Aim of the study is to evaluate wether exposure of HPA-1a negative fetuses to the maternal HPA-1a antigens during fetal life induces tolerance which may reduce the risk that HPA-1a antibodies are developed later in life.We postulate that 1) women…
ID
Source
Brief title
Condition
- Other condition
- Immune disorders NEC
Synonym
Health condition
Allo immunisatie tegen een trombocyten antigeen
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary study parameter is HPA-1a type of the "grandmothers".
2% of the Caucasian population is HPA-1a negative (HPA-1b1b). If HPA-1a
antibodies are only produced by HPA-1a negative women with HPA-1a negative
mothers (grandmothers) 20 cases will be enough to show statistical significance.
Calculation:
In the Caucasian population the HPA-1 fenotyping is distributed as follows:
HPA-1a1a 72%
HPA-1a1b 26%
HPA-1b1b 2%
HPA-1b1b mothers will have a HPA-1a1b or HPA-1b1b mother (grandmother). The
ratio HPA-1a1b:HPA-1b1b for these grandmothers is 93:7. If there is a 100%
tolerance induction all grandmothers must be HPA-1b1b and the statistical
significance (Chi Square p<0.001) will be shown with only a few grandmothers.
Possible tolerance induction will be depending on the amount of HPA-1a exposure
of the fetus. It is likely the amount of exposure varies. Possibly a certain
amount of HPA-1a exposure is necessary for tolerance induction. To show skewing
(more HPA-1b1b grandmothers than expected) we will include as many cases as
possible (goal is between 40 and 60 cases), retrospective and prospective.
To show a significant skewing at least 20% of 40 and 18% of 60 grandmothers
need to be HPA-1b1b.
Maybe there will be a partial suppression of the HPA-1a antibody production
because of fetal exposure to HPA-1a. To see if there is a correlation between
the antibody titer and the HPA-1 fenotype of the grandmother, we will include
20 women with a high HPA-1a antibody titer (>1:64) and 20 women with a low
antibody titer (<1:16).
A significant higher number HPA-1b1b grandmothers (>4 of 20) is expected in the
high antibody titer group but not in the low antibody titer group.
Secondary outcome
no secundary study parameters
Background summary
Neonatal AlloImmune Thrombocytopenia (NAIT) is caused by a platelet bloodgroup
antagonism that occurs in about 1 in 1300 random births and results from
maternal alloimmunization against platelet antigens present on fetal platelets
but absent on maternal platelets. Although 98% of the Caucasian population is
positive for the Human Platelet Antigen 1a (HPA-1a), it is the most frequently
offending antigen (75%). Approximately 10% of HPA-1a negative women produce
HPA-1a alloantibodies
Because of severe thrombocytopenia in utero, in up to 5 percent of cases
intracerebral haemorrhage occurs, often leading to severe neurological sequelae
or death.
Study objective
Aim of the study is to evaluate wether exposure of HPA-1a negative fetuses to
the maternal HPA-1a antigens during fetal life induces tolerance which may
reduce the risk that HPA-1a antibodies are developed later in life.
We postulate that 1) women who were exposed to maternal HPA-1a antigens in the
fetal period will not produce HPA-1a antibodies or 2) will have a weaker immune
response and therefore a lower HPA-1a antibody titer.
To investigate 1) we will type a cohort of 40-60 grandmothers to observe a
skewing of the HPA-1bb typing. To investigate 2) we will include 20 women with
a high HPA-1a antibody titer (>1:64) and 20 women with a low antibody titer
(<1:16).
Study design
Retrospective and prospective cases that are refered to the platelet/leukocyte
serology department for suspected NAIT and for whom maternal HPA-1a antibodies
are detected do serve as basis for this study.
Grandmothers of NAIT patients will be asked by the treating physician to give 8
ml of EDTA unclothed blood for HPA-1 genotyping.
For this treating physicians who send material for NAIT investigation to our
laboratory will be asked, if mother shows to have HPA-1a antibodies, to ask
grandmother to participate. Information and an informed consent form will be
provided by our laboratory. In case of participation, only once 8 ml of EDTA
unclothed blood will be drawn and send, by a Sanquin Courier, to our
laboratory. In this way we hope to include 40-60 cases in 2 years time.
Grandmothers will be genotyped for the HPA-1 system.
maternal HPA-1a antibody titer/quantification will be performed in the
Monoclonal Antibody Immobilization of Platelet Antigens Assay and a Logit
quantification Program
Study burden and risks
8 ml of EDTA anticoagulated blood will be drawn once by venapunction.
This study will provide knowledge concerning the risk for HPA-1a immunisation
of HPA-1a negative women and can be used in the future for the estimation of
risk of immunisation.
Plesmanlaan 125
1066 CX Amsterdam
Nederland
Plesmanlaan 125
1066 CX Amsterdam
Nederland
Listed location countries
Age
Inclusion criteria
Mothers of women with HPA-1a antibodies
Exclusion criteria
no specific exclusioncriteria
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL11748.018.06 |