I couldn't get decent info on antivenoms so I asked for some help from the PICU lists [no case details or names divulged!] and the responses are as follows:
1.. I guess the other question would then be, how much of the antibody is
taken up by the digestive tract? Or is the protein degraded by all
the trypsins, chymotrypsins, etc. I would assume that some would be
taken up, or so the theory behind all the food allergies goes, but
breast milk has been shown to delay the intestinal epithelium immune
response to protein antigens. Does that mean breast milk would be
protective? Or does any exposure to formula rev up the immune
response?
Yet another question is: how long would you ban mom from breast
feeding? One month? Three months? Two weeks? Six hours? Free Fab
levels are nearly at zero within 4 hours of administration for
envenomation, but total Fab levels can still be detected 9 days after
administration (J Int Med 241:53-58, 1997). Clinical studies have
shown return of coagulopathy in as little as 2 days after
administration of the ovine antivenom (Arch Int Med 159(7): 706-10,
1999). Does this mean that the antibodies are gone? Is the free Fab
the important level? Or the total Fab? If it's free Fab, then nurse
when you see the whites of her eyes.
My bias would be to discard the breast milk for two weeks, but that
is only a guess on my part.
2.. First of all it would be my suspicion that immediately after being nailed by
a copperhead snake, the mother would not be inclined to breastfeed.
Secondly, the new antivenin is called CroTAb, not Corfab. Snakes in the pit
viper class are called Crotalidae. The timber rattlesnake, for example,
bears the colorful moniker Crotalus horridus. CroTAb is comprised of a
combination of four specific binding antibodies directed like SCUD missiles
to the purified antigen-binding fragment (Fab portion of an IgG molecule) in
the venoms of four badass Crotalidae: Western diamondback rattlesnake,
Eastern diamondback rattlesnake, Mojave rattlesnake, and the cottonmouth or
water moccasin. Since it is developed from innocent sheep rather than
immunologically jaded horses, CroTAb is more effective and has a lower
profile for mayhem, but still has about a 20% incidence for adverse reactions
and should not be used for just anything.
Thirdly, the copperhead snake (Agkistrodon contortrix contortrix) belongs to
a somewhat different family of snakes, and its bite is not quite the scare of
envenomations from the Big Four. CroTAb is not the treatment of choice.
3.. In 1991 the Alabama Center for Envenomation looked for ovine antibodies-such
as those used in antivenin immunotherapy in porcine milk (read pre-CroFab's
Crotab by the then Therapeutic Antibodies). We found that fabulated ovine
immunoglobin (lacking the Fc receptor) was not measurable in pig milk,
whereas full ovine antibody (radio-labelled from precipitated sheep serum)
was present at high concentrations in the porcine milk. This study suggested
Fc mediated transport in breast acinar cells may participate in antibody
levels in mammalian coelostum.
Such observations raise questions about selection of xenospecies
immunotherapy in the care of pregnant or lactating women. Therapies in
question include digitoxin toxicity, botulism intoxination and in this case,
envenomation by North American crotalids or agkistrodons. The results
suggest that Fabs may have lower acinar transfer rates then polyclonal.
non-fabulated immunoglobins.
I should hasten to add that the study suffered from design flaws with regard
to our immunoassay-which may have measured antigen on the (non-existent) Fc
region of the ovine antibody molecule and therefore "missed" the fabulated
antibody. Such possibilities are less likely as I re-ran SDS PAGE gels
focusing on fabulated kD markers and found none.
If you have human breast milk obtained by a patient treated with CroFab, we
would be interested in testing it with a highly sensitive assay we produced
in 1999.
In total then there seems to be a lack of absolute certainty - but concurrence that erring on the side of caution is wise.
Tony Knox
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