DOENÇA HEMOLÍTICA PERINATAL Giovanni Fraga Lenza.

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DOENÇA HEMOLÍTICA DOENÇA HEMOLÍTICA PERINATAL PERINATAL Giovanni Fraga Lenza Giovanni Fraga Lenza

Transcript of DOENÇA HEMOLÍTICA PERINATAL Giovanni Fraga Lenza.

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DOENÇA DOENÇA HEMOLÍTICA HEMOLÍTICA PERINATALPERINATAL

Giovanni Fraga LenzaGiovanni Fraga Lenza

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1.Incompatibilidade sanguínea materno-fetal1.Incompatibilidade sanguínea materno-fetal

2.Passagem do sangue fetal para circulação 2.Passagem do sangue fetal para circulação maternamaterna

3.Reconhecimento do Ag3.Reconhecimento do Ag

4.Produção de Ac4.Produção de Ac

5.Passagem dos Ac para circulação fetal5.Passagem dos Ac para circulação fetal

6.Ação dos Ac sobre as hemácias fetais6.Ação dos Ac sobre as hemácias fetais

Doença Hemolítica PerinatalDoença Hemolítica PerinatalHistória naturalHistória natural

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J Obstet Gynaecol Can. 20122012 May;34(5):429-35. May;34(5):429-35.Anti-d in rh(d)-negative pregnant women: are at-risk Anti-d in rh(d)-negative pregnant women: are at-risk pregnancies and deliveries receiving appropriate pregnancies and deliveries receiving appropriate prophylaxisprophylaxis??Koby L, , Grunbaum A, , Benjamin A, , Koby R, , Abenhaim HA..

Department of Obstetrics and Gynecology, Royal Victoria Hospital, McGill University, Department of Obstetrics and Gynecology, Royal Victoria Hospital, McGill University, Montreal QC.Montreal QC.AbstractAbstractObjective: Although Objective: Although anti-D prophylaxis has greatly reduced the rate of Rh-anti-D prophylaxis has greatly reduced the rate of Rh-immunizationimmunization, there , there remain women who sensitizeremain women who sensitize during or after pregnancy because during or after pregnancy because of of inadequate prophylaxisinadequate prophylaxis. The purpose of this study was to compare adherence to . The purpose of this study was to compare adherence to prophylaxis recommendations for antenatal and postnatal anti-D immunoglobulin prophylaxis recommendations for antenatal and postnatal anti-D immunoglobulin administration. Methods: We conducted a retrospective cohort study of all pregnancies administration. Methods: We conducted a retrospective cohort study of all pregnancies recorded at the Royal Victoria Hospital between 2001 and 2006 to determine the rates of recorded at the Royal Victoria Hospital between 2001 and 2006 to determine the rates of antenatal and postnatal prophylaxis in Rh(D)-negative women. We compared adherence antenatal and postnatal prophylaxis in Rh(D)-negative women. We compared adherence to anti-D prophylaxis recommendations between our institution's physician-dependent to anti-D prophylaxis recommendations between our institution's physician-dependent antenatal approach and the protocol-based postpartum approach. Logistic regression antenatal approach and the protocol-based postpartum approach. Logistic regression analysis was used to estimate the odds ratio and 95% confidence intervals of analysis was used to estimate the odds ratio and 95% confidence intervals of determinants of non-adherence to current recommendations for anti-D prophylaxis. determinants of non-adherence to current recommendations for anti-D prophylaxis. Results: Antenatal administration was analyzed in 1868 pregnancies in eligible Rh-Results: Antenatal administration was analyzed in 1868 pregnancies in eligible Rh-negative women. Among these women, 85.7% received appropriate antenatal prophylaxis negative women. Among these women, 85.7% received appropriate antenatal prophylaxis and 98.5% of eligible women received appropriate postnatal prophylaxis. Factors and 98.5% of eligible women received appropriate postnatal prophylaxis. Factors independently associated with non-adherence to antepartum prophylaxis included first independently associated with non-adherence to antepartum prophylaxis included first visit in the third trimester (P < 0.001), transfer from an outside hospital (P = 0.03), and visit in the third trimester (P < 0.001), transfer from an outside hospital (P = 0.03), and physician licensing before 1980 (P = 0.04). Conclusion: Unlike hospital-based protocol-physician licensing before 1980 (P = 0.04). Conclusion: Unlike hospital-based protocol-dependent systems, physician-dependent systems for antenatal anti-D prophylaxis remain dependent systems, physician-dependent systems for antenatal anti-D prophylaxis remain subject to errors of omission. A more standardized system is needed to ensure effective subject to errors of omission. A more standardized system is needed to ensure effective antenatal prophylaxis.antenatal prophylaxis.

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História NaturalHistória NaturalIncompatibilidade sanguínea materno-fetalIncompatibilidade sanguínea materno-fetal

Passagem de sangue fetal para circulação maternaPassagem de sangue fetal para circulação materna

Reconhecimento do AG e produção de AC pela mãeReconhecimento do AG e produção de AC pela mãe Passagem de AC maternos para circulação fetalPassagem de AC maternos para circulação fetal

Ação dos AC maternos sobre as hemácias fetaisAção dos AC maternos sobre as hemácias fetais

AnemiaAnemia EritroblastoseEritroblastose Focos ectópicos de hematopoieseFocos ectópicos de hematopoiese Polidramnia e placentomegaliaPolidramnia e placentomegalia AnasarcaAnasarca MorteMorte

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INCIDÊNCIAINCIDÊNCIA

Sistema ABO e Rh – 98% 2/3 ABOSistema ABO e Rh – 98% 2/3 ABO 1/3 Rh1/3 Rh

KellKellE 2%E 2%CellanoCellanoDuffyDuffyKiddKiddoutrosoutros

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Incompatibilidade sanguínea materno-fetalIncompatibilidade sanguínea materno-fetal

Passagem de SG fetal para circulação maternaPassagem de SG fetal para circulação materna

Reconhecimento do AG e produção de AC pela mãeReconhecimento do AG e produção de AC pela mãe Passagem de AC para circulação fetalPassagem de AC para circulação fetal

Ação dos AC maternos sobre as hemácias fetaisAção dos AC maternos sobre as hemácias fetais

