Indicated for suppression of rhesus (Rh) isoimmunization in nonsensitized Rho (D)-negative women with an Rh-incompatible pregnancy, or in Rho (D)-negative individuals transfused with Rh0(D)-positive red blood cells (RBCs) or blood components containing Rh0(D)-positive RBCs. Also indicated in Rh0(D)-positive, non-splenectomized adult patients with chronic immune thrombocytopenic purpura (ITP) to raise platelet counts.
15000 international unit (IU) contains sufficient anti-Rho (D) to effectively suppress the immunizing potential of approximately 17mL of Rho (D) (D-positive) red blood cells . Human Rho(D) immune globulin therapy prevents immunization to Rho (D)-positive red blood cells (RBC) by inducing antibody-mediated immunosuppression (AMIS) effectively clearing Rho-positive RBCs by rapidly binding to them. This prevents Rho-negative mothers to produce alloantibodies to paternally inherited RhD antigen expressed on fetal erythrocytes and cause haemolytic diseases of the newborn. Rho immune globulin increase platelet counts and reduce bleeding in Rho-positive patients with ITP by inhibiting autoantibody-mediated platelet clearance.
The mechanism of action of Rho(D) immune globulin therapy is unclear. It is suggested that Rho immune globulin predominantly prevents the antibody response during incompatible pregnancy by accelerating the phagocytosis of RBC's and clearance from the circulation before the recognition by the immune system. IgG-opsonized RBCs may interact with activating IgG receptors (FcγRs) on effector cells and elicit phagocytosis via mononuclear phagocytic system, primarily by macrophages. IgG may also stimulate complement activation on the RBC surface, followed by RBC lysis or complement receptor-mediated phagocytosis but to smaller extent . Rho-specific IgG may inhibit the late stages of B cell activation by being internalized with Rho antigen by B cells, which alters the antigen processing and presentation. In response to the IgG-antigen complex formation, the immune globulin enhances the presentation of specific peptides and proliferation of epitope-specific T cells . Therapeutic efficacy of Rho (D) immune globulin in chronic immune thrombocytopenic purpura (ITP) may be explained by FcR blockade as well as the increase in the platelet count by substituting antibody-coated RBCs for antibodycoated platelets . In vitro studies of cytokine expression in human monocytes and granulocytes exposed to anti-D coated red blood cells have demonstrated enhanced secretion of interleukin 1 receptor antagonist resulting in down-regulation of FcγR mediated phagocytosis. Murine models show that RBC-specific antibodies can increase platelet counts by down-regulating FcγRIIIa on splenic macrophage, which is an opposing effect as predicted in intravenous Rho IgG .
In patients undergoing therapy for Rh isoimmunization suppression, Rho(D) immune globulin titers were detected in all women up to at least 9 weeks following either intravenous or intramuscular administration. Following intravenous administration of a single 1500 IU (300 mcg) dose, peak serum levels of Rh0(D) immune globulin ranged from 62 to 84 ng/mL after first day. The levels ranged from 7 to 46 ng/mL and were achieved between 2 and 7 days following intramuscular injection. The absolute bioavailability achieved following IM administration is 69%.
A single dose of 300ug Rho(D) Immune Globulin through intramuscular injection displays a Vd of 8.59L .
Rho (D) immune globulin is expected to undergo nonspecific catabolism.
Human immune globulin and the fragments can be detected in feces and urine.
The half life is 16 ± 4 days following IV administration and 18 ± 5 days following IM administration.
Mean systemic clearance following IV administration is 0.20 ±0.03 mL/min. Mean apparent clearance following IM administration is 0.29 ± 0.12 mL/min.
Most serious adverse reactions in patients with ITP include intravascular hemolysis, anemia, acute renal insufficiency, and death. In patients treated for Rh isoimmunization suppression, common adverse effects include nausea, dizziness, headache, pain at injection site and malaise. Common adverse effects in patients with ITP include chills, pyrexia, mild extravascular hemolysis and headache.
1. Cangene Corporation. Rho(D) immune globulin intravenous (Human): WinRho® SDF [professional package insert] Winnipeg (MB): Cangene Corporation; 2006.
