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Rh Incompatibility
Last Updated: December 11, 2001 Rate this Article Email to a olleag!e Synonyms and related keywords: rhes!s "actor AUTHOR INFOR ATION Section ! o" !# A!thor: Leon Salem$ %$ S$ FA&'(, Assistant #ro"essor, Department o" Emergenc$ %edicine, %artin &!ther 'ing (r/ harles R Drew %edical enter &eon )alem, %D, %), *A E#, is a member o" the "ollowing medical societies: American ollege o" Emergenc$ #h$sicians Editor+s,: Assaad ) Sayah$ %, hairman, Assistant linical #ro"essor, -!"ts .ni/ersit$ )chool o" %edicine, Department o" Emergenc$ %edicine, aritas 0ood )amaritan %edical enter1 Francisco Tala*era$ (harm%$ (h%, )enior #harmac$ Editor, #harmac$, e%edicine1 ark +wan,er$ %$ -A, Assistant #ro"essor, Department o" )!rger$, Di/ision o" Emergenc$ %edicine, -homas (e""erson .ni/ersit$1 )ohn Halamka$ %, hie" 2n"ormation 3""icer, are0ro!p 4ealthcare )$stem, Assistant #ro"essor o" %edicine, Department o" Emergenc$ %edicine, 5eth 2srael Deaconess %edical enter1 Assistant #ro"essor o" %edicine, 4ar/ard %edical )chool1 and Robert O.&onnor$ %$ (H, Associate #ro"essor o" )!rger$ +Emergenc$ %edicine,, -homas (e""erson .ni/ersit$1 #rogram Director, Department o" Emergenc$ %edicine, hristiana are 4ealth )$stem -ack,ro/nd: -he Rh "actor +ie, rhes!s "actor, is an er$throc$te s!r"ace antigen that was named a"ter the mon6e$s in which it was "irst disco/ered. Rh incompatibilit$ is a condition that occ!rs when a woman o" Rh7negati/e blood t$pe is e8posed to Rh7positi/e blood cells and s!bse9!entl$ de/elops circ!lating titers o" Rh antibodies. Rh incompatibilit$ can occ!r b$ 2 main mechanisms. 2t can occ!r when an Rh7negati/e mother is e8posed to Rh7positi/e "etal er$throc$tes secondar$ to "etomaternal hemorrhage d!ring the co!rse o" pregnanc$ "rom spontaneo!s or ind!ced abortion, tra!ma, in/asi/e obstetrical proced!res, or deli/er$. Rh incompatibilit$ also can occ!r when an Rh7negati/e "emale recei/es a blood trans"!sion that contains Rh antigens. -he most common ca!se o" Rh incompatibilit$ is e8pos!re to an Rh7negati/e mother b$ Rh7positi/e "etal blood d!ring pregnanc$ or deli/er$, whereb$ er$throc$tes "rom the "etal circ!lation lea6 into the maternal circ!lation. A"ter a signi"icant e8pos!re, alloimm!ni:ation or sensiti:ation occ!rs, and maternal antibodies are prod!ced against the "oreign Rh antigen.

