Rhesus D Immunoglobulin

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Rhesus (D) Immunoglobulin
Annmarie Bosco Haematology Advanced
Trainee SEALS, Prince of Wales Hospital
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• I was very upset upon seeing my doctor ... It
  was only the first time I have seen him, and I am
  not very happy. He was checking my blood test
  results and said"You are AB- blood type. We
  will give you a shot at 28 weeks and after bub is
  born".And that was all he said. No
  explanation..., he didn't even ask what DH blood
  type was.I went home and did some research of
  my own on the net ...not too impressed to find
  out it contains blood fractions and the stuff
  they used to make - ... used to contain mercury
  and can harm bub if given while pregnant.Do
  doctors think us patients are dumb and don't /
  wont question what they give us.Oh, and does
  anyone know anything about eating lots of oranges
  (the white part particularly) and capsicum during
  pregnancy to avoid shot if you are Rh-??? Someone
  told me their mum did that and had 4 perfectly
  fine children???

From BubHub Online Forum
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Overview

• Pathophysiology of D-related HDFN
• Anti-D
• Current guidelines
• Controversial issues

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Genetics

• D antigen encoded by the RHD gene on chromosome 1
• Major phenotypes D and D-
• D
• 82 - 88 Caucasians
• 97 99 Asians
• Highly immunogenic antigen
• 1 of D- mums with D fetus are immunised by end
  of 1st pregnancy

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Outcomes

• Sensitising pregnancy unaffected
• Subsequent pregnancies
• Haemolysis of fetal RBC
• Fetal anaemia
• Tissue hypoxia and acidosis
• Hydrops fetalis
• Death

Image courtesy of Ed Friedlander, Kansas City
University of Medical and Biosciences available
at http//www.pathguy.com/lectures/hydrops.jpg
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Anti-D

• Historic significance
• Mechanism of action
• Coats D RBCs which are then cleared by splenic
  macrophages
• Possibly ? downregulation of B cells or dendritic
  cells
• Needs
• Adequate dose
• To be given in time

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What is Anti-D

• CSL Australian product
• Derived from blood donors who have formed anti-D
  antibodies
• Blood donors are screened tested
• Virally inactivated
• Sterile, preservative-free use immediately after
  opening, then discard
• No mercury
• Slow intramuscular injection in deltoid

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Effects of Anti-D

• Fetal

• Maternal

• Positive DAT
• Concentration in fetus too low to cause haemolysis

• Positive antibody screen
• Local effects of im injection
• Vv rare IgA deficiency ? anaphylaxis
• Potential for transmission of agents that we
  cannot test for or that are yet unknown
• Requires informed consent
• No protection against dvpmt of other antibodies

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Management of D- patient

• Sensitised mothers
• Anti-D is of no benefit
• Cannot switch off immune response once started
• Consult with feto-maternal medicine specialist
• Unsensitised mothers
• 1 prophylaxis
• Post-partum
• Potentially sensitising events

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Dose response relationship

• Protective effect is dose-related
• 100 iu of anti-D will neutralise 1ml of fetal RBC
• Half-life of Anti-D 22-29 days
• Therapeutic concentration gone by 12 weeks post
  administration

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Rationale for prophylactic schedule

• Greatest risk for FMH is in last trimester
  during delivery
• Therefore, the earliest it should be given is 12
  weeks before term
• i.e. at 28 weeks
• Two doses ? higher concentration anti-D at term
• Therefore given at 28 and 34 weeks

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1 prophylaxis

• Group and antibody screen at booking
• Repeat antibody screen at 28/40 PRIOR to anti-D
  dose
• Then give anti-D 28/40, 34/40

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Post-partum

• Check babys blood group
• If D, give anti-D within 72 hours of delivery
• Check volume of FMH via flow cytometry or
  Kleihauer
• Give additional doses as needed

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Potentially sensitising events

• anything that leads to FMH
• normal delivery, ectopic pregnancy, miscarriage,
  termination of pregnancy
• ultrasound needle guided procedures e.g. CVS
  amniocentesis
• abdominal trauma considered sufficient to cause
  FMH
• antepartum haemorrhage, threatened abortion

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Management

• If uncertain gestation that could be more than
  12 weeks give 625 iu
• Routine prophylaxis should still be given at 28
  and 34/40

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!

