HDFN, AIHA, and DIIHA

define HDFN

the destruction of a fetus and neonate’s RBCs via antibodies produced by the mother

what causes HDFN

when mom develops IgG antibodies incompatible to baby’s antigens, mom’s antibodies cross the placenta and bind to the baby’s RBCs which destroy them

which IgG is most likely to cause early and severe hemolytic disease

IgG 1 and 3

three ways a female can stimulate antibody production

naturally (ABO) or by transfusion (4% chance of happening)

transplantation

pregnancy (most common way, 83%)

three main ways that (anti-D) HDFN can be caused

Rh negative mother with Rh positive baby

O type mother with A, B, or AB baby (anti-A,B)

antigenic exposure (Kell)

what does FMH stand for

fetomaternal hemorrhage

when can FMH occur

during spontaneous miscarriage

late in pregnancy

during delivery

what happens in FMH

the placenta separates from the uterus and fetal blood leaks into mom’s blood circulation

concept of Rh caused HDFN

in moms first pregnancy mom will develop anti-D antibodies against the baby causing mom to become immunized

first child isn’t affected though because the featl and maternal circulation are seperate

any pregnancies after this with Rh positive babies the antibodies can cause pregnancy loss as they cross the placenta and bind to baby’s cells

what does RhIG stand for

Rh immune globulin

which HDFN is most common

ABO-incompatible has become the most common now (20%) that Rh-incompatible has been prevented by rhogam

what can cause mild cases of ABO HDFN

fetal RBCs expressing less ABO antigen than adults

OR ABO blood group antigens being expressed by a variety of fetal tissue decrease the chance of attaching to fetal RBCs

for severe cases of ABO HDFN what are the primary conditions it can cause

erythroblastosis fetalis

fetal hematopoietic tissues increases RBC production because RBCs are being destroyed by maternal antibodies which release nucleated RBCs into fetal circulation

for severe cases of ABO HDFN what are the secondary conditions it can cause

hydrops fetalis

as anemia worsens excess erythropoiesis occurs in fetal liver and spleen, causing organ enlargement which decreases albumin production, producing edema, ascites, and effusions

how early in the pregnanyc can ABO HDFN show up

severe shows as early as 18-20 weeks gestation (earlier if Kell)

destruction of RBCs causes an increase of bilirubin, why is there an increase in this and what can it lead up to

the infant’s immature liver cannot metabolize the bilirubin so it accumulates in the brain causing hyperbilirubinemia and kernicterus

(as severity increases it can lead to stillbirth)

which blood system does bilirubin target

Kell

conditions that can increase the risk of FMH

aminocentesis (needle injected into belly to get amniotic fluid to test it)

chorionic villus sampling (tissue sample of placenta)

trauma to the abdomen

how often can a transplacental hemorrhage occur

7% of women during gestation and around 50% at delivery

the rate of hemolysis and severity of disease is determined by what factors

IgG subclass

amount of anitbody

number of antigenic sites on the RBC

what is key in prental evaluation

mother’s transusiona nd pregnanyc history

1st visit should get ABO/Rh and Absc (a positive Absc requires ID-ing)

purpose of an antibody titer

to determine the relative concentration of antibody (does not predict severity of HDFN)

what level is a critical antibody titration

16

what steps need to be taken when an antibody titer is critical

repeat the tier at 18-20 weeks gestation

if >32 mom need doppler imaging (after 16 weeks gestation)

if <32 mom will repeat at 4 week intervals beinning 16-20 weels gestiation followed by every 2-4 weeks during third trimester

list of anitbodies that can cause HDFN

anti-K

anti-Mia, -Dia, -Wra, and -Rd

anti-Le^a

anti-D, D+C, D+E, -C, E, -c, and e

antibodies that rarely cause HDFN

anti-Fy^a

anti-s, -M, -N, and -S

anti-Jk^a

antibodies that never cuase HDFN

anti-Le^b

anti-I and -IH

anti-P1

three procedures that can be preformed to monitor pregnancy

amniotic fluid analysis

doppler flow studies

fetal blood sampling

treatment for HDFN

transfusion to treat anemia and suppress fetal RBC production

IUT (intrauterine transfusion) inserting a needle into fetal umbilical vein and injecting donor RBCs

requirements for blood products in a IUT

Irradiated

CMV reduced/neg

Hgb S neg

O neg

antigen negative for mother’s corresponding antibodies

crossmatch compatible w/ mom’s plasma

<7 day old

equation for calculating the volume of blood needed to transfuse

fetal weight (grams) x (0.14 mL/g) x (desired hct in decimals - pretransfusion hct in decimals) divded by the hct of the RBC unit in decimals

what is done to monitor and maintain the symptoms of the neonate

phototherappy, maternal plasma exchange, IVIG, and double volume exchange (replaces 85% of blood)

how can you prevent HDFN

by giving rhogam (only effective for Rh-incompatible though)

when should you give rhogam

if terminating pregnancy 12 weeks

at 26-28 weeks

again within 72 hours of delivery if baby is Rh positive

(recommened after aminocentesis, cordocentesis, version, abortion, and abdominal trauma)

screening test for RhIG

rosette test and KB acid elution

how is the rosette test preformed

maternal RBCs are incubated with anti-D, if agglutination (rosettes) form and there’s >3 per 10 microscopic fieleds the test is positive and thr amount of FMH must be quantified

if negative, give 1 vial of rhogam (300 microliters)

how is the KB acid elution test preformed

smear of peripheral blood is placed on a slide and treated with acid, rinsed, and counterstained

the slide is read by counting 2,000 cells (light pink is mom, dark pink is baby)

a calculation is done to determine fetal bleed and how much rhogam should be given

how do you calculation the number of vials of rhogam is needed

(fetal cells counted/total cells counted) x maternal blood volume (mL) = FMH

FMH/30 = # vials

who does not need rhogam

D-negative women who gave birth to D-negative baby’s

D-negative women who have been previously immunized to the D-antigen (they’ve formed anti-D)

