/rccm.202409-1727OC. PMID: 40209087.
   • In this French study, adults with SCD and ACS were randomized to receive 7 days of therapeutic vs. prophylactic anticoagulation. Those who received therapeutic anticoagulation had faster resolution of ACS.

last updated 1/31/2026