Transcript Neonatal Thrombocytopenia

Neonatal Thrombocytopenia
Suzanne Reuter MD
SDPA 2014
Deadwood, SD
Financial Disclosure
 I have no relevant financial relationships to disclose.
Objectives
 Definition of thrombocytopenia
 Understand the pathophysiology of neonatal
alloimmune thrombocytopenia
 Review bone marrow function as it relates to platelet
production and release
 Differential Diagnosis in a well, term infant
 Differential Diagnosis in a sick, term infant
Neonatal Alloimmune
Thrombocytopenia (NAIT)
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Neonatal Alloimmune
Thrombocytopenia (NAIT)
Mom
Fetus
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Placenta
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Neonatal Alloimmune
Thrombocytopenia (NAIT)
Mom
Fetus
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Placenta
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Would you treat the severe
thrombocytopenia in NAIT?
a. Yes, the risk of bleeding is really high
b. No, this condition will spontaneously resolve and
the risk of bleeding is only a threat in premature
infants.
c. Depends on what the doctor wants to do
Would you treat the severe
thrombocytopenia in NAIT?
a. Yes, the risk of bleeding is really high
b. No, this condition will spontaneously resolve and
the risk of bleeding is only a threat in the fetus and
premature infants.
c. Depends on what the doctor wants to do
Baby Lydia – 37 weeks
 Delivered with spontaneous cry. Apgars 8/9
 Dried, suctioned, admitted to NBN
 Initial platelet count of 177,000
 Nadir 120,000 at 36 hr of age
 Bili 5.4 @ 48 hr of age
Baby ‘Lila’ – 37 weeks (No Tx)
 Delivered with spontaneous cry. Apgars 8/9
 Dried, suctioned, admitted to NICU
 Initial platelet count of 8,000
 PE: diffuse petechiae, bruising over lower extremities
 Platelet transfusion 15 ml/kg
 Administered intravenous immunoglobulin 1 gm/kg
 Repeat platelet count 4 hours later 94,000
 Platelet f/u 31,000
 IVIG repeated x2 – normalization of platelet counts
Head Ultrasound – Day 1
Neonatal Alloimmune
Thrombocytopenia (NAIT)
 Develops in first pregnancy (unlike Rh sensitization)
 Fetal platelet antigens form early in gestation
 Maternal antibodies cross early 2nd trimester
 Thrombopoietin level is normal
 Megakaryocytes and platelets produced bind to it
 Severely low platelet counts in the newborn
 < 20,000 /microL
 Normal maternal platelet count
Neonatal Alloimmune
Thrombocytopenia (NAIT)
 Most severe complication is intraventricular
hemorrhage
 Occurs in 10-20% of affected newborns
 ¼ - ½ occurs in utero
Neonatal Alloimmune
Thrombocytopenia
 Rate of recurrence in future pregnancies
 75%-90%
 As severe or more severe than previous
 Fetal therapies
 In utero platelet transfusions
 Maternal therapies
 IVIG
 Corticosteroids
Which is the best treatment for thrombocytopenia
in NAIT in the first 48 hr of life in an infant with a
platelet count of 6,000 /microL?
a. Random donor platelet transfusion
b. Washed maternal platelets
c. Intravenous Immunoglobulin
d. Methylprednisolone
Which is the best treatment for thrombocytopenia
in NAIT in the first 48 hr of life in an infant with a
platelet count of 6,000 /microL?
a. Random donor platelet transfusion
b. Washed maternal platelets
c. Intravenous Immunoglobulin
d. Methylprednisolone
What is the definition of neonatal
thrombocytopenia?
a. Platelet count < 100, 000/microL
b. Platelet count < 50,000/microL
c. Platelet count < 25, 000/microL
d. Platelet count < 150, 000/microL
What is the definition of neonatal
thrombocytopenia?
 Platelet count < 150,000 /microL
 Actually, platelet count < 5th percentile
 5th percentile decreases with decreasing gestational age
 34-36 weeks – 123, 100 /microL
 32 weeks – 104, 200 /microL
J Perinatol. 2009;29(2):130
Definition
 Platelet count < 150,000/microL
 Ensure a central sample
 Clumping with capillary specimens
Mechanisms of Thrombocytopenia
 Increased destruction
 Decreased production
The most likely physical symptom of
neonatal thrombocytopenia is:
a. Petechiae
b. Bruising
c. Oozing from the umbilical cord
d. No symptoms
The most likely physical symptom of
neonatal thrombocytopenia is:
 No physical sign or symptom is the most likely
presentation of isolated thrombocytopenia.
 Petechiae, bruising, bleeding can be appreciated on
physical exam
Treatment with which of the following
medications increases the risk of
thrombocytopenia in premature infants:
a. Quinidine
b. Digoxin
c. Indomethacin
d. Heparin
e. All of the above
Treatment with which of the following
