RBC retention in sickle whole blood clots is mediated, in part, by reduced RBC deformability, and can be partially reversed by FXIIIa inhibition or RBC exchange. (A) Number of RBCs released from clots formed ex vivo from the blood of AA subjects (n = 20), AS (n = 13), and SS patients (n = 29) in the absence (−) or presence (+) of FXIIIa inhibitor T101 (20 µM). (B) Effects of glutaraldehyde (0.1%) on AA RBC (n = 6) deformability compared with the deformability of AA (n = 6) and SS (n = 5) RBCs incubated with cold isotonic buffer at 3 Pa. (C) Serum RBC content after clot contraction performed with PRP reconstituted with AA RBCs exposed to isotonic buffer or 0.1% glutaraldehyde (n = 13). (D) Number of RBCs released from clots formed ex vivo from blood obtained from AA control subjects (n = 8), SS patients (n = 11), or SS patients undergoing RBC Ex pre- and postprocedure (n = 10). Representative gel (E) and analysis of hemoglobin content (F) in the WB, clots, and serum obtained from pre- and postexchange samples (n = 5). (G) Representative image of the clot formed in the femoral vein of SS mice (n = 4) injected with AA RBCs. Arrowheads point to the vessel wall; asterisk indicates the clot; red staining demonstrates the presence of AA RBCs within the clot. *P < .05, **P < .01, ***P < .001. Ex, exchange; gluta, glutaraldehyde; WB, whole blood.