The most frequent is:
Immunization to the Rhesus (D) Antigen i.e.: when the Rhesus (D) negative mother becomes sensitized to Rhesus (D) positive red cells either by feto-maternal hemorrhage or previous transfusion. Only IgG-type and not IgM-type antibodies may cross the placenta and cause erythroblastosis of the fetus and hemolytic disease in the newborn (HDN).
The Rhesus antigen recognized on the red cell membrane includes D, C, c, E, e (there is no "d" antigen).
Causes:
- Failure of administration of anti-D prophylaxis300 mcg (or 1500 IU) that neutralize 30 ml Rh-positive fetal blood, equivalent to 15 ml of fetal red blood cells. ~ 99,2-99,3 of women have fetomaternal haemorhage less than 4 ml and 0,3% > 15 ml.
- Antenatal sensitization: The risk is 1-2% at the time of delivery in primaparas not treated in pregnancy before delivery while a total 8% will be immunized by 6 months postpartum.. Overall, approximately 16% of Rhesus D negative women become allo-immunized after two deliveries of Rhesus D positive ABO compatible infants. These risks can be reduced to 1-2% if a single dose of immunoglobulin is given after delivery and can be further reduced to 0.1% with addition of routine antenatal administration in the third trimester.
- Several red cells antigens can cause sensitization and erythroblastosis especially anti-K, anti-E, and anti-c (see table) with a prevalence of 0.3 in Rhesus positive woman.
Screening:
All pregnant women should be "typed and screened", the blood group determined, tested for Rhesus type and have an antibody screen (indirect Coombs' Test).
Fetal rhesus determinated if the paternal pheno type is heterozygotic amniocentese for determination of fetal blood type (CPCR).
Prophylaxis:
Rhesus immunoglobulin (Rhogam) should be given to all Rhesus negative mothers in case there are no antibodies and the infant is Rhesus positive or the type is unknown in the following situations:
- After delivery: Cord blood for type and direct Coombs' Test. 300 mg or 1500 IU anti D = Rhogam within 72 hours after delivery. If this time exceeded, Rhogam should still be given as it seems effective even up to 14 days.
If delivery occurs less than 3 weeks from the administration of Rhogam (see below) repeat dose is not required at delivery unless a large fetal hemorrhage is detected.
The half life of immunoglobulin is approximately 24 days, therefore 15-20% of women who is receiving immunoglobulin of 28 weeks would have a very low titer (£ 1:4) at term.
- Before 12 weeks of gestation, some centers give 50 mg (250 units), in case of abortion, CVS, ectopic pregnancy.
- After 12 weeks 300 mg (1500 units) in case of abortions, utero-invasive procedures (like amniocentesis, CVS, blood sampling, and fetal bladder drainage), external cephalic version, abdominal trauma in case of suspicion of extent feto maternal bleeding perform, Kleihaur test to quantify the volume of fetal hemorrhage. - 10 mg Rhogam neutralize 1 ml fetal blood.
Antibody Screen Positive Patients:
Antibody titer in saline is a measurement of IgM and albumin titer reflects IgM and IgG.
- If antibody to an RBC antigen known to cause isoimmunization is identified on the Indirect Coombs' screening test, an antibody titer is determined. The father of the pregnancy should be tested for the relevant red cell antigen and if positive, tested to determine if he is homo- hetero-zygous for the antigen. If the heterozygous/ homozygous the fetal blood group can be detected by amniocentesis, CVS or cordocentesis.
- If the Coombs' titer of an Rh antibody (or other antibody) is less than 1:16 (and this the FIRST pregnancy in which a positive titer is identified) and remains so on checks every 2-4 weeks, the patient can safely be allowed to continue the pregnancy until term when induction of labor may be indicated.
- If the titer is > 1:16 (Anti-Kell > 1:8) or if this is a subsequent (second, third, etc.) pregnancy where a positive Rh titer is noted, a more aggressive management (percutaneous umbilical blood sampling (PUBS), amniotic fluid analysis) is recommended, with intensive perinatal care throughout the pregnancy, labor/delivery and the neonatal period.
- A mother who has had a previous stillborn or hydropic infant due to Rh-isoimmunization has approximately a 90% risk of losing the next Rh positive fetus unless she receives meticulous prenatal care, regardless of the antibody titer.