3nce prod!ced, maternal Rh imm!noglob!lin 0 +2g0, antibodies ma$ cross "reel$ "rom the placenta to the "etal circ!lation, where the$ "orm antigen7antibod$ comple8es with Rh7positi/e "etal er$throc$tes and e/ent!all$ are destro$ed, res!lting in a "etal alloimm!ne7ind!ced hemol$tic anemia. Altho!gh the Rh blood gro!p s$stems consist o" se/eral antigens +eg, D, , c, E, e,, the D antigen is the most imm!nogenic1 there"ore, it most commonl$ is in/ol/ed in Rh incompatibilit$. (athophysiolo,y: -he amo!nt o" "etal blood necessar$ to prod!ce Rh incompatibilit$ /aries. 2n one st!d$, less than 1 m& o" Rh7positi/e blood has been shown to sensiti:e /ol!nteers with Rh7negati/e blood. on/ersel$, other st!dies ha/e s!ggested that ;0< o" persons with Rh7negati/e blood ne/er de/elop Rh incompatibilit$, e/en when challenged with large /ol!mes o" Rh7positi/e blood. 3nce sensiti:ed, it ta6es appro8imatel$ one month "or Rh antibodies in the maternal circ!lation to e9!ilibrate in the "etal circ!lation. 2n =0< o" cases, sensiti:ation occ!rs d!ring deli/er$. -here"ore, most "irstborn in"ants with Rh7positi/e blood t$pe are not a""ected beca!se the short period "rom "irst e8pos!re o" Rh7positi/e "etal er$throc$tes to the birth o" the in"ant is ins!""icient to prod!ce a signi"icant maternal 2g0 antibod$ response. -he ris6 and se/erit$ o" alloimm!ne response increases with each s!bse9!ent pregnanc$ in/ol/ing a "et!s with Rh7positi/e blood. 2n women who are prone to Rh incompatibilit$, the second pregnanc$ with an Rh7positi/e "et!s o"ten prod!ces a mildl$ anemic in"ant, whereas s!cceeding pregnancies prod!ce more serio!sl$ a""ected in"ants who !ltimatel$ ma$ die in !tero "rom massi/e antibod$7ind!ced hemol$tic anemia. Ris6 o" sensiti:ation depends largel$ !pon the "ollowing ; "actors: 1. >ol!me o" transplacental hemorrhage 2. E8tent o" the maternal imm!ne response ;. onc!rrent presence o" A53 incompatibilit$ -he incidence o" Rh incompatibilit$ in the Rh7negati/e A53 incompatible mother is red!ced dramaticall$ to 172< and is belie/ed to occ!r beca!se the mother?s ser!m contains antibodies against the A53 blood gro!p o" the "et!s. *etal er$throc$tes apparentl$ are destro$ed in the maternal circ!lation be"ore Rh sensiti:ation can proceed to a signi"icant e8tent. Rh incompatibilit$ is onl$ o" medical concern when trans"!sion is needed and d!ring pregnanc$. Rh antibodies circ!lating in the bloodstream o" an Rh7negati/e woman ha/e no ad/erse e""ect in the nongra/id state. Fre0/ency: In the US: *i"teen percent o" the pop!lation lac6 the Rh er$throc$te s!r"ace antigen and are considered Rh7negati/e. -he /ast ma@orit$ +A5<, o" indi/id!als are considered Rh7positi/e. Rh sensiti:ation occ!rs in appro8imatel$ 1:1000 births to Rh7negati/e women. -he )o!thwest .) has an incidence appro8imatel$ 1.5 times the national a/erage, which li6el$ is ca!sed b$ immigration "actors and limited access to prenatal care. 3nl$ 17< o" pregnant women with Rh7negati/e

blood who are e8posed to Rh7positi/e "etal blood cells e/er de/elop Rh antibodies. ortality1 orbidity: -he reaction o" maternal Rh antibodies with "etal Rh7positi/e er$throc$tes res!lts in "etal a!toimm!ne hemol$sis. 2n !tero, m!ch o" the bilir!bin prod!ced b$ the "et!s "rom the brea6down o" "etal hemoglobin is trans"erred /ia the placenta to the mother and s!bse9!entl$ con@!gated and e8creted b$ the mother. 4owe/er, d!ring the postpart!m period, low le/els o" gl!c!ron$l trans"erase in the in"ant precl!de the con@!gation o" large amo!nts o" bilir!bin and ma$ res!lt in dangero!sl$ ele/ated le/els o" ser!m bilir!bin and @a!ndice. %ildl$ a""ected in"ants ma$ ha/e little or no anemia and ma$ e8hibit onl$ h$perbilir!binemia secondar$ to the contin!ing hemol$tic e""ect o" Rh antibodies that ha/e crossed the placenta. %oderatel$ a""ected in"ants ma$ ha/e a combination o" anemia and h$perbilir!binemia/@a!ndice. 2n se/ere cases o" "etal h$perbilir!binemia 6ernicter!s, a ne!rological s$ndrome ca!sed b$ deposition o" bilir!bin into central ner/o!s s$stem tiss!es ma$ de/elop. 'ernicter!s !s!all$ occ!rs se/eral da$s a"ter deli/er$ and is characteri:ed b$ loss o" the %oro +ie, startle, re"le8, post!ring, poor "eeding, inacti/it$, a b!lging "ontanelle, a high7pitched shrill cr$, and sei:!res. 2n"ants who s!r/i/e 6ernicter!s ma$ de/elop h$potonia, hearing loss, and mental retardation. Another serio!s li"e7threatening condition obser/ed in in"ants a""ected b$ Rh incompatibilit$ is er$throblastosis "etalis, which is characteri:ed b$ se/ere hemol$tic anemia and @a!ndice. -he most se/ere "orm o" er$throblastosis "etalis is h$drops "etalis, which is characteri:ed b$ high o!tp!t cardiac "ail!re, edema, ascites, pericardial e""!sion, and e8tramed!llar$ hematopoiesis. Bewborns with h$drops "etalis are e8tremel$ pale with hematocrits !s!all$ less than 5. 4$drops "etalis o"ten res!lts in death o" the in"ant shortl$ be"ore or a"ter deli/er$ and re9!ires an emergent e8change trans"!sion b$ a neonatologist to increase the in"ant?s chances o" s!r/i/al. Race:

