Hemolytic Disease of Newborn (HDN)

Hemolytic Disease of the Newborn (HDN)

• Erythroblastosis fetalis is another name
• Red cell destruction during fetal life defines this isoimmune condition
• Fetomaternal blood group incompatibility causes it
• Fetal red blood cells become coated with IgG alloantibody of maternal origin
• The IgG alloantibody targets an antigen from the father, present on fetal cells but absent in the mother

Conditions for HDN to Occur:

• The mother must be exposed to a red cell antigen she lacks through transfusion or pregnancy.
• Antigenic exposure must result in antibody production
• Antibodies must cross the placenta
• Sufficient antibodies must be present
• The infant must have an antigen corresponding to the maternal antibody

Clinical Manifestations of HDN:

• Anemia
• Jaundice
• Enlargement of the liver
• Enlargement of the spleen
• Generalized edema, otherwise known as hydrops fetalis

Categories of HDN:

• ABO incompatibility causes this in 1 in 150 births
• More common in type A or B babies of type O mothers
• Caused by poor development/reduced numbers of A and B antigen sites on fetal RBCs
• Rh-HDN

Prevention of Rh-HDN:

• Administering Rh Immunoglobulin prevents sensitization of Rh- mothers with Rh+ children
• Trade name: Rhogam
• Contains concentrated, purified anti-D gamma globulin
• Available in 300ug doses that neutralize 30mL of Rh+ blood for pregnancies beyond the first trimester
• Administer to Rh and Du negative mothers with a negative antibody screen for anti-D, and Rh positive babies

Prevention of HDN:

• Do not administer Rhogam if anti-D is already present in the mother
• Routinely administer Rhogam twice to the mother: in the third trimester (around 28 weeks) and within 72 hours of an Rh+ child's birth

Fetomaternal Hemorrhage:

• May occur before or during delivery
• Could lead to >320 mL of fetal blood entering maternal circulation

Tests for HDN:

• Fetal screen rosette method
• Add a mother's blood smear to a buffer (acidic pH)
• The mother's red blood cells burst, but the fetal red blood cells don't (resistant to acidic pH and fetal hemoglobin, or HbF)
• Mother cells look like pale ghosts, while fetal cells are dark pink
• Calculate % fetal RBCs = (number of fetal RBCs / 2,000) x 100

Kleihauer Acid Elution:

• Determines the volume of feto-maternal hemorrhage
• Determines the number of vials/dosage of Rh Ig to give
• First compute the volume of feto-maternal blood
• The formula is Volume of fetomaternal blood = % fetal RBC x 50
• Number of Rh Ig vials = volume of fetomaternal blood/30

Amniocentesis:

• Ultrasound of the mother is required
• Assesses the severity of HDN in utero
• A needle punctures the maternal abdominal wall and maternal intrauterine wall
• Aspirate amniotic fluid for bilirubin determination
• AOG occurs from 27-40 weeks, or 14 weeks
• Amniotic fluid's spectrophotometry is tested in increasing wavelengths from 350-700 nm
• Measurement is plotted on the Liley graph at 450 nm, the wavelength of bilirubin

Zones of the Liley Graph:

• Zone 3 indicates severe HDFN or fetal death
• Zone 2 indicates moderate disease, necessitates repeat determination to establish a trend
• Zone 1 indicates mild or no disease

Decision-making Based on Amniotic analysis:

• Allow pregnancy to continue or perform intrauterine transfusion or induce early labor
• Fetal Lung Maturity (FLM) prevents Respiratory Distress Syndrome (RDS)
• An L/S ratio > 2:1 generally suggests fetal lung maturity

Intrauterine Transfusion:

• Packed red blood cells are injected/infused through the fetal abdominal wall into the peritoneum
• Corrects severe anemia, prevents death in utero when risk of early delivery is high

Percutaneous Umbilical Blood Sampling/Cordocentesis:

• Also known as PUBS
• Allows cord blood diagnosis through fetal blood aspiration and direct therapy
• Cordocentesis advantages: direct transfusion to fetal circulation, antigen typing, measurement of Hb/Hct/blood type, direct AHG test

Exchange Transfusion:

• Blood should be less than 7 days old, Group O, Rh negative, compatible with mother, CMV (-), gamma irradiated, without Hb S.

