Neonatal Alloimmune Thrombocytopenia (NAIT) Parents

A: Neonatal Alloimmune Thrombocytopenia (also referred to as Fetal Alloimmune Thrombocytopenia and Fetal Maternal Alloimmune Thrombocytopenia, with the acronyms of NAIT, NAT, NATP, FAIT and FMAIT) is a disease that results in a low platelet count (thrombocytopenia) in an unborn or newborn baby that is caused by maternal IgG antibodies passing through the placenta and attacking the unborn baby's platelets.  The maternal antibodies are produced due to the mother's having a homozygous platelet type(s) that differs from that of the baby.  It is similar to Hemolytic Disease (where the baby's red blood cells come under attack due to a different RH type than the mother), but unlink Hemolytic Disease, NAIT often affects the first pregnancy and currently in the US, screening is not performed for NAIT, nor is there an attempt to prevent initial maternal sensitization like there is with the RH factor.  Testing is available where parents can have their platelets genotyped to identify incompatibilities, but few if any Ob/Gyns or MFMs inform parents of the small risk of NAIT or availability of the tests.

 

A: PUBS stands for Percutaneous Umbilical cord Blood Sampling and FBS stands for Fetal Blood Sampling.  All of these are names for a procedure where the doctor uses a needle to withdraw a blood sample from the umbilical cord and for NAIT pregnancies the purpose is to obtain a platelet count.  If the count is low, they may transfuse with matched platelets.  There are risks associated with the procedure that are generally stated as pretty low, but be careful to ask if the statistics being quoted are for the general population or ones involving NAIT.  Some of the complication statistics I have seen in NAIT research seem much higher than the general population, possibly due babies being thrombocytopenic.

 

!!!PUBS UPDATE!!! Even Dr. Bussel FINALLY has recognized or at least admitted in writing stating in the Summary section of his July 2009 article in the International Society on Thrombosis and Haemostasis, "Avoid fetal blood sampling whenever possible."   Avoiding it is always possible as it is an elective procedure, but Dr. Bussel seems to leave some wiggle room that he still may use it in some cases despite the somewhat alarming PUBS/FBS complication rates in his own data.  It would be nice if they had ever demonstrated how the risk of the procedure outweighs the alternatives, but I never saw them try to justify the risk in the numerous writings I read of theirs, and they seem to completely ignore the risk of maternal immune sensitization that can be triggered by PUBS.  Dr. Beer and Dr. Kwak-Kim absolutely stressed to avoid PUBS as early as 2000 when we first consulted them, and offered the better alternative of using non-invasive methods to monitor the treatment's effectiveness.  We emailed several noted doctors regarding this in the UK and US, and Dr. Bussel was the only one who did not respond with interest.  We give thanks that he has finally recognized the safer way to treat NAIT, and our heart goes out to those parents who may have needlessly lost a baby due to PUBS or many whose babies suffered serious complications as a result of the PUBS procedure.

 

The change in FBS/PUBS use by Bussel, Berkowitz, etal, seems to have possibly been brought about by a group of doctors in Europe publishing an article that pointed out the US group's results did not outweigh the harm caused by the invasive procedures they were recommending.  The artilce of reference is Noninvasive antenatal management of fetal and neonatal alloimmune thrombocytopenia: safe and effective and it is also noted on our NAIT Research page.

 

Here is more recent article by Dr. Bussel again stating the concensus is growing to use a non-invasive approach: Antenatal treatment of fetal alloimmune thrombocytopenia: a current perspective, Haematologica. 2010 November; 95(11): 1807–1811.

 

To be clear, we feel that for the purpose of determining how much medication to use, there are generally alternatives that are safer than PUBS/FBS, and just increasing the dosage as if you were assuming a poor PUBS count has seemed statistically safer in the Bussel data for nearly a decade, and he finally seemed to realize that in the 2009 article cited above.  The only time a PUBS would seem clearly warranted is if a bleed is detected or suspected in the baby inutero so that you could transfuse maternally matched platelets.  We feel it also may warrant higher consideration in a pregnancy where NAIT was discovered late in the pregnancy or treatment was started very late in the pregnancy and it is felt that a transfusion is needed to avoid a bleed (as possibly a TH1/TH2 cytokine ratio, titer count, etc., indicate the maternal immune response is very high.)

 

 

 

 

 

A: Zygosity in humans refers to whether you carry two like alleles (homozygous) or two different alleles (heterozygous) for a gene.  Parents with a suspected case of NAIT will undergo testing to determine their zygosity for several known platelet antigens to look for antigens where an incompatibility may result in the baby.  The most common incompatibility is with the HPA-1 antigen where the mother is homozygous HPA-1b (two like HPA-1b alleles) and the father is either homozygous or heterozygous HPA-1a (i.e., HPA-1a/HPA-1a or HPA-1a/HPA-1b).  If the the incompatibility involves a heterozygous incompatibility, the baby carries a 50% chance of inheriting the incompatible trait from the father, so generally an amniocentesis is performed early in the pregnancy to determine the baby is homozygous like the mother or heterozygous like the father.  If the baby shares the homozygous type of the mother, treatment can cease (but the child should be told of their risk for PTP or NAIT.)

A: See NAIT Treatment on this site.

A: Currently OB/Gyns and MFMs do not routinely inform parents of the risk of NAIT, so the first time you learn of it is when you deliver a severely thrombocytopenic baby, and thus there is nothing that you could have done to prevent it.  If you have a sibling that shares the rare homozygous type, they are of higher risk than the general population (they carry greater than a 25% chance of having the same homozygous type) and they should consider platelet genotyping if considering children.  Insurance should pay for this, but even if not, the cost of test may be worth it since NAIT carries a 10% or more chance of a bleed in an untreated pregnancy. 

 

NAIT has been known about since the 1950s, but its occurence is rare (many publications put the risk of NAIT around 1 in 1000 to 2000 and may often go undiagnosed), so possibly due ot the cost of screening and rareness of the condition it has yet to be adopted in the US at time of writing this in June 2009.  The frequency of research in this area seems to be growing, especially in Europe, which is promising.  Our hope is that platelet genotyping or antibody screening will become an accepted and covered practice in the US.  Encouraging our doctors to make parents aware of the risk of NAIT can help.  Does it make sense to screen for trisomy 18, which occurs in about 1 in 3000 live births, or trisomy 13 at 1 in 10,000 live births, and not NAIT?

A: Of the dozens of parents I have corresponded with over the years, I know of no cases in the US where NAIT was not covered, although due to its rarity and high costs associated with the IVIG treatments, coverage is initially denied in many cases (and this was the case with us.)  In our treated pregnancies we had to appeal the coverage denials and provide a letter of medical necessity, but eventually the charges were covered like any other illness.