A multicenter double-blind RCT published in 2025 found that adult patients hospitalized with acute chest syndrome (ACS) who received 7 days of prophylactic therapeutic anticoagulation had a shorter time to ACS resolution (by approx 1 day) and reduced opioid consumption when compared to those receiving standard VTE prophylaxis.

Additional Information

Acute Chest Syndrome (ACS) is known to be associated with severe pulmonary vascular dysfunction. Prior studies have identified local vaso-occlusion leading to pulmonary infarct as the underlying etiology of up to 16% of ACS episodes, and have demonstrated relatively high rates of PE and pulmonary microthrombi. 

The TASC (Therapeutic Anticoagulation for Acute Chest Syndrome in Sickle Cell Disease) trial randomly assigned adult patients hospitalized for acute chest syndrome with no PE on CTA to prophylactic or therapeutic low-molecular weight heparin for 7 days or until hospital discharged. 172 patients were randomized - 84 in the prophylactic-dose group and 88 in the therapeutic-dose group. Patients in the therapeutic-dose group had a shorter time to ACS resolution (4.8?±?0.4 days vs. 6.1?±?0.5 days, HR 0.71; 95% CI 0.51–0.99; P?=?0.044 ). There were no major bleeding events in either group. The therapeutic dose group used an almost 45% lower cumulative dose of parenteral opioids (124 vs 219 morphine equivalent units, difference ?96; 95% CI ?202 to ?46; P?=?0.02).

Details:

• ACS was defined by: new pulmonary infiltrate on CXR or CT AND respiratory symptom (s) OR abnormality on pulmonary auscultation
• ACS resolution was defined by “joint improvement of four criteria, including fever, chest pain, dyspnea, and hypoxemia.” The hypoxemia component was excluded in the 62% of patients who were not hypoxemic at baseline. 
• Study setting: across 12 health centers in France from 2016-2021.
• Key exclusion criteria: 
  • Age < 18
  • ACS diagnosed >48h prior
  • Body weight <40kg or >100kg
  • CrCl <60 ml/min (if enrolled, treatment was discontinued if a patient developed severe AKI with CrCl <30 ml/min)
  • RBC transfusion “deemed highly risky”
  • Interestingly, the presence or absence of active COVID infection was not discussed
• The anticoagulation used here was tinzaparin (a type of  low-molecular-weight heparin that is FDA approved but has been discontinued in the US; it has a higher molecular weight and greater anti-thrombin activity than enoxaparin). Prophylactic dosing was 4500 IU/24h and therapeutic dosing was 175 IU/kg/24h (both standard dosing for their indications).

References

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.