D-positive females

what are the serological testing of the newborn

cord blood testing or heelstick to get ABO/Rh, DAT, etc

serological treatment of the newborn

phototherapy

two immune thrombocytopenia that can occur in HDFN

FNAIT (fetal and neonatal alloimmune thrombocytopenia)

ITP (idiopathic thrombocytopenia)

requirements of neonatal transfusion

replaces one or more volumes of baby;s blood with compatible RBCs/plasma

preformed to rapidly reduce unconjugated bilirubin

what does gravid mean

a pregnant women

what does para mean

refers to the delivery of a live infant

what can gravid and para tell the MLS about the patient

gives information about a woman’s pregnancy history (ex:If a woman has had a large number of pregnancy losses, they could have been due to HDFN, etc.)

define immune hemolytic anemia

shortened RBC survival mediated through an immune response (specifically by the humoral antibody)

three categories that IHA falls under

alloimmune

autoimmune hemolytic anemia (AIHA)

drug-induced immune hemolytic anemia (DIIHA)

what kind of discrepancies can you see in your workup if patients RBCs are coated with an autoantibody

ABO

positive Rh control (should be negative)

positive DAT

two types of anemia caused by the destruction of RBCs

compensated anemia

uncompensated anemia

compensated anemia

rate of RBC production nearly equals the rate of RBC destruction

uncompensated anemia

rate of RBC destruction if greater than the rate of RBC production

diagnostic tests preformed in symptomatic patients

DAT

antibody ID (serum or eluate)

six differences between symptomatic vs asymptomatic patients

thermal amplitude of ab reactivity

IgG subclass of the ab

amount of ab bound to RBCs

ability of ab to fix complement in vivo

activity of the individual’s macrophages

change in RBC membrane (quantitative or qualitative)

temperature reactivity an autoantibody can be classified under

warm: 30-37C

cold: 4-30C

which temperature do most autoanoibodies react best at

warm (70% of reported cases, 18% cold, 12% drug-induced)

what routine testing performed at room temp can cold agglutinins interfere with

ABO typing

DAT

ab detection and ID

compatibility testing

how can a cold-reactive autoantibody be resolved

by using anti-IgG reagent, cold absorption, and prewarm techniques

what reagent can we use to eliminate false-positive reactions seen with Rh reagents when RBCs are coated with cold agglutinins

thiol reagents, monoclonal reagents, and warmed reagnents with warmed saline

what technique can help resolve problems caused by cold agglutniins

prewarming

why is the prewarming technique not performed in patients transfused within the previous 3 months

it can mask newly forming antibodies

which is the most encountered cold autoantibody

auto anti-I

thermal range of normal (benign) cold autoantibody

reactive at ≤ 20-24C

titer at 4C of normal (benign) cold autoantibody

≤ 64

reactivity of normal (benign) cold autoantibody

marginally enhanced with albumin

common specificity of normal (benign) cold autoantibody

anti-I or anti-IH

is the normal (benign) cold autoantibody capable of binding complement

yes (in vitro)

DAT: 0-1+ d/t C3 binding

is the normal (benign) cold autoantibody clinically significant

no

is normal (benign) cold autoantibody associated with disease

no

thermal range of pathological cold autoantibody

reactive at ≥ 30 C

titer at 4C of pathological cold autoantibody

≥ 1000

reactivity of pathological cold autoantibody

strongly enhanced with albumin

common specificity of pathological cold autoantibody

anti-I

is pathological cold autoantibody caoable of binding complement

yes (in vitro)

DAT: 2-4+ d/t C3 binding

is pathological cold autoantibody clinically significant

yes

is pathological cold autoantibody associated with disease

yes, may be secondary to viral infections of M. pneumoniae

which group cells react best because they have the largest amount of H antigen

group O and A₂ cells

which group cells have the least amount of H antigen causing them to react weakly

group A₁ and A₁B

pneumonia caused by what disease can lead to cold hemagglutinin disease

Mycobacterium pneumoniae

what type of immunoglobulin efficiently activates complement

IgM

in what age group does CHD predominantly occur

those older than 50 years of age

lab findings in CHD

reticulocytes (baby cells)

positive DAT due to complement only

what is the cold agglutinant titer that would indicate CHD

1,000 or greater

least common type of AIHA

paroxysmal cold hemoglobinuria (PCH)

PCH is most often seen in what age group

children associated with viral illnesses

what antibody is responsible for PCH

donath-landsteiner antibody

what test is preformed for PCH

donath-landsteiner test

patient population of PCH

children and young adults

pathogenesis of PCH

following a viral infection

clinical features of PCH

hgburia, acute attacks upon exposure to cold

severity of hemolysis in PCH

acute and rapid

site of hemolysis for PCH

intravascular

autoantibody class of PCH

IgG (anti-P specificity, biphasic hemolysin)

DAT of PCH

3-4+

monospecific C3 only

thermal range of PCH

moderate (<20C)

titer of PCH

moderate (<64)

donath-landsteiner test for PCH

positive

treatment for PCH

supportive (disorder terminates when underlying illness resolves)

patient population for CHD

elderly or middle-aged adults

pathogenesis of CHD

idiopathic, lymphoproliferative disorder following M. pneumoniae infection