Noninvasive Fetal Testing: Every 3-4 weeks
Cardiotocography (CTG) --
Sinusoidal pattern, a sign of severe anemia
Serial sonography:
- Polyhydramnios
- An increase in the size of the liver and the spleen are good predictors of anemia.
- Measurement of peak velocity of systolic blood Doppler flow in the fetal middle cerebral artery has a sensitivity of 100% and a false positive rate 12% for the detection of moderate or severe anemia. Values below 50 percentile seems to rule out anemia.
- Hydrops is a late sign of erythroblastosis.
Invasive Fetal Testing:
For fetuses at high risk of severe anemia, amniocentesis should be performed between 16-20 weeks to detect blood cell type (DNA analysis) and amniotic fluid bilirubin levels quantified by measuring the optical density by spectrometric examination. If positive, the result should be plotted in the modified Liley graph. Has been replaced by monitoring of MCA Doppler in many departments.
Zone I:
Reassuring although neonatal exchange transfusion maybe necessary, repeat amnio every 3-4 weeks. Patient with results in Zone 1 can be allowed to proceed to term.
Zone II:
Fetus may be affected, repeat amnio every 1-3 weeks. Declining values are encouraging although they do not exclude mild hemolytic disease. Stable or rising DOD measurements are a cause for concern, fetal blood sampling is indicated.
In case of declining results in the low mid zone patient can be allowed to go to 38-39 weeks.
Zone III:
Suggests severe hemolytic disease with high probability of fetal death within 7-20 days. Fetal blood sampling and transfusion is indicated.
Care should be taken to shield the amniotic fluid from light since this will falsely lower the delta OD 450. Decreases in the amniotic fluid optical density may also result from maternal corticosteroid administration.
Minor Red Blood Cell Antibodies Associated with Hemolytic Disease of the Newborn1
Blood System |
Specific Antigens |
Severity of hemolytic diseasesof the newborn (HDN) |
Kell |
K |
Mild to severe |
|
K |
Mild |
|
Kp(a) Mild |
Mild |
|
Kp(b)
|
Mild |
|
Js(a)
|
Mild |
|
Js(b) |
Mild |
Duffy |
Fy(a) |
Mild to severe |
|
Fy(3) |
Mild |
Kidd |
Jk(a) |
Mild to severe |
|
Jk(b) |
Mild to severe |
|
Jk(3) |
Mild |
Lewis |
Y |
Not a cause of HDN |
|
Fy(b) |
Not a cause of HDN |
|
P1 |
Not a cause of HDN |
MNSs |
M |
Mild to severe |
|
N |
Mild |
|
S |
Mild to severe |
|
S |
Mild to severe |
|
U |
Mild to severe |
|
Mi(a) |
Moderate |
|
Mf(a) |
Moderate |
|
Vw |
Mild |
|
Mur |
Mild |
|
Hil
|
Mild |
|
Hut |
Mild |
Lutheran |
Lut(a) |
Mild |
|
Lut(b) |
Mild |
Diego |
Di(a) |
Mild to severe |
|
Di(b) |
Mild to severe |
Xg |
Xg(a) |
Mild |
P |
PP1(k) |
Mild to severe |
|
P1 |
Not a cause of HDN |
|
|
|
1 Adapted from Weinstein, L. Clin Obstet Gynecol 1982;25:327 and Reid, ME, Toy, PTCY. in Hematology and Infancy and Children, 5th ed, Nathan, DG, Drkin, SH (Eds)m WBH Saunders, Philadelphia, 1998, p. 1768.
Reference:
(1) Cranethr C. Royal College of Obstericians and Gynecologist. Use of anti-D immuniglobolin for RH prophylacse (22) revised May 2002
(2) David W. Cohen, MA, MT (ASCP) SBB. Hemolytic disease of the newborn: RBC alloantibodies in pregnancy and associated serologic issues.
(3) www.uptodate.com 2007
Se evt. also
Crowther C, Middleton P. Anti-D administration after childbirth for preventing Rhesus alloimmunisation. 1: Cochrane Database Syst Rev. 2000;(2):CD000021
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