AnemiaAnemia EritroblastoseEritroblastose Focos ectópicos de hematopoieseFocos ectópicos de hematopoiese Polidramnia e placentomegaliaPolidramnia e placentomegalia AnasarcaAnasarca MorteMorte

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Transfusion. 1990 May;30(4):344-57. 1990 May;30(4):344-57.Fetomaternal hemorrhage: incidence, risk factors, time of occurrence, Fetomaternal hemorrhage: incidence, risk factors, time of occurrence, and clinical effects.and clinical effects.Sebring ES, , Polesky HF..Memorial Blood Center of Minneapolis, Minnesota.Memorial Blood Center of Minneapolis, Minnesota.AbstractAbstractMost women have only very small amounts of fetal blood in their circulations Most women have only very small amounts of fetal blood in their circulations following pregnancy and delivery: following pregnancy and delivery: the volume is less than 0.5 mL of the volume is less than 0.5 mL of whole blood in 93 percent of womenwhole blood in 93 percent of women, less than , less than 1 mL in 96 percent, and 1 mL in 96 percent, and less than 2 mL in 98 percent. FMH of 30 mL or more occurs in just 3 of 1000 less than 2 mL in 98 percent. FMH of 30 mL or more occurs in just 3 of 1000 womenwomen. When the FMH was 150 mL or more, 15 of 41 infants did not survive Rh-. When the FMH was 150 mL or more, 15 of 41 infants did not survive Rh-negative women with FMH of more than 30 mL of Rh-positive whole blood are at negative women with FMH of more than 30 mL of Rh-positive whole blood are at increased risk of Rh immunization, and thus the outcome of their future increased risk of Rh immunization, and thus the outcome of their future pregnancies also may be affected. ABO-compatible fetal red cells that have pregnancies also may be affected. ABO-compatible fetal red cells that have entered the maternal circulation have a life span similar to that of adult cells. entered the maternal circulation have a life span similar to that of adult cells. ABO-incompatible fetal red cells may be cleared rapidly, but in some cases they ABO-incompatible fetal red cells may be cleared rapidly, but in some cases they circulate for weeks. Most FMHs of 30 mL or more occur before labor, delivery, circulate for weeks. Most FMHs of 30 mL or more occur before labor, delivery, or cesarean section. The majority occur with minimal clinical signs and or cesarean section. The majority occur with minimal clinical signs and symptoms in apparently normal pregnancies. The identification of postpartum symptoms in apparently normal pregnancies. The identification of postpartum Rh-negative women who have 30 mL or more of Rh-positive fetal blood in their Rh-negative women who have 30 mL or more of Rh-positive fetal blood in their circulation is important so that sufficient RhIG for immune suppression can be circulation is important so that sufficient RhIG for immune suppression can be administered. It appears that more than one-half of women with FMH of 30 mL administered. It appears that more than one-half of women with FMH of 30 mL or more would not be identified if protocols were adopted to test only women in or more would not be identified if protocols were adopted to test only women in pregnancies considered to be at high risk.pregnancies considered to be at high risk.

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Hemorragia feto-maternaHemorragia feto-materna

PARTO NORMAL X CESÁREOPARTO NORMAL X CESÁREO

Hemorragias da primeira metadeHemorragias da primeira metade Abortamento espontâneo x provocadoAbortamento espontâneo x provocado Prenhez ectópicaPrenhez ectópica Doença trofoblásticaDoença trofoblástica

Hemorragias da segunda metade Hemorragias da segunda metade DPPDPP Rotura uterinaRotura uterina PPPPDequitação manualDequitação manualProcedimentos invasivosProcedimentos invasivosGemelidadeGemelidadeMaior número de gstaçõesMaior número de gstaçõesAumenta com o evoluir da gestaçãoAumenta com o evoluir da gestação

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Transfusion. 2012 Feb 8. 2012 Feb 8.

Fetomaternal hemorrhage in normal vaginal delivery and in Fetomaternal hemorrhage in normal vaginal delivery and in delivery by cesarean section.delivery by cesarean section.Lubusky M, , Simetka O, , Studnickova M, , Prochazka M, , Ordeltova M, , Vomackova K..

From the Department of Obstetrics and Gynecology, the Department of Medical Genetics and Fetal Medicine, From the Department of Obstetrics and Gynecology, the Department of Medical Genetics and Fetal Medicine, the Department of Surgery I, and the Department of Immunology, University Hospital, Olomouc, Czech the Department of Surgery I, and the Department of Immunology, University Hospital, Olomouc, Czech Republic; and the Department of Obstetrics and Gynecology, University Hospital, Ostrava, Czech Republic.Republic; and the Department of Obstetrics and Gynecology, University Hospital, Ostrava, Czech Republic.AbstractAbstractBACKGROUND: BACKGROUND: The objective was to determine the incidence and volume of fetomaternal hemorrhage (FMH) in normal The objective was to determine the incidence and volume of fetomaternal hemorrhage (FMH) in normal vaginal delivery and in delivery by cesarean section. Determination of these variables would enable vaginal delivery and in delivery by cesarean section. Determination of these variables would enable optimalization of guidelines for D alloimmunization prophylaxis.optimalization of guidelines for D alloimmunization prophylaxis.STUDY DESIGN AND METHODS: STUDY DESIGN AND METHODS: In a prospective cohort study, a total of 3457 examinations were performed, 2413 after normal vaginal In a prospective cohort study, a total of 3457 examinations were performed, 2413 after normal vaginal delivery and 1044 after cesarean delivery. FMH was assessed by flow cytometry. (FMH is fetal red blood delivery and 1044 after cesarean delivery. FMH was assessed by flow cytometry. (FMH is fetal red blood cell [RBC] volume; fetal blood volume is double [expected fetal hematocrit is 50%].)cell [RBC] volume; fetal blood volume is double [expected fetal hematocrit is 50%].)RESULTS: RESULTS: The The fetal fetal RBCRBC volume diagnosed in maternal circulation after delivery ranged from volume diagnosed in maternal circulation after delivery ranged from insignificant FMH of not more than 0.1 mL to excessive FMH of 65.9 mLinsignificant FMH of not more than 0.1 mL to excessive FMH of 65.9 mL (median, 0.7; mean, 0.78; SD, 1.48). FMH of more than 2.5 mL (immunoglobulin [Ig] G anti-D insufficient (median, 0.7; mean, 0.78; SD, 1.48). FMH of more than 2.5 mL (immunoglobulin [Ig] G anti-D insufficient dose 50 µg) was observed in 1.4% (49/3457) and excessive volumes of FMH of more than 5 mL dose 50 µg) was observed in 1.4% (49/3457) and excessive volumes of FMH of more than 5 mL (insufficient dose, 100 µg) in 0.29% (10/3457). Delivery by cesarean section presented a higher risk of (insufficient dose, 100 µg) in 0.29% (10/3457). Delivery by cesarean section presented a higher risk of incidence of FMH of more than 2.5 mL (odds ratio, 2.2; p = 0.004) when compared with normal vaginal incidence of FMH of more than 2.5 mL (odds ratio, 2.2; p = 0.004) when compared with normal vaginal delivery. It did not, however, present a significant risk factor for the incidence of excessive volumes of FMH delivery. It did not, however, present a significant risk factor for the incidence of excessive volumes of FMH of more than 5 mL.of more than 5 mL.CONCLUSION: CONCLUSION: During normal vaginal delivery as well as during delivery by cesarean During normal vaginal delivery as well as during delivery by cesarean section, FMH of less than 5 mL occurs in the great majority of cases, section, FMH of less than 5 mL occurs in the great majority of cases, and thus for the prevention of D alloimmunization, an IgG anti-D dose of 100 µg should be and thus for the prevention of D alloimmunization, an IgG anti-D dose of 100 µg should be sufficientsufficient.. Contrarily, only rarely does greater FMH occur and delivery by cesarean section does not present Contrarily, only rarely does greater FMH occur and delivery by cesarean section does not present a risk factor.a risk factor.

