IntrauterineTransfusion.

Raymond J. Allen, M.D.

Atlanta PerinatalConsultants

14 Fetal Hydrops - Pathophysiology Ongoing severe anemia ExtramedulallaryhematopoesisAbnormalliver functionPortalhypertensionCardiacfailure

15 Red-cell Alloimmunization Pathophysiology Antigen negativemother'isexposedto antigenpositiveRBCsB LymphocyteclonesRe-exposure- PlasmacelllgGproductionAnti-antigenIgGcrossesthe placentaand destroysfetal erythrocytes

16 Red-cell alloimmunization - Neonatal outcomesAnemia Hyperbilirubinemia Kernicterus Delayed anemia

17 Red-cell Alloimmunization - Magnitude of the Problem 4 million annualbirths 4,000 Rh alloimmunized 10,000 alloimmunized to other antigens 14,000 fetusesat risk per year 10% or 1,400 require transfusion

18 HDFN and Atypical Antibodiesc.C,Cw, CX,e,E,ce, Ce,Rh32, Go,Be, Evans,Riv ,Kell, Kidd ,Jsa,Jsb,Ku, Duffya,M ,N,s,U ,PPiPk,Di,Lan,L W ,Far,Good,Wr,Zd

19 Rh alloimmunization - Monitoring Antibody screen (Indirect Coombs) atinitialpre-natalvisit Titer antibodyPaternalbloodtype and genotype If Rh-and paternityis certainfurthertestingnot needed If Rh+or unknown,monthlyantibodytiters

20 Rh alloimmunization - Monitoring If maternal titers reach the "critical titer"(usually 1:16) fetal monitoring is indicated

21 Rh alloimmunization - Monitoring Liley, 1961, reported. monitoring theseverityof fetal hemolyticanemiaby analyzingamnioticfluid bilirubinlevelsSpectrophotometricmeasurement- Delta00 450 Lileycurves- 3 zones

22 Liley Curve 23 Bilirubin monitoring - Problems and,limitationsLimited data as to when to start and optimal frequency of repeated testing Errors ininterpretation of amniotic fluid bilirubin levels Poor .correlation to disease severity withKell Potential to worsen alloimmunization

24 Fetal Blood Sampling Ultrasound guided, direct measurement of anemiaHigher risk procedure than amniocentesis 1% fetal death risk Unable to reliably monitoramniotic fluid bilirubin levels afterwards Likely to worsen alloimmunization more thanamniocentesis

25 Red-cell alloimmunization - Monitoring goals Detectionof severeanemiaand interventionbyeitherbloodtransfusionor deliveryprior to fetal deathwhileminimizingpotentiallyharmful.invasiveprocedures.

26 Proposed non-invasive monitoring methods MaternalantibodytitersFetal heart size Fetal cardiac output Fetal liver size Fetal spleen size Doppler studies ofthe peripheral circulation

27 Middle Cerebral Artery Doppler Increased flow with decreased OxygendeliveryAngleof insonationapproximately0 degreesCan.measurepeakvelocitiesinsteadof ratios

28 Middle Cerebral Artery Doppler 110women with 111 fetuses at risk 41(37%)normal35 (32%)mild anemia4 (4%)moderateanemia 19 (17%)severeanemiawithouthydrops12(11%) severeanemiawith hydrops

29 Middle Cerebral Artery Doppler All fetuses with moderate or severe anemiahad PeakSystolicVelocities> 1.5 timesthe medianfor gestationalage sensitivity100%false positive12%positivepredictivevalue65% negativepredictivevalue 100%

30 Middle Cerebral Artery Doppler StrengthsMulticenterDifferentalloimmuneantibodiesLimitationsPoorfor predictingmildanemiaDatawas not usedfor patientmanagementUncertainif can be used posttransfusions

31 Fetal Transfusion - History Liley, 1963, first successful intraperitonealtransfusion(IPT)Radiopaquedye in amnioticcavityFluoroscopicguidance1975,firstIPT usingstaticultrasound1977, IPT using"realtime"ultrasound

32 Fetal Transfusion - History 1981, Rodeck - First successful fetal intravasculartransfusion( guidedby fetoscopy)1982,Bangreportedthe first successfulultrasoundguidedtransfusioninto the umbilicalvein (IVT)

33 Intravascular versus Intraperitoneal Transfusion Improvedsurvivalofhydropic fetus with intravascular versus intraperitoneal 8/44 fetal death - intraperitoneal1/44 fetal death - intravascular Procedural complications twice as frequent with IPT

34 Fetal Transfusion - Intravascular SimpletransfusionversusexchangetransfusionCombiningIVTand IPTAlternativesites IntrahepaticumbilicalveinIntracardiactransfusion

35 Blood for Fetal Transfusion Fresh or frozen, thawed PRBCs, Hct. 80-90% 0-or cross-matchedto the motherand fetusWashed,Leukocytepoor IrradiatedwithexternalbeamradiationCM\/ negativeMotherpotentialdonor source

36 Fetal Intravascular Transfusion - Procedure Ultrasound: Cord location,

estimated weight, etc. Maternal sedation, I.V. access Sterile prep and drapeCordocentesis for fetal blood sample Type, MCV, Hematocrit, Direct Coombs Fetalparalysis - Pancuronium or Vecuronium

37 Fetal Intravascular Transfusion - Procedure Assistant"pushes"warmedblood using a 3-way stopcock Ultrasound turbulence confirms proper blood flow inumbilical vein Post-transfusion hematocrit obtained 20 to 60 minutes Transfusion rate 5ml/kg/min (300 ml/kg/hr)

3839

40 Calculating Transfusion Volume PRBC Volume (mls) = Est Fetal BloodVolume(mls)X Hct.changeHematocritof PRBCto be transfusedHct. change= DesiredHct. - Initial Hct.

