Interrogation of RBC hypoxia responsiveness and clinical associations in SCD. (A) Blood deoxygenates at the micro-gas exchanger during flow. (B) Clustered patients in HR and non-HR populations, based on increase in RBC adhesion in response to hypoxia. HR patients showed significantly greater increase in the number of adhered RBCs with hypoxia compared to non-HR patients (p<0.05). (C) Patients with HR RBCs showed significantly greater reticulocyte counts compared to patients with non-HR RBCs. 7 out of 8 subjects in the HR patient subpopulation were transfused (>10% Hb A); 2 out of 15 subjects in the non-HR subpopulation were transfused. (D) Hypoxia responsive patients (N=8) were younger (<35 years). 8/16 subjects <35 years old and 0/10 subjects ≥35 years old were HR (p<0.05).