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Hemorragia feto-maternaHemorragia feto-materna

Parto normal x cesáreoParto normal x cesáreo

Hemorragias da primeira metadeHemorragias da primeira metade Abortamento espontâneo x provocadoAbortamento espontâneo x provocado Prenhez ectópicaPrenhez ectópica Doença trofoblásticaDoença trofoblástica

Hemorragias da segunda metade Hemorragias da segunda metade DPPDPP Rotura uterinaRotura uterina PPPPDequitação manualDequitação manualProcedimentos invasivosProcedimentos invasivosGemelidadeGemelidadeMaior número de gstaçõesMaior número de gstaçõesAumenta com o evoluir da gestaçãoAumenta com o evoluir da gestação

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Incompatibilidade sanguínea materno-fetalIncompatibilidade sanguínea materno-fetal

Passagem de SG fetal para circulação maternaPassagem de SG fetal para circulação materna

Reconhecimento do AG e produção de AC pela mãeReconhecimento do AG e produção de AC pela mãe Passagem de AC para circulação fetalPassagem de AC para circulação fetal

Ação dos AC maternos sobre as hemácias fetaisAção dos AC maternos sobre as hemácias fetais

AnemiaAnemia EritroblastoseEritroblastose Focos ectópicos de hematopoieseFocos ectópicos de hematopoiese Polidramnia e placentomegaliaPolidramnia e placentomegalia AnasarcaAnasarca MorteMorte

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Apenas 1 em cada 23 gestantes Rh negativo formam ACApenas 1 em cada 23 gestantes Rh negativo formam AC

0,01 à 0,03 ml de sangue fetal podem ser suficientes para sensibilizar gestante0,01 à 0,03 ml de sangue fetal podem ser suficientes para sensibilizar gestantesusceptível ( Mollison et.al., 1973 )susceptível ( Mollison et.al., 1973 )

Incompatibilidade do sistema ABOIncompatibilidade do sistema ABO

Positivção do Coombs indiretoPositivção do Coombs indireto

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Incompatibilidade sanguínea materno-fetalIncompatibilidade sanguínea materno-fetal

Passagem de SG fetal para circulação maternaPassagem de SG fetal para circulação materna

Reconhecimento do AG e produção de AC pela mãeReconhecimento do AG e produção de AC pela mãe Passagem de AC para circulação fetalPassagem de AC para circulação fetal

Ação dos AC maternos sobre as hemácias fetaisAção dos AC maternos sobre as hemácias fetais

AnemiaAnemia EritroblastoseEritroblastose Focos ectópicos de hematopoieseFocos ectópicos de hematopoiese Polidramnia e placentomegaliaPolidramnia e placentomegalia AnasarcaAnasarca MorteMorte

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IgM ( AC completos ou precoces ) alto peso molecularIgM ( AC completos ou precoces ) alto peso molecular

Não atravessam a placentaNão atravessam a placenta

IgG ( AC incompletos, bloquadores ouIgG ( AC incompletos, bloquadores ou tardios )tardios )

atravessam a placentaatravessam a placenta

Hemólise Hemólise

RESPOSTA PRIMÁRIARESPOSTA PRIMÁRIA

RESPOSTA SECUNDÁRIA OU ANAMNÉSICARESPOSTA SECUNDÁRIA OU ANAMNÉSICA

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Incompatibilidade sanguínea materno-fetalIncompatibilidade sanguínea materno-fetal

Passagem de SG fetal para circulação maternaPassagem de SG fetal para circulação materna

Reconhecimento do AG e produção de AC pela mãeReconhecimento do AG e produção de AC pela mãe Passagem de AC para circulação fetalPassagem de AC para circulação fetal

Ação dos AC maternos sobre as hemácias fetaisAção dos AC maternos sobre as hemácias fetais

AnemiaAnemia EritroblastoseEritroblastose Focos ectópicos de hematopoieseFocos ectópicos de hematopoiese Polidramnia e placentomegaliaPolidramnia e placentomegalia AnasarcaAnasarca MorteMorte

Coombs indireto positivoCoombs indireto positivo

Coombs direto positivoCoombs direto positivoDopplerDoppler

USGUSG

CTGCTG

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Acompanhamento Gestante Rh Acompanhamento Gestante Rh negativonegativo