Appro8imatel$ 15720< o" white persons, as opposed to 5710< o" A"rican American persons, ha/e the Rh7negati/e blood t$pe. Among indi/id!als o" hinese and American 2ndian descent, incidence o" Rh7 negati/e blood t$pe is less than 5<.

History: 4istor$ o" prior blood trans"!sion Rh blood t$pe o" the mother Rh blood t$pe o" the "ather +55< o" Rh7positi/e men are geneticall$ hetero:$go!s "or the Rh antigen and, there"ore, prod!ce Rh7negati/e o""spring when mating with Rh7negati/e women 50< o" the time., #re/io!s pregnancies, incl!ding spontaneo!s and electi/e abortions #re/io!s administration o" Rh 2g0

%echanism o" in@!r$ in cases o" tra!ma #resence o" /aginal bleeding and/or amniotic discharge #re/io!s in/asi/e obstetrical proced!res, s!ch as amniocentesis, cordocentesis, amnionic /illo!s sampling, or ectopic pregnanc$ 2t is important to note that a large "etal7maternal hemorrhage ma$ occ!r witho!t s$mptoms and with little or no e/idence o" tra!ma. -here"ore, a high inde8 o" s!spicion is warranted, and a low threshold "or treatment is indicated.

(hysical: E/al!ation o" the /ital signs and primar$ s!r/e$ o" the airwa$ and cardio/asc!lar s$stem are indicated to ens!re maternal stabilit$. A thoro!gh pel/ic e8amination is re9!ired. 2n sit!ations in which abdominal and/or pel/ic tra!ma is a consideration, inspect "or e/idence o" br!ising that ma$ s!ggest the possibilit$ o" signi"icant "etomaternal hemorrhage. Chen an in"ant with an Rh7negati/e mother is deli/ered in the ED, a thoro!gh ph$sical e8amination o" the in"ant m!st be per"ormed a"ter initial stabili:ation, and a neonatologist m!st be cons!lted immediatel$. #h$sical "indings ma$ /ar$ "rom mild @a!ndice to e8treme pallor and anemia with h$drops "etalis. &a/ses: *actors that in"l!ence whether or not an Rh7negati/e pregnant "emale can de/elop Rh incompatibilit$ incl!de the "ollowing: Ectopic pregnanc$ #lacenta pre/ia #lacental abr!ption Abdominal/pel/ic tra!ma 2n !tero "etal death An$ in/asi/e obstetrical proced!re +eg, amniocentesis, &ac6 o" prenatal care )pontaneo!s abortion

Other (roblems to be &onsidered: A53 incompatibilit$ A!toimm!ne hemol$tic anemia %icroangiopathic hemol$tic anemia )pheroc$tosis 4ereditar$ en:$me de"iciencies Alpha thalassemia hronic "etomaternal hemorrhage -win7twin trans"!sion Er$throblastosis "etalis 4$drops "etalis 2/ick Find

Lab St/dies: #renatal emergenc$ care

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Determination o" Rh blood t$pe is re9!ired in e/er$ pregnant "emale. 2n a pregnant woman with Rh7negati/e blood t$pe, the Rosette screening test o"ten is the "irst test per"ormed. -he Rosette test can detect alloimm!ni:ation ca!sed b$ "etomaternal hemorrhages o" as little as D77 o" R5 s. Chen a high clinical s!spicion o" large "etomaternal hemorrhage is present +E;0 m& R5 s,, the 'leiha!er75et6e acid el!tion test o"ten is per"ormed. -he 'leiha!er75et6e test is a 9!antitati/e meas!rement o" "etal red blood cells in maternal blood, and it can be /al!able "or determining i" additional amo!nts o" Rh 2g0 sho!ld be administered. -he amo!nt o" Rh 2g0 re9!ired "or treatment is at least 20 mcg/m& o" "etal R5 s.

