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Rh Program of Nova ScotiaRh Program of Nova Scotia
The presenter does not have any involvement with industry that mThe presenter does not have any involvement with industry that may be ay be perceived as potentially influencing the presentation of the eduperceived as potentially influencing the presentation of the educational cational material contained withinmaterial contained within
Blood MattersBlood MattersOct 29, 1010Oct 29, 1010
M.C. Van den HofM.C. Van den Hof
Rh Program of Nova ScotiaRh Program of Nova Scotia
Provide overview of Nova ScotiaProvide overview of Nova Scotia’’s Rh s Rh programprogramReview guidelines for perinatal antibody Review guidelines for perinatal antibody screeningscreeningReview guidelines for Rh immunoglobulin Review guidelines for Rh immunoglobulin administrationadministration
Rh Program of Nova ScotiaRh Program of Nova Scotia
History:
Early 1960’s: !% of all births were Rh(D) alloimmunized in Nova Scotia
NS infant mortality among highest in Canada
1964: Rh Committee established, modelled on Winnipeg Rh Program
2nd Fetal Transfusion in Canada --Halifax, 1964
Program GoalsProgram Goals
Reduce Rh(D) alloimmunization to lowest Reduce Rh(D) alloimmunization to lowest possible (0.4 per 1000 total pregnancies)possible (0.4 per 1000 total pregnancies)
Achieve 0% mortality & morbidity due to Achieve 0% mortality & morbidity due to red cell and platelet antibodiesred cell and platelet antibodies
Rh Program of Nova ScotiaRh Program of Nova Scotia
Effectiveness
•New Rh(D) alloimmunized women in NS: reduced from 1 per 100 in 1964 to 1.5 per 1000 in 1982 to <0.4 (.27)per 1000 total births in 2009
•Excellent Provincial compliance with guidelines
•Early detection and management of women with antibodies
Rh Program of Nova ScotiaRh Program of Nova Scotia
Program Structure:
Provincial program: NS Department of HealthIWK Health Centre-----Dept Obs & Paeds
Medical DirectorNurse coordinatorNurse part time
Rh CommitteeRCP – administrative support/ database
Rh Program of Nova ScotiaRh Program of Nova Scotia
Links
IWK Health Centre: FATC; transfusion services; nursing units; Perinatal CentreProvincial hospital transfusion services; obstetrics departmentsObstetrics clinics, physicians officesLaboratories and clinicians throughout the Maritime provincesFetal antigen testing: Wisconsin
Rh Program of Nova ScotiaRh Program of Nova ScotiaNursing Role
Promote guidelines for antibody screening & WinRho SDF administration
Review/record data: antibody screens; RhIG (WinRho SDF) administration; cord typing; Kleihauer-Betke for FMH; procedures/events; pregnancy outcomes
Maintaining/updating:- Guidelines for Perinatal Antibody Screening and RhIG administration- Patient pamphlet -Consent for WinRho SDF
Resource for:women who are Rh negative or have antibodies; family care providers; obstetricians;
nursing staff
Education: medical students, nursing staff; nursing students:; Telehealth
Database and Research
Website: www.rcp.nshealth.ca/rh
Rh Program of Nova ScotiaRh Program of Nova ScotiaManaging red blood cell & platelet antibodies
Contacting physician: letters, calls, faxes
Maternal antibody testingPaternal antigen testing
Arranging/assisting with special procedures:ultrasoundsamniocentesisfetal transfusionsdelivery alerts & followup
Rh PoliceRh Police
StimulusStimulus
Fetal red blood cells (fetoFetal red blood cells (feto--maternal maternal hemorrhage)hemorrhage)Blood transfusionBlood transfusionDrug abuse Drug abuse -- sharing needlessharing needlesNaturally occurring Naturally occurring
Primary response (IgM); may take 2wks Primary response (IgM); may take 2wks to 6 months to become IgG antibodyto 6 months to become IgG antibody
What antibodies doWhat antibodies dopermanent IgG permanent IgG antibodiesantibodies fit through fit through
placental barrierplacental barrier
attach to attach to antigenantigen on fetal red blood cellson fetal red blood cells
hemolysis causes fetal anemia antenatallyhemolysis causes fetal anemia antenatally
