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Complement inhibition significantly decreases red blood cell lysis in a rat model of acute intravascular hemolysis
Author(s) -
Shah Tushar A.,
Mauriello Clifford T.,
Hair Pamela S.,
Sharp Julia A.,
Kumar Parvathi S.,
Lattanzio Frank A.,
Werner Alice L.,
Whitley Pamela H.,
Maes Lou Ann,
Cunnion Kenji M.,
Krisheel K.
Publication year - 2014
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1111/trf.12695
Subject(s) - hemolysis , spleen , complement system , in vivo , red blood cell , medicine , coombs test , lysis , antibody , immunology , in vitro , pharmacology , chemistry , biology , biochemistry , microbiology and biotechnology
Background Prevention of acute hemolytic transfusion reactions is a worldwide concern. The objective of this study was to develop a simple rat model of complement‐mediated acute intravascular hemolysis. Study Design and Methods Human AB red blood cells ( RBC s) were incubated with complement‐sufficient or complement‐deficient W istar rat serum ( WRS ) in the presence and absence of human RBC antibody in vitro to elucidate the mechanism of hemolysis. To study the role of complement in acute intravascular hemolysis in vivo, W istar rats were treated either with or without cobra venom factor ( CVF ) to deplete complement activity. Human AB RBC s were then injected into both groups of rats, followed by serial blood draws up to 2 hours. Venous blood clearance and lysis of transfused RBC s at each time point were measured by flow cytometry and spectrophotometry. RBC sequestration was determined in the liver, spleen, and kidney by immunohistochemistry. Results In vitro incubation of human RBCs with WRS demonstrated that RBC lysis was mediated via the classical complement pathway and that hemolysis was antibody dependent. Transfusion of human RBC s into rats showed significantly less hemolysis in the CVF group versus untreated group. RBC sequestration in the spleen and liver 2 hours posttransfusion were not quantitatively different between the two groups. Conclusions Given the much higher degree of similarity for rat and human complement compared to mice, this simple rat model is ideal for testing novel inhibitors of classical pathway activation for the prevention and treatment of acute intravascular hemolysis.

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