COOMBS INDIRETOCOOMBS INDIRETO TIPAGEM MARIDOTIPAGEM MARIDO

Rh (-)Rh (-) Rh (+)Rh (+)

heterozigotoheterozigoto

PCR-DNAPCR-DNATipagem fetalTipagem fetalSangue maternoSangue materno

1ª CONSULTA1ª CONSULTA

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Gestante Rh negativoGestante Rh negativoCOOMBS INDIRETOCOOMBS INDIRETO

NEGATIVONEGATIVO

IMUNOGLOBULINA ANTI-DIMUNOGLOBULINA ANTI-Dou ou

Repetir 28,32,36,partoRepetir 28,32,36,parto

Positivo Positivo

≤ ≤ 1/81/8

Mensal ate 28 semanasMensal ate 28 semanasQuinzenal apósQuinzenal após

≥ ≥ 1/161/16

AmniocenteseAmniocenteseCordocenteseCordocenteseDopplerDoppler20-28 sem20-28 sem

Tipagem + fator RhTipagem + fator RhHgbHgbHtcHtcCoombs diretoCoombs diretoContagem de reticulócitosContagem de reticulócitos

Possível tratamentoPossível tratamento

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Routine antenatal anti-D prophylaxis in women who are Rh(D) Routine antenatal anti-D prophylaxis in women who are Rh(D) negative: meta-analyses adjusted for differences in study negative: meta-analyses adjusted for differences in study design and quality.design and quality.Turner RM, , Lloyd-Jones M, , Anumba DO, , Smith GC, , Spiegelhalter DJ, , Squires H, , Stevens JW, , Sweeting MJ, , Urbaniak SJ, , Webster R, , Thompson SG. . 2012;7(2):e30711. 2012;7(2):e30711.

Medical Research Council Biostatistics Unit, Institute of Public Health, Cambridge, United Kingdom. Medical Research Council Biostatistics Unit, Institute of Public Health, Cambridge, United Kingdom. [email protected]@mrc-bsu.cam.ac.ukAbstractAbstractBACKGROUND: BACKGROUND: To estimate the effectiveness of routine antenatal anti-D prophylaxis for preventing sensitisation in To estimate the effectiveness of routine antenatal anti-D prophylaxis for preventing sensitisation in pregnant Rhesus negative women, and to explore whether this depends on the treatment regimen pregnant Rhesus negative women, and to explore whether this depends on the treatment regimen adopted.adopted.METHODS: METHODS: Ten studies identified in a previous systematic literature search were included. Potential sources of bias Ten studies identified in a previous systematic literature search were included. Potential sources of bias were systematically identified using bias checklists, and their impact and uncertainty were quantified were systematically identified using bias checklists, and their impact and uncertainty were quantified using expert opinion. Study results were adjusted for biases and combined, first in a random-effects using expert opinion. Study results were adjusted for biases and combined, first in a random-effects meta-analysis and then in a random-effects meta-regression analysis.meta-analysis and then in a random-effects meta-regression analysis.RESULTS: RESULTS: In a conventional meta-analysis, the pooled odds ratio for sensitisation was estimated as 0.25 (95% CI In a conventional meta-analysis, the pooled odds ratio for sensitisation was estimated as 0.25 (95% CI 0.18, 0.36), comparing routine antenatal anti-D prophylaxis to control, with some heterogeneity (I²  =  0.18, 0.36), comparing routine antenatal anti-D prophylaxis to control, with some heterogeneity (I²  =  19%). However, this naïve analysis ignores substantial differences in study quality and design. After 19%). However, this naïve analysis ignores substantial differences in study quality and design. After adjusting for these, the pooled odds ratio for sensitisation was estimated as 0.31 (95% CI 0.17, 0.56), adjusting for these, the pooled odds ratio for sensitisation was estimated as 0.31 (95% CI 0.17, 0.56), with no evidence of heterogeneity (I²  =  0%). A meta-regression analysis was performed, which used the with no evidence of heterogeneity (I²  =  0%). A meta-regression analysis was performed, which used the data available from the ten anti-D prophylaxis studies to inform us about the relative effectiveness of data available from the ten anti-D prophylaxis studies to inform us about the relative effectiveness of three licensed treatments. This gave an 83% probability that a dose of 1250 IU at 28 and 34 weeks is three licensed treatments. This gave an 83% probability that a dose of 1250 IU at 28 and 34 weeks is most effective and a 76% probability that a single dose of 1500 IU at 28-30 weeks is least effective.most effective and a 76% probability that a single dose of 1500 IU at 28-30 weeks is least effective.CONCLUSION: CONCLUSION:

There is strong evidence for the effectiveness of routine There is strong evidence for the effectiveness of routine antenatal anti-D prophylaxis for prevention of sensitisationantenatal anti-D prophylaxis for prevention of sensitisation, in , in support of the policy of offering routine prophylaxis to all non-sensitised pregnant Rhesus negative support of the policy of offering routine prophylaxis to all non-sensitised pregnant Rhesus negative women. All three licensed dose regimens are expected to be effective.women. All three licensed dose regimens are expected to be effective.

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Gestante Rh negativoGestante Rh negativoCOOMBS INDIRETOCOOMBS INDIRETO

NEGATIVONEGATIVO

IMUNOGLOBULINA ANTI-DIMUNOGLOBULINA ANTI-Dou ou

Repetir 28,32,36,partoRepetir 28,32,36,parto

Positivo Positivo

≤ ≤ 1/81/8

Mensal ate 28 semanasMensal ate 28 semanasQuinzenal apósQuinzenal após

≥ ≥ 1/161/16

AmniocenteseAmniocenteseCordocenteseCordocenteseDopplerDoppler20-28 sem20-28 sem

Tipagem + fator RhTipagem + fator RhHgbHgbHtcHtcCoombs diretoCoombs diretoContagem de reticulócitosContagem de reticulócitos

Possível tratamentoPossível tratamento

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Gestante Rh negativoGestante Rh negativoCOOMBS INDIRETOCOOMBS INDIRETO

NEGATIVONEGATIVO

IMUNOGLOBULINA ANTI-DIMUNOGLOBULINA ANTI-Dou ou

Repetir 28,32,36,partoRepetir 28,32,36,parto

Positivo Positivo

≤ ≤ 1/81/8

Mensal ate 28 semanasMensal ate 28 semanasQuinzenal apósQuinzenal após

≥ ≥ 1/161/16

AmniocenteseAmniocenteseCordocenteseCordocenteseDopplerDoppler20-28 sem20-28 sem

Tipagem + fator RhTipagem + fator RhHgbHgbHtcHtcCoombs diretoCoombs diretoContagem de reticulócitosContagem de reticulócitos

Possível tratamentoPossível tratamento

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Doppler ObstétricoDoppler ObstétricoDoppler ObstétricoDoppler Obstétrico

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Obstet Gynecol 2002;100:600 –11.Obstet Gynecol 2002;100:600 –11.

