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Suzanne Reuter MD SDPA 2014 Deadwood, SD Neonatal Thrombocytopenia Slide 2 Financial Disclosure I have no relevant financial relationships to disclose. Slide 3 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 Slide 4 Neonatal Alloimmune Thrombocytopenia (NAIT) * * * * * Slide 5 Mom Fetus * * * * * Placenta Slide 6 Neonatal Alloimmune Thrombocytopenia (NAIT) Mom Fetus * * * * * Placenta Slide 7 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 Slide 8 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 Slide 9 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 Slide 10 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 Slide 11 Head Ultrasound Day 1 Slide 12 Neonatal Alloimmune Thrombocytopenia (NAIT) Develops in first pregnancy (unlike Rh sensitization) Fetal platelet antigens form early in gestation Maternal antibodies cross early 2 nd 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 Slide 13 Neonatal Alloimmune Thrombocytopenia (NAIT) Most severe complication is intraventricular hemorrhage Occurs in 10-20% of affected newborns - occurs in utero Slide 14 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 Slide 15 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 Slide 16 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 Slide 17 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 Slide 18 What is the definition of neonatal thrombocytopenia? Platelet count < 150,000 /microL Actually, platelet count < 5 th percentile 5 th percentile decreases with decreasing gestational age 34-36 weeks 123, 100 /microL 32 weeks 104, 200 /microL J Perinatol. 2009;29(2):130 Slide 19 Definition Platelet count < 150,000/microL Ensure a central sample Clumping with capillary specimens Slide 20 Mechanisms of Thrombocytopenia Increased destruction Decreased production Slide 21 Slide 22 Slide 23 The most likely physical symptom of neonatal thrombocytopenia is: a. Petechiae b. Bruising c. Oozing from the umbilical cord d. No symptoms Slide 24 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 Slide 25 Slide 26 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 Slide 27 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 Slide 28 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 Slide 29 Thrombocytopenia in a Well, Term Newborn Slide 30 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 moms platelet count? Decreased -- may be autoimmune Normal may be autoimmune of alloimmune Slide 31 (Auto)Immune Thrombocytopenia (1 st and early 2 nd 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. Slide 32 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 Slide 33 Immune Thrombocytopenia Must follow neonates platelet levels closely after birth Especially as splenic function improves Monitoring the fetus during pregnancy and labor is no longer recommended Slide 34 Which immunoglobulin does not cross the placenta? a. IgA b. IgE c. IgM d. IgG Slide 35 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) Slide 36 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 Slide 37 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 Infants platelet count is normal Slide 38 The Placenta May reveal: Congenital infection (CMV, syphilis) Vasculopathy (Preeclampsia) Hemorrhage Infarcts Thrombi Vascular malformations Slide 39 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 Slide 40 Thrombosis If you cannot explain thrombocytopenia, evaluate for clot Slide 41 Thrombocytopenia in a Sick, Term Newborn Slide 42 Birth Asphyxia True mechanism is unknown May relate to hypoxia Slide 43 Bacterial Infection Mechanism Disseminated intravascular coagulation Platelet aggregation caused by bacterial products on platelet membranes Injury to megakaryocytes too Slide 44 Congenital Infection Most common: Cytomegalovirus (CMV) Others: Toxoplasmosis Herpes Rubella Slide 45 Slide 46 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 Slide 47 Disseminated Intravascular Coagulation Due to Sepsis Asphyxia (acidosis) Meconium aspiration Severe respiratory distress syndrome Slide 48 Syndromes with Thrombocytopenia Slide 49 Thrombocytopenia, Absent Radii (TAR) Slide 50 Slide 51 Kasabach-Merritt Syndrome Capillary Hemangiomas DIC Thrombocytopenia Shortened platelet survival Sequestration in vascular malformation Slide 52 Wiskott-Aldrich Syndrome X-linked MPV (mean platelet volume) 3-5 fL (nl 7-10) Eczema Immunodeficiency Thrombocytopenia Slide 53 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 Slide 54 Slide 55 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 Slide 56