Neonatal Alloimmune Thrombocytopenia (NAIT) Parents

 

 

If your baby is found to be severely thrombocytopenic at birth, Neonatal Alloimmune Thrombocytopenia (NAIT, a.k.a., Neonatal Alloimmune Thrombocytopenia Purpura or NATP, Fetal Alloimmune Thrombocytopenia or FAIT and FNAIT, and sometimes Fetal Maternal Alloimmune Thrombocytopenia or FMAIT) is the most likely cause.  If the count is considered low enough where the doctor (generally a Pediatric Hematologist if one is on staff) feels you baby could be at a risk of a bleed, they will transfuse platelets to boost the count.  In our experience the Pediatric Hematologist where our first-born was born said he would transfuse if the count dropped below 20k, and the Pediatric Hematologist at a different hospital for our second and third deliveries preferred to transfuse if the count was below 50k. 

 

If the platelets do not match the mother's platelet type, they will be quickly destroyed by the maternal antibodies that can persist in the baby for several days and at times weeks.  For this reason, washed (removes the antibodies) maternal platelets are often used if time permits, but unmatched are often used initially to quickly boost the count until maternally matched platelets can be acquired.  Platelet counts can drop after birth, so your doctors will monitor the counts periodically.  IVIG has been shown that it can protect your baby's platelets (most likely by blocking Fc-receptor sites and inhibiting binding to effector cells), so it is often used to help your baby achieve and sustain a normal count.  In our pregnancies, the doctors planned to infuse IVIG if the count was below 100k at birth.  With our first-born, Caleb, IVIG was all that was used and his count rose from 20k to near 100k in about a day.  The response to IVIG varies.

 

Severely thrombocytopenic babies will also generally be scanned to check for internal bleeding, and especially to check for intracranial hemorrhages (ICHs).  Some doctors seem to use doppler/utrasounds, while others sometimes prefer a higher resolution imaging such as a CT or MRI.

 

Parents who have given birth to a severly thrombocytopenic baby should undergo testing to determine their platelet types and also screen for the presence of anti-platelet antibodies.  The Blood Center of Wisconsin or the Red Cross are two places that can peform this testing in the US.  There is a fair amount of research that indicates current methods for detecting maternal anti-platelet antibodies does not always detect the antibodies (due to washing or possibly even very high titer counts), but if testing shows you have an area of potential incompatibility, future pregancies are generally considered at risk for NAIT.  What percent of risk depends on how many incompatibilities and whether both parents are homozygous (two like genes) for one or more types or if one is heterozygous (one of each gene) for one or more platelet types where the other is homozygous.  Generally there is only one incompatibility, but I know of at least one case where there were two.  With one incompatibility and both parents being homozygous for it, there is essentially 100% chance for reoccurrence of NAIT in future pregnancy.  If the one parent is heterozygous, then there is a 50% chance the baby will inherit the incompatible type.  In these cases the baby's type can be tested by to determine if it is homozygous like its mother or heterozygous like it's father.  In July 2001, it was reported in that in heterozygous cases caused by the father carrying the HPA-1a antigen, that the baby's gentotype could be assessed using a noninvasive fetal human platelet antigen (HPA)-1a genotyping assay on a real-time polymerase chain reaction (PCR) platform using cell-free fetal DNA isolated from maternal blood.  In the past only amniocentesis was used early in the pregnancy and may be all that is available to you.  The noninvasive test not only eliminates the small risk of miscarriage, but also the direct risk of increasing the maternal immune response as the amnio puts the baby's platelet proteins in direct contact with the mother.  If the father is determined to by homozygous, treatment can be stopped at that point if it has already been started (which our doctors would recommend since waiting until the aminio could allow time for mom to mount a large immune response and the amnio itself will put the baby's dna in direct contact with the mom, which could trigger a stronger immune response.)  In cases where two incompatibilities are present, you can possibly have a 75% chance of NAIT.

 

