Case Study O1: Severe hemolysis in a patient with immune thrombocytopenic purpura who has received intravenous Rh immune globulin*

Author: Pat Letendre, BSc, Subject IH (CSMLS), FCSMLS(D), MEd
Originally published as 2002 Tech Sample (Immunohematology)
© 2002 American Society for Clinical Pathology. Used with permission.

*2002 ASCP Tech Sample of the Year*


  • This case has been formatted for the web and educational enhancements have beenadded.
  • Originally published on TraQ in Aug. 2003, the case was updated Sept. 2005.
  • The ASCP retains copyright, except where TraQ has added enhancements (self study questions, revised quiz); the latter are TraQ's copyright.
  • The case presents both non-SI and SI units because it was originally written for a U.S. publication.
  • Also see Case A5 (developed for TraQ by Maureen Wyatt)

Case Structure

Case History

A 71-year-old non-splenectomized woman with immune thrombocytopenic purpura (ITP) has a history of being non-responsive to corticosteroids and was being treated with intravenous immune globulin (IVIG), with multiple admissions to the hospital over the past four months.

During this time the patient, who was group A D-positive with a negative antibody screen, received a total of

  • four units of group A D-positive red blood cells (RBCs) to treat anemia
  • six group A D-positive random donor platelets.

All RBCs were crossmatched electronically and transfused without incident, the last transfusion occurring 3 months ago.

On the most recent admission the patient was started on intravenous Rh immune globulin (IV RhIG) therapy and

  • received a total dose of 3000 µg (15,000 IU) (50 µg/kg; 250 IU/kg)
  • was monitored for platelet count increase and hemoglobin level
  • and was discharged 3-days post-therapy with continued monitoring as an outpatient.

Initial Laboratory Results

Ten days later the patient returned to the hospital complaining of headache, chills, nausea, and red urine. Laboratory results (pre-IV RhIG, 7 days post-IV RhIG, and current) are shown in Table 1.

Table 1. Laboratory Test Results

LD = lactate dehydrogenase, total
* Reference range: 140,000 ? 440,000/µL (140-450 x109/L)
+Reference range (females): 12.0-16.0 g/dL (120-160 g/L)
++Reference range: 91-180 units/L(91-180 U/L)

Six units of red blood cells were ordered. Antibody screen results are shown in Table 2.

Table 2. Antibody Screen Results

Antibody Screen

LISS 37o



Cell I




Cell II




Cell III




LISS, low ionic strength saline; AHG, antihuman globulin (anti-IgG); CC, IgG sensitized rbc

Questions to Consider (as you progress through the case)

  1. What are the apparent specificities and source of the antibodies in the patient?s plasma and red cell eluate?
  2. Which factors should be considered when selecting RBCs for transfusion to this patient?
  3. Is the patient a candidate for further therapy with intravenous Rh immune globulin?
  4. Is the patient experiencing an adverse event that should be reported to the manufacturer of intravenous Rh immune globulin and the FDA's MedWatch reporting system.

Learning Outcomes

Upon completion of this exercise, the participant should be able to

  • Discuss factors that influence when crossmatch-compatible D-negative RBCs should be selected for transfusion to D-positive patients who have received intravenous Rh immune globulin (IV RhIG) versus when crossmatch-incompatible D-positive units can be selected.
  • Discuss the selection of RBCs for transfusion when passively acquired alloantibodies other than anti-D are detectable in patient sera or red cell eluates after infusion of IV RhIG. List the antibodies that have been shown to be present in IV RhIG.
  • List contraindications to receiving IV RhIG therapy for immune thrombocytopenia purpura(ITP).
  • Describe the serious complications of IV RhIG therapy for ITP, their incidence, signs and symptoms, and implications for treatment.


An extensive discussion of the case is organized as follows:

Case Conclusion

  • Six units of D- C- E- (cde/cde) RBCs were crossmatch-compatible (LISS AHG) and transfused without incident.
  • The patient?s post-transfusion hemoglobin rose to 11.5 g/dL (115 g/L) and hemoglobinuria cleared in a few days.
  • She was discharged 7 days later with a platelet count of 29,000/µL (29 x109/L) and continues to be seen as an outpatient.
  • Due to the severe hemolysis following IV RhIG therapy, further therapy with this product is contraindicated.


Rapid onset hemoglobinemia and hemoglobinuria are uncommon but potentially life-threatening complications of IV RhIG therapy for ITP. Health professionals should monitor patients for signs and symptoms of severe hemolysis, clinically compromising anemia, and renal insufficiency.

Besides anti-D, such patients may have multiple passive antibodies in their plasma and sensitizing their red cells. In patients who have been recently transfused with RBCs, these antibodies may need to be differentiated from active antibodies causing a hemolytic transfusion reaction. When these patients require RBC transfusion for anemia, donors should antigen-negative.

TraQ Quiz

After reviewing the case summary, consider these questions.

1. Which of the following are contraindications to receiving IV RhIG to treat ITP?

  1. patient with hemoglobin of 100 g/L (10 g/dL)
  2. D- negative patient
  3. D- positive patient
  4. non-splenectomized patient
  5. patient with a history of anaphylactic reaction to human globulin


2. Which of the following antibodies is LEAST likely to be present in IV RhIG?

  1. anti-A
  2. anti-C
  3. anti-E
  4. anti-Jka
  5. anti-N


3. When crossmatching for a group A D- positive patient experiencing severe hemolysis after receiving IV RhIG to treat ITP, which of the following RBCs should be selected?

  1. group A D-negative
  2. group A D-positive
  3. group O D-positive or D-negative (either is suitable)
  4. group A D-positive or D-negative (either is suitable)
  5. all of the above are suitable


4. Which of the following is MOST likely to be considered a serious and reportable complication of IV RhIG therapy to treat ITP?

  1. fever
  2. chills
  3. total drop in hemoglobin of 20g/L (2 g/dL)
  4. rapid onset hemoglobinuria
  5. nausea


5. The incidence rate of hemoglobinemia and/or hemoglobinuria following IV RhIG therapy to treat ITP is

  1. 0.5%
  2. 1%
  3. 2.0%
  4. 5.0%
  5. unknown


6. A group O D-positive patient with no prior history of RBC transfusion and whose antibody screen result was negative prior to receiving IV RhIG one day ago now has passive anti-D, anti-C, and anti-E detectable in his plasma. The patient's DAT result is positive and elutes anti-D and anti-Fya. The patient's red cell phenotype is D+ C- E- c+ e+ Fy(a+).

The patient's hemoglobin has dropped 50 g/L (5 g/dL) over the past 24 hours and he is experiencing hemoglobinuria. Which of the following group O RBCs should be selected for crossmatching?

  1. D+ C+ E+ Fy(a+)
  2. D- C- E- Fy(a-)
  3. D+ C- E- Fy(a+)
  4. D- C+ E+ Fy(a+)
  5. D- C+ E+ Fy(a-)


7. Is it unusual that a product such as IV RhIG (IgG anti-D) would cause apparent intravascular hemolysis (IVH)? Explain.

  1. yes
  2. no


8. Intravenous immune globulin (IVIG) is also used to treat ITP. Which of the following rare but serious complications hasIVIG been associated with?

  1. renal failure
  2. transfusion-related acute lung injury (TRALI)
  3. stoke
  4. myocardial infarction
  5. all of the above



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16. Added 5 Sept. 2005: Gaines, A R. Disseminated intravascular coagulation associated with acute hemoglobinemia or hemoglobinuria following Rho(D) Immune Globulin Intravenous administration for immune thrombocytopenic purpura. Blood 2005 Sep1; 106(5):1532-7.