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AutoImmune Thrombocytopenic Purpura and pregnancy: the mother, the fetus and the newborn, from diagn

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... coagulation screen, liver function tests, lupus serology, platelet immunology ... Lupus. Gestational. thrombocytopenia. Isolated thrombocytopenia. first ... – PowerPoint PPT presentation

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Title: AutoImmune Thrombocytopenic Purpura and pregnancy: the mother, the fetus and the newborn, from diagn


1
AutoImmune Thrombocytopenic Purpura and
pregnancy the mother, the fetus and the
newborn, from diagnosis to management
2
AITP and pregnancy
  • AITP is a common hematological disorder, the
    patients platelets are destroyed by
    autoantibodies (Aab)
  • AITP may affect young women, association with
    pregnancy is not a rare event
  • Transplacental passage of maternal Aab could lead
    to fetal/neonatal thrombocytopenia

3
Platelet counts and pregnancya prospective study
  • Physiological decrease of 11 of the platelet
    count whatever the initial platelet count
  • In 8,6 more pronounced drop up to 30.9 decrease
    of the platelet count leading to moderate
    thrombocytopenia prior to delivery
  • Maternal thrombocytopenia can be of immune origin
    chronic autoimmune thrombocytopenic purpura
    (AITP) and may result in fetal and neonatal
    thrombocytopenia.

4
Diagnosis strategies
  • Excluding false thrombocytopenia
  • Time of onset
  • Clinical examination, past history, familial
    cases
  • Laboratory investigations coagulation screen,
    liver function tests, lupus serology, platelet
    immunology

5
Thrombocytopenia N
Past history
Yes
6
Past history
Was the infant thrombocytopenic?
Diagnosis? Maternal Thrombocytopenia?
7
Thrombocytopenia NPast history
Yes
No
Obstetrical disorders
Yes
Hypertensive disorder Pre-eclampsia, HELLP
syndrome
No
8
Obstetrical disorders
Type 2B von Willebrand disease
congenital thrombocytopenias
No
HIV infection
Lupus
Autoimmune Thrombocytopenic purpura
Gestational thrombocytopenia
9
Isolated thrombocytopenia first discovered
during pregnancy
What are my own risks? Is there any
fetal/neonatal risk?
10
Gestational thrombocytopenia or AITP?
  • Gestational thrombocytopenia
  • Mild thrombocytopenia
  • Late second or third trimester of pregnancy
  • Absence of Aab
  • No fetal risk
  • Normal platelet count in the post-partum period
  • Autoimmunity
  • Thrombocytopenia highly variable
  • First trimester of pregnancy but could occur
    later on
  • Fetal/neonatal risk and no predictive parameter
  • Presence of Aab

11
Gestational thrombocytopenia
Autoimmunity
Placental barrier
12
Gestational thrombocytopenia revisited
  • Assessment and follow-up of 50 thrombocytopenic
    pregnant women
  • Asymptomatic autoimmunity in 48
  • Chronic thrombocytopenia in 55
  • Familial thrombocytopenia in 1 case
  • Among women with mild thrombocytopenia
  • 43 thrombocytopenic neonates
  • 57 chronic thrombocytopenia

13
Our conclusion
  • Gestational thrombocytopenia impossible to
    ascertain in primiparous women in the absence of
    previous platelet count
  • Necessary to follow-up the post-partum platelet
    counts within 6 months
  • Immunological studies should be performed to
    detect hidden autoimmunity
  • The platelet count of the newborn should be
    monitored during the 1st week of life when
    maternal thrombocytopenia first discovered during
    pregnancy

14
Laboratory diagnosis
15
Detection of antiplatelet autoantibodies
  • New techniques
  • Capture of the maternal antibody and
    identification of the target on the platelet
    (MAIPA-test)
  • These techniques are not routinely done
  • Results
  • Autoantibodies the hallmark of autoimmunity, not
    found in gestational thrombocytopenia
  • Our approach
  • Search for Aab when isolated thrombocytopenia
    discovered, and if negative results, at delivery
    and in the post-partum period

16
The fetus
and
The newborn
17
The fetal/neonatal thrombocytopenia
  • The fetal/neonatal thrombocytopenia is
    unpredictable, no predictive maternal parameter
  • 30-40 of infants born to mothers with AITP will
    be thrombocytopenic
  • 10-15 of infants will be severely
    thrombocytopenic (
  • Only 0-3 of infants will suffer intracranial
    hemorrhage
  • Neonatal thrombocytopenia
  • usually worsens during first days of life, nadir
    day 3 to 5
  • lasts from 10 to 60 days
  • unless prior thrombocytopenic sibling

18
Prospective study
  • Fetal thrombocytopenia observed as early as 20
    weeks of gestation
  • No spontaneous correction
  • Cannot be prevented or reversed by maternal
    therapy such as corticoids or intravenous
    immunoglobulins

19
The newborn
Once upon a time.
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23
Mrs R.H.(1)
  • Born in 1951
  • 1971 first pregnancy a thrombocytopenic boy
    (20.109/L) with petechiae. Thrombocytopenia
    resolved at D20. Normal maternal platelet
    count. Anti HLA ab found in the maternal sera
  • 1988 second pregnancy FBS at 23 and 37 weeks of
    gestation 195 and 212.109/L. Vaginal delivery,
    D2 petechiae 23.109/L.Platelet tfs and IvIgG
    (0.5G/Kg/d 4 days), D7 normal pl.count

