Delayed Hemolytic Transfusion Reaction

By definition, occurs 24 hours or more after transfusion, usually within 2 weeks

Due to anamnestic immune response in patients previously alloimmunized by certain RBC antigens; hemolysis is usually extravascular

Cannot be detected by pretransfusion antibody screening tests or crossmatches because antibodies are present in low concentrations, have low affinity for antigen or indicator antigen is missing from test red cells

Antibodies are usually IgG reactive at 37°C, fix complement; Duffy (Fya) and Kidd (Jka) are most likely

Associated with prolonged intervals between initial and subsequent transfusions, as antibodies decrease to undetectable levels

Rarely is due to a primary immune response with no prior exposure (Immunohematol 2004;20:184)

Symptoms: usually mild hemolysis, fever, falling hematocrit, jaundice; may have “bystander hemolysis” affecting non-transfused red cells, due to complement activation and deposition of C3d on non-transfused red cells

Sickle cell patients usually have non-severe symptoms (Transfusion 2002;42:37), but may have acute pain syndrome with life threatening anemia due to bystander hemolysis (hyperhemolysis, Pediatrics 2003;111:e661)

Laboratory: anemia, mild hemolysis, reticulocytes, hyperbilirubinemia (unconjugated), increased serum LDH and WBCs, low haptoglobin, positive DAT, new RBC antibody present, spherocytes due to removal of portions of red cell membranes by splenic phagocytic cells

Prevention: accurate recordkeeping of prior red cell alloantibodies and avoiding reexposure; obtain accurate patient history of other transfusions and contact those institutions for their records; minimize transfusions; sickle cell patients should have their extended red cell antigen phenotype determined (ABO, Rh, Kell, Kidd, Duffy, Lewis, MNS) before transfusion therapy and receive units phenotypically matched for C, E, and Kell (Transfusion 2001;41:1086)

Case reports: severe reaction due to anti-At(a) (Transfusion 1999;39:834), due to anti-D (Transfusion 1998;38:459), due to anti-Go(a) (Am J Hematol 1996;53:248), due to anti-Jk(a) (Acta Chir Iugosl 2005;52:111), due to anti-Jk3 after massive postpartum hemorrhage requiring transfusion (Archives 1999;123:949), multiple episodes due to different antibodies (Transfus Sci 2000;23:107)

sickle cell patients – due to anti-c (Sao Paulo Med J 1999;117 n.1), due to anti-Js(a) (AJCP 1997;108:658), due to anti-s (J Pediatr Hematol Oncol 1999;21:70), with pregnancy (Obstet Gynecol 2007;110:471), with Serratia marcescens infection and death (J Natl Med Assoc 2006;98:1697)


  • Usually careful followup only; may need exchange transfusion if large number of antigen positive red cells; IV immunoglobulin may prevent transfusion reactions if compatible blood cannot be obtained


  • xxx