the case of the not so mild hdfn - heart of america ... · abo antibodies are primarily igm...
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KATELYN BRIER
The case of the not so mild HDFN
Baby Billie’s Presentation of Complications
� A newborn, Baby “Billie-Rubin”, appears to be having complications after birth� Jaundiced skin
� Low RBC count- 1.66 x 106/uL
� Low Hgb- 7.4 g/dL
� High neonate bilirubin- 18.6 mg/dL
� Respiratory distress
� Possible HDFN is suspected
Hemolytic Disease of the Fetus and Newborn
� Defined as the destruction of fetal and newborn red cells by maternal alloantibodies specific for inherited paternal red cell alloantigens
� Maternal IgG antibody is transported across the placenta where it targets the corresponding red cell antigen in the fetus’ circulation
� Targeted red cells are then destroyed by macrophages in the fetal spleen
HDFN
� In utero, the hemoglobin and bilirubin from the RBC destruction is cleared from circulation by the maternal liver.
� After birth, the baby’s liver is too immature to conjugate the bilirubin to clear it and jaundice occurs.
� Too much unconjugated bilirubin causes serious brain damage called kernicterus� Neurological deficits, abnormal reflexes and eye movements,
and seizures
Signs of HDFN
� Jaundice
� Hyperbilirubinemia
� Anemia
� Erythroblastosis fetalis- increase of premature nucleated red cells in circulation
� Respiratory distress
� Thrombocytopenia
� Severe- Kernicterus
HDFN
� ABO incompatibilities between mother and baby are typically mild to moderate cases� Treat the baby’s jaundice with UV lights
� ABO antibodies are primarily IgM naturally occurring antibodies directed against the missing A and B antigens� O mother’s have IgG as the primary anti-A and anit-B
isoantibody
� A and B mother’s primarily have IgM isoantibodies, but a small amount of IgG antibody can be present
Mother’s Prenatal History
� Mother “Peg Nancy” had previously been typed during her prenatal care� Had an ABO discrepancy
� Typed as a possible subgroup of A
� A2 is not as common as A1
� No unexpected antibodies were detected in the antibody screen
The Mother’s Testing
� Mother Peg Nancy’s typing had an ABO discrepancy
� Forward type looks like an A, reverse looks like an O
� The A1 cells should be negative
� Subgroup of A is investigated� A1 is the most common subtype of A by 80%
� A2 is the second most common by 20%
� A3, Ax, Am, and Ael are extremely weak and rare subgroups
Anti A Anti B Anti-D A1 cells B cells
4+ 0 4+ 1+ 4+
Phenotype Occurrence
Type Caucasians (%) Blacks (%)
A1 33 19
A2 10 8
B 9 20
O 44 49
A1B 3 3
A2B 1 1
The Mother’s Testing
� To determine the Mother Peg Nancy’s unique A group, antigen typing is performed with Anti-A1 against A1 cells, A2 cells, and the mother’s cells
� Mother is presumed to be an A2 type because she is negative to A1
A1 (Pos control)
A2(Neg control)
Mother
Anti-A1 4+ 0 0
Interpretation A1 + A1 = A1 =
The A2 Subgroup
� Is a weak subgroup of A and is recessive to A1
� It’s a result of a nucleotide deletion and frameshift � Causes an enzyme with an additional 21 amino acids at the C
terminus of the molecule
� Compared to A1, A2 only has 1/5th the amount of antigen sites as A1.� Fewer antigen sites make it a weak A because there was
inefficient conversion of H antigen to A antigen.
� Can test with anti H lectin to type A2. A1 will not react with anti H while A2 will.
