Hemolytic Disease of the Newborn - Medicine/8-2... · PDF fileHemolytic Disease of the...

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Transcript of Hemolytic Disease of the Newborn - Medicine/8-2... · PDF fileHemolytic Disease of the...

  • Hemolytic Disease of the Newborn

    Qun Lu, M.D.

    Assistant Professor

    Dept. of Pathology and Laboratory Medicine

    David Geffen School of Medicine at UCLA

    Los Angeles, CA

  • Clinical History

    06/25/05: 36 y o, gravita 3, para 0, 10 1/7

    weeks pregnant AA female, came to ER due

    to left-sided abdominal pain

    PMH:

    lost two pregnancies in first trimesters, no

    RhoGam administration, her blood type is B

    negative,

    last pap was 3 y ago and normal

    Hypothyroidism diagnosed at age of 8, not

    compliant with med

  • PE

    General: BP 110/50, HR 112. T and R normal, a

    well- developed, well-nourished, in mild distress.

    LUNGS /HEART: WNL

    ABDOMEN: Some guarding, but bowel sounds

    and had bilateral fullness in both quadrants.

    PELVIC: normal external female genitalia, scant

    discharge was noted from the cervix. The GC and

    Chlamydia cultures were obtained. No blood was

    noted. Pelvic bimanual examination revealed

    masses up to the umbilicus.

  • ER work-up

    Lab: WBC of 16, HB 3.9, HCT 12.8, PLT

    287,000, MCV 64.7, BMP- normal, UA - 1+

    Hb and 1+ leukocyte esterase, beta HCG -

    291,000.

    Pelvic US: IUP at 10-1/7th weeks and also

    complex bilateral adnexal masses with

    cysts. Each was approximately 10 x 14 x 7

    and 10 x 12 x 8 centimeters.

  • ER Treatment

    Admission

    IV fluids

    Evaluation of her anemia

    Transfusion with 2 units of blood

    Evaluation of bilateral adnexal masses: CA-

    125. Consider further imaging.

  • Issues

    Blood Bank issues: B negative, anti-D (1:256)

    and anti-C(1:1) present, concerned with HDN,

    currently 10+ weeks pregnancy, not a

    candidate for RhoGam

    Anemia: iron deficient, started on iron

    supplement, no source of bleeding found,

    smear 2+ spherocytes, 3+ microcytes, 2+

    fragmented cells, HB studies 98% Hb A, 1.2%

    Hb A2, 0.5%Hb F, no Hb S, C

  • Issues Adneal masses: CT - no lymphadenopathy, no

    metastasis, cystic mass with no papillary

    projections or solid part, c/w overstimulation

    syndrome. TSH high (41.7), T4

  • Hemolytic Disease of Newborn

    Definition: a hemolytic disease in the newborn

    caused by blood-type incompatibility between

    mother and child

    Maternal Ig G antibodies can cross the placenta

    and coating fetal RBCs hemolysis

    Maternal sensitization: history of transfusion or

    pregnancy

  • Common RBC antigens causing

    HDN

    --Rh antigens. Most common is D antigen, next is c

    antigen. IgG can cross placenta.

    ABO antigens: only in infants born to group O

    mothers because some have IgG anti-A, anti-B,

    anti-A,B antibodies without sensitization, usually

    mild HDN

    Kell: Kell antigens are expressed in early fetal

    RBCs and bone marrow hematopoietic cells

    cause hemolysis and bone marrow suppression

    severe and early HDN

    Kidd, MNSs, Duffy antigens: rare, but increasing

  • Prevention of HDN

    Nearly all women with Rh negative or weak D

    type are identified in early pregnancy by blood

    testing.

    If mother is Rh-, anti-D is negative,usually given

    Rh immunoglobulin (RhIg), also known as

    RhoGAM

    1 vial (300 mcg), around the 28th week of

    pregnancy

    at time when vaginal bleeding occurs (calculate)

    at the time of delivery within 72 hours

  • Maternal-Fetal Bleeding Screening

    After vaginal bleeding or delivery, if

    screening is negative, just give 1 vial (300

    mcg) RhIG. If +, give minimal 2 vials and

    add more vials after calculation

  • Calculating Dosage of RhoGam

    First perform the Kleihauer-

    Betke test to get the

    percentage of fetal red

    cells in the mother

    Mechanism

    Blood smear stained with

    acid elution

    Hb F is more acid resistant

    Fetal RBC darkly stained,

    Maternal RBC "ghosts"

    Fetal Blood

    Maternal Blood

  • Calculating Dosage of RhoGam

    Hemoglobin electrophoresis on

    cellulose acetate Hemoglobin HPLC

  • Calculating Dosage of RhoGam

    Method 1:

    % of fetal RBC X 50 / 30

    Method 2:

    If the decimal 0.5, round up and

    then round up again

  • First Sensitized Pregnancy

    Father RBC phenotyping:

    negative for the offending antigen then no further

    testing is necessary

    positive for the antigen, serial antibody titer

    monitoring is required

    Anti-K: HDN tends to happen early and severe

    Frequency of monitoring: every 4 weeks to 28

    weeks, then every 2 weeks until birth

    Critical titer: 1:8 or above

  • First Sensitized Pregnancy

    Non anti-K antibodies Frequency of monitoring: first at 12 weeks gestation,

    then at 28, 32 weeks gestation

    Critical titer : the IAT titer is > 1:32 or albumin titer > 1:16 (it varies from hospital to hospital)

    IAT titers of < 1:32 or less are managed non-invasively with repeat antibody titers every 2-4 weeks.

    IAT > 32: Doppler Ultrasound to measure peak systolic velocity of middle cerebral artery or amniocentesis or umbilical blood sampling q 2 to 3 weeks to detect fetal anemia . (N Engl J Med. 2000 Jan 6;342(1):9-14 )

  • Open circles indicate fetuses with either no anemia or mild anemia ( 0.65 multiples of

    the median hemoglobin concentration). Triangles indicate fetuses with moderate or

    severe anemia (

  • Amniocentesis

    Bilirubin level: measured by spectrophotometrically measuring absorbance at the 450-nm wavelength in a specimen of amniotic fluid that has been shielded from light ---- Liley curve

    Fetal genotyping For RhE, Rhe, RhC, Rhc, Kell ,and Cellano (k) the

    parents' DNA should be tested concurrently

    Cytogenetic testing to screen for congenital disease

  • The Liley Curve

    Amniotic fluid bilirubin level (log), vs weeks of pregancy

    Zone 1: low risk

    Zone 2: intermediate

    risk

    Zone 3: high risk

  • Umbilical Cord Blood Sampling

    Direct measurement of fetal blood bilirubin

    and hemoglobin level

    Fetal RBC phenotyping

    Technique can be used for fetal blood

    transfusion or exchange

    More complications

  • Hemoglobin Concentrations in 265 Normal Fetuses and 111 Fetuses That

    Underwent Cordocentesis

    http://content.nejm.org/content/vol342/issue1/images/large/02f1.jpeg

  • Previously Affected Pregnancy

    For patients with a previously affected

    pregnancy, the timing of the initial procedure

    (serial amniocentesis) is determined by past

    clinical history. It is usually performed at

    least 4-8 weeks earlier than the prior

    gestational age at which significant

    morbidity occurred.

  • In women with extremely high titers ( > 256), at

    less than 28 weeks, where the fetus does not

    demonstrate hydrops, and there is a documented

    history of fetal death due to hydrops ---- IVIG

    might be offered. The dose is 400 mg/kg per day

    for 5 days, with repeat infusions every 15 to 21

    days. Specific contraindications to intravenous

    immunoglobulin use include a previous episode of

    IVIG-induced anaphylaxis (rare) and selective IgA

    deficiency.

  • Symptoms of HDN During pregnancy:

    Mild anemia, hyperbilirubinemia, and jaundice

    Severe anemia with enlargement of the liver and spleen

    Hydrops fetalis - The heart begins to fail due to severe anemia and large amounts of fluid build up in the tissues and organs, at great risk of being stillborn.

    After birth:

    Severe hyperbilirubinemia and jaundice

    Kernicterus - the most severe form of hyperbilirubinemia and results from the buildup of bilirubin in the brain. This can cause seizures, brain damage, deafness and death.

  • Diagnosis

    Mothers blood: RBC antibodies

    Doppler Ultrasound - to detect organ enlargement or fluid buildup in the fetus.

    Amniocentesis - to measure the amount of bilirubin in the amniotic fluid.

    Fetal umbilical cord blood: antibodies, bilirubin, and anemia

    Newborn: umbilical cord blood for blood group, red blood cell count and antibodies, newborn peripheral blood testing for bilirubin levels.

  • Treatment

    During pregnancy:

    Intrauterine blood transfusion of red blood cells, into the

    abdominal cavity of the fetus or directly into the umbilical

    cord vein

    Early delivery if the fetus develops complications -prevent

    worsening of HDN.

    After birth:

    Blood transfusions (for severe anemia).

    Phototherapy

    Intravenous fluids (for low blood pressure).

    Help for respiratory distress using oxygen or a mechanical

    ventilation

    Exchange transfusion