24
Mrs R.H.(2)
  • 1990 third pregnancy, FBS at 23 and 32
    week-gestation, normal pl.count. Birth, at 32
    weeks of gestation, pl.count 157.109/L. 12 hours
    later petechiae, umbilical hemorrhage and severe
    thrombocytopenia 17.109/L. Maternal pl.tfs,
    Exchange Tfs, IvIgG were ineffective, the
    thrombocytopenia lasted 11 days.
  • Specific maternal Aab (anti GPIb-IX)
  • Maternal platelet life span study compensated
    thrombocytolysis

25
Hidden maternal autoimmunity(1)
  • 11 mothers normal platelet counts, no previous
    immunological or platelet disorders
  • 17 newborns with severe and transient
    thrombocytopenia. The fetal/neonatal
    thrombocytopenia differ in severity and duration
  • Specific Aab in 10/11 mothers and 3/4 infants
  • Compensated thrombocytolysis and/or hypersplenism
    found in 10/11 women

DIAGNOSIS mild AITP
26
Hidden maternal autoimmunity(2)
  • Increase susceptibility of fetal/neonatal
    platelet to the anti GPIb-IX antibody? (fetal
    platelet conformation?)
  • However pregnant women with anti GPIb-IX
    without thrombocytopenic infant (8 of normal
    post-partum control study).Natural autoantibodies
    (Aab)?
  • Are these Aab different from those found in
    hidden autoimmunity and overt AITP ?
  • What is the predictive value of these antibodies
    for the fetal or neonatal risk ?

27
When to perform laboratory testing for maternal
autoimmunity?
  • When fetal or neonatal thrombocytopenia is
    unexpected
  • When intracranial hemorrhage is diagnosed by
    ultrasound
  • Autoimmunity should be considered among other
    etiological factors in unexplained in utero
    death, or miscarriages
  • Well-versed laboratory required

28
Management
Optimum managementof pregnant women with AITP
requires close collaboration between the
physician, obstetrician and neonatologist
29
During pregnancy (1)
  • Maternal risk
  • Low, most of the pregnant women without any
    therapy
  • However, therapy could be required if there is a
    thrombocytopenia below 50.109/L , or hemorrhagic
    syndromes (easy bruising, petechiae)
  • Epidural anesthesia is not allowed if the
    platelet count is

30
During pregnancy (2)
  • Maternal therapy
  • Corticosteroids (CS) 1mg/kg/d (prepregnancy
    weight),
  • response to therapy 3 days to 2 weeks,
  • then low doses to maintain a safe platelet
    count.
  • Prednisone_at_ is safe for the fetus
  • however adverse effect have been reported for
    the mother such as hypertensive disorder,
    gestational diabetes.

31
During pregnancy (3)
  • Maternal therapy
  • Intravenous immunoglobulins (IvIgG) 1g/kg (
    prepregnancy weight),
  • response 24 to 48h, maximum efficacy à D4.
  • IvIgG can be given in the pre-delivery period.
  • In case of failure CS can be associated with
    IvIgG
  • Splenectomy rarely done (2nd trimester)

32
Delivery (1)
  • Conservative approach
  • No more assessment of the fetal platelet count
  • Fetal scalp blood sampling after membrane rupture
    and partial cervix dilatation
  • falsely low platelet counts
  • Fetal blood sampling complication rate 0-5,
    fetal ICH 0-3 of cases, no effect of antenatal
    therapy
  • not recommended in that setting, more risks than
    potential clinical benefits.

33
Delivery (2)
  • Way of delivery
  • Controversies still exist concerning the best
    way of delivery to avoid intracerebral
    hemorrhages for severely thrombocytopenic fetuses
  • C-section advocated to avoid ICH
  • Vaginal delivery been suggested to bear a higher
    risk
  • No prospective study showing C-section more
    effective

34
Delivery (3)
  • Our approach
  • Vaginal delivery
  • In case of obstetrical complications and
    suspicion of severe fetal thrombocytopenia,
    C-section

35
The newborn
  • Close monitoring of the platelet counts at
    birth, 24 hours later, Days 3 and 5
  • In case of severe thrombocytopenia or
    hemorrhagic syndromes IvIgG 1g/kg/d
  • Breast-feeding is not discouraged

36
In conclusion
  • AITP common hematological disorder and
    association with pregnancy not a rare event
  • Distinction between AITP and gestational
    thrombocytopenia difficult when thrombocytopenia
    first discovered during pregnancy
  • Serious maternal risks uncommon
  • Severe fetal/neonatal thrombocytopenia with ICH
    only in 0-3 of cases, no predictive maternal
    parameter. Close monitoring necessary.
  • More conservative management

37
  • Bicètre Hospital
  • Pr Gil Tchernia
  • Dr Marie Dreyfus
  • Dr Nadine Ajzenberg
  • Dr Jeanine Yvart
  • Puericulture Institute
  • Dr Fernand Daffos
  • Pr François Forestier
  • The Immune Working Group
  • Dr Elisabeth Verdy
  • Pr Serge Uzan
  • And colleagues from the AP-HP
  • National Institute of Blood Transfusion
  • Marie-Christine Morel-Kopp
  • Dr Cécile Kaplan
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