RhRh DiseaseDiseased th F td th F tand the Fetuand the Fetu

Samantha MSamantha MDepartmenDepartmen

University of ArkansasUniversity of Arkansasyy

No FinanciaNo Financia

e, e, HydropsHydrops/ N b/ N bus / Newbornus / Newborn

cKelvey, MDcKelvey, MDt of t of ObGynObGyn

s for Medical Sciencess for Medical Sciences

al Interestsal Interests

ObjecObjecObjecObjecHelp you interpret a blood type Help you interpret a blood type p y p ypp y p ypvalues that need attentionvalues that need attentionHelp you to anticipate “the nextHelp you to anticipate “the nextAll i i tiAll i i tiAlloimunizationAlloimunizationDiscuss how Discuss how RhRh AlloimmunizatiAlloimmunizatiFetalisFetalis andand HydropsHydropsFetalisFetalis and and HydropsHydropsHelp you recognize findings assHelp you recognize findings assFetalisFetalis and and HydropsHydropsHelp you become familiar with tHelp you become familiar with taffected patientsaffected patientsTeach you how to preventTeach you how to prevent RhRh AATeach you how to prevent Teach you how to prevent RhRh AA

ctivesctivesctivesctivesreport and recognize abnormal report and recognize abnormal p gp g

t step” in working up t step” in working up RhRh

ionion can cause can cause ErythroblastosisErythroblastosis

sociated with sociated with ErythroblastosisErythroblastosis

treatment options available to treatment options available to

AlloimmunizationAlloimmunizationAlloimmunizationAlloimmunization

Definitions: IMDefinitions: IMDefinitions: IMDefinitions: IM

RhRh AlloimmunicationAlloimmunication == RRRhRh AlloimmunicationAlloimmunication RRdisease”disease”hemolytic disease of thehemolytic disease of theyyerythroblastosiserythroblastosis fetalisfetalis (s(sin the NBin the NB““HydropsHydrops” = ” = hydropshydrops fetfetmassive massive ascitesascites in the fein the fehh RhRh di BUT CAdi BUT CAthe the RhRh disease BUT CAdisease BUT CA

THINGS!THINGS!HYDROPS IS NOT THEHYDROPS IS NOT THEHYDROPS IS NOT THEHYDROPS IS NOT THEALLOIMMUNIZATIONALLOIMMUNIZATION

MPORTANT!MPORTANT!MPORTANT!MPORTANT!

RhRh isoimmunizationisoimmunization = “= “RhRhRhRh isoimmunizationisoimmunization RhRh

e newborn (mild)= e newborn (mild)= ( )( )severe) = severe) = resulting disease resulting disease

talistalis (VERY SEVERE) (VERY SEVERE) = = etus/neonate = endpoint of etus/neonate = endpoint of N BE CAUSED BY OTHERN BE CAUSED BY OTHERN BE CAUSED BY OTHER N BE CAUSED BY OTHER

E SAME THING ASE SAME THING AS RhRhE SAME THING AS E SAME THING AS RhRh

HydropsHydropsHydropsHydrops

MORE THAN ONE TOMORE THAN ONE TOMORE THAN ONE TO MORE THAN ONE TO ascitesascitesl l ff il l ff ipleural effusionpleural effusion

pericardial effusionpericardial effusionscalp/skin edemascalp/skin edemaplacental thickening/edeplacental thickening/edeplacental thickening/edeplacental thickening/ede

ss FetalisFetalisss FetalisFetalis

MAKE DIAGNOSIS:MAKE DIAGNOSIS:MAKE DIAGNOSIS:MAKE DIAGNOSIS:

emaemaemaema

HydropsHydrops FetalisFetalis: : vsvs NonimmuNonimmu

“Immune“Immune HydropsHydrops” =” = RhRhImmune Immune HydropsHydrops = = RhRhaccounts for ~13% of accounts for ~13% of hyhypreventable cause!)preventable cause!)preventable cause!)preventable cause!)

