Case B5: Severe Delayed Hemolytic Transfusion Reaction

We Welcome Feedback: Contact This email address is being protected from spambots. You need JavaScript enabled to view it.

Last Updated: Oct. 28, 2016 [All links fixed]

If you find errors or have suggestions, fire away!

Learning Outcomes

Upon completion of this exercise, participants should be able to:

  1. Discuss the concept of dosage as it relates to cells used for antibody screening.
  2. Describe the follow-up investigation required when a patient has a positive antibody screen.
  3. Explain the risk involved in releasing donor units that are crossmatch-compatible before the patient's antibody has been identified.
  4. Discuss reasons  why a patient with a clinically significant antibody may have a negative antibody screen while experiencing a hemolytic transfusion reaction.
  5. Describe what happens to antibody levels (antibody kinetics) following primary and secondary immune responses to red blood cell antigens.
  6. Discuss best practices aimed at preventing delayed hemolytic transfusion reactions.

Case Report

A 60-year-old female (SJ) was admitted to hospital complaining of bloody diarrhea and dizziness. Two days later she experienced severe GI bleeding and underwent emergency surgery. A crossmatch for 6 units of RBC was ordered.


  • Transfusion: none
  • Pregnancy: four (uneventful)
  • Medications: Patient reported occasional aspirin use and had been on hormone replacement therapy since menopause.

Laboratory results (Day 0*)

  • Hemoglobin:70 g/L (reference range:120 - 160 g/L)
  • Total bilirubin: 8.6 µmol/L (reference range: 1.7 - 17.1 µmol/L)
  • Lactate dehydrogenase: 224 U/L (reference range: 113-226 U/L)

* As used for this case study, Day 0 is the day of the first transfusion. Day 3, etc., refers to days post-transfusion.

Transfusion Service Results

Initial pretransfusion testing results (Day 0)

The technologist notified the attending physician that the patient had an unexpected antibody (or antibodies) present but that units crossmatched by indirect antiglobulin method were compatible and available if needed. Because the transfusion service performs only Type and Screen/Crossmatch the samples were sent to a reference laboratory to have the antibody identified.

  • The decision was made to transfuse the donor RBC before the positive antibody screen had been resolved and the patient received all six units over the next 24 hours without complication.
  • The cause of SJ's bleeding was found to be diverticulitis and a colectomy was performed. Her hemoglobin rose as expected and at Day 5 her hemoglobin was 127g/L.

Reference laboratory results (Reported on Day 3)

On Day 8 SJ's condition deteriorated. Peripheral blood smears were consistent with acute hemolysis (anisocytosis, poikilocytosis, nucleated RBCs). Her reticulocyte count was 8.8 percent.

Additional laboratory results (Day 8)

  • Hemoglobin: 72 g/L (reference range:120 - 160 g/L)
  • Total bilirubin: 59.9 µmol/L  (reference range: 1.7 - 17.1 µmol/L)
  • Lactate dehydrogenase: 1055 U/L (reference range: 113-226 U/L)

Transfusion reaction investigation results (Day 8)

Follow-Up and Case Outcome

  • The patient stabilized and was later transfused with 2 units of crossmatch-compatible Jk(a-) RBC.
  • By Day 14 her antibody screen was again positive, reacting 2+ with Jk(a+b-) screen cells and 1+ with Jk(a+b+) screen cells.
  • Her DAT remained  positive upon discharge three weeks after admission.


See the case discussion, including interactive questions with feedback.

Final Quiz

This quiz is offered as a self assessment.

  1. Why is dosage an important concept in pretransfusion antibody screening tests?
  2. Which follow-up tests are routinely done when investigating possible delayed hemolytic transfusion reactions?
  3. Why should donor units that are crossmatch-compatible NOT be released, unless life-threatening, before the antibody is identified?
  4. Why can a patient with a clinically significant antibody sometimes have a negative antibody screen while experiencing a delayed hemolytic transfusion reaction in which antibody levels are rising?
  5. Provide six best practices for preventing delayed hemolytic transfusion reactions.

Further Reading

Cash KL, Brown T, Sausais L, Uehlinger J, Reed LJ.Severe delayed hemolytic transfusion reaction secondary to anti-At(a). Transfusion 1999 Aug;39(8)834-7. [Medline]

Davenport RD. Hemolytic transfusion reactions. In: Popovsky M, editor. Transfusion reactions, 2nd ed. Arlington, VA: AABB Press;2001. p.1-44.

Heddle NM, Soutar RL, O'Hoski PL, Singer J, McBride JA, Ali MA, Kelton JG. A prospective study to determine the frequency and clinical significance of alloimmunization post-transfusion. Br J Haematol 1995 Dec;91(4):1000-5. [ Medline ]

Hillman NM. Fatal delayed hemolytic transfusion reaction due to anti-c + E. Transfusion 1979 Sep-Oct;19(5)548-51. [ Medline ]

Pineda AA, Vamvakas EC, Gorden LD, Winters JL, Moore SB. Trends in the incidence of delayed hemolytic and delayed serologic transfusion reactions. Transfusion 1999 Oct;39(10):1097-103.  [ Medline ]

Sazama K. Reports of 355 transfusion associated deaths:1976 through 1985. Transfusion 1990;30:583-90. [ Medline ]

Schonewille H, Haak HL, van Zijl AM. RBC antibody persistence. Transfusion 2000 Sep;40(9):1127-31. [ Medline ]