In 1984 Salama and colleagues7 reported a clinical trial that used an IV IgG anti-D to treat ITP (IgG anti-Rho(D), Biotest, Frankfurt, FGR). Three years earlier Bowman et al. 8 had announced the development of WinRhoTM (Cangene, Winnipeg, Canada) an Rh immune globulin for IV use prepared from human plasma by anion-exchange column chromatography to prevent hemolytic disease of the newborn due to D immunization.8
- WinRhoTM was shown to be effective in preventing antenatal and postnatal anti-D stimulation; had the benefit of being given intravenously (a route that causes patients less discomfort and immediately results in high anti-D levels); and had lower levels of contaminating IgA and IgM.8
1. Rh immune globulin (RhIG) is used to prevent anti-D production resulting from pregnancy and transfusion. One use relates to transfusion of platelet concentrates from D-positive donors to Rh negative recipients, especially recipients of child bearing age or younger.
Since platelets do not have D antigens, why is RhIG needed?
It was not until 1995 that WinRho SDTM (manufactured by Cangene, Winnipeg, Canada; distributed by Nabi®, Boca Raton, FL) was licensed in the United States for D prophylaxis (IM or IV) and to treat ITP (IV) in D-positive patients who have not been splenectomized.
- The product was now called WinRho SDTM (SD for solvent detergent inactivation of lipid-enveloped viruses).
- The current product is named WinRho SDFTM (F for nanofiltration, using a 35 nm virus filter to remove non-lipid-enveloped viruses such as hepatitis A and B-19 parvovirus).9
- It remains the only IV RhIG to be licensed to treat ITP in the USA.
- WinRho SDFTM is a sterile, freeze-dried gamma globulin fraction containing IgG anti-D available in 120 µg, 300 µg vials, and 1000 µg vials (600 IU, 500 IU, and 5000 IU, respectively). A 300 µg vial can suppress immunization from approximately 17 mL of D-positive red cells. The product contains approximately 5 µg/mL IgA per 120 µg (600 IU) vial.
The mechanism of action of IV RhIG remains controversial with several proposed immunoregulatory effects.10 The leading hypothesis is that it induces a transient blockade of mononuclear-macrophage Fc receptors by forming complexes of anti-D and autologous D+ red cells, thereby sparing the patient's IgG-coated platelets.11
Efficacy. Since its licensing, hundreds of papers have been published on the efficacy of IV RhIG to treat ITP.
- nbsp;In patients who respond, an increased platelet count is usually observed within 1?3 days, peaking at 7?14 days, and persisting for approximately 30 days.
- The dose and subsequent treatment depends on the patient?s initial response and a myriad of other clinical factors.12
- Typical of the papers with positive results is the large study by Scaradavou et al3 which showed a mean platelet increase of 76,000/µL (76 x 109/L) and an overall response rate of 72%.
Indications for Use and Dosage
The manufacturer9 recommends IV RhIG to treat ITP where platelet counts must be increased to control bleeding, more specifically to treat these non- splenectomized D-positive patients:
- children with chronic or acute ITP
- adults with chronic ITP, and children
- adults with ITP secondary to HIV infection.
Also recommended is
- an initial dose of 50 µg /kg (250 IU/kg) for patients with hemoglobin of at least 10 g/dL (100 g/L)
- for those with hemoglobin levels between 8 and 10 g/dL (80 and 100 g/L), a reduced dose of 25-40 µg /kg (125 to 200 IU/kg) to minimize the risk of increasing the severity of anemia.
Several researchers have used higher off-label doses of 75 µg /kg (375 IU/kg).4
Despite the many studies showing its efficacy and minimal toxicity, the role of RhIG in treating the various clinical categories of ITP is far from clear. 4
- The optimal dose has not been established and more data are needed on its use in prolonged treatment at higher off-label doses, including comparisons to IVIG.4
- Some clinicians believe that IV RhIG is an attractive alternative for long-term medical treatment of patients with ITP.3
- Posttransfusion symptoms are generally mild and the cost is lower than that of comparable IVIG treatment. 3
- For others IV RhIG is indicated only in special circumstances such as a few selected adult patients with life-threatening chronic ITP in whom other treatments fail or are contraindicated.10
WinRho SDFTM should not be given to persons who are D-negative or who have been splenectomized, as it has not been shown to be effective in these patients.
- It is also contraindicated in those who have had an anaphylactic or severe systemic reaction to human globulin.9
- Because it contains trace amounts of IgA, it may cause anaphylactic reactions in individuals who are IgA-deficient.
- Although not contraindicated, IV RhIG should be used with caution in patients with hemoglobins levels less than 8 g/dL (80 g/L). 9