Sickle cell disease (SCD) is characterized by recurrent vaso-occlusive pain crisis (VOC), which may evolve to acute chest syndrome (ACS), the most common cause of death among adult patients with SCD. Currently, there is no etiologic treatment to abort ACS. Therefore, management of ACS mostly involve a symptomatic approach including in routine, and as per recommendations, hydration, analgesics, supplemental oxygen, and transfusion.

The polymerisation of sickle haemoglobin (HbS) is one major feature in the pathogenesis of vaso-occlusion. Current guidelines recommend red blood cell exchange transfusion (REX) in patients with severe ACS in order to improve oxygenation and reduce HbS concentration to blunt sickling. REX is often preferred over simple transfusion in this setting because it rapidly reduces HbS without raising final haematocrit. There are currently two methods for REX: manual (with sequential phlebotomies and transfusions) or automated (erythrocytapheresis). The former allows a sober use of red blood cell packs, while the latter achieves haematological targets (HbS and haematocrit) quickly and more consistently, but requires a special equipment and trained staff. As a result of inflammation and intravascular hemolysis, the plasma of patients with ACS may also contain several components that promote vaso-occlusion, lung injury and organ failure, including cytokines (e.g., IL-6), free haemoglobin and free haem. Conversely, it is depleted in haptoglobin and hemopexin, which normally bind to and clear cell-free haemoglobin. The addition of therapeutic plasma exchange to erythrocytapheresis during automated REX may therefore have a dual beneficial effect in patients with overt intravascular hemolysis: i) deplete the inflammatory mediators and products of hemolysis; ii) replete haptoglobin and hemopexin. REX modalities (automated vs manual) have not been tested during ACS.

The hypothesis is that early-goal directed automated REX may accelerate the resolution of severe ACS as compared to manual REX.

Inclusion Criteria:

• Age ≥ 18 years
• Patient with major sickle cell disease syndrome (SS, SC, Sβ0 or Sβ+)
• ACS, as defined by the association of fever and/or acute respiratory symptoms with a new pulmonary infiltrate on chest imaging
• Requiring supplemental oxygen ≥ 2 L/min for SpO2 ≥ 95%
• With an indication for REX given the hypoxemic ACS, as per recommendations
• Express informed consent from the relatives or the patient himself, or emergency inclusion procedure in case of inability of patient or proxy relatives to give consent NB: Patients not affiliated to social security will be included in the study given the precarious social situation of many patients with SCD

Exclusion Criteria:

• Patient having both ACS criteria and need for supplemental oxygen ≥ 2 L/min for SpO2 ≥ 95% since more than 72 hours
• Red blood cell transfusion or REX during the current ACS episode
• Any past medical history of delayed haemolytic transfusion reaction
• History of < 12 transfused RBC or anti-red blood cell antibody production on the one hand and no possibility for matching on Rh/K, antibody specificity, and extended to Duffy (Fya), Kidd (Jka and Jkb) and MNS (M, N, S and s) phenotypes on the other hand (12)
• Known legal incapacity (guardianship, curatorship)
• Prisoners or subjects who are involuntarily incarcerated
• Anatomical factors precluding placement of an adequate venous access
• Known pregnancy or current lactation

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