Transfusion Exchanges and Cognition in Sickle Cell Disease

DREPA-COG is a non-interventional, multicenter observational study investigating the effect of exchange transfusions on cognitive performance in adults with severe sickle cell disease (SS or Sβ0). Cognitive complications, including slowed information processing and executive dysfunction, are frequent and disabling in this population. Exchange transfusion, a standard therapy replacing sickled red blood cells with donor cells, may positively influence cognition, but systematic evidence is lacking.

The study evaluates information processing speed as a potential neurological marker across the transfusion cycle. Participants complete three brief neuropsychological assessments remotely by videoconference: before the transfusion, one week after, and prior to the next transfusion. The Symbol Digit Modalities Test (SDMT) is the primary measure, complemented by validated assessments of global cognition, attention, memory, fatigue, mood, and pain.

Primary analysis will use mixed-effects models to assess changes in processing speed over time, adjusting for demographic and clinical covariates. This minimal-risk, fully remote study requires no additional hospital visits and aims to establish processing speed as a reproducible and clinically relevant outcome measure in sickle cell disease.

• Global Cognitive Function - Montreal Cognitive Assessment (Telephone version, T-MoCA) [Time frame: Time Point 1 (Baseline): within 48 hours before the scheduled exchange transfusion. Time Point 2 (Post-transfusion): 7 to 9 days after the exchange transfusion. Time Point 3 (End of cycle): within 48 hours before the next scheduled exchange transfusion]
• Fatigue Severity Score (FSS) [Time frame: Time Point 1 (Baseline): within 48 hours before the scheduled exchange transfusion. Time Point 2 (Post-transfusion): 7 to 9 days after the exchange transfusion. Time Point 3 (End of cycle): within 48 hours before the next scheduled exchange transfusion]
• Anxiety and Depression Symptoms (Hospital Anxiety and Depression Scale, HADS [Time frame: Time Point 1 (Baseline): within 48 hours before the scheduled exchange transfusion. Time Point 2 (Post-transfusion): 7 to 9 days after the exchange transfusion. Time Point 3 (End of cycle): within 48 hours before the next scheduled exchange transfusion]
• Pain Intensity (Numeric Rating Scale, NRS) [Time frame: Time Point 1 (Baseline): within 48 hours before the scheduled exchange transfusion. Time Point 2 (Post-transfusion): 7 to 9 days after the exchange transfusion. Time Point 3 (End of cycle): within 48 hours before the next scheduled exchange transfusion]
• Change in Information Processing Speed Measured by the Symbol Digit Modalities Test (SDMT) [Time frame: Within 48 hours before exchange transfusion 7-9 days after exchange transfusion Within 48 hours before the next scheduled exchange transfusion]
• Working Memory - WAIS-IV Digit Span Subtest [Time frame: Time Point 1 (Baseline): within 48 hours before the scheduled exchange transfusion. Time Point 2 (Post-transfusion): 7 to 9 days after the exchange transfusion. Time Point 3 (End of cycle): within 48 hours before the next scheduled exchange transfusion]