““N iN i H dH d ””““NonimmuneNonimmune HydropsHydrops” ” other than blood type isother than blood type is

Immune Immune HydropsHydropsuneune HydropsHydropshh Disease It onlyDisease It onlyhh Disease. It only Disease. It only ydropsydrops (most (most

D t thiD t thi= Due to something = Due to something ssuesssues

““NonimmuneNonimmune HydropsHydrops” = D” = Dy py pblood type issues =blood type issues =

Anomalies (vascular, puAnomalies (vascular, puAnomalies (vascular, puAnomalies (vascular, puFetal Anemia (blood disoFetal Anemia (blood disoChromosome anomaliesChromosome anomaliesChromosome anomaliesChromosome anomaliesInfection (Infection (ToxoToxo, CMV, , CMV, PaPaTwin To Twin TransfusioTwin To Twin TransfusioTwin To Twin TransfusioTwin To Twin Transfusio

IDIOPATHICIDIOPATHIC 88 22%22%IDIOPATHIC IDIOPATHIC –– 88--22%22%

ue to something other than ue to something other than gg= ~90% of = ~90% of hydropshydrops

lmonary, cardiac)lmonary, cardiac) -- ~40%~40%lmonary, cardiac) lmonary, cardiac) 40%40%order) order) -- ~10~10--30%30%ss –– ~10%~10%s s 10%10%arvoarvo, Syphilis) , Syphilis) -- ~10%~10%onon SyndSynd ~4%~4%on on SyndSynd -- ~4%~4%

HYDROPSHYDROPSHYDROPSHYDROPSS:S: AscitesAscitesS: S: AscitesAscites

HYDROPS: PlHYDROPS: PlHYDROPS: PlHYDROPS: Plleuralleural EffusionEffusionleural leural EffusionEffusion

HYDROPS: PerHYDROPS: Perricardial ricardial EffusionEffusion

HYDROPSHYDROPSHYDROPSHYDROPSS: EdemaS: EdemaS: EdemaS: Edema

HYDROPS: PlacHYDROPS: PlacHYDROPS: PlacHYDROPS: Placcentalcental ThickeningThickeningcental cental ThickeningThickening

RhRh DisDisRhRh DisDis

Most preventaMost preventaMost preventaMost preventahydropshydrops CausCaushydropshydrops. Caus. Caussevere diseassevere diseassevere diseassevere diseasstarts with youstarts with youyyAccounts for ~10% of Accounts for ~10% of hh

seaseseaseseasesease

able cause ofable cause ofable cause of able cause of ses the mostses the mostses the most ses the most se! Preventionse! Preventionse! Prevention se! Prevention u!u!ydropsydrops..

Risk assessment sblood type and sblood type and s

prenat

Maternal Blood type is:

B +B +What does that mean?

starts with a routine screen at the firstscreen at the first tal visit

++

Interpreting aInterpreting a

Maternal Blood type is:Maternal Blood type is:

B+ABO grouping BLikewise:

B-ABO grouping B

a Blood Typea Blood TypeThis patient is RhD positive( I di t C b t t)( + Indirect Coombs test)

+This patient is negative for RhDThis patient is negative for RhD(negative indirect Coombs test)

11stst prenatal visit:prenatal visit:11 prenatal visit: prenatal visit:

Indirect Coombs’ testIndirect Coombs’ testIndirect Coombs testIndirect Coombs testmaternal serum incubatematernal serum incubateantigen of interestantigen of interestantigen of interestantigen of interestCoombs’ serum (antiCoombs’ serum (anti--huhuif agglutination occurs aif agglutination occurs aif agglutination occurs, aif agglutination occurs, amaternal serummaternal serumIf antibody present seriaIf antibody present seriaIf antibody present, seriaIf antibody present, seriaestimate quantity of antibestimate quantity of antib

Antibody ScreenAntibody ScreenAntibody ScreenAntibody Screen

ed with cells known to have ed with cells known to have

man IgG) addedman IgG) addedantibody is present inantibody is present inantibody is present in antibody is present in

al dilutions performed toal dilutions performed toal dilutions performed to al dilutions performed to bodybody