2. Hong F, Ruiz R, Price H, Griffiths A, Malinoski F, Woloski M. Safety profile of WinRho anti-D. Semin Hematol. 1998;35(Suppl 1):9–13.[PubMed]
3. Tarantino MD, Young G, Bertolone SJ, Kalinyak KA, Shafer FE, Kulkarni R, Weber LC, Davis ML, Lynn H, Nugent DJ Acute ITP Study Group. Single dose of anti-D immune globulin at 75 µg/kg is as effective as intravenous immune globulin at rapidly raising the platelet count in newly diagnosed immune thrombocytopenic purpura in children. J Pediatr. 2006;148:489–494.[PubMed]
4. Bussel J. Treatment of immune thrombocytopenic purpura in adults. Semin Hematol. 2006;43(3 Suppl 5):S3–S10.[PubMed]
5. Scaradavou A, Cunningham-Rundles S, Ho JL, Folman C, Doo H, Bussel JB. Superior effect of intravenous anti-D compared with IV gammaglobulin in the treatment of HIV-thrombocytopenia: results of a small, randomized prospective comparison. Am J Hematol. 2007;82:335–341.[PubMed]
6. 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;89:2689–2700.[PubMed]
7. George JN, Raskob GE, Vesely SK, Moore D, Jr, Lyons RM, Cobos E, Towell BL, Klug P, Guthrie TH. Initial management of immune thrombocytopenic purpura in adults: a randomized controlled trial comparing intermittent anti-D with routine care. Am J Hematol. 2003;74:161–169.[PubMed]
8. Bussel JB, Graziano JN, Kimberly RP, Pahwa S, Aledort LM. Intravenous anti-D treatment of immune thrombocytopenic purpura: analysis of efficacy, toxicity, and mechanism of effect. Blood. 1991;77:1884–1893.[PubMed]
9. Kjaersgaard M, Hasle H. A review of anti-D treatment of childhood idiopathic thrombocytopenic purpura. Pediatr Blood Cancer. 2006;47(5 Suppl):717–720.[PubMed]
10. Blanchette V, Adams M, Wang E, McMillan J, Imbach P, Andrew M, Milner R, Ali K, Barnard D, Bernstein M, Esseltine D, Chan KW, DeVeber B, Israels S, Kobrinsky N, Luke N. Randomised trial of intravenous immunoglobulin G, intravenous anti-D, and oral prednisone in childhood acute immune thrombocytopenic purpura. Lancet. 1994;344:703–707.[PubMed]
11. Freiberg A, Mauger D. Efficacy, safety, and dose response of intravenous anti-D immune globulin (WinRho SDF) for the treatment of idiopathic thrombocytopenic purpura in children. Semin Hematol. 1998;35(1 Suppl 1):23–27.[PubMed]
12. Tarantino MD, Bolton-Maggs PH. Update on the management of immune thrombocytopenic purpura in children. Curr Opin Hematol. 2007;14:526–534.[PubMed]
13. Tarantino MD, Bussel JB, Cines DB, McCrae KR, Gernsheimer T, Liebman HA, Wong WY, Kulkarni R, Grabowski E, McMillan R. A closer look at intravascular hemolysis (IVH) following intravenous anti-D for immune thrombocytopenic purpura (ITP) [letter. Blood. 2007;109:5527.[PubMed]
14. Gaines AR. Acute onset hemoglobinemia and/or hemoglobinuria and sequelae following Rho(D) immune globulin intravenous administration in immune thrombocytopenic purpura patients. Blood. 2000;95:2523–2529.[PubMed]
15. Barbolla L, Nieto S, Llamas P, Moreno C, Contreras M, Lubenko A, Garner S. Severe immune haemolytic anaemia caused by intravenous immunoglobulin anti-D in the treatment of autoimmune thrombocytopenia [letter. Vox Sang. 1993;64:184–185.[PubMed]
16. El Alfy MS, Mokhtar GM, El-Laboudy MA, Khalifa AS. Randomized trial of anti-D immunoglobulin versus low-dose intravenous immunoglobulin in the treatment of childhood chronic idiopathic thrombocytopenic purpura. Acta Haematol. 2006;115:46–52.[PubMed]
17. Gaines AR. Disseminated intravascular coagulation associated with acute hemoglobinemia and/or hemoglobinuria following Rho(D) immune globulin intravenous administration for immune thrombocytopenic purpura. Blood. 2005;106:1532–1537.[PubMed]
18. Ortho Pharmaceuticals. Physician's desk reference. Oradell (NJ): Medical Economics; 1981. Rho(D) immune globulin (Human): RhoGAM™[professional package insert]
19. Friesen AD, Bowman JM, Price HW. Column ion exchange preparation and characterization of an Rh immune globulin (WinRho) for intravenous use. J Appl Biochem. 1981;3:164–175.
20. Bowman JM, Friesen AD, Pollock JM, Taylor WE. WinRho: Rh immune globulin prepared by ion exchange for intravenous use. Can Med Assoc J. 1980;123:1121–1127.[PMC free article][PubMed]
21. Yu X, Wagner FF, Witter B, Flegel WA. Outliers in RhD membrane integration are explained by variant RH haplotypes. Transfusion. 2006;46:1343–1351.[PubMed]
22. Sandler SG, Mallory D, Trimble J, Nance ST. Intravenous anti-D treatment for immune thrombocytopenic purpura [letter. Blood. 1998;91:2624–2625.[PubMed]
23. Klein HG, Anstee DJ. Mollison's blood transfusion in clinical medicine. Malden (MA): Blackwell Publishing Ltd; 2005.
24. Daniels G. Human blood groups. Malden (MA): Blackwell Publishing Ltd; 2002.
25. Sandler SG. Intravenous Rh immune globulin for treating immune thrombocytopenic purpura. Curr Opin Hematol. 2001;8:417–420.[PubMed]
26. Petz LD, Garratty G. Immune hemolytic anemias. Philadelphia (PA): Churchill Livingstone; 2004.
27. Harmening DM. Modern blood banking and transfusion practices. Philadelphia (PA): F.A. Davis; 2005.
28. Davenport RD. Pathophysiology of hemolytic transfusion reactions. Semin Hematol. 2005;42:165–168.[PubMed]
29. Brecher M. Technical manual. Bethesda (MD): American Association of Blood Banks; 2005.
30. Hoffman R, Benz EJ, Shattil SJ, Furie B, Cohen HJ, Silberstein LE, McGlave P. Hematology: basic principles and practice. New York: Churchill Livingstone; 2005.
