1. Thrombocytopenia in Pregnancy
David Marinoff, MD
March 10,2010

2. How Dinosaurs Became Extinct

3. Platelets, or thrombocytes (from Greek θρόμβος — «clot» and κύτος — «cell»)

4. Platelets produced in bone marrow from megakaryocytes
platelets produced per megakaryocyte
35,000-50,000 platelets/microL produced daily
8-10 day survival

5. Normal Platelet Count
150, ,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 Jan;95(1):  

6. Causes of Thrombocytopenia in Pregnancy
Benign Thrombocytopenia of Pregnancy
ITP
Preeclampsia
Other (Drug related, SLE, HIV, Antiphospholipid syndrome, Viral, TTP, HIT, pseudothrombocytopenia, DIC, Giant Cavernous Hemangioma (Kasabach-Merritt syndrome)

7. 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

8. Benign Thrombocytopenia of Pregnancy
Mild and asymptomatic thrombocytopenia
No past history of thrombocytopenia
Occurrence during late gestation
No association with fetal thrombocytopenia
Spontaneous resolution after delivery

9. Immune Thrombocytopenic Purpura (ITP)
Mild cases clinically difficult to differentiate from benign thrombocytopenia of pregnancy

10. Immune Thrombocytopenic Purpura (ITP)
Acquired disorder
Decreased platelet count – otherwise normal CBC and smear
No obvious alternative clinical condition or drug related etiology

11. Immune Thrombocytopenic Purpura (ITP)
Antiplatelet antibodies not required for diagnosis
Not demonstrable in all patients with ITP
Do not affect management decisions

12. Immune Thrombocytopenic Purpura (ITP)
Pathogenesis
Increased platelet destruction
Autoantibodies inhibit platelet production

13. Immune Thrombocytopenic Purpura (ITP)
Surgically significant bleeding <50,000
Significant bleeding rare if platelets >10,000
Spontaneous remission common in children, rare in adults

14. 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

15. 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

16. 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

17. 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

18. Preeclampsia 15% develop thrombocytopenia HELLP syndrome
Delivery is treatment
Platelet nadir may occur post delivery – usually begins rising by day 3 after delivery

19. Avoid aspirin and NSAID’s in patients with thrombocytopenia
Inhibits

20. Life threatening thrombocytopenia
Platelet transfusion
Concurrent IVIG
Methylprednisolone
If no response – recombinant factor VIIa

21. Neonatal Alloimmune Thrombocytopenia (NAIT)
Maternal IgG crosses placenta and attacks foreign platelet antigen in fetus
Can occur in first pregnancy
1/ births
Mother is asymptomatic – normal platelet count
75-90% recurrence rate with increased severity

22. Neonatal Alloimmune Thrombocytopenia (NAIT)
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 May;47(5):

23. Neonatal Alloimmune Thrombocytopenia (NAIT)
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
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

24. 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 high-risk group with an initial count of less than 10,000/mL3 for whom IVIG 1 gm/kg/wk was shown to be inadequate.

25. 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)

26. Neonatal Alloimmune Thrombocytopenia (NAIT)
Obstet Gynecol 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.

27. 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)

28. Neonatal Alloimmune Thrombocytopenia (NAIT)
Obstet Gynecol Aug;110(2 Pt 1):
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.