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 Benign Thrombocytopenia of Pregnancy ITP Preeclampsia Other (Drug related, SLE, HIV, Antiphospholipid syndrome, Viral, TTP, HIT, pseudothrombocytopenia, DIC, Giant Cavernous Hemangioma (Kasabach-Merritt 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 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 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 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) 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):901-10.

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

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.

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.