If rhogam is IgG why doesn't it cross the placenta??

[Taus]

I can't think of a logical reason why this IgG wouldn't just go kick the babies a$$.... I remember goljan saying something about it but don't have time right now to re-listen to it

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[cdql]

I could be wrong but I thought that Rhogam did cross the barrier. It's just meant to be a blocking antibody so it binds to the Rh+ cells and does nothing. (well, by nothing, I mean it prevents the mother from creating antibodies)

Whereas the anti-Rh antibody from the mother (also IgG) will cross the placenta and cause an immune reaction.

 

[lord_jeebus]

I'm pretty sure Rhogam doesn't cross the placenta, but I don't know why.

 

[SOUNDMAN]

In his RR pg. 282.. B.2.b - Anti-D globulin does NOT cross the placenta. Lasts 3 months, given at 28 weeks and after delivery. Also in his HY blue notes: "Special tests are performed on the mother's blood that detect fetal RBC's in her blood. The amount of fetal blood is quantified so that the appropriate amount of anti-D globulin is given to the mother....so that the mother does not host an antibody response against the D antigen."

Hope that helps.

 

[somnolent]

I actually had a UW question about this today. Basically they said that IgG is used b/c the Fc receptors on the phagocytes have a greater affinity for the Fc fragments on IgG than the other isotypes. So while this told me that IgG is used because it was the "best" for fetal antigens, it didn't explain why it doesn't just cross over into the baby.

So, I checked with goljan. He was pretty vague. He said that anti-D comes from sensitized mothers, and it's been heat treated, and stuff. So I guess it's one of those "just because" answers. I can't find a better answer anywhere else. My guess is that it's packaged in a way so that it doesn't.

 

[automan2]

Some kid actually just asked our professor this, and rhogam does cross the placenta. Think about it. It's IgG, and we have been told for our whole lives the IgG crosses. Why would this one be any different. Goljan is the man, but he explains concepts so we understand them, he doesn't always use scientific fact.


Clinnically, it isn't used very often during pregnancy anymore. And those that do get it, typically are given a does that quickly bind the fetal cells before crossing the placenta. (Yes, I know this is a bad theory, and my profesor doesn't agree with it either, but that is what is being used to make clinical decisions)

The majority of the time rhogam is used, is post partum so there is no worry about it crossing the placenta.

Bottom line: yes it does cross the placenta, but it is dosed to have minimal effect.

 

[Miami_med]

Some kid actually just asked our professor this, and rhogam does cross the placenta. Think about it. It's IgG, and we have been told for our whole lives the IgG crosses. Why would this one be any different. Goljan is the man, but he explains concepts so we understand them, he doesn't always use scientific fact.


Clinnically, it isn't used very often during pregnancy anymore. And those that do get it, typically are given a does that quickly bind the fetal cells before crossing the placenta. (Yes, I know this is a bad theory, and my profesor doesn't agree with it either, but that is what is being used to make clinical decisions)

The majority of the time rhogam is used, is post partum so there is no worry about it crossing the placenta.

Bottom line: yes it does cross the placenta, but it is dosed to have minimal effect.

I promise that it's still used during pregnancy.

 

[Army DOC DO]

Some kid actually just asked our professor this, and rhogam does cross the placenta. Think about it. It's IgG, and we have been told for our whole lives the IgG crosses. Why would this one be any different. Goljan is the man, but he explains concepts so we understand them, he doesn't always use scientific fact.


Clinnically, it isn't used very often during pregnancy anymore. And those that do get it, typically are given a does that quickly bind the fetal cells before crossing the placenta. (Yes, I know this is a bad theory, and my profesor doesn't agree with it either, but that is what is being used to make clinical decisions)

The majority of the time rhogam is used, is post partum so there is no worry about it crossing the placenta.

Bottom line: yes it does cross the placenta, but it is dosed to have minimal effect.

