Transcript Document 7109814

Thrombocytopenia in
Pregnancy
David Marinoff, MD
March 10,2010
How Dinosaurs Became Extinct
• Platelets, or thrombocytes (from Greek
θρόμβος — «clot» and κύτος — «cell»)
• Platelets produced in bone marrow from
megakaryocytes
• 1000-5000 platelets produced per
megakaryocyte
• 35,000-50,000 platelets/microL produced
daily
• 8-10 day survival
• Normal Platelet Count
• 150,000-450,000/microL
• May be slightly decreased in pregnancy
(Platelet count at term pregnancy: a
reappraisal of the threshold. Boehlen F;
Hohlfeld P; Extermann P; Perneger TV; de
Moerloose P Obstet Gynecol. 2000
Jan;95(1):29-33.
Causes of Thrombocytopenia in
Pregnancy
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Benign Thrombocytopenia of Pregnancy
ITP
Preeclampsia
Other (Drug related, SLE, HIV,
Antiphospholipid syndrome, Viral, TTP,
HIT, pseudothrombocytopenia, DIC, Giant
Cavernous Hemangioma (KasabachMerritt syndrome)
Benign Thrombocytopenia of
Pregnancy
• Usually platelet count greater than 70,000
• 5% occurrence rate
• Does not increase incidence of
thrombocytopenia in newborn
• No effect on pregnancy management with
exception of possible steroid boost near
term to allow for regional anesthesia
Benign Thrombocytopenia of
Pregnancy
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Mild and asymptomatic thrombocytopenia
No past history of thrombocytopenia
Occurrence during late gestation
No association with fetal
thrombocytopenia
• Spontaneous resolution after delivery
Immune Thrombocytopenic
Purpura (ITP)
• Mild cases clinically difficult to differentiate
from benign thrombocytopenia of
pregnancy
Immune Thrombocytopenic
Purpura (ITP)
• Acquired disorder
• Decreased platelet count – otherwise
normal CBC and smear
• No obvious alternative clinical condition or
drug related etiology
Immune Thrombocytopenic
Purpura (ITP)
• Antiplatelet antibodies not required for
diagnosis
• Not demonstrable in all patients with ITP
• Do not affect management decisions
Immune Thrombocytopenic
Purpura (ITP)
• Pathogenesis
• Increased platelet destruction
• Autoantibodies inhibit platelet production
Immune Thrombocytopenic
Purpura (ITP)
• Surgically significant bleeding <50,000
• Significant bleeding rare if platelets
>10,000
• Spontaneous remission common in
children, rare in adults
Immune Thrombocytopenic
Purpura (ITP)
• Treatment
• Treat in 30,000-50,000 range
• Goal – Safe platelet count to prevent
major bleed, not normalized count
• Mortality < 1%
• Increased bleeding risks in pregnancy –
lower treatment threshold
• Prednisone 1mg/kg/day
• Most respond within one week
• Supplement with Calcium and Vitamin D if
greater than 3 months Rx
• Unresponsive – IVIG 1 gr/kg/day over 1-2
days
• Unresponsive to medical therapy splenectomy
• Splenectomy
• Removes primary site of destruction of
antibody coated platelets
• Decreases antiplatelet antibody production
• If successful remission usually within two
weeks of surgery
• 65% long term remission
Immune Thrombocytopenic
Purpura (ITP)
• C-Section for obstetric indications
• Poor correlation with maternal platelet
count or fetal scalp platelet count
• PUBS is contraindicated – procedure
related mortality significantly greater than
disease related mortality
Preeclampsia
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15% develop thrombocytopenia
HELLP syndrome
Delivery is treatment
Platelet nadir may occur post delivery –
usually begins rising by day 3 after
delivery
• Avoid aspirin and NSAID’s in patients with
thrombocytopenia
• Inhibits
Life threatening thrombocytopenia
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Platelet transfusion
Concurrent IVIG
Methylprednisolone
If no response – recombinant factor VIIa
Neonatal Alloimmune
Thrombocytopenia (NAIT)
• Maternal IgG crosses placenta and attacks
foreign platelet antigen in fetus
• Can occur in first pregnancy
• 1/1000-5000 births
• Mother is asymptomatic – normal platelet
count
• 75-90% recurrence rate with increased
severity
Neonatal Alloimmune
Thrombocytopenia (NAIT)
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200 cases NAIT
Anti-HPA-1a — 75 percent
Anti-HPA-5b — 16 percent
Anti-HPA-15b — 4 percent
Management and outcome of 200 cases of
fetomaternal alloimmune thrombocytopenia.