Research shows that subsequent NAIT pregnancies are often more severely affected if left untreated since the mother's immune system has essentially been immunized against the baby's platelet type.  At time of writing, in the US IVIG is the most commonly used drug in treating NAIT pregnancies.  Prednisone is also used either solely, but more often in addition to IVIG.  Dr. Kwak-Kim also frequently treats with Progesterone during the first trimester.  The primary differences in the US seem to be on when treatment is started, how its effectiveness is monitored, if and when Prednisone is used and when delivery is scheduled.  We were convinced by the evidence and science that suggests that treating earlier in the pregancy makes it easier to control the maternal immune response.  Surprisingly to us, Dr. Kwak-Kim is one of the few in the US who use this methodology and seems to be achieving very good outcomes.  Many still wait to treat at a time when severe thrombocytopenia is frequently observed, such as 20 weeks.  Possibly this is because doctors are unwilling change their ways or feel they need evidence to justify the cost of IVIG.  I am not sure why, but for us, we would rather try to treat to avoid the thrombocytopenia than wait for it to occur and hope you can keep it from getting worse.  Some doctors will only prescribe earlier treatment after you have a bleed in a previous pregnancy.  We clearly decided to avoid doctors who used that rationale and sought out doctors who wanted to treat EVERY baby cautiously.  There are no do-overs for parents when it comes to avoiding life-threatening bleeds and there is research that states "In 48% of the ICH cases, the previous sibling had thrombocytopenia but not ICH," (Will it ever be possible to balance the risk of intracranial haemorrhage in fetal or neonatal alloimmune thrombocytopenia against the risk of treatment strategies to prevent it?, Vox Sang. 2003 May;84(4):318-25.) which seems to indicate ICHs occur about as equally following a previous ICH as a pregancy without one.

 

IVIG is a blood product created by collecting and processing the IgG immunoglobulins (antibodies) from screened donors.   It is administered intravenously and can have several side effects, the most common being headaches and fatigue.  More serious reactions can occur, so the first infusion is generally administered at a medical facility.  In our treated pregnancies, we used a home healthcare nurse to administer most of the IVIG treatments in our home.  IgG America is a company in the US that specializes in home IVIG treatments.  In our treated cases, we started IVIG at around 5 weeks, which is about when the baby's heart begins beating.  The dosage was 400mg/kg every 3 weeks unless tests Dr. Kwak-Kim uses to monitor the treatment's effectiveness indicated more was needed.  In our second child, Grace, the dosage remained at that rate other than a couple extra doses used during a some hemorrhaging near the implantation site early in the pregnancy the dosage doubled (two-days of treatment) right before delivery.  Other parents under Dr. Kwak-Kim's care have needed larger and more freqeunt doses to control the immune response.  In our second treated pregnancy, we also needed more, with the most being 800mg/kg every two weeks.  In the more common US protocols, IVIG is started later in the pregnancy at large doses of 1g/kg per week and sometimes higher.  This is generally successful a high percentage of the time, but severe thrombocytopenia and a very low percentage of ICHs still occur.  Dr. Kwak-Kim has not published her NAIT work, but I know of at least six of her treated NAIT cases and none were below 40k at birth and treatment was started several weeks after when Dr. Kwak-Kim prefers in the cases with the lower counts.

 

Prednisone is a fairly commonly used steroid that has generally been shown to be an effective NAIT treatment.  Prednisone works primarily by weakening the maternal immune response.  While it can be used solely to treat NAIT and has been shown to work well, when used in combination with IVIG, results are generally even better since you both drugs address different areas.  Prednisone is relatively cheap, and IVIG is very expensive, so if cost is a factor, then a treatment protocol favoring Prednisone is sometimes favored.  In the US, IVIG still seems to take the lead, with Prednisone being added in at times.  Determining when to use Prednisone and at what dosage varies by doctor.  In our cases, Dr. Kwak-Kim used low dosage Prednisone in the first trimester and again ten days prior to birth, but our blood test monitoring numbers were kept in good ranges using IVIG.  I know of other cases treated by her where Prednisone was used for the entire pregnancy.  The side effects of Prednisone are generally manageable, but should be considered.  Dr. Kwak-Kim was primarily concerned of the thinning of the membrane caused by Prednisone and it rupturing and causing early delivery.  Early labor can also be more likely with prolonged Prednisone use.  These factors must be factored into the equation.

 

