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Rho(D) immune globulin

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"Anti-D" redirects here. For the song by alternative-pop group, The Wombats, see Anti-D (song).
Rho(D) immune globulin
Clinical data
Trade namesRhoGAM, others
Pregnancy
category
  • C
Routes of
administration		intramuscular injection
ATC code
Legal status
Legal status
Identifiers
ChemSpider
  • none
  (verify)

Rho(D) immune globulin or Rh0(D) immune globulin (letter o and digit zero are both widely attested; more at Rh blood group system - Rh nomenclature) is a medicine given by intramuscular injection that is used to prevent the immunological condition known as Rh disease (or hemolytic disease of newborn). It is sold under various brand names. The medicine is a solution of IgG anti-D (anti-RhD) antibodies that take out any fetal RhD-positive erythrocytes which have entered the maternal blood stream from fetal circulation, before the maternal immune system can react to them, thus preventing maternal sensitization.[2] In a Rhesus-negative mother, Rho(D) immune globulin can prevent temporary sensitization of the maternal immune system to Rh D antigens, which can cause rhesus disease in the current or in subsequent pregnancies. With the widespread use of Rho(D) immune globulin, Rh disease of the fetus and newborn has almost disappeared. The risk that a D-negative mother can be alloimmunized by a D-positive fetus can be reduced from approximately 16% to less than 0.1% by the appropriate administration of RhIG.[3][4][5]

Rho(D) immune globulin is composed of IgG antibodies and therefore is able to cross the placenta. In rare cases this can cause a baby to have a weakly positive DAT (direct antiglobulin test) due to sensitization of fetal cells from mothers who have received multiple doses of Rho(D) Immune Globulin. However, no treatment is necessary as the clinical course is benign.[6] It is on the World Health Organization's List of Essential Medicines, a list of the most important medication needed in a basic health system.[7]

Medical uses

In a pregnancy where the mother is D-negative and the father is D-positive, there is a 50%-100% chance, depending on whether the father is heterozygous or homozygous for RhD, that the fetus will be D-positive and the mother is therefore at risk for D alloimmunization. These women are candidates for RhIG prophylaxis.

The medication has an FDA Pregnancy Category C. It is given by intramuscular injection as part of modern routine antenatal care at about 28 weeks of pregnancy, as recommended by the American College of Obstetricians and Gynecologists (ACOG).[8] The '28 weeks' recommendation comes from the fact that 92% of women who develop an anti-D during pregnancy do so at or after 28 weeks gestation.[9][10][11]

RhIG is recommended in the UK after antenatal pathological events that are likely to cause a feto-maternal hemorrhage.[12] Applicable 'pathologic events' include accidents which may induce fetomaternal hemorrhage (motor vehicle accidents, falls, abdominal trauma), following obstetric/gynecologic procedures during pregnancy, and at the time of threatened- or spontaneous-/elective abortions, regardless of gestational age.

There is not good evidence that the use of Rho(D) immune globulin after a spontaneous miscarriage is needed and a Cochrane review recommends that local practices be followed.[13]

Postpartum administration

A D-negative mother who is not alloimmunized to D should also receive an appropriate dose of RhIG after delivery of a D-positive infant. After delivery, a cord blood sample from infants born to D-negative mothers should be tested for the D antigen. If the neonate is D-negative, no further RhIG is needed. However, if the infant is D-positive, the mother should have a postpartum blood sample screened for fetomaternal hemorrhage in order to determine the appropriate dosage of RhIG to be administered. (the presence of residual anti-D from antepartum RhIG administration does NOT indicate ongoing protection from alloimmunization- repeat administration of RhIG is necessary).

The rosette test is a sensitive method to detect fetomaternal hemorrhage of 10 cc or more. A rosette test will be positive if fetal D-positive cells are present in the maternal sample, indicating a significantly large fetomaternal hemorrhage has occurred. A rosette test may be falsely positive if the mother is positive for the weak D phenotype and falsely negative if the neonate is weak D. If the rosette test is negative, then a dose of 300 micrograms of RhIG is given (sufficient to prevent alloimmunization after delivery in 99% of cases).[14][15] The RhIG dose suppresses by up to 30 cc of whole blood.

If a fetomaternal hemorrhage in excess of 30 cc has occurred, additional testing is mandatory in order to determine the appropriate dosage of RhIG to prevent alloimmunization. A positive rosette test should be followed by a quantitative test such as the Kleihauer-Betke test (acid/elution) or an alternative approach such as flow cytometry. See article on Kleihauer-Betke test for details on how the volume of fetomaternal hemorrhage is calculated.