Ghevaert C; Campbell K; Walton J; Smith GA;
Allen D; Williamson LM; Ouwehand WH;
Ranasinghe E Transfusion. 2007 May;47(5):90110.
Neonatal Alloimmune
Thrombocytopenia (NAIT)
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Table 2. Risk Stratification and Treatment Protocol
High Risk Standard Risk
Stratification Initial fetal platelet count 20,000/mL3, or
sibling with a perinatal intracranial
hemorrhage
Initial platelet count 20,000 /mL3,
and no sibling intracranial
hemorrhage
First fetal blood
sampling
20 wk estimated gestational age 20 wk estimated gestational age
Treatment After sampling, randomize between:
IVIG 1 g/kg/wk plus prednisone 1 mg/kg/d
or IVIG 1 g/kg/wk
After sampling, randomize between:
IVIG 1 g/kg/wk or prednisone
0.5 mg/kg/d
Study definition of
response to therapy
Fetal platelet count 25,000/mL3 at the time of the second sampling, provided that it had
increased by 10,000/mL3 from the value obtained at the first sampling or Fetal platelet
count 40,000/mL3 provided that it had not decreased by 10,000/mL3 from the previous
value
Intensification IVIG prednisone arm: increase IVIG to
2 g/kg/wk and continue prednisone
IVIG arm: add prednisone 1 mg/kg/d
Prednisone arm: add IVIG 1 g/kg/d
IVIG arm: A) add prednisone 1 mg/kg/d; B) if
no response to IVIG and prednisone, then
increase IVIG to 2 g/kg/wk and continue
prednisone
If no response to IVIG and prednisone
in either arm, then increase IVIG to
2 g/kg/wk and continue prednisone
Neonatal Alloimmune
Thrombocytopenia (NAIT)
• The standard-risk group appears to
respond well to either IVIG 1 gm/kg/wk or
prednisone 0.5 mg/kg/d.
• Substantial number of patients in the highrisk group with an initial count of less than
10,000/mL3 for whom IVIG 1 gm/kg/wk
was shown to be inadequate.
Neonatal Alloimmune
Thrombocytopenia (NAIT)
• Empiric therapy without knowing the fetal
platelet count may be either unnecessary or
inadequate. The former needlessly overtreats
the mother while the latter allows the fetal
platelet count to remain dangerously low.
• The fetal-neonatal morbidity and mortality
associated with fetal blood sampling was
substantial (14% emergent delivery or death in
utero due to serious PUBS complication)
Neonatal Alloimmune
Thrombocytopenia (NAIT)
• Obstet Gynecol. 2006 Jan;107(1):91-6.
• Parallel randomized trials of risk-based
therapy for fetal alloimmune
thrombocytopenia.
• Berkowitz RL, Kolb EA, McFarland JG,
Wissert M, Primani A, Lesser M, Bussel
JB.
Neonatal Alloimmune
Thrombocytopenia (NAIT)
• 73 women with documented alloimmune
thrombocytopenia, patients were randomized to
receive either intravenous immunoglobulin
(IVIG) 2 g/kg/wk (group A) or IVIG 1 g/kg/wk plus
prednisone 0.5 mg/kg/d (group B), starting at
approximately 20 weeks of gestation. Fetal
blood sampling was performed at approximately
32 weeks of gestation, and those with fetal
platelet counts less than 30,000/mL(3) were
given salvage therapy (IVIG 2 g/kg/wk plus
prednisone 0.5 mg/kg/day)
Neonatal Alloimmune
Thrombocytopenia (NAIT)
• Obstet Gynecol. 2007 Aug;110(2 Pt
1):249-55.
• Antepartum treatment without early
cordocentesis for standard-risk
alloimmune thrombocytopenia: a
randomized controlled trial.
• Berkowitz RL, Lesser ML, McFarland JG,
Wissert M, Primiani A, Hung C, Bussel JB.