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Obstet Gynecol 2002;100:600 –11.Obstet Gynecol 2002;100:600 –11.

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Doença Hemolítica Doença Hemolítica PerinatalPerinatal

TRATAMENTOTRATAMENTO

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PROFILAXIAPROFILAXIA

IMUNOGLOBULINA ANTI-RH APÓS O IMUNOGLOBULINA ANTI-RH APÓS O PARTOPARTO

SANGRAMENTO DURANTE A GRAVIDEZSANGRAMENTO DURANTE A GRAVIDEZ

PROCEDIENTOS INVASIVOSPROCEDIENTOS INVASIVOS

ROTINA 28 SEMANASROTINA 28 SEMANAS

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Acta Obstet Gynecol Scand. 2012 May;91(5):587-92. 2012 May;91(5):587-92. Pharmacokinetics of 250 μg anti-D IgG in the third trimester of pregnancy: An Pharmacokinetics of 250 μg anti-D IgG in the third trimester of pregnancy: An

observational study.observational study. Tiblad E, , Wikman A, , Rane A, , Jansson Y, , Westgren M.. Department of Obstetrics and Gynecology, Karolinska University Hospital and Karolinska Department of Obstetrics and Gynecology, Karolinska University Hospital and Karolinska

Institute, Stockholm, Sweden Department of Immunology and Transfusion Medicine, Karolinska Institute, Stockholm, Sweden Department of Immunology and Transfusion Medicine, Karolinska University Hospital and Karolinska Institute, Stockholm, Sweden Department of Clinical University Hospital and Karolinska Institute, Stockholm, Sweden Department of Clinical Pharmacology, Karolinska University Hospital and Karolinska Institute, Stockholm, Sweden.Pharmacology, Karolinska University Hospital and Karolinska Institute, Stockholm, Sweden.

AbstractAbstract Objective. We present a pharmacokinetic study evaluating a single intramuscular dose of Objective. We present a pharmacokinetic study evaluating a single intramuscular dose of 250 μg 250 μg

anti-D immunoglobulinanti-D immunoglobulin in the third trimester of pregnancy. The aim of the study was to in the third trimester of pregnancy. The aim of the study was to determine the kinetic profile and duration of detectable levels of anti-D. Design. Prospective determine the kinetic profile and duration of detectable levels of anti-D. Design. Prospective observational study. Setting. Antenatal outpatient clinic. Population. Healthy Rhesus D (RhD)-observational study. Setting. Antenatal outpatient clinic. Population. Healthy Rhesus D (RhD)-negative pregnant women with an RHD-positive fetus. Methods. Serial plasma anti-D negative pregnant women with an RHD-positive fetus. Methods. Serial plasma anti-D quantitations following antenatal administration of anti-D immunoglobulin were performed using quantitations following antenatal administration of anti-D immunoglobulin were performed using flow cytometry. Kinetic profiles for anti-D levels were generated from the concentration values at flow cytometry. Kinetic profiles for anti-D levels were generated from the concentration values at predetermined sampling time points. The half-lives were calculated by linear regression analysis. predetermined sampling time points. The half-lives were calculated by linear regression analysis. Main outcome measures. Time vs. concentration profile, half-life and anti-D concentration ≥1 Main outcome measures. Time vs. concentration profile, half-life and anti-D concentration ≥1 ng/mL close to term. Results. ng/mL close to term. Results. The maximal plasma concentration of anti-D was usually seen The maximal plasma concentration of anti-D was usually seen at 3-10 days postinjection,at 3-10 days postinjection, with a median value of 25 ng/mL. with a median value of 25 ng/mL. The half-life varied The half-life varied between individuals, with a median of 23 daysbetween individuals, with a median of 23 days. We found detectable levels of anti-D . We found detectable levels of anti-D IgG within two weeks of parturition in 11 of 12 women. Conclusions. The preparation of anti-D IgG within two weeks of parturition in 11 of 12 women. Conclusions. The preparation of anti-D immunoglobulin used in the present study, if administrated in pregnancy week 28-30, is immunoglobulin used in the present study, if administrated in pregnancy week 28-30, is associated with detectable levels of anti-D in most women at the time of delivery. Although the associated with detectable levels of anti-D in most women at the time of delivery. Although the half-time is 23 days, half-time is 23 days, it is uncertain whether all mothers have adequate it is uncertain whether all mothers have adequate anti-D concentrations at term.anti-D concentrations at term. Alternative strategies may be evaluated in the future, Alternative strategies may be evaluated in the future, with repeated administration of antenatal prophylaxis at term rather than conventional with repeated administration of antenatal prophylaxis at term rather than conventional postpartum administration of anti-D.postpartum administration of anti-D.

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Best Pract Res Clin Obstet Gynaecol. 2012 Feb;26(1):119-32. Epub 2011 Nov 2012 Feb;26(1):119-32. Epub 2011 Nov 26.26.

