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NEONATAL ALLOIMMUNE
THROMBOCYTOPENIA
DR.RAVI KUMAR
PEDIATRIC RESIDENT
MGMCRI
10-04-2018 NAIT 2
OBJECTIVES
Introduction
Epidemiology
Morbidity
Pathophysiology
Natural History
Diagnosis
Management
Antenatal Management
INTRODUCTION
NAIT - Neonatal AlloImmune Thrombocytopenia
Common cause of early onset neonatal thrombocytopenia
 Associated with significant fetal and neonatal morbidity and mortality
The most dreadful complication - Intracranial haemorrhage as a result of severe
thrombocytopenia leading to death or major neurological damage
10-04-2018 NAIT 3
10-04-2018 NAIT 4
EPIDEMIOLOGY
Incidence: 1/2000 pregnancies
Anti – HPA-1a accounts for 80-90% of cases in Caucasians
10 - 15% of cases are associated with anti - HPA- 5b
In Asians NAIT occurs secondary to anti-HPA-4
10-04-2018 NAIT 5
MORBIDITY
20% of affected - Intracranial hemorrhage (ICH)
20% of survivors of ICH - long term neurodevelopmental sequelae
About 50% of ICH occur in utero
Recurrence rate >75% for subsequent pregnancies, requiring referral to high risk
obstetrics clinic for subsequent pregnancies
10-04-2018 NAIT 6
PATHOPHYSIOLOGY
10-04-2018 NAIT 7
NAIT is caused by maternal
alloantibodies directed against
incompatible fetal platelet antigens
inherited from the father.
In the setting of an antigen-negative
mother, transplacental passage of
maternal immunoglobulin G (IgG)
antibodies results in the accelerated
destruction of fetal platelets expressing
the corresponding antigen.
NATURAL HISTORY
Following delivery : Petechiae, Ecchymoses & Cephalohematoma
Some are asymptomatic, with incidentally detected severe thrombocytopenia on first
day of life.
One of the most serious complications is ICH and can occur in the fetal or neonatal
period
The majority of IC bleeding occurs after 30 weeks of gestation, but some studies
reported to appear as early as 20 weeks.
10-04-2018 NAIT 8
Cephalohematoma
Ecchymosis
10-04-2018 NAIT 9
CRITERIA
All the following criteria are necessary to diagnose fetal/neonatal alloimmune
thrombocytopenia :
1. Fetal or Early onset Neonatal thrombocytopenia
2. Identification of a paternal, fetal, or neonatal platelet antigen that the mother lacks
3. Identification of maternal antibodies to that antigen
10-04-2018 NAIT 10
DIAGNOSIS
When NAIT is suspected, blood should be collected from the mother and father for
antigen screening for detection of HPA 1, 3, and 5 ( 90% of cases )
If the diagnosis is strongly suspected/ Initial evaluation is negative, further testing for
HPA 9 and 15 can be done
Level of maternal HPA -1a antibodies
10-04-2018 NAIT 11
10-04-2018 NAIT 12
MANAGEMENT
AFFECTED NEONATE
CONFIRM
THROMBOCYTOPENIA ON
REPEAT BLOOD SAMPLE
IF PLATELET COUNT
<1,00,000
SUSPECT
NAIT IF CAUSE IS UNCERTAIN
NEONATAL STUDIES
1. Careful History &
Examination
2. Test for DIC
3. R/O TORCH/KMP/
TAR Syndrome
4. NSG to r/o ICH
MATERNAL STUDIES
1. Careful Antenatal History
2. Maternal CBC
URGENT STUDIES
Maternal & Paternal Sample for
detection of Antibodies against HPA-
1a
10-04-2018 NAIT 13
MANAGEMENT
PLATELET COUNT <30,000
& CLINICALLY SIGNIFICANT
BLEEDING
TRANSFUSE PLATELET
10-20ml/kg
POST
TRANSFUSIO
N PLATELET
> 30,000
POST
TRANSFUSIO
N PLATELET
< 30,000
Perform Daily Platelet,
Transfusion Irradiated
Washed Plasma
Depleted Maternal
Platetlet
PLATELET COUNT > 30,000 &
NO E/O BLEEDING
Observe, Follow Daily Platelet,
Await For Initial Serological
Studies & Do Not Transfuse
Consider 2nd Dose of RDP,
Administer IV IG (1g/kg/dose)
If Platelet Count is <1,00,000
With clinical bleeding
GUIDELINES FOR PLATELET
TRANSFUSION
10-04-2018 NAIT 14
ANTENATAL MANAGEMENT
Treatment options include :
1. Fetal Blood Sampling (FBS)
2. Maternal intravenous immunoglobulin (IVIG)
3. Maternal corticosteroid treatment
4. Intrauterine platelet transfusion (IUT)
5. Early delivery
10-04-2018 NAIT 15
FETAL BLOOD SAMPLING
FBS is used to diagnose and determine
Degree of thrombocytopenia
Intra uterine platelet transfusion
To measure response to direct therapy
However, there are significant risks associated with this procedure, including bleeding,
premature delivery and death.
