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Neonatal Thrombocytopenia

Neonatal Thrombocytopenia. Suzanne Reuter MD SDPA 2014 Deadwood, SD. Financial Disclosure. I have no relevant financial relationships to disclose. Objectives. Definition of thrombocytopenia Understand the pathophysiology of neonatal alloimmune thrombocytopenia

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Neonatal Thrombocytopenia

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  1. Neonatal Thrombocytopenia Suzanne Reuter MD SDPA 2014 Deadwood, SD

  2. Financial Disclosure • I have no relevant financial relationships to disclose.

  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

  4. Neonatal Alloimmune Thrombocytopenia (NAIT) * * * * *

  5. Neonatal Alloimmune Thrombocytopenia (NAIT) Mom Fetus * * * Placenta * *

  6. Neonatal Alloimmune Thrombocytopenia (NAIT) Mom Fetus * * * Placenta * *

  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

  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

  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

  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

  11. Head Ultrasound – Day 1

  12. Neonatal Alloimmune Thrombocytopenia (NAIT) • Develops in first pregnancy (unlike Rh sensitization) • Fetal platelet antigens form early in gestation • Maternal antibodies cross early 2nd 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

  13. Neonatal Alloimmune Thrombocytopenia (NAIT) • Most severe complication is intraventricular hemorrhage • Occurs in 10-20% of affected newborns • ¼ - ½ occurs in utero

  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

  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

  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

  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

  18. What is the definition of neonatal thrombocytopenia? • Platelet count < 150,000 /microL • Actually, platelet count < 5th percentile • 5th percentile decreases with decreasing gestational age • 34-36 weeks – 123, 100 /microL • 32 weeks – 104, 200 /microL J Perinatol. 2009;29(2):130

  19. Definition • Platelet count < 150,000/microL • Ensure a central sample • Clumping with capillary specimens

  20. Mechanisms of Thrombocytopenia • Increased destruction • Decreased production

  21. The most likely physical symptom of neonatal thrombocytopenia is: a. Petechiae b. Bruising c. Oozing from the umbilical cord d. No symptoms

  22. 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

  23. 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

  24. 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

  25. 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

  26. Thrombocytopenia in a Well, Term Newborn

  27. 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 mom’s platelet count? • Decreased -- may be autoimmune • Normal – may be autoimmune of alloimmune

  28. (Auto)Immune Thrombocytopenia(1st and early 2nd 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 .

  29. 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

  30. Immune Thrombocytopenia • Must follow neonate’s platelet levels closely after birth • Especially as splenic function improves • Monitoring the fetus during pregnancy and labor is no longer recommended

  31. Which immunoglobulin does not cross the placenta? a. IgA b. IgE c. IgM d. IgG

  32. 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)

  33. 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

  34. 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 • Infant’s platelet count is normal

  35. The Placenta • May reveal: • Congenital infection (CMV, syphilis) • Vasculopathy (Preeclampsia) • Hemorrhage • Infarcts • Thrombi • Vascular malformations

  36. 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

  37. Thrombosis • If you cannot explain thrombocytopenia, evaluate for clot

  38. Thrombocytopenia in a Sick, Term Newborn

  39. Birth Asphyxia • True mechanism is unknown • May relate to hypoxia

  40. Bacterial Infection • Mechanism • Disseminated intravascular coagulation • Platelet aggregation caused by bacterial products on platelet membranes • Injury to megakaryocytes too

  41. Congenital Infection • Most common: • Cytomegalovirus (CMV) • Others: • Toxoplasmosis • Herpes • Rubella

  42. 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

  43. Disseminated Intravascular Coagulation • Due to • Sepsis • Asphyxia (acidosis) • Meconium aspiration • Severe respiratory distress syndrome

  44. Syndromes with Thrombocytopenia

  45. Thrombocytopenia, Absent Radii (TAR)

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