Phototherapy:

• Exposure to UV light destroys excess bilirubin and avoids exchange transfusion need
• Collect and store blood sample for bilirubin determination away from direct light

Rh Immune Globulin (RHOGAM) Application:

• Given to pregnant women to produce Anti-D when exposed to D+ RBCs
• Prevents immunization to the D antigen when using high-titer RhIg
• During pregnancy/delivery, fetal and maternal blood mix
• Up to 9% chance of forming Anti-D if Rh-negative mother carries Rh-positive fetus
• Sensitization risk is 1.5-1.9% before delivery, indicating fetal RBC entry to maternal circulation
• Greatest immunization risk is at delivery

Dosage Availability:

• Mini/Microdose Rhogam contains 50 ug Anti-D
• Protects 5ml D+ WB or 2.5 ml D+ RBCs
• Indicated in first 12 weeks pregnancies that are Rh negative, for abortions/ectopic pregnancies
• Full Dose Rhogam contains 300 ug Anti-D
• Protects up to 30ml WB or 15ml RBCs
• Indicated after first 12 weeks, Rh negative, for abortions/ectopic pregnancies
• 120 ug dose Rhogam is advised after week 34 when amniocentesis is performed
• Antepartum dose is 300 ug Anti-D IM or IV
• Postpartum dose requires blood sample screening to test for fetomaternal hemorrhage, FMH

Rh Immune Globulin (RHOGAM) Application

• If negative, the mother gets a full dose of RhIG within 72 hours of deliver
• Additionally, if the newborn is D-positive, give the mother a full dose of RhIg

Categories of Donors:

• Voluntary, Family or Replacement, Paid or Professional/Commercial

Voluntary Donors:

• Receive nothing in return (any form of payment)
• Lower incidence and prevalence of transfusion transmissible Infections.
• Absence of risk of anemia on the part of the donors through depletion of their iron source.
• Donors are more willing to donate blood more regularly.
• Donors express a commitment to donate blood during emergencies

Family Donors:

• Required to give blood when a family member requires it

Paid Donors:

• Give blood, receive money
• High incidence and prevalence of transfusion transmissible infections
• Often undernourished and of poor health

Standard Screening Procedures:

• Registration, Medical History Questionnaire, Physical Examination, Blood Unit Collection, Post-donation instructions

3 Categories of Donors:

• Voluntary/ Non-enumerated, Family/ Replacement, Paid/ Professional/ Commercial

Physical Examination:

• General Appearance
• Weight should be at least 10.5ml/kg of donor’s weight, inclusive of the weight of the pilot tube
• If donor weight is less than 110 lbs, blood collection must be reduced proportionately, as well as the anticoagulant.

Amount of Blood to be Drawn:

• Uses donor’s weight to determine
• Donor's weight (lb) X 450 mL / 110 lb = Allowable amount (mL)

Medical History:

• All blood units must be tested and processed before releasing
  • ABO/Rh grouping
  • Antibody screen, especially with previous pregnancies and transfusions
  • Serologic test for syphilis
  • HBsAg, Anti-HCV, Anti-HIV1/2, Anti-HTLV I/II, HIV 1&2, p24 Ag, Malaria*

ABO/Rh Grouping of Blood:

• Test the donor blood to establish its ABO/Rh group

Amount of Anticoagulant:

• Uses to determine how much anticoagulant is needed and to remove
• Allowable amount / 100 X 14 = Anticoagulant needed
• 63mL - anticoagulant (mL) = Anticoagulant to be removed

Temperature:

• Donor temperature must be 37.5°C or 99.5°F

Types of Crossmatching:

• Immediate spin Crossmatch:
  • "Type and Screen", Detects ABO incompatibility, PSDR

AHG Test:

• If the AGH result is positive, cross out the antigens that are negative.

Cold storage procedure:

• Uses current additives to preserve blood for longer such as refrigeration
• Add chemical to preserve blood by stopping it from binding and clotting

Hemolytic Disease of the Newborn (HDN) is an isoimmune condition characterized by the destruction of red cells. It results from blood group incompatibility between mother and fetus. Maternal IgG antibodies target paternal antigens on fetal red blood cells, leading to anemia and jaundice.