Ah your professor is incorrect, it does not cross the placenta. an IGG does but Rhogam is an Anti-D globulin, it comes from other women who have been sensitized and it is heat treated and all that stuff, so it does not cross. if it crossed the placenta it would not do its job, it would cause a hemolytic anemia in the baby if it crossed over. not doing its job. Its a prophylaxis. The idea of Anti-D (rhogam is to prevent the mothers sensitization to the fetal/maternal mixing of blood. which can occur pre delivery and of course at delivery. Anti Globulin D jumps onto the fetal RH+ blood if the mother gets exposed to it and masks the binding Sites or Destroys the fetal RBC so the mother does not mount an antibody response. it does ot work if the mother has already had a Rh+ pregnancy and she is RH- she is sensitized and the Rhogam will do nothing. and the event of another pregnancy could result in kernicterus, a combined left and right sided heart failure, leading to hydrops fetalis etc. because the anti D IGG crosses over and attached to baby RBC, and splenic macrophages cause a hemolytic anemia.
now one protecting thing is for a ABO type O mother is that they have the IGM circulating anti-A or Anti-B. so if she has a ABO baby that is type A, even if a fetal RBC gets into circulation that RBC will last a mili-second and be destroyed and thus protect the mother from mounting an anti-D antibody. but Rhrogam is given just the same because nothing is perfect. Happy Nerding all.

 

[automan2]

Ah your professor is incorrect, it does not cross the placenta. an IGG does but Rhogam is an Anti-D globulin, it comes from other women who have been sensitized and it is heat treated and all that stuff, so it does not cross. if it crossed the placenta it would not do its job, it would cause a hemolytic anemia in the baby if it crossed over. not doing its job. Its a prophylaxis. The idea of Anti-D (rhogam is to prevent the mothers sensitization to the fetal/maternal mixing of blood. which can occur pre delivery and of course at delivery. Anti Globulin D jumps onto the fetal RH+ blood if the mother gets exposed to it and masks the binding Sites or Destroys the fetal RBC so the mother does not mount an antibody response. it does ot work if the mother has already had a Rh+ pregnancy and she is RH- she is sensitized and the Rhogam will do nothing. and the event of another pregnancy could result in kernicterus, a combined left and right sided heart failure, leading to hydrops fetalis etc. because the anti D IGG crosses over and attached to baby RBC, and splenic macrophages cause a hemolytic anemia.
now one protecting thing is for a ABO type O mother is that they have the IGM circulating anti-A or Anti-B. so if she has a ABO baby that is type A, even if a fetal RBC gets into circulation that RBC will last a mili-second and be destroyed and thus protect the mother from mounting an anti-D antibody. but Rhrogam is given just the same because nothing is perfect. Happy Nerding all.

Maybe you should go back to school........... I think you are getting Anti-D and IgG confused. They call it RhoGam for a reason. Its short name is RhIG, an IgG antibody against Rh. It crosses the placenta. Period.

Straight from the Rhogam Literature.....

"Use in pregnancy. RhIG is administered to Rh negative women who are pregnant (or recently delivered) and do not already have alloimmunization to the D antigen. Routinely one vial is administered at 28 weeks of gestation and a second within 72 hours following delivery. These time recommendations are somewhat arbitrary. RhIG can and should be administered even if 4 or 5 days have elapsed since delivery. No one is really sure when the time cut-off for effectiveness is, so it's best to go ahead and give it just to be sure. Additional vials of RhIG may be indicated at the time of delivery if a larger-than-normal fetomaternal hemorrhage occurred. See the section on fetomaternal hemorrhage detection for further details.
RhIG is also indicated at the time of ectopic pregnancy, amniocentesis, abortion or miscarriage, or abdominal trauma in Rh negative, unimmunized women.
RhIG is IgG antibody. It will cross the placenta and can cause a weakly positive DAT in the fetus/infant. However, the titer of anti-D is too weak to cause any clinically significant RBC destruction. An Rh negative woman administered RhIG will generally develop a detectable anti-D with a titer in the range of 1 to 4. Occasional women sampled right after RhIG administration may have a titer of up to 8. Any higher titer of anti-D should be considered suspicious of true alloimmunization. However, if there is doubt as to whether an anti-D detected prenatally represents true alloimmunization or not, further RhIG probably should be administered at the time of delivery to make sure.
The anti-D of RhIG can be detected in some women for 3 to 5 months after administration of RhIG.