Coomb’sCoomb’s TestingTestingDirectDirect--

g: Indirectg: Indirect-- Mom, Mom, -- BabyBaby

““KellKell Kills LKills LAntigens other than Antigens other than RhRh

di f hdi f h

KellKell Kills, LKills, L

disease of thdisease of thSystem Antigen

+++Rhesus D+++

C++ E+++ Kell K++++ Duffy Fya ++++Duffy FyKidd Jka +++ MNSs M+++ N+ S+++

+ mild

++ moderate

Lewis Lives”Lewis Lives”hh can cause hemolytic can cause hemolytic h bh b

Lewis LivesLewis Lives

he newbornhe newbornn Isoform

c+++ e++ k+++ FybFy Jkb +++ s+++

+++ severe

++++ hydrops

AntibodAntibodAntibodAntibod

Follow every 3Follow every 3--4 weeks4 weeksFollow every 3Follow every 3 4 weeks4 weeksIf If ≥ 1:32, move on to am≥ 1:32, move on to amK llK ll idid ii ttKellKell: consider : consider amnioamnio at at

GET HELP!GET HELP!GET HELP!GET HELP!

y Titersy Titersy Titersy Titers

ssssmniotic fluid testingmniotic fluid testing1 161 161:161:16

PathophysioPathophysio

Mom doesn’t have finherited from fatheinherited from fatheenter mom’s circulareaction from momreaction from mom RBC’s mom’s anpass to fetus and dRBC’s ErythroblaRBC s Erythrobla

ology of EBFology of EBF

fetal blood group er fetal cellser fetal cells ation Immune to foreign fetalto foreign fetal

ntibodies (IgG) estroy fetal

astosis Fetalisastosis Fetalis

Pathophysiology analoMom likes chicken soup. DadMom likes chicken soup. Daddetermined to make soup withthan mom’s preferred chickeninherits a taste for wild duck m

Duck (fetal RBC’s) gets pu( t l bl d) M i k(maternal blood) Mom pickssoup and throws it away, becaTOLERATE WILD GAME IN HTOLERATE WILD GAME IN HSOUP (forms an immune rea

Mom gets so disgusted witg gthat she decides to throw ALLdown the disposal (mom’s and t f t l RBC’ ) All thdestroy fetal RBC’s) All the destroyed or severely impaire

ogy for hunting seasond, an avid hunter, isd, an avid hunter, is h his wild duck meat rather n. Unfortunately, the baby meat in his soup like his dad ut into mom’s chicken soup

ll th d k t f ths all the duck out of the ause she WILL NOT HER PERFECTLY GOODHER PERFECTLY GOOD ction against Fetal RBC’s) th the wild duck in her soup, pL of Dad’s wild duck soup tibodies pass to fetus and

(f t ) isoup (fetus) is now ed (Erythroblastosis Fetalis)

ErythroErythroyy(analogy: pieces of wild duc(analogy: pieces of wild duc

Prorubricytes

Rubricytes

Metarubricytesy

oblasts oblasts ck in maternal chicken soup)ck in maternal chicken soup)

Basic PathophyBasic PathophyBasic PathophyBasic PathophyRh Rh -- mother is expomother is expo

RBC’ hi h iRBC’ hi h ion RBC’s which is non RBC’s which is n“self”“self”she develops an IgGshe develops an IgGresponseresponseIgG transferred throIgG transferred throfetusfetusFetal D+ cells are lyFetal D+ cells are ly

ysiology (again)ysiology (again)ysiology (again)ysiology (again)osed to the D antigen osed to the D antigen

t i dt i dnot recognized as not recognized as

G type antibody G type antibody

ough the placenta to ough the placenta to

ysed causing EBFysed causing EBF

QUESQUESIn order for Rh Isoimmunizthe Rh type of the mother bRh negativeIn order for Rh Isoimmunizthe Rh type of the fetus be?Rh itiRh positiveWhat is the risk of isoimmublood type is Rh neg and thblood type is Rh neg and thneg?0%

STIONSTIONation to occur, what must ,be?

ation to occur, what must ?

unization if the mother’s he fetal blood type is Rhhe fetal blood type is Rh

Genetics ofGenetics ofGenetics of Genetics of 3 genetic loci, 2 major alleles at each 3 genetic loci, 2 major alleles at each possible combinationspossible combinations

C DC Dc

C DExample: this person is RhD p

c DExample: this person is RhD poExample: this person is RhD po

Ccc

Example: this person is

Rh SystemRh SystemRh SystemRh Systemloci (one from each parent), results in 8 loci (one from each parent), results in 8

EEe

Epositive, heterozygous

eositive, homozygousositive, homozygous

Eee

Rh negative

PUNNETTPUNNETTPUNNETT PUNNETT Rh pos mom w/

D Rmmom w/

Rh pos dadD DD D

mRd

D DD(Rh pos)

D(Rh pos)

D(Rh pos) (Rh neg!)