31. Rushin J, Rumsey DH, Ewing CA, Sandler SG. Detection of multiple passively acquired alloantibodies following infusions of IV Rh immune globulin. Transfusion. 2000;40:551–554.[PubMed]
32. Garratty G. Immune hemolytic anemia—a primer. Semin Hematol. 2005;42:119–121.[PubMed]
33. Josephson CD, Mullis NC, Van Demark C, Hillyer CD. Significant numbers of apheresis-derived group O platelet units have “high-titer” anti-A/A,B: implications for transfusion policy. Transfusion. 2004;44:805–808.[PubMed]
34. Harris SB, Josephson CD, Kost CB, Hillyer CD. Nonfatal intravascular hemolysis in a pediatric patient after transfusion of a platelet unit with high-titer anti-A. Transfusion. 2007;47:1412–1417.[PubMed]
35. Kim DD, Song WC. Membrane complement regulatory proteins. Clin Immunol. 2006;118:127–136.[PubMed]
36. Yazdanbakhsh K. Review: complement receptor 1 therapeutics for prevention of immune hemolysis. Immunohematology. 2005;21:109–118.[PubMed]
37. Garratty G. Do we really understand immune red cell destruction? [slide presentation. 25th Annual Scientific Meeting. Glasgow, Scotland: British Blood Transfusion Society; 2007. Sep 14, [cited 2008 Feb 9]. Available from: http://www.bbts.org.uk/diary/details.cfm?eventId=1268.
38. Griffiths HL, Kumpel BM, Elson CJ, Hadley AG. The functional activity of human monocytes passively acquired with monoclonal anti-D suggests a novel role for Fc gamma RI in the immune destruction of blood cells. Immunology. 1994;83:370–377.[PMC free article][PubMed]
39. Garratty G. Immune hemolytic anemia associated with negative routine serology. Semin Hematol. 2005;42:156–164.[PubMed]
40. Chun NS, Savani B, Seder RH, Taplin ME. Acute renal failure after intravenous anti-D immune globulin in an adult with immune thrombocytopenic purpura. Am J Hematol. 2003;74:276–279.[PubMed]
41. Kees-Folts D, Abt AB, Domen RE, Freiberg AS. Renal failure after anti-D globulin treatment of idiopathic thrombocytopenic purpura. Pediatr Nephrol. 2002;17:91–96.[PubMed]
42. Levendoglu-Tugal O, Jayabose S. Intravenous anti-D immune globulin-induced intravascular hemolysis in Epstein-Barr virus-related thrombocytopenia. J Pediatr Hematol Oncol. 2001;23:460–463.[PubMed]
43. Rewald MD, Francischetti MM. After eight-year-tolerance minimal i.v. anti-D infusions unleash hemolysis in a patient with immune thrombocytopenic purpura (ITP) Transfus Apher Sci. 2004;30:105–110.[PubMed]
44. Olofinboba KA, Greenberg BR. Successful treatment of infectious mononucleosis-associated immune thrombocytopenia with WinRho anti-D immunoglobulin complicated by severe hemolysis [letter. Am J Hematol. 2000;65:178.[PubMed]
45. Parker C. Intravenous Rho[D] immune globulin [human] (WinRho SDF): suspected hemolytic/renal adverse reactions. Can Med Assoc J. 163:881–885.[PubMed]
46. Roberti I, Bagtas J, Reisman L, Murphy S. Severe acute renal failure due to hemoglobinuria after use of WinRho for the treatment of idiopathic thrombocytopenic purpura [letter. Clin Pediatr. 2001;40:61–62.[PubMed]
47. Schwartz J, Spitalnik S, Grima KM. Severe hemolysis following administration of Rh(o)(D) immune globulin in an ITP patient associated with anti-C [letter. Blood. 2006;107:2585.[PubMed]
48. Alioglu B, Avci Z, Ozyurek E, Ozbek N. Anti-D immunoglobulin-induced prolonged intravascular hemolysis and neutropenia. J Pediatr Hematol Oncol. 2007;29:636–639.[PubMed]
49. Behring AG. Rho(D) immune globulin intravenous (human): Rhophylac [professional package insert] Berne, Switzerland: CSL; 2007.
50. Meyer O, Kiesewetter H, Hermsen M, Salama A. Efficacy and safety of anti-D given by subcutaneous injection to patients with autoimmune thrombocytopenia [letter. Eur J Haematol. 2004;73:71–72.[PubMed]