 

[Army DOC DO]

hey I am going off of my pharm/ OB lectures and and the Goljan Path book and his Audio lecture for Boards, yes it is an IgG, however, it comes from sensitized mothers, and is heat treat and various other things that makes it unable to cross the placenta. I have 4 different sources that says it doesn't sorry. Just going on what I have.

 

[Pinkertinkle]

Sounds like something a little too controversial for the boards to actually test.

 

[automan2]

agreed! Wise words from pink

 

[Army DOC DO]

agreed! Wise words from pink

yeah Goljan, states in his laudio lecture that they just want you to know that it covers the RBC of the Rh+ fetal blood if it gets into the mothers circulation to "hide the receptors" from the the mothers immune system so she never mounts a response to it.

 

[Freshnstylin]

Sounds like something a little too controversial for the boards to actually test.

Not to put a kink into your debate but I had one question on Rhogam on the USMLE (took it last week). It was confusing so I picked and clicked.

 

[NEATOMD]

Not to put a kink into your debate but I had one question on Rhogam on the USMLE (took it last week). It was confusing so I picked and clicked.

I think the point is that they aren't going to ask...
"Does Rhogam cross the placenta?"
a.) yes
b.) no
c.) I'm not sure because my mom says it does but I read a Goljan lecture that said it didn't.
d.) "I was just talking about Shaft."

 

[Snelgrave]

yeah i thought this was interesting when i read it in UW, but I imagine this detailed discussion is low yield.

 

[Twptophan]

It has to do with the dose, and how much fetal blood actually gets into the mom. In a typical pregnancy, only a few ml of fetal blood gets into the mother. If she is RH -, then she has no D antigen anywhere in her body, and thus only a very small about of the anti-D (i.e., rhogam) is needed to prevent sensitization in the mom. Think of the amount of a usual maternal total body blood volume (about 6-7 liters) and if only a few ml of fetal blood gets into mom, then not much rhogam is needed to soak up these few fetal D antigens.

Yes, the rhogam does cross the placenta, and but so little is used in the mom, that the amount that gets into baby is not enough to cause a clinically significant fetal hemolysis.

If there is a more significant fetal-maternal hemorrhage, (like with placental abruption or trauma) then they can do maternal D titers and figure out exactly how much rhogam is needed, there are formulas for this.

 

[NRAI2001]

Ah your professor is incorrect, it does not cross the placenta. an IGG does but Rhogam is an Anti-D globulin, it comes from other women who have been sensitized and it is heat treated and all that stuff, so it does not cross. if it crossed the placenta it would not do its job, it would cause a hemolytic anemia in the baby if it crossed over. not doing its job. Its a prophylaxis. The idea of Anti-D (rhogam is to prevent the mothers sensitization to the fetal/maternal mixing of blood. which can occur pre delivery and of course at delivery. Anti Globulin D jumps onto the fetal RH+ blood if the mother gets exposed to it and masks the binding Sites or Destroys the fetal RBC so the mother does not mount an antibody response. it does ot work if the mother has already had a Rh+ pregnancy and she is RH- she is sensitized and the Rhogam will do nothing. and the event of another pregnancy could result in kernicterus, a combined left and right sided heart failure, leading to hydrops fetalis etc. because the anti D IGG crosses over and attached to baby RBC, and splenic macrophages cause a hemolytic anemia.
now one protecting thing is for a ABO type O mother is that they have the IGM circulating anti-A or Anti-B. so if she has a ABO baby that is type A, even if a fetal RBC gets into circulation that RBC will last a mili-second and be destroyed and thus protect the mother from mounting an anti-D antibody. but Rhrogam is given just the same because nothing is perfect. Happy Nerding all.

