Transfusion medicine
Transfusion reaction
Delayed hemolytic transfusion reaction (DHTR)

Topic Completed: 1 September 2011

Revised: 5 April 2019

Copyright: 2002-2019,, Inc.

PubMed Search: Delayed hemolytic transfusion reaction [title]

Huy Phu Pham, M.D., M.P.H.
Page views in 2018: 1,869
Page views in 2019 to date: 996
Cite this page: Pham HP Delayed hemolytic transfusion reaction (DHTR). website. Accessed June 25th, 2019.
Definition / general
  • Occurs after 24 hours, usually within 2 weeks after transfusion of pRBCs products that appeared compatible
  • Occurs in patients with previous alloimmunization to minor antigens from previous transfusions, pregnancy or transplants; pretransfusion testing failed to detect those antibodies due to low titer; amnestic response occurs after re-exposure to those antigens
  • Antigens implicated most often are in Kidd, Duffy, Kell, MNS systems; antibodies are usually IgG reactive at 37°C, fix complement
  • Rarely due to primary immune response with no prior exposure (Immunohematol 2004;20:184)
  • Extravascular hemolysis usually if patient hemolyzes
  • In most cases, amnestic antibody production does NOT cause detectable hemolysis - this is called delayed serologic transfusion reaction (DSTR)
  • Incidence: 1:1,500 transfusion for both DHTR and DSTR
  • Prior exposure through pregnancy or transfusion → sensitization to minor antigens on RBCs → primary immune response
  • Alloantibody titer decreases over time with no transfusion / pregnancy, so pretransfusion testing is negative
  • Re-exposure to RBC with those antigens → amnestic response → production of IgG → extravascular hemolysis
  • Severity depends on thermal range, antibody specificity, IgG subclass
Clinical features
  • Unexpected drop in hemoglobin or less than expected rise in hemoglobin posttransfusion
  • Fevers, chills, jaundice, malaise
  • Patients with sickle cell can present with vaso-occlusive crisis as a symptom of DHTR (Transfusion 2002;42:37)
  • Can also have hyperhemolysis - hemolysis of bystander RBCs besides the transfused pRBCs (Pediatrics 2003;111:e661)
  • Report to transfusion medicine service
  • Send new sample for antibody identification and DAT
  • Positive antibody screen with newly identified alloantibody or positive DAT are suggestive of DHTR
  • If DAT positive, then eluation should be performed

Other lab findings suggestive of DHTR:
  • Reticulocytosis, unconjugated hyperbilirubinemia, urine urobilinogen, spherocytes on peripheral smear
  • Case reports

    Sickle cell patients:
    • Usually not indicated if asymptomatic
    • Close communication between transfusion medicine physician and clinical team is critical
    • If patient requires pRBCs before workup is completed, then benefit of transfusion must be weighed against risk of hemolysis
    • After workup is completed, patient should receive pRBCs negative for antigen they have the alloantibody against
    • AABB Standards mandates permanent preservation of all records of potentially clinically significant antibodies, as well as review of previous records prior to pRBC transfusion
    • Once a clinically significant alloantibody against an antigen is identified, patient will receive pRBC units that lack that antigen in the future
    • Obtain accurate transfusion history
    • Contact other hospital or transfusion medicine services for records
    • Patients with chronic transfusion (such as sickle cell patients) should have RBCs phenotyped for ABO, Rh, Kell, Duffy, Kidd, MNS antigens before transfusion therapy and should receive pRBCs phenotypically matched for C, E, and Kell (Transfusion 2001;41:1086)
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