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