Awesome explanation...even though whether or not Rhogam crosses the placenta is still controversial (I think the consensus here on SDN is leaning towards it crossing). You made a few really good points:

1) Rhogam basically does the mothers immune systems job of picking off the Rh+ RBCs... hence the mother never developes the IgGs.

2) If Rhogam were to cross the placenta (even if engineered not to do so, some would still invariable cross) it would cause kernicturus in the fetus.. the result we are specifically attempting to avoid..

3) I also read in Goljan how O- mothers have the added benefit of having preformed anti A and anti B Abs against fetal RBCs, allowing for rapid removal of any fetal blooding mixing before IgG can be formed..

4) So the source of Rhogam is from other sensitized women?? Sorry my pharm is a bit rusty. How does heat treating it effect it? Does it prevent a maternal reaction against the rhogam?

 

[buckeye12]

Awesome explanation...even though whether or not Rhogam crosses the placenta is still controversial (I think the consensus here on SDN is leaning towards it crossing). You made a few really good points:

1) Rhogam basically does the mothers immune systems job of picking off the Rh+ RBCs... hence the mother never developes the IgGs.

2) If Rhogam were to cross the placenta (even if engineered not to do so, some would still invariable cross) it would cause kernicturus in the fetus.. the result we are specifically attempting to avoid..

3) I also read in Goljan how O- mothers have the added benefit of having preformed anti A and anti B Abs against fetal RBCs, allowing for rapid removal of any fetal blooding mixing before IgG can be formed..

4) So the source of Rhogam is from other sensitized women?? Sorry my pharm is a bit rusty. How does heat treating it effect it? Does it prevent a maternal reaction against the rhogam?

So does Rhogam target Rh+ RBCs for destruction before an immune response can be formed, or does it just hide the D antigen by competitively and irreversibly blocking that antigen?

 

[turkeyjerky]

It has to do with the dose, and how much fetal blood actually gets into the mom. In a typical pregnancy, only a few ml of fetal blood gets into the mother. If she is RH -, then she has no D antigen anywhere in her body, and thus only a very small about of the anti-D (i.e., rhogam) is needed to prevent sensitization in the mom. Think of the amount of a usual maternal total body blood volume (about 6-7 liters) and if only a few ml of fetal blood gets into mom, then not much rhogam is needed to soak up these few fetal D antigens.

Yes, the rhogam does cross the placenta, and but so little is used in the mom, that the amount that gets into baby is not enough to cause a clinically significant fetal hemolysis.

If there is a more significant fetal-maternal hemorrhage, (like with placental abruption or trauma) then they can do maternal D titers and figure out exactly how much rhogam is needed, there are formulas for this.

as much as I hate to think a pre-med is gonna come in here and school a bunch of med students and residents, this makes sense to me...

 

[NRAI2001]

So does Rhogam target Rh+ RBCs for destruction before an immune response can be formed, or does it just hide the D antigen by competitively and irreversibly blocking that antigen?

Competitive and irreversibly blocking? I think those terms are used more for receptor kinetics... IgG binds the Rh+ RBCs and leads to splenic removal. You were correct in that the goal of this is to quickly do this before the mothers immune system can notice and mount its own attack..

 

[NRAI2001]

It has to do with the dose, and how much fetal blood actually gets into the mom. In a typical pregnancy, only a few ml of fetal blood gets into the mother. If she is RH -, then she has no D antigen anywhere in her body, and thus only a very small about of the anti-D (i.e., rhogam) is needed to prevent sensitization in the mom. Think of the amount of a usual maternal total body blood volume (about 6-7 liters) and if only a few ml of fetal blood gets into mom, then not much rhogam is needed to soak up these few fetal D antigens.

Yes, the rhogam does cross the placenta, and but so little is used in the mom, that the amount that gets into baby is not enough to cause a clinically significant fetal hemolysis.