medications increases the risk of
thrombocytopenia in premature infants:
a. Quinidine
b. Digoxin
c. Indomethacin
d. Heparin
e. All of the above
 If maternal thrombocytopenia follows drug exposure
and is mediated by IgG antibody, the Ab may cross the
placenta and affect fetal platelets.
 Indomethacin and Heparin have been implicated in
neonatal thrombocytopenia.
 Indomethacin – platelet dysfunction
 Heparin – development of platelet antibodies
Thrombocytopenia in a Well, Term
Newborn
Well, Term Newborn
 Maternal history
 History of immune thrombocytopenic purpura (ITP) or
systemic lupus erythematosus (SLE)?
 Previous infant with thrombocytopenia or family
history?
 Any infections during pregnancy?
 Drug/medication use during pregnancy?
 History of HELLP, preeclampsia
 What is mom’s platelet count?
 Decreased -- may be autoimmune
 Normal – may be autoimmune of alloimmune
(Auto)Immune Thrombocytopenia
(1st and early 2nd trimester)
•Antibodies coat platelets
•When traversing the
spleen, the platelets are
“eaten” by splenic
macrophages
•At birth, infants have
minimal splenic function
•After birth, splenic
function increases and
risk of severe
thrombocytopenia .
Splenic Function at Birth
•Not functional at
birth
•Howell-Jolly bodies
on smear – DNA
remnants left over in
RBC
•Usually Howell-Jolly
bodies removed on
passage of RBC thru
spleen
Immune Thrombocytopenia
 Must follow neonate’s platelet levels closely after
birth
 Especially as splenic function improves
 Monitoring the fetus during pregnancy and labor is no
longer recommended
Which immunoglobulin does not
cross the placenta?
a. IgA
b. IgE
c. IgM
d. IgG
Which immunoglobulin does not
cross the placenta?
a. IgA (300,000 D)
b. IgE (190,000 D)
c. IgM (900,000 D)
d. IgG (150,000 D)
Gestational Thrombocytopenia
 Mild and asymptomatic thrombocytopenia
 No past history of thrombocytopenia (except possibly
during a previous pregnancy)
 Occurrence during late gestation
 No association with fetal thrombocytopenia
 Spontaneous resolution after delivery
Gestational Thrombocytopenia
 Considered benign
 Mild and transient ITP?
 Less antibodies compared to ITP
 No thrombocytopenia in neonate
 To make the diagnosis:
 Thrombocytopenia not severe
 Occurs during last part of pregnancy/term
 Platelet count returns to normal after pregnancy
 Infant’s platelet count is normal
The Placenta
 May reveal:
 Congenital infection (CMV, syphilis)
 Vasculopathy (Preeclampsia)
 Hemorrhage
 Infarcts
 Thrombi
 Vascular malformations
Maternal Pre Eclampsia
 Estimated 1 in 100 births
 Thrombocytopenia, neutropenia in newborns
 Decreased production
 Neutrophil, platelet inhibitor
 Present at birth
 Nadir is 2-4 days of age
Thrombosis
 If you cannot explain thrombocytopenia, evaluate for
clot
Thrombocytopenia in a Sick, Term
Newborn
Birth Asphyxia
 True mechanism is unknown
 May relate to hypoxia
Bacterial Infection
 Mechanism
 Disseminated intravascular coagulation
 Platelet aggregation caused by bacterial products on
platelet membranes
 Injury to megakaryocytes too
Congenital Infection
 Most common:
 Cytomegalovirus (CMV)
 Others:
 Toxoplasmosis
 Herpes
 Rubella
Disseminated Intravascular Coagulation
 Systemic process producing:
 Thrombosis
 Hemorrhage
 Characterized by:
 Prolonged protime (PT)
 Prolonged activated partial thromboplastin time (PTT)
 Decrease in fibrinogen
 Increase in fibrin split products or D-Dimers
 Decreased platelets
Disseminated Intravascular Coagulation
 Due to
 Sepsis
 Asphyxia (acidosis)
 Meconium aspiration
 Severe respiratory distress syndrome
Syndromes with Thrombocytopenia
Thrombocytopenia, Absent Radii (TAR)
Kasabach-Merritt Syndrome
•Capillary Hemangiomas
•DIC
•Thrombocytopenia
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Shortened platelet survival
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Sequestration in vascular
malformation
Wiskott-Aldrich Syndrome
 X-linked
 MPV (mean platelet volume) 3-5 fL (nl 7-10)
Immunodeficiency
Eczema
Thrombocytopenia
Summary Points
 Neonatal Thrombocytopenia
 Platelet levels < 150,000
 Neonatal Alloimmune Thrombocytopenia
 Severely low fetal platelet levels
 Maternal platelet value – normal
 Obtain a good accurate specimen
 Central specimen
References

NeoReviews Vol. 14 No. 2 February 1, 2013, pp. e74 -e82

Incidence and Consequences of Neonatal Alloimmune Thrombocytopenia: A Systematic Review.
Pediatrics. 2014 Mar 3.

Neonatal Thrombocytopenia, Up to Date 2014.

Wiedmeier SE, Henry E, Sola-Visner MC, Christensen RD, SO. J Perinatol. 2009;29(2):130