Research Articles:
Note: All articles are copyright of their respective owners
Search the US National Institute of of Health's website for latest Neonatal Alloimmune Thromboctyopenia articles by following this link:
www.PubMed.gov.
Here are a select few NAIT research articles, but we have many more we have purchased over the years, please
contact us if you are looking for any specific research and we would be happy to try to help.
This is another article by the Bussel, Berkowitz, McFarland, et. al., group that helps illustrate how they use a different measurement for success than Laura, myself and hopefully the doctors who treated us or are treating you. Please read the summary and make up your own mind:
"RESULTS: Five of 37 fetuses suffered ICHs. Two ICHs had platelet counts >100,000/mL, and 1 was grade I. The other 2 ICHs were unequivocal treatment failures; both were grade III-IV and resulted in fetal demise. CONCLUSION: These findings demonstrate the success of stratified treatment in these HR patients, which tailored interventions according to the timing of the sibling's ICH."
In my opinion, this spiltting of hairs on the timing of the previous child's ICH proves little, is not completely sound from an immunological standpoint, and the results are certainly not what I would call a "success" with five of 37 having an ICH. Statitistics was my technical elective when studying Engineering at the University of Illinois, and quite frankly, a sample size of 37 is quite small to really predict represenative outcomes in a larger scale. Speaking as a parent, zero ICHs out of the 37 would be reason to call it a "success of stratified treatment". Also, I think most parents would consider a Grade I ICH a treatment failure, too, but clearly it is much better than death. If you wonder why we were drawn to the late Dr. Beer's stated treatment protocol goal to achieve a birth count above 50,000, which is above what is considered severe thrombocytopenia, in 100% of treated cases, I think the above groups protocol that includes deaths in what they define as succes stands in stark contrast. They may be right that if we treated in a way to avoid all the bleeds and achieve higher counts, we might over-use IVIG in some cases. My point is so what? Isn't it better than running the risk of some babies dying? If you feel as we do, I suggest you follow Dr. Beer's advice and accept no lesser protocol than his. I know of no NAIT parents who regret making that choice, and only one who had a birth count below 50k. It was 42k, but delivery was scheduled later than Dr. Kwak-Kim recommended. We have purchased this article for our library, so please
contact us if you would like more information in this article.
This summary compares three treatment protocols used on 98 pregnancies with no ICHs and only one death related to a FBS (Fetal Blood Sampling) procedure.
This is the first publication we have seen that finally seemed to state what has seemed obvious to us and others for years with the Berkowitz, Bussel, etal, data related to PUBS/FBS, and it appears this group's writings changed to say to avoid PUBS, possibly motivated by seeing this in writing:
“In conclusion, the studies by Birchall et al. and Berkowitz et al. describe a considerable number of complications and adverse outcomes associated with FBS. However, such risks could be acceptable if the invasive management would result in a better overall outcome when compared with a completely noninvasive approach. This, as our data suggest, does not seem to be the case.”
This article also is the first we have seen that mentions the risk of FBS/PUBS increasing the maternal immune response that Dr. Kwak-Kim warned of almost a decade ago in our consultation with her when asking about the use of PUBS that we had seen in others' writings. The article states (bold added for emphasis only):
“Controversy exists whether FBS, with its inherent risks of bleeding, boosting of antibody levels, emergency (preterm) caesarean section and fetal loss, should remain part of the management of FNAIT.” The full text of this article is availble through the above link.
This is the full text of a large Norwegian study of more than 100,000 pregnancies, that sheds some light that the initial NAIT maternal sensitization may not occur in the first pregnancy as much as once thought and that delivery or a previous miscarriage/sponstaneous abortion may cause it more than previously thought. It also cites the articles that link higher antibody counts to severe thrombocytopenia and seems to concur with that thought, despite Bussel and others still sayiing there is no non-invasive tests available. We clearly have seen evidence that non-invasive testing, including antibody binding, TH1/TH2 ratio and Natural Killer (NK) assay can be useful guide in treating NAIT. Of the seven treated NAIT cases I am aware of that used these tests, the birth counts were 152k, 194k, 265k, 56k, 42k, 56k and 127k, and testing appeared to correlate to the results in six of the seven, and in the other case we were not provided the doctor's determination on the tests. The full text of this article is availble through the above link.