3btaining maternal Rh antibod$ titers can be help"!l "or "!t!re "ollow7!p care o" pregnant "emales who are 6nown to be Rh7negati/e and ma$ be initiated "rom the ED.
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4igh le/els o" maternal Rh antibodies s!ggest that Rh sensiti:ation has occ!rred, and "!rther st!dies, s!ch as amniocentesis and/or cordocentesis, ma$ be necessar$ to e/al!ate the health o" the "et!s.

#ostnatal emergenc$ care

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2mmediatel$ a"ter the birth o" an$ in"ant with an Rh7negati/e mother in the ED or prehospital setting, e8amine blood "rom the !mbilical cord o" the in"ant "or A53 blood gro!p and Rh t$pe, meas!re hematocrit and hemoglobin le/els, per"orm a ser!m bilir!bin anal$sis, obtain a blood smear, and per"orm a direct oombs test. A positi/e direct oombs test res!lt con"irms the diagnosis o" antibod$7 ind!ced hemol$tic anemia, which s!ggests the presence o" Rh incompatibilit$. Ele/ated ser!m bilir!bin meas!rements, low hematocrit, and ele/ated retic!loc$te co!nt "rom the neonate can help determine i" an earl$ e8change trans"!sion is necessar$. An emergent e8change trans"!sion b$ a neonatologist speciali:ing in this proced!re is re9!ired in in"ants born with er$throblastosis "etalis, h$drops "etalis, or 6ernicter!s.

Ima,in, St/dies: 2n the ED, !ltraso!nd imaging st!dies o" a pregnant "emale with s!spected Rh incompatibilit$ is limited to the pel/ic !ltraso!nd.

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*etal ascites and so"t tiss!e edema are de"inite signs o" se/ere in/ol/ement. 3nce h$drops "etalis has de/eloped, the sonographic e/idence incl!des scalp edema, cardiomegal$, hepatomegal$, ple!ral e""!sion, and ascites.

Other Tests: #er"orm "etal monitoring in cases o" s!spected "etal distress. Abnormal "etal heart tones and !ltraso!nd e/idence o" "etal or placental in@!r$ are indications o" worsening "etal condition re9!iring emergent deli/er$, ideall$ in a center speciali:ing in high7ris6 obstetrical care. (rehospital &are: Chen possible, prehospital care personnel sho!ld direct their e""orts on stabili:ation o" the mother and in"ant, "ollowed b$ immediate transport to a "acilit$ speciali:ing in high7ris6 obstetrical and neonatal care. 'mer,ency %epartment &are: ED care o" the pregnant woman with Rh7negati/e blood and a s!spected "etomaternal hemorrhage /aries depending on the presentation o" the patient and the gestational age o" the "et!s. 3btain the Rh stat!s o" the pregnant "emale.
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2" the mother has Rh7negati/e blood and has not been sensiti:ed pre/io!sl$, administer h!man anti7D imm!ne glob!lin +Rh 2g0, and re"er the woman to an obstetrician "or "!rther e/al!ation. 2" the mother has been sensiti:ed pre/io!sl$, as determined b$ ele/ated maternal Rh antibodies, administration o" Rh 2g0 is o" no /al!e. 2n this sit!ation, prompt re"erral to a center speciali:ing in high7ris6 obstetrics is warranted.

Chen an in"ant with Rh incompatibilit$ is deli/ered in the ED, a more aggressi/e approach is re9!ired, centering on respirator$ and hemod$namic stabili:ation o" the in"ant and determining the need "or an emergent e8change trans"!sion and phototherap$ b$ a neonatologist.

&ons/ltations: Re"er e/er$ pregnant "emale with Rh incompatibilit$ to a medical center speciali:ing in high7ris6 obstetrical care.

