Article

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

Armand Mekontso DessapGroupe de Recherche Clinique CARMAS, Institut Mondor de Recherche Biomédicale, Université Paris Est Créteil, Créteil, FranceAnoosha HabibiUnité des Maladies Génétiques du Globule Rouge, Centre de référence Syndromes Drépanocytaires MajeursJean‐Benoît ArletDepartment of Internal Medicine, French National Reference Center for Sickle Cell Disease, Thalassemia and Other Red Blood Cell and Erythropoiesis Disorders andMuriel FartoukhGroupe de Recherche Clinique CARMAS, Institut Mondor de Recherche Biomédicale, Université Paris Est Créteil, Créteil, FranceLaurent GuérinService de Médecine Intensive Réanimation, Hôpital Bicêtre, AP-HP, Le Kremlin-Bicêtre, FranceConstance GuillaudDépartement d’Aval des UrgencesDamien RouxService de Médecine Intensive Réanimation, DMU ESPRIT, Université Paris Cité andJohanna OzielService de Réanimation Médico-Chirurgicale, Hôpital Avicenne, AP-HP, Université Sorbonne Paris Nord, Bobigny, FranceStéphanie NgoService de Médecine Interne andBenjamin CarpentierService d’Hématologie Clinique, Hôpital Saint Vincent de Paul, Groupe Hospitalier de l’Institut Catholique de Lille, Lille, FranceMarilucy Lopez‐SubletService de Médecine Interne, Centre d’Excellence Européen en Hypertension Artérielle, Hôpital Avicenne, AP-HP, Avicenne, FranceLouis AffoService de Médecine Interne, AP-HP, Hôpital Louis Mourier, AP-HP, Colombes, FranceGiovanna MelicaService d’Immunologie Clinique et Maladies InfectieusesMaryse Etienne‐JulanUnité Transversale de la Drépanocytose, Centre de Référence Syndromes Drépanocytaires Majeurs, CHU de la Guadeloupe, Pointe-à-Pitre, FranceIsabelle DelacroixService de Médecine Interne andFrançois LionnetService de Médecine Interne, Hôpital Tenon, AP-HP, Sorbonne Université, Hôpital Tenon, Paris, FranceGylna LokoCentre de la Drépanocytose, CHU de Martinique, Le Lamentin, FranceDaniel SilvaService de Médecine Intensive Réanimation, Hôpital Delafontaine, Saint-Denis, FranceMarc MichelService de Médecine Interne, andKeyvan RazaziGroupe de Recherche Clinique CARMAS, Institut Mondor de Recherche Biomédicale, Université Paris Est Créteil, Créteil, FranceAnaïs Charles‐NelsonUnité de Recherche Clinique, Hôpital Européen Georges Pompidou, AP-HP, Paris-Cité University, Paris, FrancePablo BartolucciINSERM U955, Université Paris Est Créteil, Créteil, FranceSégolène GendreauGroupe de Recherche Clinique CARMAS, Institut Mondor de Recherche Biomédicale, Université Paris Est Créteil, Créteil, FranceSandrine KatsahianUnité de Recherche Clinique, Hôpital Européen Georges Pompidou, AP-HP, Paris-Cité University, Paris, FranceBernard MaîtreGroupe de Recherche Clinique CARMAS, Institut Mondor de Recherche Biomédicale, Université Paris Est Créteil, Créteil, France

American Journal of Respiratory and Critical Care Medicinejournal2025en

ABI

Abstract

Abstract Rationale Patients with sickle cell disease hospitalized for acute chest syndrome (ACS) are at high risk of in situ pulmonary microthrombosis. Objectives We evaluated whether therapeutic anticoagulation could shorten ACS duration. Methods 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. Measurements and Main Results 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; P = 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; P = 0.02. Other short- and long-term secondary outcomes were similar between groups. Conclusions 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).

Topics

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Identifiers

DOI: 10.1164/rccm.202409-1727oc

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