Peptide inhibitor of complement C1 modulates acute intravascular hemolysis of mismatched red blood cells in rats.
Acute hemolytic transfusion reactions have a broad clinical presentation from mild and transitory signs and symptoms to shock, disseminated intravascular coagulation, renal failure, and death. We have recently developed a rat model of acute intravascular hemolysis showing that the classical complement pathway mediates antibody-dependent hemolysis. The objective of this study was to evaluate the role of the classical pathway inhibitor peptide inhibitor of complement C1 (PIC1) in this animal model.



Male Wistar rats received a 15% transfusion of human red blood cells (RBCs) and blood was isolated from the animals up to 120 minutes. Animals received PIC1 either 2 minutes before or 0.5 minutes after transfusion. Sham-, vehicle-, and cobra venom factor (CVF)-treated animals were used as control groups with a subset of rats also receiving an equivalent dose of intravenous immunoglobulin (IVIG) before transfusion. Blood was analyzed for transfused RBC survival by flow cytometry and free hemoglobin (Hb) in isolated plasma by spectrophotometry.



Vehicle-treated rats showed decreased human RBC survival and increased free Hb as expected. Rats receiving PIC1 before transfusion showed increased human RBC survival and decreased Hb similar to CVF-treated rats. Notably, rats receiving PIC1 after initiation of transfusion showed similar decreases in hemolysis as animals receiving PIC1 before transfusion. Compared to IVIG and saline controls, PIC1-treated animals demonstrated decreased hemolysis and protection from acute kidney injury.



These results demonstrate that PIC1 has efficacy in an animal model of acute intravascular hemolysis in both prevention and rescue scenarios.
Department of Pediatrics.
Parvathi S
PS
Kumar
Department of Pediatrics.
Haree K
HK
Pallera
Department of Pediatrics.
Pamela S
PS
Hair
Department of Pediatrics.
Magdielis Gregory
MG
Rivera
Department of Pediatrics.|Department of Microbiology and Molecular Cell Biology.|Children's Hospital of the King's Daughters.|Children's Specialty Group, Norfolk, Virginia.
Tushar A
TA
Shah
Department of Pediatrics.|Children's Hospital of the King's Daughters.|Children's Specialty Group, Norfolk, Virginia.
Alice L
AL
Werner
Department of Physiological Sciences, Eastern Virginia Medical School.
Frank A
FA
Lattanzio
Department of Pediatrics.|Department of Microbiology and Molecular Cell Biology.|Children's Hospital of the King's Daughters.|Children's Specialty Group, Norfolk, Virginia.
Kenji M
KM
Cunnion
Department of Pediatrics.|Department of Microbiology and Molecular Cell Biology.
Neel K
NK
Krishna
D000818:Animals; D001787:Blood Group Incompatibility / Q000188:drug therapy; D003172:Complement C1 / Q000037:antagonists & inhibitors*; D004906:Erythrocyte Count; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects; D006454:Hemoglobins / Q000378:metabolism; D006461:Hemolysis / Q000187:drug effects*; D006801:Humans; D008297:Male; D010455:Peptides / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D065227:Transfusion Reaction / Q000188:drug therapy
D003172:Complement C1; D006454:Hemoglobins; D010455:Peptides