• Please DOCUMENT date that anti-D was given on
  Group Screen form

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Controversies

• Testing of father prior to prophylaxis
• Dose
• Guidelines vary between countries
• Model of non-intervention
• last pregnancy

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Management of alloimmunisation

• Genotype phenotype father, paternity assurance
• Titres quantification q4weekly then q2weekly
  after 32/40

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Management of alloimmunisation

• Rising titres or absolute gt 116 is indication
  for ? fetal monitoring
• Amniocentesis genotyping
• Free fetal DNA in maternal serum
• MCA doppler ultrasound
• Invasive management FBS, IUT
• Post partum exchange transfusion, phototherapy

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Useful information
http//manual.transfusion.com.au/Pregnancy-and-ant
i-D/Educational-support-materials.aspx
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CSL Website
http//www.csl.com.au/docs/800/383/Fax20Request2
0Sheet_0228.pdf
http//www.csl.com.au/docs/603/830/CT36600198E.pdf
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References

• Background information
• Contreras M. The prevention of Rh hemolytic
  disease of the newborn - general background. BJOG
  1998105, s187-10
• Lee D. Preventing RhD hemolytic disease of the
  newborn. 1998 3161611
• NSW Health Rh D Immunoglobulin Policy Directive
  avail at http//www.health.nsw.gov.au/policies/pd/
  2006/pdf/PD2006_074.pdf accessed 1 Nov 2008
• ARCBS Guidelines for the use of Rh (D)
  Immunoglobulin (Anti-D), available at
  http//manual.transfusion.com.au/Pregnancy-and-Ant
  i-D/
• Anti-D mechanism of action, kinetics
• Kumpel BM. On the immunologic basis of Rh immune
  globulin (anti-D) prophylaxis. Transfusion 2006
  461652-1656
• MacKenzie IZ, Roseman F, Findlay J, Thompson K,
  Jackson E, Scott J, Reed M. The kinetics of
  routine antenatal prophylactic intramuscular
  injections of polyclonal anti-D immunoglobulin.
  BJOG. 2006 Jan113(1)97-101.
• CSL Bioplasma Rh(D) Immunoglobulin VF Product
  Information available at http//www.csl.com.au/do
  cs/603/830/CT36600198E.pdf accessed 1 Nov 2008
• Bichler J, Schöndorfer G, Pabst G, Andresen I.
  Pharmacokinetics of anti-D IgG in pregnant
  RhD-negative women. BJOG. 2003 Jan110(1)39-45.

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References contd

• Serological testing
• de Silva PM, Knight RC. Serological testing
  during pregnancy in women given routine antenatal
  anti-D Ig prophylaxis. Transf Med. 1997
  Dec7(4)323-4.
• Management of alloimmunization
• Moise KJ. Red blood cell alloimmunization in
  pregnancy. Semin Hematol 2005 42169 178
• Controversies
• Jabara S, Barnhart KT. Is Rh immune globulin
  needed in early first-trimester abortion? A
  review. AmJObGyn 2003 188 623-7
• Weinberg L. Use of anti-D immunoglobulin in the
  treatment of threatened miscarriage in the
  accident and emergency department. EmergMed J
  2001 18444-447
• Hannafin B, Lovecchio F, Blackburn P. Do
  Rh-negative women with first trimester
  spontaneous abortions need Rh immune globulin?
  AmJEmergMed 2006 24487-489
• Auguston B, Fong EA, Grey DE, Davies JI, Erber
  WN. Postpartum anti-D can we safely reduce the
  dose? MJA 2006 184 (12) 611-613