hemolysis causes neonatal anemia and hemolysis causes neonatal anemia and hyperbilirubinemiahyperbilirubinemia
Antibody typesAntibody typesRh antibodies: (D*, C, c, E, e) Rh antibodies: (D*, C, c, E, e)
**preventable (17% of pop. Rh neg, preventable (17% of pop. Rh neg, missing Rh antigen on RBCmissing Rh antigen on RBC’’s)s)
Other examples (nonOther examples (non--preventable): preventable): KellKellDuffy (Fya, Fyb)Duffy (Fya, Fyb)Kidd (Jka, Jkb)Kidd (Jka, Jkb)
From: Ortho Diagnostics Inc. (1968). Blood group antigens and antibodies as applied to hemolytic disease of the newborn. Raritan, NJ: Author
From: Ortho Diagnostics Inc. (1968). Blood group antigens and antibodies as applied to hemolytic disease of the newborn. Raritan, NJ: Author
From: Ortho Diagnostics Inc. (1968). Blood group antigens and antibodies as applied to hemolytic disease of the newborn. Raritan, NJ: Author
From: Ortho Diagnostics Inc. (1968). Blood group antigens and antibodies as applied to hemolytic disease of the newborn. Raritan, NJ: Author
From: Ortho Diagnostics Inc. (1968). Blood group antigens and antibodies as applied to hemolytic disease of the newborn. Raritan, NJ: Author
From: Ortho Diagnostics Inc. (1968). Blood group antigens and antibodies as applied to hemolytic disease of the newborn. Raritan, NJ: Author
In-utero bilirubin metabolism
From: Ortho Diagnostics Inc. (1968). Blood group antigens and antibodies as applied to hemolytic disease of the newborn.Raritan, NJ: Author
Kernicterus risk
From: Ortho Diagnostics Inc. (1968). Blood group antigens and antibodies as applied to hemolytic disease of the newborn. Raritan, NJ: Author
GenotypingGenotypingMOM is Rh neg = missing D antigenMOM is Rh neg = missing D antigen
DAD is Rh neg = also missing D antigenDAD is Rh neg = also missing D antigen
BABY will be Rh (D) neg (cannot inherit D)BABY will be Rh (D) neg (cannot inherit D)
Genotyping (continued)Genotyping (continued)MOM is Rh neg (d/d = missing D antigen)MOM is Rh neg (d/d = missing D antigen)DAD is Rh pos (carries D antigen)DAD is Rh pos (carries D antigen)
Dad can be D / d Dad can be D / d 50% chance baby will be D50% chance baby will be D--pospos
OR Dad can be D / DOR Dad can be D / D100% chance baby will be D100% chance baby will be D--pospos
Laboratory TestingLaboratory Testing
Initial Initial ------ ABO; Rh; screenABO; Rh; screen
Positive antibody for HDNPositive antibody for HDN
Repeat titres q monthly or as directed by Rh ProgramRepeat titres q monthly or as directed by Rh ProgramMay require further investigations depending on titreMay require further investigations depending on titreMay require antenatal Rx depending on investigationsMay require antenatal Rx depending on investigations
Neonatal bloodsNeonatal bloods ------ ABO; Rh; DAT; Hgb; BiliABO; Rh; DAT; Hgb; Bili
Laboratory TestingLaboratory Testing
Initial Initial ------ ABO; Rh; screenABO; Rh; screen
No antibody associated with HDNNo antibody associated with HDNRh neg (check father)Rh neg (check father)------ repeat screen at 28 weeks; repeat screen at 28 weeks;
repeat at deliveryrepeat at delivery
Rh pos Rh pos ------ repeat screen at 24repeat screen at 24--28 weeks28 weeks
Neonatal bloodsNeonatal bloods ------ ABO; Rh; DATABO; Rh; DAT
Antibody screeningAntibody screening““group & screengroup & screen””
1st prenatal visit (all women)1st prenatal visit (all women)28 weeks (all women)28 weeks (all women)delivery (Rhdelivery (Rh-- or or HDN antibodies)HDN antibodies)prepre-- Rho(D) immune globulin (RhRho(D) immune globulin (Rh--))
MONTHLY or q 2 wks (if antibodies MONTHLY or q 2 wks (if antibodies causing HDN are detected)causing HDN are detected)
Risk of Rh (D) immunizationRisk of Rh (D) immunization
<28 weeks:<28 weeks: 0.1%0.1%28 weeks to delivery:28 weeks to delivery: 1.7%1.7%Postpartum: Postpartum: 2 to 8 %2 to 8 %Spontaneous abortion:Spontaneous abortion: 22--3%3%Therapeutic abortion:Therapeutic abortion: 44--5%5%Antenatal bleeding:Antenatal bleeding: ??