Red-cell and platelet alloimmunisation in pregnancy.Red-cell and platelet alloimmunisation in pregnancy. Egbor M, , Knott P, , Bhide A.. SourceSource Department of Obstetrics and Gynaecology, and Fetal Medicine Unit, St Helier Department of Obstetrics and Gynaecology, and Fetal Medicine Unit, St Helier

University Hospital, Surrey, UK.University Hospital, Surrey, UK. AbstractAbstract The management of red-cell alloimmunisation has been revolutionised by the The management of red-cell alloimmunisation has been revolutionised by the

widespread use of anti-D administration for mothers who are rhesus negative, widespread use of anti-D administration for mothers who are rhesus negative, and the availability of non-invasive, ultrasound-based techniques for reliable and the availability of non-invasive, ultrasound-based techniques for reliable detection of moderate-to-severe fetal anaemia. With reduced frequency of detection of moderate-to-severe fetal anaemia. With reduced frequency of alloimmunisation to the D antigen, antibodies to c and Kell antigen are alloimmunisation to the D antigen, antibodies to c and Kell antigen are increasingly responsible for red-cell alloimmunisation. Ultrasound-based, non-increasingly responsible for red-cell alloimmunisation. Ultrasound-based, non-invasive diagnosis is now so reliable that invasive techniques are sparingly invasive diagnosis is now so reliable that invasive techniques are sparingly used to detect significant fetal anaemia. Treatment of fetal anaemia using used to detect significant fetal anaemia. Treatment of fetal anaemia using ultrasound-guided intravascular transfusions is highly successful. Advances in ultrasound-guided intravascular transfusions is highly successful. Advances in molecular biology have led to the successful determination of fetal blood group molecular biology have led to the successful determination of fetal blood group using free fetal DNA from maternal blood. This development is highly likely to using free fetal DNA from maternal blood. This development is highly likely to allow use of anti-D in only those pregnant women carrying rhesus-positive allow use of anti-D in only those pregnant women carrying rhesus-positive fetuses. Sensitisation to non-D group antibodies continues to occur owing to fetuses. Sensitisation to non-D group antibodies continues to occur owing to the lack of available prophylaxis for other blood-group antigens.the lack of available prophylaxis for other blood-group antigens.

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Immunohematology. 2011;27(1):6-11. 2011;27(1):6-11. Serologic and molecular characterization of D variants in Brazilians: impact for typing and Serologic and molecular characterization of D variants in Brazilians: impact for typing and

transfusion strategy.transfusion strategy. Credidio DC, , Pellegrino J, , Castilho L.. SourceSource Instituto Nacional de Ciência e Tecnologia do Sangue, Hemocentro, UNICAMP, Rua Carlos Chagas, Instituto Nacional de Ciência e Tecnologia do Sangue, Hemocentro, UNICAMP, Rua Carlos Chagas,

480, Caixa Postal 6198, CEP 13081-970 Barão Geraldo, Campinas, SP, Brazil.480, Caixa Postal 6198, CEP 13081-970 Barão Geraldo, Campinas, SP, Brazil. AbstractAbstract Rh discrepancies are a problem during routine testing because of partial D or weak D phenotypes. Rh discrepancies are a problem during routine testing because of partial D or weak D phenotypes.

Panels of monoclonal antibodies (MoAb) are being developed to identify D variants such as partial D Panels of monoclonal antibodies (MoAb) are being developed to identify D variants such as partial D and weak D when there are anomalous D typing results; however, molecular characterization offers and weak D when there are anomalous D typing results; however, molecular characterization offers a more specific classification of weak and partial D. The weak D and partial D phenotypes are a more specific classification of weak and partial D. The weak D and partial D phenotypes are caused by many different RHD alleles encoding aberrant D proteins, resulting in distinct serologic caused by many different RHD alleles encoding aberrant D proteins, resulting in distinct serologic phenotypes and the possibility of anti-D immunization. We evaluated currently used serologic phenotypes and the possibility of anti-D immunization. We evaluated currently used serologic methods and reagents to detect and identify D variants and correlated the results with molecular methods and reagents to detect and identify D variants and correlated the results with molecular analyses. A total of 306 blood samples from Brazilian blood donors and patients with discrepant analyses. A total of 306 blood samples from Brazilian blood donors and patients with discrepant results in routine D typing were analyzed. In total, 166 (54.2%) weak D, 136 (44.4%) partial D, 3 results in routine D typing were analyzed. In total, 166 (54.2%) weak D, 136 (44.4%) partial D, 3 (1%) DEL, and 1 (0.3%) DHAR variants were identified. Among weak D samples, 76 weak D type 1 (1%) DEL, and 1 (0.3%) DHAR variants were identified. Among weak D samples, 76 weak D type 1 (45.8%), 75 weak D type 2 (45.2%), 13 weak D type 3 (7.8%), and 2 weak D type 5 (1.2%) alleles (45.8%), 75 weak D type 2 (45.2%), 13 weak D type 3 (7.8%), and 2 weak D type 5 (1.2%) alleles were found. Among the partial D samples, 49 type 4.0 weak partial D (36%), 9 DAR (6.6%), 24 DFR were found. Among the partial D samples, 49 type 4.0 weak partial D (36%), 9 DAR (6.6%), 24 DFR (17.6%), 6 DBT (4.4%), 1 DHMi (0.73%), 26 DVI (19%), 14 DVa (10.3%), 5 DIVb (3.7%), and 2 DVII (17.6%), 6 DBT (4.4%), 1 DHMi (0.73%), 26 DVI (19%), 14 DVa (10.3%), 5 DIVb (3.7%), and 2 DVII (1.5%) were observed. Two samples identified as DEL by adsorption-elution were characterized by (1.5%) were observed. Two samples identified as DEL by adsorption-elution were characterized by molecular analyses as RHD(IVS5–38DEL4) and one sample was characterized as RHD(K409K). One molecular analyses as RHD(IVS5–38DEL4) and one sample was characterized as RHD(K409K). One sample was characterized as DHAR, a CE variant positive with some monoclonal anti-D. Our results sample was characterized as DHAR, a CE variant positive with some monoclonal anti-D. Our results showed that the use of different methods and anti-D reagents in the serologic routine analysis showed that the use of different methods and anti-D reagents in the serologic routine analysis revealed D variants that can be further investigated. Molecular methods can help to differentiate revealed D variants that can be further investigated. Molecular methods can help to differentiate between partial D and weak D and to characterize the weak D types, providing additional between partial D and weak D and to characterize the weak D types, providing additional information of value in the determination of D phenotypes. This distinction is important for information of value in the determination of D phenotypes. This distinction is important for optimized management of D– RBC units and for the prevention of anti-D–related hemolytic disease optimized management of D– RBC units and for the prevention of anti-D–related hemolytic disease of the fetus and newborn.of the fetus and newborn.

