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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), MEd
Originally published as 2002 Tech Sample (Immunohematology)
© 2002 American Society for Clinical Pathology. Used with permission.

*2002 ASCP Tech Sample of the Year*

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Notes:

This case has been formatted for the web and educational enhancements have been added.

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)

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Case history
Initial laboratory results
Questions to be considered
Learning outcomes
Discussion
Case conclusion
Summary
Quiz
References

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.

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

	Platelet Count* /µL (x10⁹)	Hemoglobin⁺ g/dL (g/L)	LD⁺⁺ units/L (U/L)
Day of IV RhIG (pre)	14,000 (14)	12.5 (125)	70 (70)
7 days post-IV RhIG	61,000 (61)	11.0 (110)	120 (120)
Current admission	33,000 (33)	6.0 (60)	650 (650)

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 37^o	AHG	CC
Cell I	0	1+
Cell II	0	1+
Cell III	0	0

LISS, low ionic strength saline; AHG, antihuman globulin (anti-IgG); CC, Combs’ control cells =2+

Antibody identification results are shown in Figure 1.

Figure 1. Initial Antibody Identification Results (Plasma)

Cell	Rhesus						Kell			Duffy		Kidd		MNSs				P	Lewis		Lu	Results			Cell
	D	C	E	c	e	C^w	K	k	Kp^a	Fy^a	Fy^b	Jk^a	Jk^b	M	N	S	s	P₁	Le^a	Le^b	Lu^a	LISS
	D	C	E	c	e	C^w	K	k	Kp^a	Fy^a	Fy^b	Jk^a	Jk^b	M	N	S	s	P₁	Le^a	Le^b	Lu^a	37^o	AHG	CC
1	+	+	0	0	+	0	0	+	0	+	0	+	0	0	+	+	+	+^S	+	0	0	0	1+		1
2	+	+	0	0	+	+	0	+	0	+	0	+	0	0	+	+	+	+^S	+	0	0	0	1+		2
3	+	0	+	+	0	0	0	+	0	+	+	0	+	0	+	+	0	+	0	+	0	0	1+		3
4	0	+	0	+	+	0	0	+	0	+	0	0	+	0	+	0	+	+	+	0	0	0	w+		4
5	0	0	+	+	+	0	+	0	0	+	+	0	+	+	0	+	0	+	0	+	0	0	0	ü	5
6	0	0	0	+	+	0	0	+	0	+	+	+	0	+	0	+	0	+	0	+	0	0	0	ü	6
7	0	0	0	+	+	0	0	+	0	0	+	+	+	+	0	+	0	+^S	0	+	+	0	0	ü	7
8	0	0	0	+	+	0	0	+	0	0	+	+	0	0	+	0	+	+	+	0	0	0	0	ü	8
9	0	0	0	+	+	0	+	+	0	+	0	0	+	+	0	0	+	+	+	0	0	0	0	ü	9
10	+	0	0	+	+	0	0	+	0	+	0	+	+	+	0	+	0	+^S	0	+	0	0	w+		10
auto																						0	3+		auto

LISS, low ionic strength saline; AHG, antihuman globulin (anti-IgG); CC, Combs’ control cells ü=2+

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.

Discussion

An extensive discussion of the case is organized as follows:

Proceed to discussion.

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.

Summary

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?

patient with hemoglobin of 100 g/L (10 g/dL)
D- negative patient
D- positive patient
non-splenectomized patient
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?

anti-A
anti-C
anti-E
anti-Jk^a
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?

group A D-negative
group A D-positive
group O D-positive or D-negative (either is suitable)
group A D-positive or D-negative (either is suitable)
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?

fever
chills
total drop in hemoglobin of 20g/L (2 g/dL)
rapid onset hemoglobinuria
nausea

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

0.5 %
1%
2.0 %
5.0 %
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-Fy^a. 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?

D+ C+ E+ Fy(a+)
D- C- E- Fy(a-)
D+ C- E- Fy(a+)
D- C+ E+ Fy(a+)
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.

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

renal failure
transfusion-related acute lung injury (TRALI)
stoke
myocardial infarction
all of the above

References

1. McMillan R. Therapy for adults with refractory chronic immune thrombocytopenic purpura. Ann Intern Med.1997;126:307–314. [ full text ]

2. George JN, Woolf SH, Raskob GE, Wasser JS, Aledort LM, Ballem PJ, et al. Idiopathic thrombocytopenic purpura: a practice guideline developed by explicit methods for the American Society of Hematology. Blood.1996;88:3–40. [ full text ]

3. Scaradavou A, Woo B, Woloski BMR, Cunningham-Rundles S, Ettinger LJ, Aledort LM, et al. Intravenous anti-D treatment of immune thrombocytopenic purpura: Experience in 272 patients. Blood 1997;89(8):2689–2700. [ full text ]

4. Sandler SG. Treating immune thrombocytopenic purpura and preventing Rh alloimmunization using intravenous rho (D) immune globulin (review). Transfus Med Rev. 2001;15(1):67–76.

5. Robertson VM, Dickson LG, Romond EH, Ash RC. Positive antiglobulin tests due to intravenous immunoglobulin in patients who received bone marrow transplant. Transfusion. 1987;27(1):28–31. [ Medline ]

6. Epstein JS, Zoon KC. U. S. Food and Drug Administration, Center for Biologics Evaluation and Research, Important Drug Warning: Immune Globulin Intravenous (Human). November 13, 1998. [ full text ]

7. Salama A, Kiefel V, Amberg R, Mueller-Eckhardt C. Treatment of autoimmune thrombocytopenic purpura with rhesus antibodies (anti-Rh_o(D). Blut. 1984;49(1):29–35. [ Medline ]

8. Bowman JM, Friesen AD, Pollock JM, Taylor WE. WinRho: Rh immune globulin prepared by ion exchange for intravenous use. Can Med Assoc J. 1980;123(11):1121–7. [ Medline ]

9. Cangene Corporation. Product monograph. WinRho SDF™. [ full text ]

10. Engelfriet CP, Reesink HW, Bussel J, Godeau B, Bierling P, Panzer S, et al. The treatment of patients with autoimmune thrombocytopenia with intravenous IgG-anti-D (International Forum). Vox Sang. 1999;76(4):250–5.

11. Ware RE, Zimmerman SA. Anti-D: mechanisms of action. Semin Hematol. 1998;35(1 Suppl 1):14–22. [ Medline ]

12. Gaines AR. Acute onset hemoglobinemia and/or hemoglobinuria and sequelae following Rh_o(D) immune globulin intravenous administration in immune thrombocytopenic purpura patients. Blood. 2000;95(8):2523–9. [ full text ]

13. Rushin J, Rumsey DH, Ewing CA and Sandler SG. Detection of multiple passively acquired alloantibodies following infusions of IV Rh immune globulin. Transfusion. 2000;40(5):551–4. [ abstract -AABB members log-in for full text]

14. Cangene Corporation and Nabi^®. Important prescribing information regarding WinRho SDF™. [Available at FDA MedWatch ]

15. Rizk A, Gorson KC, Kenney L, Weinstein R. Transfusion-related acute lung injury after the infusion of IVIG. Transfusion 2001 Feb;41(2):264-8. [ Medline ] [ abstract -AABB members log-in for full text]

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):1532–37. | Printable version from FDA website |