Rh 2g0, "irst released "or general !se in 1=FA, has been remar6abl$ s!ccess"!l in the pre/ention o" Rh incompatibilit$. 2n the Rh7negati/e mother, the preparation is administered a"ter a s!spected "etomaternal hemorrhage. -he e8act mechanism b$ which passi/e administration o" Rh 2g0 pre/ents Rh imm!ni:ation is !n6nown. -he most li6el$ h$pothesis is that the Rh imm!ne glob!lin coats "etal R5 s containing Rh antigens on their s!r"ace. -hese e8ogeno!s antibod$7antigen comple8es cross the placenta be"ore

the$ can stim!late the maternal endogeno!s imm!ne s$stem 5 cells to prod!ce 2g0 antibodies. )ince Rh 2g0 became the standard o" care in the .), the ris6 o" Rh incompatibilit$ has been red!ced "rom 10720< to less than 1<. 5eca!se o" its short hal"7li"e, Rh 2g0 ro!tinel$ is administered once at 2A7;2 wee6s gestation and again within 72 ho!rs a"ter birth to all Rh7negati/e pregnant "emales as a part o" ro!tine prenatal care. -he c!rrent recommendation is that e/er$ Rh7negati/e nonimm!ni:ed woman who presents to the ED with antepart!m bleeding or potential "etomaternal hemorrhage sho!ld recei/e ;00 mcg o" Rh 2g0 2%. *or e/er$ ;0 m& o" "etal whole blood e8posed to maternal circ!lation, ;00 mcg o" Rh 2g0 sho!ld be administered. A lower 507mcg dose preparation o" Rh 2g0 is a/ailable and recommended "or Rh7negati/e "emales who ha/e termination o" pregnanc$ in the "irst trimester when "etomaternal hemorrhage is belie/ed to be minimal. Dr!g ategor$: Blood derived product 77 E""ecti/e in pre/enting Rh isoimm!ni:ation. %r/, Name 4!man anti7D imm!ne glob!lin +Rho0A%, 77 )!ppresses imm!ne response o" nonsensiti:ed Rh 3 +D, negati/e mothers e8posed to Rh 3 +D, positi/e blood "rom the "et!s as a res!lt o" a "etomaternal hemorrhage, abdominal tra!ma, amniocentesis, abortion, "!ll7term deli/er$, or trans"!sion accident. )ho!ld be administered i" the patient is Rh7negati/e, !nless the "ather also is Rh7negati/e. Ad/lt %ose G1; w6 gestation: 50 mcg 2% E1; w6 gestation: ;00 mcg 2% (ediatric %ose Administer as in ad!lts &ontraindications Doc!mented h$persensiti/it$1 patients who ha/e recei/ed Rho+D,7positi/e blood within the last ; mo Interactions Bone reported (re,nancy 7 )a"et$ "or !se d!ring pregnanc$ has not been established. (reca/tions a!tion in thromboc$topenia, bleeding disorders, or 20A de"icienc$1 when administered close to deli/er$, ma$ inter"ere with Rh t$ping o" the newborn F/rther Inpatient &are: A"ter administering Rh 2g0 in the ED, promptl$ re"er the Rh7negati/e pregnant mother o" an Rh7positi/e "et!s to an obstetrician at an instit!tion e9!ipped "or high7ris6 obstetrical care. %eterrence1(re*ention: )tress the importance o" earl$ prenatal care to each pregnant "emale presenting to the ED. Earl$ administration o" Rh 2g0 in con@!nction with earl$ prenatal care is the best means to pre/ent Rh incompatibilit$. &omplications: Emergent deli/er$ o" an in"ant born with h$drops "etalis sho!ld be as nontra!matic as possible. 2deall$, a neonatologist who is prepared to per"orm an e8change trans"!sion sho!ld attend to the in"ant immediatel$.

edical1Le,al (it"alls: #otential reasons "or postpart!m clinical "ail!res incl!de the "ollowing:
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*ail!re to t$pe the patient?s blood d!ring the ED /isit *ail!re to administer Rh 2g0 when indicated Error in t$ping the mother?s, "ather?s, or in"ant?s blood .nrecogni:ed "etomaternal hemorrhage 2nade9!ate Rh 2g0 dosage "or the /ol!me o" "etomaternal hemorrhage

5ibliograph$ Agre #, )mith 5&, 4artel7)chen6 ): 5iochemistr$ o" the er$throc$te Rh pol$peptides: a re/iew. Hale ( 5iol %ed 1==0 )ep73ct1 F;+5,: DF177I%edlineJ. American ollege o" 3bstetricians and 0$necologists: #re/ention o" D isoimm!ni:ation. A 30 -echnical 5!lletin 1D71 1==0. American ollege o" 3bstetricians and 0$necologists: %anagement o" isoimm!ni:ation in pregnanc$. A 30 -echnical 5!lletin 1DA1 1==0.