Delayed hemolytic transfusion reaction in sickle cell disease patients: evidence of an emerging syndrome with suicidal red blood cell death.
BACKGROUND
Delayed hemolytic transfusion reaction (DHTR) is a life-threatening complication in sickle cell disease (SCD) characterized by recurrence of disease complications, recipient red blood cell (RBC) destruction, and frequently no detectable antibody. Phosphatidylserine (PS) exposure signs suicidal RBC death or eryptosis and is involved in vasoocclusive crisis (VOC).


METHODS
Transfusion was monitored in 48 SCD patients for up to 20 days. PS exposure was evaluated in vivo on patient RBCs (PS-RBCs) at five time points and in vitro after incubation of donor RBCs with pretransfusion plasma.


RESULTS
Three VOC patients displayed DHTR with recurrent SCD features and no detectable antibody in two cases. In vitro, PS-RBC percentage was significantly increased by incubating donor RBCs with pretransfusion plasma samples from DHTR patients with no detectable antibody. No such increase was observed with samples from other patients. This result indicates that donor RBCs may be damaged by the environment of SCD patients, increasing the physiologic clearance of apoptotic RBCs. In vivo, PS-RBC percentage increased in all three cases after destruction of transfused RBCs, indicating that DHTR induces PS-RBCs and, possibly, subsequent VOC and autologous RBC destruction.


CONCLUSIONS
This study clearly demonstrates that DHTR can occur in the absence of detectable antibody. In these cases, a mechanism of excessive eryptosis is proposed.
Etablissement Français du Sang, Ile de France, Hôpital Henri Mondor, Créteil, France.
Philippe
P
Chadebech
Anoosha
A
Habibi
Ruben
R
Nzouakou
Dora
D
Bachir
Natacha
N
Meunier-Costes
Philippe
P
Bonin
Martine
M
Rodet
Btissam
B
Chami
Frederic
F
Galacteros
Philippe
P
Bierling
France
F
Noizat-Pirenne
D000328:Adult; D000755:Anemia, Sickle Cell / Q000097:blood / Q000276:immunology / Q000628:therapy*; D016923:Cell Death; D004912:Erythrocytes / Q000166:cytology* / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006461:Hemolysis / Q000276:immunology*; D006801:Humans; D008297:Male; D010718:Phosphatidylserines / Q000378:metabolism; D013577:Syndrome; D065227:Transfusion Reaction; D055815:Young Adult
D010718:Phosphatidylserines