The dosage of RhIG is calculated from the volume of fetal hemorrhage (in mL). Ex: 50 mL fetal hemorrhage / 30 ml = 1.667 (round up to 2) then add 1 = 3 vials of RhIG.

Postpartum RhIG should be administered within 72 hours of delivery. If prophylaxis is delayed, the likelihood that alloimmunization will be prevented is decreased. However, ACOG still recommends that RhIG be administered because partial protection still occurs.[16][17] If the D-type of a newborn or stillborn is unknown or cannot be determined, RhIG should be administered.

Immune thrombocytopenia

Primary Immune Thrombocytopenia (ITP) is an acquired immune mediated disorder characterized by isolated thrombocytopenia, defined as a peripheral blood platelet count less than 100 x 109/L, and the absence of any obvious initiating and/or underlying cause of the thrombocytopenia. Symptoms of ITP include abnormal bleeding and bruising due to the reduction in platelet count.[18] Rho(D) Immune Globulin Intravenous [Human; Anti-D] is indicated for use in non-splenectomized, Rho(D)-positive children with chronic or acute ITP, adults with chronic ITP, and children and adults with ITP secondary to HIV infection. Anti-D must be administered via the intravenous route when used in clinical situations requiring an increase in platelet count. The mechanism of action of anti-D is not fully understood however, after administration the anti-D coated red blood cell complexes saturate Fcγ receptors sites on macrophages, resulting in preferential destruction of red blood cells (RBCs), therefore sparing antibody-coated platelets.[19] Anti-D is recommended as a first-line therapy for ITP, along with corticosteroids and intravenous immune globulin (IVIG).[20][21] WinRho SDF is an anti-D manufactured, distributed and marketed by Cangene Corporation in the US.

Contraindications

The following females are NOT candidates for RhIG:

  • D-negative females whose fetus is known to be D-negative
  • D-negative females who have been previously alloimmunized to D (they have an anti-D antibody)
  • Any D-positive females (women who test positive for the weak D phenotype should be considered D-positive and not receive RhIG).

History

The first Rho(D) immune globulin treatment "skymed" was introduced by Ortho-Clinical Diagnostics, a subsidiary holding of Jskymed, and was first administered on May 29, 1968 to Marianne Cummins in Teaneck, NJ.[22]

In 1996 ZLB Bioplasma (part of CSL Behring) was given approval to sell Rhophylac in Europe, and in 2004 Rhophylac was approved in the United States.[23]

Manufacturing and safety

Rho(D) immune globulin is a derivative of human plasma. The most common way anti-D products are manufactured is by a form of the Cohn cold ethanol fractionation method developed in the 1950s. Variations of the Cohn method developed in the 1950s may not completely clear aggregates of immunoglobulins, which can cause problems for patients if administered intravenously, and is a primary reason why most anti-Ds are for intramuscular use only. A non-Cohn manufacturing variation is ChromaPlus process approved by the U.S. Food and Drug Administration (FDA) that is used to make Rhophylac.[24] Rho(D) immune globulin may trigger an allergic reaction. Steps are taken in the plasma-donor screening process and the manufacturing process to eliminate bacterial and viral contamination, although a small, residual risk may remain for contamination with small viruses. There is also a theoretical possibility of transmission of the prion responsible for Creutzfeldt-Jakob disease, or of other, unknown infectious agents.[25]

Routes of administration

RhIG can be administered either by either intramuscular (IM) or intravenous (IV) injection, depending on the preparation. The IM-only preparation should never be administered IV due to the risk of complement system activation. Multiple IM doses should be given at different sites or at different times within the 72-hour window. Or, multiple IV doses can be administered according to the instructions in the package insert.

Commercialization

Rhophylac is manufactured by CSL Limited. RhoGAM and MICRhoGam are brand names of Johnson & Johnson. Other brand names are BayRHo-D, Gamulin Rh, HypRho-D Mini-Dose, Mini-Gamulin Rh, Partobulin SDF (Baxter), Rhesonativ (Octapharma), and RhesuGam (NBI). KamRho-DI.M.are brand name of kamada Ltd.