41 Normal Fetal Hemoglobin

42 Fetal Response to Transfusion Decreased cardiac output Normalizes in 24hours IncreasedbloodviscosityDecreasedstrokevolume IncreasedRightatrialandumbilicalvenouspressuresDecreasedfetal heartrate

43 Fetal Response to Transfusion General peripheral arterial vasodilatationResponse to increased afterload Lower blood pH Less 02 delivery with adulthemoglobin Increas.edvenous 02 partial pressure Increased 2-3 DPG (facilitates tissue02 delivery) .

44 Intravascular Transfusion - Complications Perinatalloss rate1-3% -

ChorioamnionitisCordbleedingandthrombosisFetalbradycardiaappx.4% EmergencypretermdeliveryIncreasedmaternalantibodysensitization

45 Post-Transfusion Monitoring After transfusion, the majority of circulatingRBCs donor Half life approximately 60 days Estimated decline in Hct. appx. 1% per dayRepeat transfusion 2 -4 weeks Final transfusion 32 - 35 weeksMCA Dopplers appear helpful in monitoring fetal anemia after transfusion

.4§ Intravascular Transfusion - Outcomes 41'Lnatients, 1982- 1994(20studies) 84% survival overall 74% survival with hydrops 94% survival no hydropsProcedure related fet~lloss 2%

47 Intrauterine Transfusion - Postnatal Findings ImprovedgrowthpatternIronoverloadDelayedpostnatalanemiaSuppressedhematopoesisLongtermneurologicoutcomesand health appeargood Limiteddata

48 Kell alloimmunization 90% of partnersK~IInegativeCriticaltiter as low as 1:8Bilirubinlevelscorrelatepoorlyto severityof anemiaSuppressedhematopoesis

49

50 Parvovirus 819 Erythemainfectiosum( fifth disease) in childrenAsymptomaticor milddiseasein adultsAplastic anemia- impairedRaC productionor survival

51 Parvovirus 819 in Pregnancy Can cause severe fetal anemia, hydrops anddeath Estimatedfetal death risk with matemalinfection3-6% Spontaneousresolutionofhydropsmayoccur

52 Effect of Intrauterine Transfusion on Fetal Hydrops FromParvovirus

53 Effect of Intrauterine Transfusion on Fetal Hydrops FromParvovirus

54 Parvovirus 819 in Pregnancy Management Documentmatemalinfection(Igm+) Weeklyultrasoundsuntil8"weeksfrom infectionStart monitoringat 18weeksMonitor12-16weekstotal Considertransfusionfor moderateto severehydrops

.55 Alloimmune Thrombocytopenia Alloimmune thrombocytopenia (AIT) -platelet equivalent to red-cell HDFN MatemallgG anti-platelet antibodies PI-A1 mostcommon antigen Progressive thrombocytopenia Intracranial hemorrhage, stillbirthWorsening severity with subsequent pregnancies

56 Alloimmune Thrombocytopenia Generallytreatedwith gam.ma-globulinandsteroidsPlatelettransfusionsfor refractorycasesMotherpreferreddonor source1-5 mJ.<30wee~s;.5-10ml. >30weeks

57 Hematopoietic Stem Cell Transplantation Rh all~immunizationAlpha andBetathalassemiaMetachromaticleukodystrophyBareIymp~ocytesyndromeSeverecombinedimmunodeficiencysyndromeChediak-HigashisyndromeHurlersyndrome

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1 Intrauterine Tiansfusion RaymondJ. Alle~,M.D. Atlanta r\S'-;'-lota: Cu,-,';;u:taiits

2 Indications for Fetal Transfusion Anemia Thrombocytopenia Stem-celltransplantation

3 Fetal Anemia - Causes Blood loss Underproductionof RBCsDestructionofRBCs

4 Fetal Hemorrhage ExternalPlacental:Abruption,PlacentapreviaCordVelamentousinsertion,nuchalcord FetoplacentalFetomaternalTwin-twintransfusion

5 Causes of Fetal Anemia - Underproduction ParvovirusB19 Humanparvovirushaspropensityfor erythroidprecursorscausingaplasiaSevereanemiaandfetal deathmayresult Homozygousalpha-thalassemia

6 Causes of Fetal Anemia - Destruction of RBCs Red-cellalloimmunization.

Mostcommonindicationfor intrauterinetransfusiontherapyCauseshemolyticdiseaseof the fetus and newborn(HDFN)

7 Red-cell Alloimmunization - Etiology Exposure of antigen negative mother toantigenpositiveRBCsRe-exposure- PlasmacelllgG productionAnti-antigenantibodiescrossplacentaand destroysfetal erythrocytes

8 Red-cell alloimunization - Neonatal outcomes AnemiaHyperbilirubinemiaKernicterus Delayed anemia

9 Fetal Physiologic Response to Anemia Decreased Oxygen ContentIncreasedCardiacWork

10 Fetal Physiologic Response to Anemia Increased Ca(diac OutputBiventricular output increases from 644 to 879 ml/kg/min (Copel) decreased bloodviscosity - increased pre-load Peripheral vasodilatation - decreased afterload NormalRightheartdominancepersists . .

11 Fetal Physiologic Response to Anemia Cerebral vasodilatationExtramedulallryhematopoesi$- liver..$pleenFp.talHydropsFetal Death.

12 Hydrops - Ultrasound Findings Fluidaccumulationin bodycavitiesThickened place,nt~ EdefT)a Hepatomegaly Splenomegaly Card!ac E;mlargement

13 Fetal Hydrops