Case A5: Adverse Reaction to Intravenous Rh Immune Globulin in a Patient with ITP (HM)

Contributed by:
Maureen Wyatt, ART
Kelowna General Hospital

History Mr. H.M. is an 83 year-old male diagnosed with immune thrombocytopenic purpura (ITP).   On November 20 HM presented to his physician's office with nosebleeds. Subsequent investigations showed an underlying low grade lymphoproliferative disorder. His medical history includes ischemic heart disease, treated with medical therapy after occlusion of a bypass graft performed in 1971 and chronic obstructive pulmonary disease. He is considered a high surgical risk, therefore, splenectomy is not an option. At the time of admission he was treated with oral prednisone for the ITP. This was followed by two courses of high dose intravenous immunoglobulin (IVIG) therapy. He initially responded well but was unable to sustain the platelet increments. In January vincristine was prescribed. While not recommended as a primary treatment it has been shown to be useful in ITP that is refractory to steroids and splenectomy. On January 4, the hematologist ordered Rh immune globulin (RhIG). Allergies: no known drug allergies Transfusion: no record of any transfusions at Kelowna General Hospital prior to November 21 Medications propranolol cimetidine enteric coated aspirin finasteride dilitazem omeprazole nitroglycerin spray furosemide Reference Ranges Hemoglobin 131-169 g/L Platelets 140 - 450 X 109/L Creatinine 50 - 130 mmol/L Haptoglobin 0.60 - 2.00 g/L Total bilirubin 3 - 17 mmol/L

November 20 - 24

HM was admitted to hospital for hematological workup following numerous uncontrolled nosebleeds.

Initial Laboratory Results (Nov. 20) Reference Range
Hemoglobin	83 g/L
Platelets	2 X 109/L
Creatinine	109 mmol/L
Haptoglobin	0.85 g/L

The hematologist requested 0.4 gm IVIG /kg x 5 days. Patient weight was 81.9 kg. Patient was also started on prednisone.

• Initial pretransfusion testing results

Based on these results, red cells were electronically crossmatched and Mr. HM was transfused with one unit of RBC on November 20 and two RBC on each of 3 days (November 21-23) as he exhibited anemia-related symtoms. No adverse reactions were reported.

35 gm IVIG (Nov.20) and 30 gm IVIG (Nov. 21, 22, 23) were also transfused without incident.

 

Laboratory Results (Nov. 21-24) Reference Range
Date	Hemoglobin	Platelets
Nov. 21	86 g/L	3 X 109/L
Nov. 22	100 g/L	5 X 109/L
Nov. 23	122 g/L	13 X 109/L
Nov. 24	136 g/L	31 X 109/L

November 25 - December 28

• Dec. 5: Discharged with a Hgb of 167 g/L and a platelet count of 24 X 10⁹/L.
• Dec. 8: Re-admitted (Hgb 144 g/L; platelets 35 X 10⁹/L). 30 gm IVIG were transfused daily (Dec.8 - 11).
• Dec. 15: Discharged (Hgb 135 g/L; platelets 38 X 10⁹/L; creatinine 99 mmol/L).
• Dec. 28: Hemoglobin 138 g/L; platelet 17 X 10⁹/L. The first of four doses of vincristine was ordered.

December 30 - January 11

Five platelet concentrates were requested by the on-call oncologist on Dec. 30. The patient was ABO and Rh retyped and the platelets were transfused as a pool without incident.

On Jan. 4, HM's hemoglobin was 129 g/L and his platelet count was 13 X 10⁹/L. 4000 micrograms of RhIG were given in the ambulatory care unit.

 

Laboratory Results (Jan. 11) Reference Range
Hemoglobin	103 g/L
Platelets	73 X 109/L
Creatinine	122 mmol/L
Haptoglobin	0.06 g/L
Total bilirubin	12 mmol/L

January 17 - 18

HM came to Emergency complaining of chest pain and was admitted to hospital.

Laboratory Results (Jan. 17) Reference Range
Hemoglobin	79 g/L
Platelets	34 X 109/L
Creatinine	121 mmol/L

The patient's hemoglobin dropped 50g/L (129 g/L on Jan. 4 to 79 g/L on Jan. 17).

Two red cell concentrates were ordered.

• Antibody screen and DAT results (Jan 17)
• Antibody identification (eluate)

Two group O Rh negative red cell concentrates were crossmatched (PEG-IAT) and transfused without incident on Jan. 17. The patient's chest pain had abated, his CBC showed a satisfactory increment, and he was discharged on Jan.18.

Laboratory Results (Jan. 18) Reference Range
Hemoglobin	92 g/L
Platelets	31 X 109/L
Creatinine	104 mmol/L
Haptoglobin	<0.06 g/L
Total bilirubin	17 mmol/L

January 25 - 26

On Jan. 25 two red cell concentrates were ordered. Two group O Rh positive RBC were crossmatched (PEG-IAT) and transfused without incident on Jan. 26 in the Ambulatory Care Unit. The patient's DAT was still positive but weaker (1+).

Laboratory Results (Jan. 25 - 26) Reference Range
	Jan. 25	Jan. 26
Hemoglobin	91 g/L	113 g/L
Platelets	15 X 109/L	56 X 109/L

Case Summary and Quiz

After reviewing the case summary, consider these questions.

1. What laboratory tests should be ordered on patients being considered for RhIG therapy for ITP?

 

 

2. Should patients who have a drop in hemoglobin that triggers a transfusion be given Rh positive or Rh negative red cells?

 

 

3. Should RhIG be given to outpatients?

 

 

4. What are contraindications to receiving RhIG therapy for ITP?

 

 

5. What is the expected drop in hemoglobin in Rh positive patients receiving intravenous RhIG?

 

 

6. What should be checked prior to giving Rh positive patients subsequent doses of intravenous RhIG?

 

 

7. What is the mechanism of action of RhIG in the treatment of ITP?

 

 

8. What is the cost benefit of using RhIG compared to IVIG for the treatment of ITP?

 

 

9. Have deaths ever resulted from intravascular hemolysis secondary to transfusing Rh positive patients with RhIG to treat ITP?

 

 

10. What is the pathogenesis and incidence of ITP?

 

 

Further Reading

American Society of Hematology. Diagnosis and Treatment of Idiopathic Thrombocytopenic Purpura: Recommendations of the American Society of Hematology(Annals of Internal Medicine 1997;126:319-26.)

Blanchette V,Freedman J, Garvey B. Management of chronic immune thrombocytopenic purpura in children and adults. Semin Hematol. 1998 Jan;35(1 Suppl 1):36-51.

Cangene Corporation. Product monograph. WinRho SDF™. 

Cangene Corporation and Nabi^®.(available at FDA Medwatch) Important prescribing information regarding WinRho SDF™.

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. 

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.

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

Sandler SG, Novak, SC, Roland B. The cost of treating immune thrombocytopenic purpura using intraveous Rh immune gloulin versus intravenous immune globulin. (Am J Hematol 2000 Mar;63(3):156-8.)

Scaradavou A, Woo B, Woloski BM, Cunningham-Rundles S, Ettinger LJ, Aledort LM, Bussel JB. Intravenous anti-D treatment of immune thrombocytopenic purpura: experience in 272 patients. Blood 1997 Apr 15;89(8):2689-700.

Simpson KN, Couglin CM, Eron J, Bussel JB. Idiopathic thrombocytopenia purpura:Treatment patterns and an analysis of cost associated with intravenous immunoglobulin and anti-D therapy. Semin Hematol 1998 Jan;35(1 Suppl 1):58-64. [ Medline ]

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

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