The United States distribution rights for WinRho SDF (another brand name) were transferred from Baxter to the manufacturer, Cangene, in 2010; they had been held by Baxter since 2005.[26] Sales of WinRho fell every year under the agreement with Baxter, the supposition being that Baxter was favoring the sale of its own product over WinRho; according to one analyst, "WinRho was always an afterthought for a big company like Baxter."[27]

See also

References

  1. ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 Oct 2023.
  2. ^ Lehne, Richard. Pharmacology for Nursing Care. Saunders and Elsevier, St. Louis. Seventh Edition. p. 819
  3. ^ Roback et al. AABB Technical Manual, 16th Ed. Bethesda, AABB Press, 2008.
  4. ^ Bowman JM (1988). "The Prevention of Rh Immunization". Transfus Med Rev. 2: 129–50.
  5. ^ Bowman JM (1985). "Controversies in Rh Prophylaxis. Who Needs Rh Immune Globulin and When Should it be Given?". Am J Obstet Gynecol. 151: 289–94.
  6. ^ Rudmann, Sally V. 2005. "Textbook of Blood Banking and Transfusion Medicine 2nd Edition." ELSEVIER Saunders. pp 439-441
  7. ^ "WHO Model List of EssentialMedicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014.
  8. ^ "Pregnancy - routine anti-D prophylaxis for RhD-negative women". National Institute for Health and Clinical Excellence. May 2002.
  9. ^ Roback et al. AABB Technical Manual, 16th Ed. Bethesda, AABB Press, 2008.
  10. ^ Bowman JM (1988). "The Prevention of Rh Immunization". Transfus Med Rev. 2: 129–50.
  11. ^ Prevention of Rh D Alloimmunization. ACOG Practice Bulletin Number 4. Washington, DC: American College of Obstetricians and Gynecologists, 1999.
  12. ^ "Use of Anti-D Immunoglobulin for Rh Prophylaxis". Royal College of Obstetricians and Gynaecologists. May 2002.
  13. ^ Karanth, L; Jaafar, SH; Kanagasabai, S; Nair, NS; Barua, A (Mar 28, 2013). "Anti-D administration after spontaneous miscarriage for preventing Rhesus alloimmunisation". The Cochrane database of systematic reviews. 3: CD009617. doi:10.1002/14651858.CD009617.pub2. PMID 23543581.
  14. ^ Roback et al. AABB Technical Manual, 16th Ed. Bethesda, AABB Press, 2008.
  15. ^ Klein Hg and Anstee DJ. Haemolytic Disease of the Fetus and Newborn. In: Mollison's Blood Transfusion in Clinical Medicine. 11th Ed. Oxford: Blackwell, 2005: 496-545.
  16. ^ Roback et al. AABB Technical Manual, 16th Ed. Bethesda, AABB Press, 2008.
  17. ^ Prevention of Rh D Alloimmunization. ACOG Practice Bulletin Number 4. Washington, DC: American College of Obstetricians and Gynecologists, 1999.
  18. ^ Provan D, Stasi R, Newland AC, et al. (2010). "International consensus report on the investigation and management of primary immune thrombocytopenia". Blood. 115 (2): 168–186. doi:10.1182/blood-2009-06-225565. PMID 19846889.
  19. ^ Winrho SDF current prescribing information. Available: www.winrho.com.
  20. ^ Provan D, Stasi R, Newland AC, et al. (2010). "International consensus report on the investigation and management of primary immune thrombocytopenia". Blood. 115: 168–186. doi:10.1182/blood-2009-06-225565. PMID 19846889.
  21. ^ Neunert C, Lim W, Crowther M, et al. (2011). "The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia" (PDF). Blood. 117 (16): 4190–4207. doi:10.1182/blood-2010-08-302984. PMID 21325604.
  22. ^ RhoGAM product label, includes clinical trial data and prescribing information
  23. ^ History of HDN Treatment
  24. ^ ChromaPlus Manufacturing Process
  25. ^ RhoGAM Ultra-Filtered PLUS Rho(D) Immune Globulin (Human) Information Site
  26. ^ Staff (5 May 2010). "Cangene assumes U.S. commercialization rights for WinRho SDF". Biotech Week. United States – via HighBeam Research.
  27. ^ Cash, Martin (16 June 2010). "Cangene Corp. begins transformation project". Winnipeg Free Press – via HighBeam Research.
  • Friesen A.D., Bowman J.M., Price H.W. (1981). "Column Ion Exchange Preparation and Characterization of an Rh Immune Globulin (WinRho) for Intravenous Use". J. Appl. Biochem. 3: 164–175.{{cite journal}}: CS1 maint: multiple names: authors list (link)
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