Rho(D) immune globulin

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"Anti-D" redirects here. For the song, see Anti-D (song).
Rho(D) immune globulin
Clinical data
Trade namesWinRho, RhoGAM, others:
Other namesRh0(D) immune globulin, anti-D (Rh0) immunoglobulin, immunoglobulinum humanum anti–D
AHFS/Drugs.comMonograph
Pregnancy
category
  • C
Routes of
administration		Intramuscular injection
ATC code
Legal status
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Identifiers
ChemSpider
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Rho(D) immune globulin (RhIG) is a medication used to prevent

human blood plasma.[3]

Common side effects include

red blood cells.[2] It is believed to work by blocking a person's immune system from recognizing this antigen.[2]

Rho(D) immune globulin came into medical use in the 1960s,

rhesus blood group system.[5]

RhIG is on the World Health Organization's List of Essential Medicines.[6][7]

Medical uses

Prevention of alloimmunization

Alloimmunization: mechanism, timing

Image of a positive Kleihauer–Betke test; the pink smudges are foetal-haemoglobin-containing red blood cells that have entered maternal circulation.

Even in normal pregnancies, a small number of fetal blood cells enters the maternal bloodstream (fetomaternal hemorrhage). If a mother is RhD negative, but the fetus is RhD positive, the mother's immune system may develop an immune response (develops

erythroblastosis fetalis and can be fatal to the fetus.[8]

The RhD status of the fetus is determined by genetic inheritance. In a pregnancy where the mother is RhD negative and the father is RhD positive, the probability of the fetus having RhD positive blood is dependent on whether the father is

heterozygous (i.e., only one RhD allele is present). If the father is homozygous, the fetus will necessarily be RhD positive, as the father will necessarily pass on a RhD positive allele. If the father is heterozygous, there is a 50% chance that the fetus will be RhD positive, as he will randomly pass on either the RhD positive allele or not.[9]
: 130 

Exposure to fetal blood cells that can cause RhD alloimmunization can happen during normal pregnancy and delivery, miscarriage, amniocentesis, cordocentesis, chorionic villus sampling, external cephalic version, trauma.[3][8] 92% of women who develop an anti-D during pregnancy do so at or after 28 weeks gestation.[10][9][11]

In an RhD negative mother, RhIG can temporarily prevent sensitization of the maternal immune system to RhD

newborn has almost disappeared in the developed world. The risk that an RhD negative mother can be alloimmunized by a RhD positive fetus can be reduced from approximately 16% to less than 0.1% by the appropriate administration of RhIG.[10][9][13] In countries without Rh immune globulin (RhIG) protocols, as many as 14% of affected fetuses are stillborn and 50% of live births result in neonatal death or brain injury.[8]

Recommendations for use

The

antenatal care. Despite excellent results, the medication retains an FDA Pregnancy Category C.[citation needed
]

RhIG is recommended in the UK after antenatal pathological events that are likely to cause a feto–maternal hemorrhage. Applicable 'pathologic events' include accidents that 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. RhIG is also recommended after normal delivery, with amounts detailed in the next section.[12]

There is insufficient 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.[15]

Rh 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

direct antiglobulin test (DAT) due to sensitization of fetal cells from mothers who have received multiple doses of RhIG. However, no treatment is necessary as the clinical course is benign.[16]

Following delivery

Widespread use of RhIG started with postpartum administration, as delivery is the main source of significant fetomaternal hemorrhage. 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. (In older recommendations, the Rh status of the infant is only known at delivery from testing of cord blood.)[9] 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.)[12]

The

weak D phenotype and falsely negative if the neonate is weak D. If the mother is positive for the weak D phenotype, the rosette test should not be used; instead, a quantitative test such as the Kleihauer–Betke test or flow cytometry should be utilized. 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).[10][17] The RhIG dose suppresses the immune response to up to 30 cc of whole fetal blood (15 cc of red blood cells). 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 or an alternative approach such as flow cytometry. See the 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.[citation needed
]

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.[10][11] If the D-type of a newborn or stillborn is unknown or cannot be determined, RhIG should be administered.

Immune thrombocytopenia

Primary

platelets.[19] Anti-D is recommended as a first-line therapy for ITP, along with corticosteroids and intravenous immune globulin (IVIG).[18][20] [WinRho SDF is an anti-D manufactured, distributed and marketed by Cangene in the US. There is a black box warning on WinRho SDF due to the risk of potentially fatal intravascular hemolysis when used in the treatment of ITP.[19] Life-threatening anemia, kidney failure, and disseminated intravascular coagulation (DIC) have occurred in people treated with WinRho SDF for ITP.[citation needed
]

Contraindications

The following females are not candidates for 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, New Jersey.[22]

In 1996, ZLB Bioplasma (part of CSL Behring) was given approval to sell Rhophylac in Europe. Effectiveness was demonstrated in a clinical trial in 2003 and in 2004 Rhophylac was approved in the United States.[23]

