Endothelial dysfunction and hypercoagulability in severe sickle-cell acute chest syndrome

Etienne-Marie Jutant; Guillaume Voiriot; Vincent Labbé; Laurent Savale; Hayat Mokrani; Patrick Van Dreden; Grigorios Gerotziafas; Muriel Fartoukh

doi:10.1183/23120541.00496-2021

Endothelial dysfunction and hypercoagulability in severe sickle-cell acute chest syndrome

ERJ Open Res. 2021 Dec 13;7(4):00496-2021. doi: 10.1183/23120541.00496-2021. eCollection 2021 Oct.

Authors

Etienne-Marie Jutant¹, Guillaume Voiriot^{1

2}, Vincent Labbé^{1

2}, Laurent Savale^{3

4

5}, Hayat Mokrani^{2

6

7}, Patrick Van Dreden⁸, Grigorios Gerotziafas^{2

6

7}, Muriel Fartoukh^{1

2}

Affiliations

¹ Service de Médecine Intensive Réanimation, Département Médico-Universitaire APPROCHES, Hôpital Tenon, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
² Faculté de Médecine, Sorbonne Université, Paris, France.
³ Université Paris-Saclay, School of Medicine, Le Kremlin-Bicêtre, France.
⁴ INSERM UMR_S 999 "Pulmonary Hypertension: Pathophysiology and Novel Therapies", Hôpital Marie Lannelongue, Le Plessis-Robinson, France.
⁵ Assistance Publique - Hôpitaux de Paris (AP-HP), Dept of Respiratory and Intensive Care Medicine, Pulmonary Hypertension National Referral Center, Hôpital Bicêtre, Le Kremlin-Bicêtre, France.
⁶ Research group "Cancer, Haemostasis and Angiogenesis", INSERM U938, Centre de Recherche Saint-Antoine, Institut Universitaire de Cancérologie, Paris, France.
⁷ Service d'Hématologie Biologique Hôpital Tenon, Hôpitaux Universitaires de l'Est Parisien, AP-HP, Paris, France.
⁸ Clinical Research Dept, Diagnostica Stago, Gennevilliers, France.

Abstract

Rationale: Acute pulmonary hypertension (PH) may develop during sickle-cell acute chest syndrome (ACS), and is associated with an increased mortality. Its mechanisms remain poorly known. We questioned whether there is endothelial dysfunction and hypercoagulability in severe ACS, with and without acute PH.

Methods: In a prospective monocentre cohort follow-up study, all sickle-cell adult patients with ACS admitted to the intensive care unit underwent transthoracic echocardiography and measurement of biomarkers of coagulation, endothelial activation and platelet and erythrocyte activation. Acute PH was defined as a high echocardiographic probability of PH. The biological profiles of sickle-cell patients were analysed at the time of ACS, contrasting with the existence of acute PH, and compared with steady-state and with non-sickle-cell controls (healthy subjects and community-acquired pneumonia).

Results: Most patients (36 patients with 39 ACS episodes; 23 males; median age 27 years) had thoracic pain, dyspnoea and computed tomography scan lung consolidation. Acute PH was diagnosed in seven (19%) patients. Erythrocyte- and platelet-derived microparticles and the pro-coagulant activity of microparticles were higher in ACS patients with acute PH, compared with their counterparts. Compared with healthy controls, ACS patients had higher levels of tissue factor, fibrin monomers, D-dimer, release of pro-coagulant microparticles and erythrocyte- and platelet-derived microparticles. Compared with community-acquired pneumonia patients, ACS patients had increased levels of fibrin monomers and erythrocyte- and platelet-derived microparticles.

Conclusions: Severe ACS is characterised by endothelial dysfunction and hypercoagulability, with a marked pro-coagulant profile in cases of associated PH.