10-04-2018 NAIT 16
10-04-2018 NAIT 17
Prenatal treatment will be based on the severity of the thrombocytopenia and the
presence or absence of ICH in the previously affected fetus.
10-04-2018 NAIT 18
Current recommendations:
 Maternal IVIG (1 to 2g/kg/week) &
 +/- Prednisone (0.5 to 1 mg/kg/day)
 Starting at 12 wk (or) 20 to 26 wks of gestation, depending upon whether the
morbidity or mortality previously affected fetus
10-04-2018 NAIT 19
Most recent studies showed that the combination of IVIG and steroids is the most
efficient treatment.
Elective cesarean section is recommended in most countries, regardless of ICH
status, to avoid ICH.
Mothers who delivered an infant with NAIT should be followed in high-risk obstetric
clinics during all future pregnancies
TAKE HOME MESSAGE
Newborn with petechiae & ecchymosis with severe thrombocytopenia in the first day of life,
should be strongly suspected NAIT
Clinically, NAIT is a diagnosis of exclusion.
Intracranial hemorrhage is responsible for most neonatal morbidity and mortality, occurs in 7
to 20 percent of cases
Random-donor platelet transfusions +/- IVIG is the first line of therapy
10-04-2018 NAIT 20
THANK YOU
10-04-2018 NAIT 21

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NAIT

  • 3. INTRODUCTION NAIT - Neonatal AlloImmune Thrombocytopenia Common cause of early onset neonatal thrombocytopenia  Associated with significant fetal and neonatal morbidity and mortality The most dreadful complication - Intracranial haemorrhage as a result of severe thrombocytopenia leading to death or major neurological damage 10-04-2018 NAIT 3
  • 5. EPIDEMIOLOGY Incidence: 1/2000 pregnancies Anti – HPA-1a accounts for 80-90% of cases in Caucasians 10 - 15% of cases are associated with anti - HPA- 5b In Asians NAIT occurs secondary to anti-HPA-4 10-04-2018 NAIT 5
  • 6. MORBIDITY 20% of affected - Intracranial hemorrhage (ICH) 20% of survivors of ICH - long term neurodevelopmental sequelae About 50% of ICH occur in utero Recurrence rate >75% for subsequent pregnancies, requiring referral to high risk obstetrics clinic for subsequent pregnancies 10-04-2018 NAIT 6
  • 7. PATHOPHYSIOLOGY 10-04-2018 NAIT 7 NAIT is caused by maternal alloantibodies directed against incompatible fetal platelet antigens inherited from the father. In the setting of an antigen-negative mother, transplacental passage of maternal immunoglobulin G (IgG) antibodies results in the accelerated destruction of fetal platelets expressing the corresponding antigen.