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Transfusion. 2012 Feb;52(2):241-6. doi: 10.1111/j.1537-2995.2011.03266.x. Epub 2011 Jul 25. 2012 Feb;52(2):241-6. doi: 10.1111/j.1537-2995.2011.03266.x. Epub 2011 Jul 25. Partial D phenotypes and genotypes in the Chinese population.Partial D phenotypes and genotypes in the Chinese population. Ye L, , Wang P, , Gao H, , Zhang J, , Wang C, , Li Q, , Han S, , Guo Z, , Yang Y, , Zhu Z.. SourceSource Shanghai Institute of Transfusion Medicine, Shanghai Blood Center, and School of Life Science, East China Normal Shanghai Institute of Transfusion Medicine, Shanghai Blood Center, and School of Life Science, East China Normal

University, Shanghai, China.University, Shanghai, China. AbstractAbstract BACKGROUND: BACKGROUND: The D variant phenotypes are often categorized into weak D types and partial D types. Although the molecular basis The D variant phenotypes are often categorized into weak D types and partial D types. Although the molecular basis

underlying the partial D phenotype has been investigated in several races, data from Chinese populations are rare.underlying the partial D phenotype has been investigated in several races, data from Chinese populations are rare. STUDY DESIGN AND METHODS: STUDY DESIGN AND METHODS: We collected partial D samples from 1,274,540 blood donors, as well as from sporadic patients in the Chinese We collected partial D samples from 1,274,540 blood donors, as well as from sporadic patients in the Chinese

population, over a 4-year period. Samples with partial D phenotype were determined by commercial monoclonal anti-D population, over a 4-year period. Samples with partial D phenotype were determined by commercial monoclonal anti-D panels and molecular methods. Blood samples with discrepant results of serologic and molecular methods were further panels and molecular methods. Blood samples with discrepant results of serologic and molecular methods were further investigated by polymerase chain reaction (PCR) with sequence-specific primers and nucleotide sequencing of RHD investigated by polymerase chain reaction (PCR) with sequence-specific primers and nucleotide sequencing of RHD exons. The detection of antibodies was performed.exons. The detection of antibodies was performed.

RESULTS: RESULTS: A total of 44 samples with partial D phenotypes were confirmed. Molecular typing revealed five different known A total of 44 samples with partial D phenotypes were confirmed. Molecular typing revealed five different known

aberrant alleles as well as four new RHD alleles. As described previously, DVI represented the most frequent partial D aberrant alleles as well as four new RHD alleles. As described previously, DVI represented the most frequent partial D type in China with a total of 36 samples. However, discrepant results were observed in four DVI samples with type in China with a total of 36 samples. However, discrepant results were observed in four DVI samples with serotyping and genotyping (i.e., DVI category identified by D-screen test and grossly intact RHD gene identified by serotyping and genotyping (i.e., DVI category identified by D-screen test and grossly intact RHD gene identified by multiplex PCR). We also found four novel alleles, termed DFR-4, DCS-3, DCC, and DLX.multiplex PCR). We also found four novel alleles, termed DFR-4, DCS-3, DCC, and DLX.

CONCLUSION: CONCLUSION: To date, this study presents the most comprehensive report on partial D in China. The distribution of partial D types in To date, this study presents the most comprehensive report on partial D in China. The distribution of partial D types in

China was found to be complicated and polymorphic, whereas RhD genotyping of DVI-variant samples might give China was found to be complicated and polymorphic, whereas RhD genotyping of DVI-variant samples might give inaccurate results due to a relatively high incidence of RHD(1227G>A) in the Chinese population.inaccurate results due to a relatively high incidence of RHD(1227G>A) in the Chinese population.

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Obstet Gynecol. 2012 Feb;119(2 Pt 2):426-8. 2012 Feb;119(2 Pt 2):426-8. New laboratory procedures and Rh blood type changes in a pregnant woman.New laboratory procedures and Rh blood type changes in a pregnant woman. Sandler SG, , Li W, , Langeberg A, , Landy HJ.. SourceSource Georgetown University Hospital, Washington, DC 20007, USA. Georgetown University Hospital, Washington, DC 20007, USA.

[email protected]@gunet.georgetown.edu AbstractAbstract BACKGROUND: BACKGROUND: A woman's candidacy for Rh immune globulin depends on whether her blood type is Rh-A woman's candidacy for Rh immune globulin depends on whether her blood type is Rh-

positive (D antigen-positive) or Rh-negative (D antigen-negative). New molecular blood-positive (D antigen-positive) or Rh-negative (D antigen-negative). New molecular blood-typing methods have identified variant D antigens, which may be reported as Rh-positive or typing methods have identified variant D antigens, which may be reported as Rh-positive or Rh-negative depending on the laboratory method. We describe a case illustrating the effect Rh-negative depending on the laboratory method. We describe a case illustrating the effect of the new laboratory methods on a woman's candidacy for Rh immune globulin and of the new laboratory methods on a woman's candidacy for Rh immune globulin and present recommendations for interpreting the new test results.present recommendations for interpreting the new test results.

CASE: CASE: A 40-year-old woman presented for management of her third pregnancy. During her first A 40-year-old woman presented for management of her third pregnancy. During her first

pregnancy, she was typed as Rh-positive ("D") and did not receive Rh immune globulin. pregnancy, she was typed as Rh-positive ("D") and did not receive Rh immune globulin. During her second pregnancy, she was typed as Rh-negative, in accordance with revised During her second pregnancy, she was typed as Rh-negative, in accordance with revised Rh-typing procedures. Anti-D antibody was detected. During her third pregnancy, she was Rh-typing procedures. Anti-D antibody was detected. During her third pregnancy, she was genotyped as a partial D antigen, which was reported as Rh-negative.genotyped as a partial D antigen, which was reported as Rh-negative.

CONCLUSION: CONCLUSION: Revisions in laboratory procedures for Rh typing may present as a change in the Rh blood Revisions in laboratory procedures for Rh typing may present as a change in the Rh blood

type of pregnant women-and as a change in their eligibility for Rh immune globulin.type of pregnant women-and as a change in their eligibility for Rh immune globulin.