Some doctors prefer to use a PUBS (a.k.a., cordocentesis, Fetal Blood Sampling or FBS, see definition on our FAQ page) to obtain a platelet count and use a low count as a justification to add in Prednisone to an IVIG treatment plan.  From the research data I have read, the risks associated with the PUBS procedure in a NAIT pregnancy seem to bring into question whether PUBS carries a higher risk than just adding in Prednisone or increasing the IVIG dosage.  One of the primary risks of PUBS is premature birth, so early term PUBS are being used less frequently due to documented deaths associated with the early PUBS procedure.  Doctors performing PUBS seem to do them more around 32 weeks now if they do them at all.  The NAIT research doctor Dr. James Bussel recently changed his direction on PUBS saying to avoid it whenever possible in a 2009 article referenced on our NAIT Research page.  We still hear of doctors consulting him and they are still recommending PUBS, so we hope Dr. Bussel will bring some clarity to this soon.  A BJOG article that came out in 2007 said that Dr. Berkowitz, et. al., could not justify their use of PUBS based on their results.  This surely made that group take note.  We are just pleased they finally noticed what many had seen in their numbers for many years, including Laura and me.  We had long questioned how the benefits of PUBS outweighed just adding in Prednisone or increasing IVIG dosage as that was often the stated goal of justifying the PUBS, despite is known and considerable risks of serious complications in NAIT babies.  We did not receive a reassuring answer when we inquired about PUBS/FBS initially, but possibly another doctor would have one for you.  In our cases, Dr. Kwak-Kim uses maternal blood tests to monitor the NK (Natural Killer cell) assay and TH1/TH2 Cytokine assay to help determine how well the treatment is working and changes in the maternal immune response.  She and Dr. Beer have used these tests to help guide treatment of immune-caused recurrent miscarriage for many years in hundreds of cases.  While it is not as exact as a PUBS, it also carries no direct risk to the baby, plus does not put the baby's blood in direct contact with the mothers, which could trigger a stronger immune response if the IVIG and Prednisone had previously been able to mask exposure and a heightened secondary immune response.  I know of two of Dr. Kwak-Kim's NAIT cases where she felt that the test numbers were not as good as she would like an both of those were born with lower platelet counts.  In our two cases and one other I know of where she felt the test results were looking very good, all three resulted in babies born with normal platelet counts.  While that is too small of a sample size to give a definitive conclusion to the test's effectiveness, it does seem to at least show promise.  I have emailed NAIT research doctors Dr. Janice McFarland, Dr. James Bussel, Dr. Peter Soothill and Dr. Charles Rodeck regarding these tests and Dr. Soothill and Rodeck were gracious enough to kindly reply and seemed intrigued by our excellent results.  Recently Dr. Cecile Kaplan (of France), Betrand, et. al., published an article showing a correlation between antibody concentration and platelet counts, so I emailed her regarding Dr. Kwak-Kim's methods and the two have since corresponded hoping to possibly collaborate.  In our opinion, Dr. Kwak-Kim's protocol of treating early, monitoring using non-evasive means, and ramping up the treatment based on the test results was the safest and most soundly based treatment protocol available in the US.  In an article in the January 2011 issue of Blood, Prediction of the fetal status in non-invasive management of alloimmune thrombocytopenia, the authors do state that non-invasive tests related to antibody titer counts do have significance, so we continue to support efforts to develop these or investigate Dr. Kwak-Kim's approach further.  We would love to hear of better ones and list them hear, so please feel free to contact us on our Contact Us page!

 

Delivering at 36 weeks if the lungs tested mature was very common in NAIT cases, but recently some MFMs seem to be planning for later dates closer to 38 weeks or term.  There is research that shows that platelet count often trend lower during the pregnancy and often substantially.  With NAIT, they want to balance the risks of premature labor agains those of a bleed in your baby.  As you near term, the preemie risks get much lower and the risks of a bleed increase.  We also wanted to avoid going into labor for several reasons.  1. to have matched platelets ready, the staff on hand we know that were prepped for a scheduled NAIT birth, and 2., to avoid having strong contractions and a vaginal delivery.  If the baby happened to be severely thrombocytopenic, avoiding pressure on the baby's head (and body in general) is obviously recommended.  The last thing we wanted was to be stuck in Chicago traffic having strong contractions while wondering if we were going to make it to the hospital and if the doctors familiar with our case were available.  If the lungs test mature at 36 weeks, the preemie risks are generally considered quite low, but cannot be discounted.  MFMs deal a lot more with preemies than NAIT, so sometimes you need to remind them that your baby is in a very hostile environment and that the mother's body is trying to kill the baby, so this is a situation you want to remove your baby from as soon as the preemie risks become low.

 

I have read research in mice related to using monoclonal antibodies (mAb) specifically created to block the anti-platelet antibodies that showed promise, but Professor Rodeck said at the time that it could be years to make it to human testing and economics also play a factor (Dr. Lorna Williamson, Dr. Mike Clark, Dr. Kathryn Armour and Dr. Willem Ouwehand in the UK are researchers to follow in this area.)  Ultimately, we would like to see screening for NAIT similar to the RH factor.  There is a fair amount of research in this area and lowering the cost and raising the awareness are two things that are needed to help.  We would also like to see treatment developed to then avoid initial maternal sensitization similar to how it is available for the RH factor using RhoGam.

 

Please visit our Contact Us page and contact us if you would like more information, copies of research referenced on this website, or to see if we have heard of any NAIT doctors in your area from other parents.  We have corresponded with hundreds of NAIT parents, and many already in 2011.

 

 

 

This page was last modified on Wednesday, August 31, 2011 01:50:19 PM