If both mom and dad areIf both mom and dad are RhRh ppIf both mom and dad are If both mom and dad are RhRh ppbaby? YES, 25%baby? YES, 25%If both mom and dad are If both mom and dad are RhRh nnwill have an will have an RhRh negneg baby? 10baby? 10

SQUARESSQUARESSQUARESSQUARESRh negmom w/mom w/Rh negdad

(Rh neg!) (Rh neg!)(Rh neg!) (Rh neg!)

pos can the ha e anpos can the ha e an RhRh negneg

(Rh neg!) (Rh neg!)

pos, can they have an pos, can they have an RhRh negneg

negneg, what is the chance they , what is the chance they gg, y, y00%00%

POSITIVE AntibodyPOSITIVE Antibody

Request paternal bloRequest paternal bloand request speciali

screen: What’s Next?screen: What s Next?

ood type testingood type testing, st consultation!

Monitoring &Monitoring &Monitoring & Monitoring &

MonitoringMonitoringMonitoringMonitoringantibody titer antibody titer q 4 wks q 4 wks until 24 weeks then quntil 24 weeks then quntil 24 weeks, then q until 24 weeks, then q 2 wks2 wksamniotic fluidamniotic fluidamniotic fluid amniotic fluid analysis analysis for fetal for fetal genotype if critical titer genotype if critical titer is reachedis reachedAmnioAmnio for OD 450 and for OD 450 and MCA MCA dopplerdoppler

ManagementManagementManagementManagement

ManagementManagementManagementManagementPUBS for fetal PUBS for fetal hematocrit if critical hematocrit if critical values are reached values are reached with MCA or OD450with MCA or OD450intraperitonealintraperitonealintraperitoneal intraperitoneal transfusiontransfusionintravascularintravascularintravascular intravascular transfusiontransfusionpreterm deliverypreterm deliveryyy

PUPUPUPUBSBSBS BS

Prevention of IMMRhog

Passive immunoglobulinPassive immunoglobulinneg mother from producagainst the D antigen thagainst the D antigen thSENSITIZATION

Prevention of NHYDROHYDRO

Causes are too

MUNE HYDROPS: gamn that prevents the Rhn that prevents the Rh cing the antibodies hereby PREVENTINGhereby PREVENTING

NON-IMMUNE OPS: ?OPS: ?o diverse to say.y

Preventionl f h

All the wild duck in the w

analogy for huAll the wild duck in the wblood) is combined with(rhogam) to make duck(rhogam) to make duck gumbo is introduced to recognizes that there isrecognizes that there is forms an aversion to theshe never throws it dowshe never throws it dow

n: Rhogami

wild duck soup (fetal

unting seasonwild duck soup (fetal

h spices and roux gumbo When thegumbo. When the mom, she never duck in it and neverduck in it, and never

e duck or the gumbo, and wn the sick to destroy it!wn the sick to destroy it!

Rh Immune Rh Immune RhogRhog

Given postpartum to moGiven postpartum to moGiven postpartum to moGiven postpartum to moinfants within infants within 72 hours72 hoursA t tA t t d i i t td i i t tAntepartumAntepartum administratadministratincidence of immunizatiincidence of immunizatiweeksweeksEffect lasts 12 weeksEffect lasts 12 weeksEffect lasts ~12 weeksEffect lasts ~12 weeks

ProphylaxisProphylaxis®®gamgam®®

others of D positiveothers of D positiveothers of D positive others of D positive s of deliverys of deliveryi f th di f th dion further reduces ion further reduces onon–– usually given usually given at at 28 28

RhogamRhogamRhogamRhogam

Only comes inOnly comes in 50 mcg and 30

Can’t give too m

If in doubt, GIVIf in doubt, GIV

m Dosingm Dosingm Dosingm Dosing

two dosestwo doses. 0 mcg.

much.

VE IT!VE IT!

