BACKGROUND: Patients with sickle cell disease hospitalised for acute chest syndrome (ACS) are at high risk of in situ pulmonary microthrombosis. We evaluated whether therapeutic anticoagulation could shorten ACS duration.
METHODS: TASC is a randomized, controlled, double-blind trial conducted in 12 French hospitals (December 2016-April 2021) in adult ACS patients with no initial thrombosis on chest computerised tomography with pulmonary angiogram. We randomised 172 patients (1:1) to receive either prophylactic or therapeutic doses of low-molecular-weight tinzaparin for 7 days. The primary efficacy outcome was time to ACS resolution. The primary safety outcome was major bleeding. Main secondary outcomes included parenteral opioids consumption, transfusion, mortality at hospital discharge, and hospital readmissions at 6 months.
FINDINGS: The primary efficacy outcome, time to ACS resolution, analysed using a Cox model, was shorter with therapeutic anticoagulation than with prophylactic doses (hazard ratio 0.71; 95% CI: [0.51-0.99]; p=0.044). As a supplemental estimate, the restricted mean time to ACS resolution (over a 15-day horizon or discharge) was shorter with therapeutic doses (4.8±0.4 vs 6.1±0.5 days). The primary safety outcome (major bleeding) did not occur in either group. The cumulative dose of parenteral opioids was lower with therapeutic anticoagulation: (124 [80;272] vs 219 [65;378] mg morphine equivalent, difference: -96, 95%CI: -202 to -46, p=0.02). Other short- and long-term secondary outcomes were similar between groups.
INTERPRETATION: In adult patients with ACS, a therapeutic anticoagulation shortened ACS duration and reduced opioids consumption compared with prophylactic doses, without increasing bleeding risk. Clinical trial registration available at www.
CLINICALTRIALS: gov, ID: NCT02580773.
| Specialty Area | Score |
|---|---|
| Respirology/Pulmonology | |
| Hematology | |
| Hospital Doctor/Hospitalists | |
| Internal Medicine |
This is a very important paper for those who treat this condition. This appears to be a safe and easily implemented therapy that would be widely available and appears to have a remarkable clinical effect.
Randomized patients appear to have milder ACS (judged by few RBC exchanges and transfusions, very few requiring ventilators, no deaths), so cannot be extrapolated to severe cases.
Multi-center French study that demonstrated faster resolution of acute chest syndrome, pain, and opiate use in adult sickle cell patients with therapeutic anticoagulation compared with prophylactic dosing, and without increased bleeding. This should provide strong impetus to change standard care.
This reports a well-conducted RCT in (French) patients with acute chest syndrome that found faster recovery and reduced opioid use with therapeutic anticogulation compared with standard care (prophylactic anticoagulation dosing). This is a common clinical scenario and an unanswered question - the results of this trial are important and useful.
ACP JournalWise is copyrighted © 2025 by the American College of Physicians
Powered by McMaster Premium Literature Service (PLUS)