Prevention: Prevention: Rh Immune Globulin (WinRho SDFRh Immune Globulin (WinRho SDF™™))
28 weeks (Rh28 weeks (Rh-- Dad?)Dad?)postpartum postpartum (Rh+baby)(Rh+baby)abortion/ectopicabortion/ectopicantepartum bleedingantepartum bleedingspecial procedures special procedures (amniocentesis, (amniocentesis, cordocentesis, CVS)cordocentesis, CVS)
external versionexternal versionplatelet transfusionplatelet transfusionabdominal traumaabdominal traumapartial molar partial molar pregnancypregnancyblighted ovumblighted ovuminadvertent inadvertent transfusion Rh+ bloodtransfusion Rh+ blood
From: Ortho Diagnostics Inc. (1968). Blood group antigens and antibodies as applied to hemolytic disease of the newborn. Raritan, NJ: Author
Rho(D) Immune GlobulinRho(D) Immune Globulin““WinRho SDFWinRho SDF™”™” ““RhoGAMRhoGAM™”™”
WinRho SDFWinRho SDF™™ used in Canadaused in Canadablood product blood product deep I.M. deep I.M. OrOr I.V. routeI.V. routeALWAYS draw antibody screen ALWAYS draw antibody screen firstfirst120 120 µµg g or or 300 300 µµg doseg doseKleihauer when indicatedKleihauer when indicatedobtain informed consent (may refuse)obtain informed consent (may refuse)
Informed ConsentInformed Consent
blood product (from plasma)blood product (from plasma)donors screened for Hep B, C, HIVdonors screened for Hep B, C, HIVviral inactivation stepviral inactivation stepno reports of disease transmissionno reports of disease transmissionrisk of Rh disease from 1:10 to 1:1000risk of Rh disease from 1:10 to 1:1000mandated by Krever Inquirymandated by Krever Inquiry
KleihauerKleihauer--Betke TestBetke Test% fetal red blood cells in maternal circulation% fetal red blood cells in maternal circulation
AmniocentesisAmniocentesisantenatal bleeding (2nd & 3rd trimester)antenatal bleeding (2nd & 3rd trimester)postpartum (Rhpostpartum (Rh-- mom/Rh+ baby)mom/Rh+ baby)Formula for Kleihauer > 0.2% Formula for Kleihauer > 0.2% Massive fetoMassive feto--maternal hemorrhage maternal hemorrhage (abruptio, stillbirth) Rh (abruptio, stillbirth) Rh -- or Rh+or Rh+
Kleihauer slideKleihauer slide
Fetus at RiskFetus at Risk
Fetal anemia diagnosed by: Fetal anemia diagnosed by: amniocentesisamniocentesiscordocentesiscordocentesisultrasoundultrasound
hydropshydropsmiddle cerebral artery Dopplermiddle cerebral artery Doppler
Treatment:Treatment:intravascular fetal transfusionintravascular fetal transfusionpreterm birthpreterm birth
Infant at RiskInfant at RiskDiagnosis:Diagnosis:
history of HDN antibodies?history of HDN antibodies?early jaundice < 24 hoursearly jaundice < 24 hourscord DAT (cord DAT (““CoombCoomb’’ss””) ) positive positive (due to HDN (due to HDN or ABO antibodies)or ABO antibodies)
Treatment:Treatment:PhototherapyPhototherapyExchange or Direct blood transfusionExchange or Direct blood transfusion
CORD blood testingCORD blood testingDirect Antiglobulin Test (DAT) Direct Antiglobulin Test (DAT)
oror““Direct CoombDirect Coomb’’ss””
POSITIVE test = antibodies on babyPOSITIVE test = antibodies on baby’’s s red blood cellsred blood cells
Cord DAT testCord DAT testMost COMMON reason for POSITIVE DAT:Most COMMON reason for POSITIVE DAT:1. ABO incompatibility1. ABO incompatibility
eg. Mom group O, baby group A or Beg. Mom group O, baby group A or B
2. Winrho (anti2. Winrho (anti--D) from MomD) from Mom’’s recent s recent injection coats some of babyinjection coats some of baby’’s red blood s red blood cellscells
Cord DAT positiveCord DAT positiveOther reasons, less common:Other reasons, less common:
Hemolytic disease causing antibodies Hemolytic disease causing antibodies crossed over from mother crossed over from mother (anti(anti--D, c, Kell, Duffy, etc)D, c, Kell, Duffy, etc)
Case StudyCase Study
27 y o G1 P0 is Rh neg; partner is Rh pos27 y o G1 P0 is Rh neg; partner is Rh pos
Has antibody screen and WinRho at 28 weeksHas antibody screen and WinRho at 28 weeksAntibody screen is positive Antibody screen is positive
What has happened?What has happened?
Case StudyCase Study
27 y o G1 P0 is Rh neg; partner is Rh pos27 y o G1 P0 is Rh neg; partner is Rh pos
Has antibody screen and WinRho at 28 weeksHas antibody screen and WinRho at 28 weeksAntibody screen is positive Antibody screen is positive
What has happened?What has happened?