I found this research fascinating a few years back and that that a monoclonal antibody (H22) looked to inhibit antibody binding as effectively as IVIG in the testing. I contacted Professor Rodeck and he said while promising, there are still hurdles to clear. Here is the conclusion of the study:
"In conclusion, our results suggest that FccRI plays a major role in anti-HPA-1a-mediated platelet phagocytosis by mononuclear phagocytes while FccRIIa, is of little or minor importance only. Any role of FccRIII in the process has to be studied with macrophages as effectors. Moreover, the findings indicate the use of H22 as an alternative to ivIg in the management of the FAIT/NAIT."
Blockade of maternal anti-HPA-1a-mediated platelet clearance by an HPA-1a epitope-specific F(ab') in an in vivo mouse model of alloimmune thrombocytopenia. , Transfusion. 2009 Feb;49(2):265-70. Epub 2008 Nov 4.
A more recent article with a similar study to the one above using monoclonal antibody (MoAb), SZ21.
This article gives good basic information about NAIT (AIT) and what causes it, how to treat a newborn and information on Dr. Bussel's ongoing study. What I found most encouraging is they do not seem to be pushing the PUBS/FBS as much as they used to, and given their past published percentages of serious complications resulting from PUBS/FBS, it seems they are hopefully realizing what we and others saw in their data years ago and that is the rewards generally do not seem to outweigh the risks of the procedure. The article states: "In the past, we advocated fetal blood sampling to determine response to therapy. All current treatment programs minimize or even eliminate the use of fetal sampling."
This article covers a large study that concludes that 66% of the cases where a sibling had a servere count less than 20k, but no ICH, were already severely thrombocytopenic prior to treatment. I feel this is a strong argument against waiting until 20 weeks to treat. Here is an exerpt from the article we purchased:
"In conclusion, 92% of cases with a sibling history of antenatal ICH had severe thrombocytopenia prior to treatment at a median gestation of 24 weeks, and 66% of cases with a sibling platelet count of < 20 x 109/l also had severe thrombocytopenia prior to treatment at a median gestation of 28.5 weeks. The high incidence of hazards associated with FBS and the effectiveness of maternal therapy suggest that maternal therapy without an initial FBS should be used as initial therapy in these groups. This should be considered from or before 16-weeks gestation in the cases with antenatal ICH, because the earliest reports of ICH are at 16 weeks (Murphy et al, 1994), perhaps starting maternal therapy a few weeks later in the group with a sibling history of severe thrombocytopenia but no antenatal ICH."
We have heard of some moms via email that they had severely thrombocytopenic babies, were tested to have incompatible platelet type with the father, but had no anti-platelet antibodies detected. This article may help shed some light to the limitations of antibody testing. I know of a few others that I hope to post soon, or please email me for them if needed sooner.
The Bussel, Berkowitz, McFarland articles all provide a lot of useful data. While I do not agree with some of their conclusions (especially on what warrants early treatment), the data is useful and it helps highlight the serious complications they have encountered with the PUBS/FBS procedure in a significant percentage of their cases.
This study states that "In 48% of the ICH cases, the previous sibling had thrombocytopenia but not ICH." I feel this raises some questions to Dr. Bussel, Bekowitz, McFarland, etal's conclusion that an ICH is the only reliable predicter for what babies warrant early IVIG. Our question was why wait for something bad to happen before treating earlier? We were told by one doctor that in the unlikely event we did have an ICH if we started treatment later like he recommended, that he would treat us earlier on the next one. I can think of no parallel in medicine that uses this approach of requiring one of your children to possibly die of the same disease before treating a sibling more cautiously. This is just one more reason we felt Dr. Beer and Dr. Kwak-Kim were the doctors we wanted to use to manage our NAIT treatment.
This page was last modified on Tuesday, June 29, 2010 04:50:46 PM