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

Abstract

<b>Rationale:</b> Patients with sickle cell disease hospitalized for acute chest syndrome (ACS) are at high risk of <i>in situ</i> pulmonary microthrombosis. <b>Objectives:</b> We evaluated whether therapeutic anticoagulation could shorten ACS duration. <b>Methods:</b> TASC (Therapeutic Anticoagulation for Acute Chest Syndrome in Sickle Cell Disease) is a randomized, controlled, double-blind trial conducted in 12 French hospitals (December 2016-April 2021) in adult patients with ACS with no initial thrombosis on chest computed tomography with pulmonary angiogram. We randomized 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 opioid consumption, transfusion, mortality at hospital discharge, and hospital readmissions at 6 months. <b>Measurements and Main Results:</b> The primary efficacy outcome, time to ACS resolution, analyzed using a Cox model, was shorter with therapeutic anticoagulation than with prophylactic doses (hazard ratio, 0.71; 95% confidence interval, 0.51 to 0.99; <i>P</i> = 0.044). As a supplemental estimate, the restricted mean time to ACS resolution (over a 15-d horizon or discharge) was shorter with therapeutic doses (4.8 ± 0.4 vs. 6.1 ± 0.5 d). The primary safety outcome (major bleeding) did not occur in either group. The cumulative dose of parenteral opioids was lower with therapeutic anticoagulation: median [interquartile range] of 124 [80 to 272] vs. 219 [65 to 378] mg morphine equivalent; difference, -96; 95% confidence interval, -202 to -46; <i>P</i> = 0.02. Other short- and long-term secondary outcomes were similar between groups. <b>Conclusions:</b> In adult patients with ACS, a therapeutic anticoagulation shortened ACS duration and reduced opioid consumption compared with prophylactic doses, without increasing bleeding risk. Clinical trial registered with www.clinicaltrials.gov (NCT02580773).