� A2 individuals can develop an anti-A1 that is IgM in nature
H antigen vs A and B antigenswww.ncbi.nlm.nih.gov
The Baby’s Testing
� Baby Billie-Rubin’s forward type, Ab screen, and DAT were performed from a heelstick� Only forward type is performed because baby has not
developed antibodies yet
Anti A Anti B Anti-D Monoclonal control
DAT
3+ 4+ 4+ 0 3+
SC I SC II SC III
0√ 0√ 0√
The Baby’s Testing
� A and B cells are tested with the antibody screen to determine if the mother’s ABO antibodies are crossing the placenta
� Positive result is from the mother’s anti B that crossed the placenta� Babies do not develop ABO isoantibodies until 3 to 6 months,
so if present, they are from the mom
A cells B cells
0 3+
The Baby’s Testing
� Baby Billie-Rubin typed as A2B
� A2B is a rare type; found in 1% of the population
� A2 is from the mother and B is from the father� Antigen typing was used again to determine the possible A2 type
� 25% of A2B individuals have an alloanti-A1 in their sera
� Important to find compatible blood to prevent development of an anti-A1
A1 (Pos control)
A2(Neg control)
Baby
Anti-A1 4+ 0 0
Interpretation A1 + A1 = A1 =
Anti B
� Anti B in an A mother is typically IgM in nature
� There have only been a few cases reported of IgG anti B in A2 mothers causing HDFN in B type babies
� IgG anti B can be naturally occurring, but is in small quantities
� A higher titer IgG anti-B may be naturally occurring or develop after being sensitized to B antigens in previous pregnancies
The Baby’s Laboratory Results
RBC (at birth 3.9-0.65 x103 /uL)
Bilirubin Direct (0.0-0.3 mg/dL)
Bilirubin Total (0-1 day old 1.4-8.7 mg/dL)
Day 101:15
Day 105:17
Day 117:30
Day 205:35
Day 305:00
1.66 4.58 3.75 3.60 3.57
Day 101:15
Day 105:17
Day 117:30
Day123:30
Day 205:35
Day 305:00
0.8 0.5 0.7 0.6 0.6 0.6
Day 101:15
Day 105:17
Day 117:30
Day 123:30
Day 205:35
Day 305:00
18.6 9.8 12.7 10.5 9.5 6.1
Laboratory Significance
� RBC- the count is below the normal range for a newborn, showing that RBC destruction is occurring� Baby won’t be receiving enough oxygen to tissues when RBC
count is low
� Bilirubin Direct- bilirubin by product of RBC destructionn; direct measures the conjugated bilirubin
� Bilirubin Total- measures the conjugated and unconjugated bilirubin present in high levels in RBC destruction� High levels of bilirubin in the baby’s system can cause brain
damage if untreated (kernicterus)
The Baby’s Laboratory Results
Hemoglobin (14.5- 22.5 g/dL)
Platelets (150-400 x103 /uL)
NRBC (0 %)
Day 101:15
Day 105:17
Day 117:30
Day 2 05:35
Day 305:00
Day 404:00
214 57 66 69 77 106
Day 101:15
Day 105:17
Day 117:30
Day 205:35
Day 305:00
202 128 49 22 4
Day 101:15
Day 105:17
Day 117:30
Day 2 05:35
Day 305:00
Day 404:00
7.4 14.1 11.6 11.2 10.8 12.7
Laboratory Significance
� Hemoglobin- decrease of hemoglobin is seen in an increase of RBC destruction; there is free hemoglobin that gets broken down into bilirubin
� Platelets- a decrease in platelets is a result of intravascular hemolysis from the HDFN� Platelets are being consumed as RBC’s are being destroyed
� NRBC- increased when the bone marrow is trying to push out more RBCs sooner to compensate for a RBC decrease
Treatment
� Transfusion was performed to treat the anemia
� O negative type blood was used� Blood needs to be compatible with mother and baby since baby
has mom’s antibodies
� AB Fresh Frozen Plasma� FFP needs to be compatible with baby and donor cells
� Baby’s lab results improved to a better level after the transfusion and use of phototherapy, and continued to reach normal levels as time progressed as the antibody decreased
Summary
� A2 mother gives birth to an A2B baby who is experiencing HDFN
� HDFN is determined to be caused by an IgG anti B from the mother
� Only IgG antibodies cross the placenta
� Mother either had a high titer of natural IgG anti-B or was sensitized from a previous pregnancy
� Baby was treated with phototherapy and a transfusion
References
� Roback, John D.; et al. Technical Manual. AABB. 17th
edition. 2011.
� Chaudhari, Surg; et al. Transfusion in Blood Groups A2B with Anti A Recipient. 2008. 64:371-372.
� Jeon, H.; Calhoun, B.; et al. Significant ABO hemolytic disease of the newborn in a group B infant with a group A2 mother. Immunohematology. 2000. 16(3):105-108.
� Mckenzie, Shirlyn; William, J. Lynne. Clinical Laboratory Hematology. 2nd edition. 2010.
Special Thanks
Mary SignaigoClinical Laboratory Educator at Mercy Hospital St. Louis
Dr. LudwigPathologist at Mercy Hospital St. Louis