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AutoImmune Thrombocytopenic Purpura and pregnancy

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					   AutoImmune Thrombocytopenic
       Purpura and pregnancy:
the mother, the fetus and the newborn,
    from diagnosis to management
            AITP and pregnancy
• AITP is a common hematological disorder, the
  patient’s 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
         How to diagnose AITP when
        thrombocytopenia is first discovered
        during pregnancy?
         What is the fetal/neonatal risk?
     Platelet counts and pregnancy:
           a 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.
       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
      Thrombocytopenia
         N<150.109/L




Yes       Past history
               Past history
Thrombocytopenia
       in
    infancy

Thrombocytopenia
                         Was the infant
      during           thrombocytopenic?
previous pregnancy

Thrombocytopenic
    neonate                Diagnosis?
                           Maternal
                       Thrombocytopenia?
                                  Thrombocytopenia
                                    N<150.109/L


         Yes                         Past history



                                         No




           Yes                   Obstetrical disorders


  Hypertensive disorder
Pre-eclampsia, HELLP syndrome…
                                         No
                    Obstetrical disorders


                                               Type 2B
    congenital               No             von Willebrand
thrombocytopenias                               disease


 HIV infection                                 Lupus


  Autoimmune                             Gestational
Thrombocytopenic                      thrombocytopenia
    purpura
                  What are my own
                         risks?
                     Is there any
                 fetal/neonatal risk?


Isolated thrombocytopenia
      first discovered
     during pregnancy
       Gestational thrombocytopenia or
                    AITP?
Gestational               Autoimmunity
 thrombocytopenia           – Thrombocytopenia
  – Mild                      highly variable
    thrombocytopenia        – First trimester of
  – Late second or third      pregnancy but could
    trimester of pregnancy    occur later on
  – Absence of Aab          – Fetal/neonatal risk
  – No fetal risk             and no predictive
  – Normal platelet count     parameter
    in the post-partum      – Presence of Aab
    period
                            Gestational
                         thrombocytopenia




    Y                       Autoimmunity
        YY
Y




             Placental barrier
“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
            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
Laboratory diagnosis
    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
  The fetus

   and
The newborn
    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 (<50.109/L)
    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
          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
The newborn
 Once upon a
   time….
        Marie Charlotte : 1988, P1G1

• Full term infant, vaginal delivery, normal Apgar score.
• Petechiae : 8x109pl./L, normal maternal platelet count
• Neurological symptoms and ICH
• IVIgGx2, exchange transfusion, maternal platelet
  transfusions were without any effect.
• Thrombocytopenia resolved spontaneously at D15
• Hydrocephaly, neurological derivation, death at D22.

    Maternal platelet life span study: compensated
                   thrombocytolysis
     Marie Charlotte : 1989 P2G2
• fetal blood sampling by cordocentesis
  (FBS) 35 weeks gestation : 7x109pl./L
• Maternal therapy: IvIgG 0.5g/kg/2days
  during 2 weeks
• C-section, full term baby: Agathe
• Petechiae 5x109 pl. /L.
• Thrombocytopenia lasted 45 days despite
  IVIgG
• Specific maternal Aab (antiGPIb-IX)
                      M a rga ux , born on june 1 2 ,1 9 9 1 ,
                              C -s e c tion, no F BS
                      300
p latelets (10 /L )



                                                                 IvIg G 1 g k g /d
                      250
9




                      200
                                   IvIgG 0.5g/kg 2d
                      150
                                                   Day 54
                      100
                       50
                        0




                                                               7/8




                                                                                            4/9
                            12/6


                                     26/6


                                            10/7


                                                      24/7




                                                                           21/8
                                                      D AY S
                                                                                                                    E d g a r, b o rn o n ju ly 1 7 ,1 9 9 5
                                                                                                                                 (C -s e c tio n )

                                                                                                           140

                                                                                     pla telets (x10 /L)
                                                                                                           120
                                                                                     9                           IV IgG
                                                                                                           100
                                                                                                                 1g /K g
                                                                                                            80
                                                                                                            60
                                                                                                            40
                                                                                                            20
                                                                                                             0
                                                                                                            /7



                                                                                                                     /7



                                                                                                                              /7




                                                                                                                                                     /8



                                                                                                                                                           /8
                                                                                                                                         8
                                                                                                                                        7/
                                                                                                           17



                                                                                                                  24



                                                                                                                            31




                                                                                                                                                 14



                                                                                                                                                          21
                                                                                                                                      D a ys
                Mrs R.H.(1)
• Born in 1951
• 1971 first pregnancy: a thrombocytopenic
  boy (20.109/L) with petechiae.
  Thrombocytopenia resolved at D+20.
  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, D+2: petechiae
  +23.109/L.Platelet tfs and IvIgG (0.5G/Kg/d 4
  days), D+7 normal pl.count
                 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
 “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
 “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 ?
 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
Management
  Optimum management
  of pregnant women
  with AITP requires
  close collaboration
  between the
  physician,
  obstetrician and
  neonatologist
       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 <80.109/L
        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@ is safe for the fetus
   • however adverse effect have been
     reported for the mother such as
     hypertensive disorder, gestational
     diabetes….
     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)
                   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.
             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
          Delivery (3)

Our approach
 Vaginal delivery
 In case of obstetrical
  complications and suspicion of
  severe fetal thrombocytopenia,
  C-section
           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
              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
Bicètre Hospital
• Pr Gil Tchernia                 Puericulture Institute
• Dr Marie Dreyfus                • Dr Fernand Daffos
•Dr Nadine Ajzenberg              • Pr François Forestier
•Dr Jeanine Yvart


           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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