RhogamRhogamRhogamRhogam

Rh Immunoglobin

Situation

threatened abortion spontaneous abortion, <13 weeks spontaneous abortion, >13 weeks ectopic pregnancy, <13 weeks ectopic pregnancy >13 weeks ectopic pregnancy, >13 weeks amniocentesis percutaneous umbilical blood sampling chorionic villus sampling external cephalic version external cephalic version antepartum prophylaxis delivery de

K† From American College of Obstetricians and Gynecologists: P

Bulletin 147 Washington DC 1990 Bulletin 147. Washington, DC, 1990. ‡ Bowman JM: Hemolytic disease (erythroblastosis fetalis), in C

Medicine: Principals and Practice, ed 3. Philadelphia, WB Sa

m Dosingm Dosingm Dosingm Dosing

Prophylaxis†

Recommended dose

300µg IM, repeat q 12 weeks‡ 50µg IM

300µg IM 50µg IM

300µg IM 300µg IM 300µg IM 300µg IM 300µg IM 300µg IM 300µg IM 300µg IM

ependent on cord blood Rh type and Kleihauer-Betke test

Prevention of D isoimmunization. ACOG Technical

Creasy RK, Resnick R (eds): Maternal-Fetal aunders, 1993, p 736.

Think abouThink abouSituations that pose high risk foh h i l dhemorrhage include:a. Abdominal traumab. Placental abruptionpc. Placenta previad. Intrauterine manipulatione Multiple gestatione. Multiple gestationf. Manual removal of the placen

ut it when:ut it when:or excessive fetal-maternal

nta

Rhogam AdRhogam Ad

RhoGAM® should NOTRhoGAM® should NOTfollowing:1 Rh (D) positive woma1. Rh (D) positive woma2. Sensitized Rh (D) ne3. Rh (D) negative womto an Rh (D) negative b4. Never give RhoGAM®

dministrationdministration

T be given to theT be given to the

anangative

man who has given birth aby® to a baby.

TricTric

A T&S should be drawnA T&S should be drawnthe administration of Rh

Administration of RhogaRESULTS OF THE MARESULTS OF THE MAFOR ANTIBODY TO TH

d! G t tiscared! Get your patien

cky!cky!

n on all patients beforen on all patients before hogam.

am WILL MAKE THE ATERNAL T&S POSITIVEATERNAL T&S POSITIVE HE D ANTIGEN. Don’t be

t’ hi t !nt’s history!

SUMMARY KSUMMARY KSUMMARY. KSUMMARY. KCheck T&S during prenatal Check T&S during prenatal IfIf AbAb screen is abnormal rescreen is abnormal reIf If AbAb screen is abnormal, rescreen is abnormal, repaternal blood type ispaternal blood type isAbAb screen: “screen: “KellKell Kills LewisKills LewisAbAb screen: screen: KellKell Kills. LewisKills. LewisIf critical titer, REFERIf critical titer, REFERGiveGive rhogamrhogam at 28 wks andat 28 wks andGive Give rhogamrhogam at 28 wks and at 28 wks and Cant give too much Cant give too much rhogamrhogamfrequentlyfrequentlyfrequentlyfrequentlyHydropsHydrops is not always from is not always from suspectsuspect hydropshydrops take a gootake a goosuspect suspect hydropshydrops, take a goo, take a goocause.cause.

KEY POINTSKEY POINTSKEY POINTS.KEY POINTS.carecarequest titer and ask what thequest titer and ask what thequest titer and ask what the quest titer and ask what the

s Lives ”s Lives ”s Lives.s Lives.

within 72 hrs of deliverywithin 72 hrs of deliverywithin 72 hrs of deliverywithin 72 hrs of deliverymm, and cant give it too , and cant give it too

RhRh DISEASE! If you DISEASE! If you od history to define theod history to define theod history to define the od history to define the

REFERREFERREFERREFER

ACOG Technical BulletACOG Technical BulletACOG Technical BulletACOG Technical BulletIsoimmunizationIsoimmunization in Pregin PregEducational Bulletin 22Educational Bulletin 22Educational Bulletin 22Educational Bulletin 22Aug 1996Aug 1996ACOG Practice BulletinACOG Practice BulletinACOG Practice BulletinACOG Practice BulletinAlloimmunizationAlloimmunizationMay 1999May 1999May 1999May 1999ANGELS GUIDELINEANGELS GUIDELINE

ENCESENCESENCESENCES

in: Management ofin: Management ofin: Management of in: Management of gnancygnancy27272727

: Prevention of: Prevention of RhRh: Prevention of : Prevention of RhRh