Society and culture

Manufacturing and safety

Human plasma

Conventional Rho(D) immune globulin is extracted from human blood plasma. Excluding autoimmunity, only people who are themselves Rho(D) negative can make the anti-D antibody. As a result, there is a limited pool of people from which to draw plasma that can contain the desired IgG. Special anti-D donation programs are set up to account for this rarity.[24] Volunteers are given an injection containing the D antigen in order to make their immune system start producing the antibody (alloimmunization) or to boost the amounts. Only men and women who have no ability to become pregnant may apply.[25]

The most common way anti-D products are manufactured is by a form of the

U.S. Food and Drug Administration (FDA) that is used to make Rhophylac.[26] 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.[27]

Cell culture

There has been continual attempts to produce a monoclonal anti-D IgG formulation suitable for replacing the current polyclonal formulation.[28] A monoclonal antibody can be produced without requiring human donors (and associated supply and disease risks) and would be more consistent from batch to batch.[8]

India has approved a monoclonal formulation called Rhoclone (Bharat Serums and Vaccines Ltd.),

CHO cells.[30]

Roledumab and Rozrolimupab are two other formulations that have undergone some clinical trials. The former is a monoclonal IgG. The latter is a recombinant mixture of 25 IgGs.[8]

Routes of administration

RhIG can be administered 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.[citation needed]

Names

Rho(D) immune globulin is also spelled Rh0(D) immune globulin (letter

zero are both widely attested; more at Rh blood group system - Rh nomenclature
).

Rhophylac is manufactured by CSL Limited. RhoGAM and MICRhoGam are brand names of Kedrion Biopharma. Other brand names are BayRHo-D, Gamulin Rh, HypRho-D Mini-Dose, Mini-Gamulin Rh, Partobulin SDF (Baxter), Rhesonativ (Octapharma), and RhesuGam (NBI). KamRho-D I.M. is a 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.[31] 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."[32]

See also

References

  1. FDA
    . Retrieved 22 Oct 2023.
  2. ^ a b c d e f g h i j k "Rho(D) Immune Globulin". Drugs.com. The American Society of Health-System Pharmacists. Archived from the original on 9 January 2017. Retrieved 8 January 2017.
  3. ^
    ISBN 9780857111562
    .
  4. OCLC 968617246
    – via Google Books.
  5. ^ Probyn A (2022-11-01). "A vial of human serum, an ice box and an illegal flight: how an Australian doctor saved millions of babies' lives". ABC News. Retrieved 2022-11-02.
  6. hdl:10665/325771
    . WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  7. hdl:10665/345533
    . WHO/MHP/HPS/EML/2021.02.
  8. ^
    S2CID 26083215
    .
  9. ^
    PMID 2856526
    .
  10. ^
    ISBN 978-1-56395-260-9
    .
  11. ^ a b Prevention of Rh D Alloimmunization. ACOG Practice Bulletin (Report). Washington, DC: American College of Obstetricians and Gynecologists. 1999.
  12. ^ a b c "Use of Anti-D Immunoglobulin for Rh Prophylaxis". Royal College of Obstetricians and Gynaecologists. May 2002. Archived from the original on 2008-12-30.
  13. PMID 2982267
    .
  14. National Institute for Health and Clinical Excellence. May 2002. Archived
    from the original on 2008-08-28.
  15. PMID 23543581
    .
  16. ISBN 9780721603841
    .
  17. ^ Klein H, Anstee DJ (2005). "Haemolytic Disease of the Fetus and Newborn.". Mollison's Blood Transfusion in Clinical Medicine (11th ed.). Oxford: Blackwell. pp. 496–545.
  18. ^
    PMID 19846889
    .
  19. ^ a b "Winrho SDF prescribing information" (PDF). www.winrho.com.
  20. S2CID 12375241
    .
  21. ^
    S2CID 586699
    .
  22. ^ "RhoGAM product label, includes clinical trial data and prescribing information" (PDF). rhogam.com.
  23. ^ "History of HDN Treatment". CSL Behring. Archived from the original on 2008-11-21.
  24. ^ "Anti-D donor Steve Gansberg is just happy to help". Lifeblood.com.au. 9 June 2022.
  25. ^ "Anti-D: Rh-negative Plasma Donation". CSL Plasma.
  26. ^ "ChromaPlus Manufacturing Process". rhophylac.com. Archived from the original on 2008-11-21.
  27. ^ "RhoGAM Ultra-Filtered PLUS Rho(D) Immune Globulin (Human) Information Site". Johnson & Johnson Services, Inc. Archived from the original on 2006-03-11.
  28. PMID 16580863
    .
  29. PMID 31598044
    .
  30. PMID 32489976
    .
  31. ^ Staff (5 May 2010). "Cangene assumes U.S. commercialization rights for WinRho SDF". Biotech Week. United States. Archived from the original on 29 March 2015. Retrieved 28 December 2014.
  32. ^ Cash M (16 June 2010). "Cangene Corp. begins transformation project". Winnipeg Free Press. Archived from the original on 29 March 2015. Retrieved 28 December 2014.

External links

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