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Am J Hematol. 2012 Apr;87(4):417-23. doi: 10.1002/ajh.22255. Epub 2012 Jan 9. 2012 Apr;87(4):417-23. doi: 10.1002/ajh.22255. Epub 2012 Jan 9. Detection of fetomaternal hemorrhage.Detection of fetomaternal hemorrhage. Kim YA, Makar RS., Makar RS. SourceSource Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Department of Pathology, Massachusetts General Hospital, Harvard Medical School,

Boston, MA 02114, USA. [email protected], MA 02114, USA. [email protected] AbstractAbstract The prevention of Rhesus D alloimmunization through Rh immune globulin (RhIg) The prevention of Rhesus D alloimmunization through Rh immune globulin (RhIg)

administration is the major indication for the accurate detection and quantification of administration is the major indication for the accurate detection and quantification of fetomaternal hemorrhage (FMH). In the setting of D incompatibility, D-positive fetal cells fetomaternal hemorrhage (FMH). In the setting of D incompatibility, D-positive fetal cells can sensitize the D-negative mother, resulting in maternal anti-D alloantibody production. can sensitize the D-negative mother, resulting in maternal anti-D alloantibody production. These anti-D alloantibodies may lead to undesirable sequelae such as hemolytic disease of These anti-D alloantibodies may lead to undesirable sequelae such as hemolytic disease of the newborn (HDN). Since the widespread adoption of FMH screening and RhIg the newborn (HDN). Since the widespread adoption of FMH screening and RhIg immunoprophylaxis, the overall risk of Rh alloimmunization and infant mortality from HDN immunoprophylaxis, the overall risk of Rh alloimmunization and infant mortality from HDN has substantially decreased. The rosette screen, the initial test of choice, is highly sensitive has substantially decreased. The rosette screen, the initial test of choice, is highly sensitive in qualitatively detecting 10 mL of fetal whole blood in the maternal circulation. As the in qualitatively detecting 10 mL of fetal whole blood in the maternal circulation. As the screen is reliant on the presence of the D antigen to distinguish fetal from maternal cells, it screen is reliant on the presence of the D antigen to distinguish fetal from maternal cells, it cannot be used to detect FMH in D-positive mothers or in D-negative mothers carrying a D-cannot be used to detect FMH in D-positive mothers or in D-negative mothers carrying a D-negative fetus. The Kleihauer-Betke acid-elution test, the most widely used confirmatory negative fetus. The Kleihauer-Betke acid-elution test, the most widely used confirmatory test for quantifying FMH, relies on the principle that fetal RBCs contain mostly fetal test for quantifying FMH, relies on the principle that fetal RBCs contain mostly fetal hemoglobin (HbF), which is resistant to acid-elution whereas adult hemoglobin is acid-hemoglobin (HbF), which is resistant to acid-elution whereas adult hemoglobin is acid-sensitive. Although the Kleihauer-Betke test is inexpensive and requires no special sensitive. Although the Kleihauer-Betke test is inexpensive and requires no special equipment, it lacks standardization and precision, and may not be accurate in conditions equipment, it lacks standardization and precision, and may not be accurate in conditions with elevated F-cells. Anti-HbF flow cytometry is a promising alternative, although its use is with elevated F-cells. Anti-HbF flow cytometry is a promising alternative, although its use is limited by equipment and staffing costs. Hematology analyzers with flow cytometry limited by equipment and staffing costs. Hematology analyzers with flow cytometry capabilities may be adapted for fetal cell detection, thus giving clinical laboratories a capabilities may be adapted for fetal cell detection, thus giving clinical laboratories a potentially attractive automated alternative for quantifying FMH.potentially attractive automated alternative for quantifying FMH.

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Am J Obstet Gynecol. 2005 Dec;193(6):1966-71.Am J Obstet Gynecol. 2005 Dec;193(6):1966-71. Noninvasive prenatal RHD genotyping by real-time polymerase chain reaction Noninvasive prenatal RHD genotyping by real-time polymerase chain reaction

using plasma from D-negative pregnant women.using plasma from D-negative pregnant women. Zhou L, Thorson JA, Nugent C, Davenport RD, Butch SH, Judd WJ.Zhou L, Thorson JA, Nugent C, Davenport RD, Butch SH, Judd WJ.

Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA. Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA. [email protected]@case.edu

AbstractAbstract OBJECTIVE: OBJECTIVE: Prenatal noninvasive determination of fetal Rh status is an important aid to the Prenatal noninvasive determination of fetal Rh status is an important aid to the

management of hemolytic disease of the fetus and newborn. We performed real-time management of hemolytic disease of the fetus and newborn. We performed real-time polymerase chain reaction on fetal DNA derived from maternal plasma to determine fetal polymerase chain reaction on fetal DNA derived from maternal plasma to determine fetal Rh status.Rh status.

STUDY DESIGN: STUDY DESIGN: Cell-free plasma DNA from 98 D-negative pregnant women was tested for the presence of Cell-free plasma DNA from 98 D-negative pregnant women was tested for the presence of

exons 4, 5, and 10 of RHD. The presence of fetal DNA was confirmed by detection of SRY exons 4, 5, and 10 of RHD. The presence of fetal DNA was confirmed by detection of SRY or biallelic insertion/deletion polymorphisms in the maternal plasma and buffy coat.or biallelic insertion/deletion polymorphisms in the maternal plasma and buffy coat.

RESULTS: RESULTS: Seventy-two D-positive infants and 26 D-negative infants were determined by serologic Seventy-two D-positive infants and 26 D-negative infants were determined by serologic

studies. All 3 RHD exon sequences were detected in 68 of 72 mothers of D-positive studies. All 3 RHD exon sequences were detected in 68 of 72 mothers of D-positive infants. The presence of fetal DNA in mothers of D-negative infants was confirmed in all infants. The presence of fetal DNA in mothers of D-negative infants was confirmed in all 10 boys and in 14 of 16 girls.10 boys and in 14 of 16 girls.

CONCLUSION: CONCLUSION: Fetal RHD genotyping in this study correctly predicted fetal Rh status in 92 of 98 (94%) Fetal RHD genotyping in this study correctly predicted fetal Rh status in 92 of 98 (94%)

cases.cases.