September 1995


 INTRAVENOUS (HUMAN) Rho(D) IMMUNE GLOBULIN

A new preparation for the treatment of ITP and Rh isoimmunization


Katherine A. Anderegg, M.D., Fellow, The Institute For Transfusion Medicine

Darrell J. Triulzi, M.D., Medical Director, The Institute For Transfusion Medicine


Introduction

The FDA recently approved the use of a solvent detergent treated Rh immune globulin (RhIg) preparation for intravenous use in the setting of immune thrombocytopenic purpura (ITP) and suppression of Rh isoimmunization. This is the first such intravenous RhIg preparation approved in the U.S. 

 

Description

RhIg-intravenous (RhIg-IV) is a sterile freeze dried gamma globulin fraction containing antibodies to Rho (D). It is derived from pooled human plasma and undergoes a viral inactivation process using solvent/detergent to inactive lipid enveloped viruses. RhIg-IV is marketed under the trade name of WinRho SDä and comes in 300m g (1500 IU) and 120 m g (600 IU) vials.1

 

Indications

1) Treatment of ITP: RhIg-IV can be used to treat Rh (D) positive patients with ITP who have not undergone splenectomy.2 Patients who respond best are Rh positive children with acute3 or chronic4 ITP (79-84% response rate), adults with chronic ITP2 (88% response rate) or adults or children with HIV related ITP2 (90% response rate). It has limited or no efficacy in Rh negative individuals. The recommended intravenous dose for treatment of ITP is 50 m g (250 IU)/kg given as a single dose or in two divided doses on separate days. Significant increases in platelet count occur within 1-3 days with peak counts observed a mean of 8 days after infusion.2 Hemolysis is expected, peaking approximately 6 days after treatment with a mean hemoglobin decrease of 1.7 gm/dl (range 0.6 to 6.1 g/dl) after a full dose. Patients with moderate anemia (hemoglobin 8-10 gm/dl) should receive a reduced dose of 25-40 m g /kg. At the reduced dose the mean hemoglobin decrease is 0.8 gm/dl although severe hemolysis (decrease of 8 gm/dl) has been reported.5 RhIg-IV cannot be given by the intramuscular route for treatment of ITP. The primary advantage of RhIg-IV over standard IVIG preparations is its lower cost (approximately 1/10th the cost).

2) Suppression of Rh isoimmunization related to transfusion or pregnancy: Intramuscular RhIg has been successfully used to prevent the development of Rho (D) antibodies for years. However, there are several limitations to use of the IM preparation. Injections are painful and thus limit the ability to provide large doses (multiple vials). The risk of bleeding due to an intramuscular injection may also limit its use in patients with thrombocytopenia or a coagulopathy. RhIg-IV provides an intravenous alternative for these situations.

The dosage is similar to that of intramuscular RhIg preparations. In Rh negative unsensitized women, a 1,500 IU (300mg) dose is administered at 28 weeks gestation, after amniocentesis before 34 weeks gestation, after chorionic villus sampling, and for threatened abortion. A 1500 IU (300mg) dose is recommended within 72 hours of delivery of an Rho(D) positive baby to an unsensitized Rho(D) negative mother, but may be of benefit up to 28 days after delivery. The dose can also be employed following abortion or amniocentesis after 34 weeks gestation. If a sensitizing event occurs early in pregnancy, the initial dose should be repeated every 12 weeks during the pregnancy.1

For transfusion related sensitization, treatment is recommended for Rh-negative children and women of childbearing age who received Rh-positive red cell containing components (i.e. red cells, platelets, or granulocytes). One 1,500 IU (300mg) vial will neutralize 30 cc of whole blood or 15 cc of red cells, and should be administered I.M. or I.V. within 72 hours of the transfusion. A 600 IU (120mg) dose will neutralize 12 cc of whole blood or 6 cc of red cells. An 8-pool of Rh-positive platelets contains approximately 4 ml of red cells (0.5 ml RBC/unit) and would be neutralized by a single dose of 600 IU (120 m g).

 

Mechanism of Action

The mechanism by which intravenous anti-D globulin works to treat ITP is not entirely clear. It appears to involve the binding of the Fc portion of the red cell bound anti-D antibody by splenic macrophages and competitive inhibition of the phagocytosis of lgG sensitized platelets. RhIg is felt to prevent Rho (D) isoimmunization by mediating rapid clearance of D positive red cells before primary sensitization of the immune system to the D antigen can occur.

 

Adverse Reactions

The side effects of intravenous anti-Rho(D) globulin preparations are rare and are otherwise similar to those of IVIG: headache, chills, and fever. The product does contain trace amounts of IgA and this must be considered in the treatment of IgA deficient patients at risk for anaphylaxis.

 

Ordering RhIg-IV

This product is stocked by The Institute For Transfusion Medicine, Centralized Transfusion Service, and can be supplied, with medical approval by calling (412)456-1866.

 

References

  1. Win Rho SD package insert. Manufactured by Rh Pharmaceuticals, Winnipeg, Canada, 1995.

  2. Bussel, J.B., et al. (1991). Intravenous anti-D treatment of immune thrombocytopenic purpura: Analysis of efficacy, toxicity, and mechanism of effect. Blood, 77:9:1884-1893.

  3. Blanchette, V. et al. (1994). Randomised trial of intravenous immunoglobulin G, intravenous anti-D, and oral prednisone in childhood acute immune thrombocytopenic purpura. Lancet, 344:703-707.

  4. Andrew, M. et al. (1992). A multicenter study of the treatment of childhood chronic idiopathic thrombocytopenic purpura with anti-D. J. Pediatrics, 120:522-527.

  5. Barbolla, L. et al. (1993). Severe immune hemolytic anaemia caused by intravenous immunoglobulin anti-D in the treatment of autoimmune thrombocytopenia. Vox Sang., 64:184-185.

 

Copies of the Transfusion Medicine Update can be obtained by contacting
Deborah Small at (412) 209-7320