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Transfusion medicine

Tranfusion reaction

Delayed hemolytic transfusion reaction (DHTR)

Reviewer: Huy Phu Pham, M.D. (see Reviewers page)
Revised: 1 November 2011, last major update September 2011
Copyright: (c) 2007-2011, PathologyOutlines.com, Inc.


● 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; pre-transfusion 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 37C, 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 pre-transfusion 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 post-transfusion
● 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


● 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 s/he has 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)

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 (Arch Pathol Lab Med 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) (Am J Clin Pathol 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)

End of Transfusion Medicine > Tranfusion reaction > Delayed hemolytic transfusion reaction (DHTR)

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