Neonatal Alloimmune Thrombocytopenia (NAIT) Parents

Bussel, Berkowitz, et. al.

Not that we are aware as of Jan. 2011.

Quite frankly, who on earth would say something does not exist when there was clearly an indication in existing research that it possibly does?  No one knows everything that is being used or reseached!

There was research prior to Dr. Bussel's statment indicating some promise, and in Jan. 2011, this article stands in contrast to Dr. Bussel's statement:

Prediction of the fetal status in non-invasive management of alloimmune thrombocytopenia, Blood. 2011 Jan 14.

Non-invasive testing has been used for many years in the field of Reproductive Immunology to guide the dosage of IVIG and Prednisone.  Just because Dr. Bussel writes no reliable non-invasive tests do not exist, does not mean they are not useful, and there has been past research related to antibody concentrations that showed some promise, plus a strong correlation in the research by Gerald Bertrand, Moustapha Drame, Corinne Martageix and Cecile Kaplan  See the article immediately below.

Prediction of the fetal status in non-invasive management of alloimmune thrombocytopenia, Blood. 2011 Jan 14.
"In this study we confirm that a high maternal alloantibody concentration measured before 28wg and before any treatment is correlated with a severe fetal thrombocytopenia.¹² We refined the antibody concentration threshold, now corresponding to 28 IU/mL. This threshold allows improvement in the sensitivity (81.2%) and the specificity (91.7%) of the testing, with high positive and negative predictive values (respectively 92.3% and 79.9%) (Table 3). Under
the threshold of 28 IU/mL, the antibody concentration cannot be considered as a predictive parameter of the fetal status.

This maternal parameter allows recognition of high-risk fetuses and the need for therapy."

The above group had also published some initial data in Journal of Thrombosis and Haemostasis 2006, 4: 628–637, and article titled Predictive value of sequential maternal anti-HPA-1a antibody
concentrations for the severity of fetal alloimmune
thrombocytopenia, but in that article stated they could not draw any conclusions.  Possibly this is what Dr. Bussel was referring to in 2009, but he could have simply stated that none were widely used or established at the time of printing and not summarily dismissed the existance of non-invasive tests just because he did not choose to use or research them.  The late Dr. Alan Beer felt he established reliable non-invasive tests, and seem to have worked well in every treated NAIT case that I am aware.

There is some good citations on this in this article:

Mouzaki A, Theodoropoulou M, Gianakopoulos I,  Vlaha V, Kyrtsonis MC, Maniatis A.  Expression  patterns of Th1 and Th2 cytokine genes in  childhood idiopathic thrombocytopenic purpura (ITP)

at presentation and their modulation by intravenous  immunoglobulin G (IVIg) treatment: their role in prognosis.   Blood. 2002 Sep 1;100(5):1774-9.

Panitsas FP, Theodoropoulou M, Kouraklis A, Karakantza M,  Theodorou GL, Zoumbos NC, Maniatis A, Mouzaki A.   Adult chronic idiopathic thrombocytopenic purpura (ITP)

is the manifestation of a type-1 polarized immune response.   Blood. 2004 Apr 1;103(7):2645-7. Epub 2003 Dec 11.

Hunt JS, Petroff MG, McIntire RH, Ober C.  HLA-G  and immune tolerance in pregnancy.   FASEB J. 2005 May;19(7):681-93.

No, and never has due to direct risks

and risk of increasing maternal

immune sensitization

Recommended PUBS always for well over a decade  (despite reporting alarmingly high serious complication rates)

until in a 2009 statement seemingly

 While the PUBS complication rates in the general population are often said to be as low as 1%, the complication rates in NAIT cases, especially those cited in the Bussel, et. al.,  research, are much higher, affecting over 18% of the pregnancies in a 2002 report.  PUBS/FBS is very dependent on the skill of he doctor, and there is research showing a skilled operator can have an extremely low complication rate with NAIT, but clearly with others the risk can be considerable.

PUBS also can put the baby's platelet's antigens in direct contact with the mother and can cause a heightened immune response if the immune system  was not previously exposed to the baby's platelets.  This was recently cited in the same BJOG article that basically said the the protocols in the US using FBS and other's results did not justify their use of FBS.  Dr. Kwak-Kim mentioned FBS increasing maternal sensitization as a strong possibility, plus there is evidence of sensitization occuring from amnios in RH disease.  So in effect, they could find a great platelet count, but if the PUBS triggered a stronger maternal immune reponse, things could change a good deal for the worse in the following weeks. While I am sure the Bussel, et. al., group meant well, to us and many observers it was clear they were doing more harm than good with the Fetal Blood Sampling, and for years on end.  If they were clearly wrong on the use of FBS for so many years, it certainly should bring into question their other methods and statements, primarily the unproven way they choose when to begin treatment and not using non-invasive testing that others use.  The bottom line is that babies are still dying or being born severely thrombocytopenic using their protocol.  In our opinion, if you are looking for thought and result leaders for NAIT, that group is currently not it.  To their credit they do publish frequently with much useful information, but it is the results that matter.

 Reported in 7/2002 "211 FBS procedures in 91

patients were complicated by 3 fetal deaths,

and 14 deliveries precipitated by FBS,

among other complications. Taking these

complications into account, the new

protocols under current study emphasize

 early treatment with stratification according

 We have always felt the risks reported with PUBS seemed greater than the risks associated with just assuming a bad count and treating more aggressively if following the Bussel, etal, protocol.  With the risk of a bleed in a  treated case being low, having complication rates in the  double digits surely seemed to be doing more harm than good, and European doctors pointed this out in a BJOG article referecnced on our NAIT Reseach page.  Given that the stated risk of an ICH in an untreated NAIT pregancy is 10% to 20%, and obviously much lower than that in treated pegancies, I have no idea why anyone would continue recommending PUBS/FBS for many years after reporting serious complications associated with it in over 18% of their treated pregnancies in 2002.  While surely well intentioned, your doctors cannot ignore the flaw of this group's judgement with PUBS/FBS, and to us it surely lessens the credibility of their other questionable judgements, mainly how late they choose to start treatment and their feeling that non-invasive tests can be beneficial.

I realize Dr. Bussel, et. al., has helped many of the NAIT parents I know, which we greatly appeciate, but I also know parents who suffered complications from PUBS/FBS or who encountered an ICH after starting treatment at 20 weeks.  Frankly if I told you there were two doctors treating a rare cancer that had an untreated death rate of 10% to 20%, and one had treated several hundred patients with the rare cancer and chose to treat using an invasive operation and started chemo at stage II with chemo working 96% to 98% of the time, but the operation itself added a serious complication rate of over 6% -- and the other doctor had only treated a dozen cases with this rare cancer, but had expeience treating thousands with a similar cancer, and that doctor chose to avoid the operation that seemed to do more harm that good, and to treat earlier at stage I with chemo, and had never lost a patient to the rare cancer, which doctor would you recommend?  The choice seems quite easy when it does not involve your doctor, right?  With no disrepect to Dr. Bussel, Dr. Berkowitz, et. al., we simply feel there are other doctors treating NAIT erroring more on the side of caution and achieving better outcomes.

One noted UK research doctor told us he would only recommend a vaginal delivery if the count was over 100K,

but that PUBS to determine that count after 34 weeks  are higher risk, so that is why a C-section is almost always recommended.  You want to avoid as much trauma to the baby as possible in the case it might be severely thrombocytopenic. 

36 weeks

Risks associated with premature birth decrease with gestational age, but the risks of a NAIT bleed increase, so they want to  find a point where they premature risks are lower than the NAIT risks, and 36 weeks is generally accepted as that point.