Comparison of Prophylactic and Therapeutic Doses of Anticoagulation for Acute Chest Syndrome in Sickle Cell Disease: The TASC Randomized Clinical Trial.

Abstract

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.