Sickle cell disease (SCD) is the most frequent inherited disorder in France, where it predominantly affects patients from Africa and West Indies. The SCD population in France is about 8000 patients. Transfusion is a life-sustaining therapy in SCD. Transfusion decreases morbidity and mortality by treating acute chest syndrome, stroke, splenic sequestration. Moreover, Intensive transfusion therapy prevents cerebral vasculopathy in children with SCD. Delayed haemolytic transfusion reactions (DHTR) are a life threatening hazard of transfusion that is frequently encountered in SCD patients.
This complication is unpredictable and under-recognized because of the clinical presentation that resembles to a vaso occlusive crisis. The pathogenesis is not well understood. DHTR usually occur between 5 to 10 days following transfusion and is characterized by a marked hemoglobin drop with the destruction of both transfused and autologous RBCs, and exacerbation of SCD symptoms. Further transfusion can worsen the anemia.
While this may be an oversimplification, the pathogenesis of DHTR can be reduced to two situations (i) the classical conflict between antigen on transfused RBCs and antibodies against transfused RBCs evidenced in the patient plasma. In this classical situation, it is possible that the developed antibodies are not known to be dangerous, are auto-antibodies, or are related to rare blood group phenotypes in the patient. (ii) More enigmatic are situations without detectable antibodies. However, we have previously shown that an apoptotic effect on RBCs (eryptosis) could be involved explained by a toxic effect induced by the inflammatory environment of the patient plasma on transfused RBCs.
The aims of this project are twofold: first, to determine the frequency and characterize the clinical and immuno-hematological presentation of DHTR in transfused SCD patients; and second, to study the pathogenesis of this syndrome in order to prevent and treat it greater efficiency.
In this prospective study, we will collect pre transfusion samples of at least 1500 transfused patients. Further samples will be collected for those who develop a DHTR following transfusion, in order to reach 100 cases. In 2010, 1500 patients have been transfused in the Paris area (Ile de France), sometimes more than once. Thirty cases of transfusion reactions have been declared to the regional hemovigilance system. This number of reactions is under estimated, as the syndrome is not well recognized as a post-transfusion reaction. We will collect all clinical and biological data related to the transfusion and to the DHTR for those experiencing an accident. In vitro studies will be performed in order to support our hypothesis of an “eryptosis” effect, to determine the plasmatic factors responsible for this effect, and finally, to characterize the plasmatic and/or cellular factors leading to the destruction of these altered transfused RBCs, especially when no antibodies are detectable.
This large scale prospective study is the first one on a national and international level. This study can be organized because of our unique cohort of patients with extensive clinical data in the Paris area. The organization of transfusion within one unique establishment, the Etablissement Français du Sang (EFS) and its centralized information system, as well as the network of SCD reference centers, as well as the well organized hemovigilance system are major advantages for the success of this study. This project is also a major public health issue, as it has as one of the main aims to evaluate the incidence and consequences of an emerging syndrome in a growing patient population in France. Managing SCD transfusion is also a major issue for the EFS, and this study will bring epidemiologic and physiopathologic data that will help the EFS adapt the collection of RBC donor and transfusion procedures, to the needs of SCD patients and optimize transfusion safety.
Madame France NOIZAT-PIRENNE (UNIVERSITE PARIS-EST CRETEIL VAL DE MARNE) – firstname.lastname@example.org
The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.
UPEC UNIVERSITE PARIS-EST CRETEIL VAL DE MARNE
Help of the ANR 259,200 euros
Beginning and duration of the scientific project: October 2011 - 24 Months