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.
20
(No Transcript)
21
(No Transcript)
22
(No Transcript)
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