1) Isoimmunization or1) Isoimmunization or2) Antibody screen taken after injection instead of before2) Antibody screen taken after injection instead of before
Case StudyCase Study
29 y o G3 P1 A1 at 28 weeks 29 y o G3 P1 A1 at 28 weeks A neg ; Positive screen for Fya 1/64A neg ; Positive screen for Fya 1/64What are the next two steps?What are the next two steps?
Case StudyCase Study
29 y o G3 P1 A1 at 28 weeks 29 y o G3 P1 A1 at 28 weeks A neg ; Positive screen for Fya 1/64A neg ; Positive screen for Fya 1/64What are the next two steps?What are the next two steps?
Assess for fetal anemia; paternal genotypeAssess for fetal anemia; paternal genotypeWinRhoWinRho
Case StudyCase Study
29 y o G2 P1 presents @ 29 weeks with 29 y o G2 P1 presents @ 29 weeks with antenatal bleeding, U/S shows small antenatal bleeding, U/S shows small marginal abruption, fetus well, uterus nonmarginal abruption, fetus well, uterus non--tendertenderOther important Mx issues?Other important Mx issues?
Case StudyCase Study
29 y o G2 P1 presents @ 29 weeks with 29 y o G2 P1 presents @ 29 weeks with antenatal bleeding, U/S shows small antenatal bleeding, U/S shows small marginal abruption, fetus well, uterus nonmarginal abruption, fetus well, uterus non--tendertenderOther important Mx issues?Other important Mx issues?
Check Rh; pt is neg and had just received Check Rh; pt is neg and had just received her WinRho 300ug 5 days earlier; Is this her WinRho 300ug 5 days earlier; Is this adequate?adequate?
Case StudyCase Study
29 y o G2 P1 presents @ 29 weeks with 29 y o G2 P1 presents @ 29 weeks with antenatal bleeding, U/S shows small marginal antenatal bleeding, U/S shows small marginal abruption, fetus well, uterus nonabruption, fetus well, uterus non--tendertenderOther important Mx issues?Other important Mx issues?
Check Rh; pt is neg and had just received her Check Rh; pt is neg and had just received her WinRho 300ug 5 days earlier; Is this adequate?WinRho 300ug 5 days earlier; Is this adequate?NoNo------needs Kleihauerneeds Kleihauer
[With permission]
A healthy baby after A healthy baby after six insix in--utero utero transfusionstransfusions
BILIRUBIN BILIRUBIN In UTERO = unconjugated changed to In UTERO = unconjugated changed to
conjugated; excreted by mother conjugated; excreted by mother
After Birth = baby cannot do this wellAfter Birth = baby cannot do this wellUnconjugated bilirubin causes JAUNDICE Unconjugated bilirubin causes JAUNDICE
and risk of KERNICTERUS (staining of and risk of KERNICTERUS (staining of brain cells) if not treatedbrain cells) if not treated
FetoFeto--maternal hemorrhagematernal hemorrhageBabyBaby’’s and mothers and mother’’s blood systems are s blood systems are
separate in placentaseparate in placenta
Break in barrier can let come babyBreak in barrier can let come baby’’s red s red blood cells enter motherblood cells enter mother’’s circulations circulation
WinRho DosingWinRho Dosing300 ug 28 weeks300 ug 28 weeks
antenatal bleed*antenatal bleed*amniocentesis, etc*amniocentesis, etc*abd trauma*abd trauma*>12 wk preg loss>12 wk preg loss
120 ug postpartum*120 ug postpartum*<12 wk preg loss<12 wk preg lossexternal versionexternal versionplatelet transfusionplatelet transfusion
* Kleihauer* Kleihauer------ 120 ug for <0.2%; 300ug for <0.5%120 ug for <0.2%; 300ug for <0.5%
Antibody typesAntibody typesRh antibodies: (D*, C, c, E, e) Rh antibodies: (D*, C, c, E, e)
**preventable (17% of pop. Rh neg, preventable (17% of pop. Rh neg, missing Rh antigen on RBCmissing Rh antigen on RBC’’s)s)
Other examples (nonOther examples (non--preventable): preventable): KellKellDuffy (Fya, Fyb)Duffy (Fya, Fyb)Kidd (Jka, Jkb)Kidd (Jka, Jkb)
Cause of antiCause of anti--D sensitization [NS residents]D sensitization [NS residents]
Presumed Cause 1988-2000 2001-2009Failed 28 week injection 10 7Failed postpartum injection 14 9Sensitized before 28 weeks 27 1228 week not given 5Postpartum not given 2Antenatal bleeding – not given 2Spontaneous abortion – not given 6Mismatched blood – not given (plasma) 1Therapeutic abortion – not given 1Patient refusal 2Unknown sensitization time 4 16Not given before protocol establishedTOTALS (% based on # Rh-/yr reported to Rh Program)
73 (0.32%) 45 (0.27%)