If there is a more significant fetal-maternal hemorrhage, (like with placental abruption or trauma) then they can do maternal D titers and figure out exactly how much rhogam is needed, there are formulas for this.

"Routinely one vial is administered at 28 weeks of gestation and a second within 72 hours following delivery.."

Why is it that only one dose is needed for mothers? Does the rhogam remain in the mothers system for the next couple of weeks? If it does remain for so long how does it not eventually cause jaundice in the fetus (even if it only enters at low levels)??

 

[Twptophan]

"Routinely one vial is administered at 28 weeks of gestation and a second within 72 hours following delivery.."

Why is it that only one dose is needed for mothers? Does the rhogam remain in the mothers system for the next couple of weeks? If it does remain for so long how does it not eventually cause jaundice in the fetus (even if it only enters at low levels)??

IgG has a half life of 21 days. I'm not sure what the half life of Rhogam is though, but Rhogam is an IgG.
There will be some hemolysis in the fetus, though will not be significant (due to the low dose). It would probably be hard to distinguish it from physiological jaundice of the newborn which is due to a short-lived lacking of bilirubin conjugation enzymes.

 

[gok]

It does cross the placenta. But the dose you administer is too low to go cause hemolysis in the fetus. (300 mg at 26-28w)

Followed by KB test based dose within 72h to prevent sensitization to the mum.

 

[Furious Curious]

This has been a fascinating discussion, and I really appreciate all the comments. I too, wondered why RhoGAM doesn't cause hemolytic anemia in the fetus, when after all, it is IgG. Wouldn't it cross the placenta like any other IgG? After reading everyone's comments, I read the actual product literature and...BUMMER! it didn't say a word about whether RhoGAM does/doesn't cross the placenta. I believe it DOES, else the product literature would have explain how they had modified the IgG somehow so it doesn't cross. Sorry, I tried to include the link to the product literature, but the forum would not allow it. If it is making you crazy, you will have to search for it.

Still, I did find out a few things from the literature that are relevant:
1. RhoGAM is a IM shot, not an IV. Its not a direct IV into the maternal-fetal highway. I suppose that slows it down a bit?

2. The prophylactic RhoGaAM dose given after an accidental exposure allowing maternal-fetal blood mixing, is titrated to the amount of fetal hemoglobin in the mother. Yes, that test is done first. For example, 1 dose of MicRHOgam suppresses 2.5 mL of fetal Rh+ RBCs. So you only give just enough to neutralize what's in her blood. Probably pretty important to do the math right!

3. A shot of Rhogam is given within 72 hours AFTER delivery. Obviously, by this time the baby is OUT, and there is no danger of it being affected by the Rhogam. And there's no placenta anymore, either.

4. Think about it, giving a limited, single dose of RH antibodies, is not the same as the immune system mounting a full-out response. When the immune system is activated, it keeps pumping out antibodies till 100% of the antigens are neutralized. The mother's immune response would be satisfied with nothing less than total destruction. Those plasma B cells will just keep secreting antibodies till the baby is dead. In contrast, giving a small dose doesn't have continuing action. So the baby can handle a single-time, small insult. It can't survive the full, unremitting onslaught.

5. The product literature did say "Some babies born to women given RhoGAM antepartum have weakly positive direct antiglobulin Coombs test at birth." This suggests that RhoGAM does cross the placenta, and does reach the baby, but only in small amounts.

My conclusions:
A. Yes, RhoGAM does cross the placenta. But the small, dose, given IM, has a limited effected on the fetus, very minor compared to what the mother's immune system would have done. When giving RhoGAM, make sure the dose is only enough to neutralize the exact amount of fetal hemoglobin got into the mother's blood stream.

B. Wow, there's a lot they left out in medical school. This is such an obvious question, yet it was like being an FBI investigator, to find the answer. Why didn't they teach us this at the time they taught the whole alloimmunization story?

C. You guys are awesome. I have learned as much from these forums as I have from the professors.

Truly,
Furious Curious