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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

Notes de l'éditeur

  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.