  • 8. NATURAL HISTORY Following delivery : Petechiae, Ecchymoses & Cephalohematoma Some are asymptomatic, with incidentally detected severe thrombocytopenia on first day of life. One of the most serious complications is ICH and can occur in the fetal or neonatal period The majority of IC bleeding occurs after 30 weeks of gestation, but some studies reported to appear as early as 20 weeks. 10-04-2018 NAIT 8
  • 10. CRITERIA All the following criteria are necessary to diagnose fetal/neonatal alloimmune thrombocytopenia : 1. Fetal or Early onset Neonatal thrombocytopenia 2. Identification of a paternal, fetal, or neonatal platelet antigen that the mother lacks 3. Identification of maternal antibodies to that antigen 10-04-2018 NAIT 10
  • 11. DIAGNOSIS When NAIT is suspected, blood should be collected from the mother and father for antigen screening for detection of HPA 1, 3, and 5 ( 90% of cases ) If the diagnosis is strongly suspected/ Initial evaluation is negative, further testing for HPA 9 and 15 can be done Level of maternal HPA -1a antibodies 10-04-2018 NAIT 11
  • 12. 10-04-2018 NAIT 12 MANAGEMENT AFFECTED NEONATE CONFIRM THROMBOCYTOPENIA ON REPEAT BLOOD SAMPLE IF PLATELET COUNT <1,00,000 SUSPECT NAIT IF CAUSE IS UNCERTAIN NEONATAL STUDIES 1. Careful History & Examination 2. Test for DIC 3. R/O TORCH/KMP/ TAR Syndrome 4. NSG to r/o ICH MATERNAL STUDIES 1. Careful Antenatal History 2. Maternal CBC URGENT STUDIES Maternal & Paternal Sample for detection of Antibodies against HPA- 1a
  • 13. 10-04-2018 NAIT 13 MANAGEMENT PLATELET COUNT <30,000 & CLINICALLY SIGNIFICANT BLEEDING TRANSFUSE PLATELET 10-20ml/kg POST TRANSFUSIO N PLATELET > 30,000 POST TRANSFUSIO N PLATELET < 30,000 Perform Daily Platelet, Transfusion Irradiated Washed Plasma Depleted Maternal Platetlet PLATELET COUNT > 30,000 & NO E/O BLEEDING Observe, Follow Daily Platelet, Await For Initial Serological Studies & Do Not Transfuse Consider 2nd Dose of RDP, Administer IV IG (1g/kg/dose) If Platelet Count is <1,00,000 With clinical bleeding
  • 15. ANTENATAL MANAGEMENT Treatment options include : 1. Fetal Blood Sampling (FBS) 2. Maternal intravenous immunoglobulin (IVIG) 3. Maternal corticosteroid treatment 4. Intrauterine platelet transfusion (IUT) 5. Early delivery 10-04-2018 NAIT 15
  • 16. FETAL BLOOD SAMPLING FBS is used to diagnose and determine Degree of thrombocytopenia Intra uterine platelet transfusion To measure response to direct therapy However, there are significant risks associated with this procedure, including bleeding, premature delivery and death. 10-04-2018 NAIT 16
  • 17. 10-04-2018 NAIT 17 Prenatal treatment will be based on the severity of the thrombocytopenia and the presence or absence of ICH in the previously affected fetus.
  • 18. 10-04-2018 NAIT 18 Current recommendations:  Maternal IVIG (1 to 2g/kg/week) &  +/- Prednisone (0.5 to 1 mg/kg/day)  Starting at 12 wk (or) 20 to 26 wks of gestation, depending upon whether the morbidity or mortality previously affected fetus
  • 19. 10-04-2018 NAIT 19 Most recent studies showed that the combination of IVIG and steroids is the most efficient treatment. Elective cesarean section is recommended in most countries, regardless of ICH status, to avoid ICH. Mothers who delivered an infant with NAIT should be followed in high-risk obstetric clinics during all future pregnancies
  • 20. TAKE HOME MESSAGE Newborn with petechiae & ecchymosis with severe thrombocytopenia in the first day of life, should be strongly suspected NAIT Clinically, NAIT is a diagnosis of exclusion. Intracranial hemorrhage is responsible for most neonatal morbidity and mortality, occurs in 7 to 20 percent of cases Random-donor platelet transfusions +/- IVIG is the first line of therapy 10-04-2018 NAIT 20

Editor's Notes

  1. Similar to HDNB
  2. (mental and physical retardation, blindness, and hydrocephalus) ICH among term neonates is associated with perinatal death in up to 10% of cases or lifelong neurological disabilities in up to 20% of cases.
  3. The mother has had a normal pregnancy with no history of autoimmune disease, thrombocytopenia or drugs that may cause thrombocytopenia.