Post-transfusion effects of red blood cell storage lesion

Postgraduate Thesis uoadl:2880826 318 Read counter

Unit:
Κατεύθυνση Εφαρμογές της Βιολογίας στην Ιατρική
Library of the School of Science
Deposit date:
2019-09-19
Year:
2019
Author:
Anastasiadi Alkmini
Supervisors info:
Μαριάννα Αντωνέλου, Επίκουρη Καθηγήτρια, Τμήμα Βιολογίας, Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών
Original Title:
Μετα-μεταγγισιακές συνέπειες της αποθηκευτικής βλάβης του ερυθροκυττάρου
Languages:
Greek
Translated title:
Post-transfusion effects of red blood cell storage lesion
Summary:
All cells, including red blood cells (RBCs) undergo a series of alterations and lesions during their ex vivo storage. Concerning RBCs, these changes are collectively reffered to as RBC storage lesion. Storage lesions can be categorized into membrane (protein carbonylation), mechanical (transformation into spheroechinocytes) and biochemical (ATP depletion and drop of pH) changes that affect the morphology and function of RBCs. Stored RBCs usually present a premature senescent phenotype, which can be responsible for their early clearance post transfusion. Blood banking’s gold standards, that indicate the effectiveness of the transfusion, are the end of storage hemolysis of RBCs and their 24h recovery in vivo.
RBC storage capability is related to the duration and the preservative solution (volume and composition) of storage, performance or not of leukoreduction, the type of the plasticizer used in the blood bag and donor variation in both genetical and not background. Sex, hemoglobin mutations (b-thalassaemia heterozygotes), deficiencies in enzymatic activities (G6PD), smoking and age are just some of the many donor characteristics that affect RBC storage capacity and post-transfusion recovery. Moreover, recipient characteristics cannot be overlooked since they too play a role in transfusion outcome. It seems that not all donor/recipient combinations are ideal.
The aim of this thesis was:
(a) The study of the effect of body temperature as well as of recipient plasma upon RBCs of early (day 2), middle (day 21) and late (day 42) storage in several time intervals during the first 24 hours (24h) post mixing, using an in vitro model of transfusion. Packed RBCs of 7 CPD-SAGM blood bags were reconstituted with healthy plasma collected by 27 volunteers and incubated at 37°C. Reconstituted samples of 2 blood bags’ RBCs and 5 donors’ plasma were studied for several time intervals during 24 hours post-mixing, whereas the rest only at the end of the 24h incubation. Hemolysis with and without exogenous (osmotic and mechanical) stimuli, as well as ROS levels with or without stimulation by oxidants were measured.
(b) The comparative examination of the hematological and biochemical features of fresh (non-stored) blood from regular blood donors with or without beta-thalassaemia traits before blood processing for transfusion purposes. 204 healthy blood donors were recruited and several hematological (RBC general indices), physiological (eg osmotic fragility test) and biochemical (measurement of cholesterol, uric acid, electrolytes etc) assays were performed.
Concerning the first part of the study, hemolysis and susceptibility of stored RBCs to exogenous hemolysis stresses were in general lower in the presence of plasma compared to the preservation medium, with the exception of mechanical hemolysis. In the latter case, an early increase in the mechanical fragility index was observed, especially in middle-aged RBCs, and plasma deteriorated the mechanical state of the cells. ROS generation seemed to be an early stress response of young and middle-aged RBC to transfusion mimicking conditions, with plasma being either an antioxidant or a prooxidant factor depending on the storage age and the molecular targeting of the exogenous oxidant used. Overall, some parameters vary substantially 24h post-mixing, reaching in the meanwhile levels that differ from the 24h traditional interval measurements and the state inside the blood bag.
As for the second part of the study, it was clear that β-thalassaemia heterozygotes comprise a non negligible proportion of the total donor population in Greece. They present many similarities to the general cohort, but differ in some fine characteristics of their RBC physiology, one of them being their resistance to hemolysis. The differential networking of hematological and redox parameters that has emerged might play a critical role in respect to blood processing and storage of these RBCs for transfusion purposes.
Main subject category:
Science
Keywords:
red blood cell, blood transfusion, storage lesion, beta-thalassemia, blood donation
Index:
No
Number of index pages:
0
Contains images:
Yes
Number of references:
233
Number of pages:
74
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