Presentation on theme: "Neonatal Jaundice and Hematology Raegan Wetzel, M.D. Oct 5, 2010."— Presentation transcript:
Neonatal Jaundice and Hematology Raegan Wetzel, M.D. Oct 5, 2010
Causes of Anemia Accelerated Loss Hemorrhage, Twin-twin transfusion, early umbilical cord clamping, fetal-maternal transfusion Hemorrhage, Twin-twin transfusion, early umbilical cord clamping, fetal-maternal transfusion Accelerated Destruction Immune hemolytic anemia, hemoglobinopathies, enzyme defects, membrane defects, mechanical destruction, infection, vit E deficiency Immune hemolytic anemia, hemoglobinopathies, enzyme defects, membrane defects, mechanical destruction, infection, vit E deficiency Diminished Production Anemia of prematurity, Fanconi/Diamond-Blackfan anemia, parvovirus, iron deficiency Anemia of prematurity, Fanconi/Diamond-Blackfan anemia, parvovirus, iron deficiency
Case 1 You are called to an emergent C/S for twins now with decelerations. You are unable to get much history from L&D except that they are 33 4/7 weeks, twin A with EFW 1700 g and twin B at 1200 g. At delivery, Twin A is a female who appears LGA with ruddy appearance. Twin B also female appears smaller with pallor and poor perfusion. What is the diagnosis ?
Twin to Twin Transfusion Who is at risk and why ? Monozygotic/monochornic twins 13-33% of twin pregnancies Donor Anemia Anemia Recipient Hyperbili, Hyperviscosity Hyperbili, Hyperviscosity
Blood Loss Fetal-placental Infant position after delivery Infant position after delivery Cord abnormalities Velamentous insertion, short cords, chord rupture with precipitous delivery or entanglement, nuchal/knot Velamentous insertion, short cords, chord rupture with precipitous delivery or entanglement, nuchal/knot Placental abnormalities Abruption or previa Abruption or previa Fetal-maternal What should you order ? What should you order ? Kleihauer-Betke Kleihauer-Betke
Case 2 Ex 27 week preemie, now 5 weeks old “feeding and growing” is noted to have poor weight gain, increased A/B’s, and new flow murmur. Lab results reveal: normocytic normochromic anemia (hct 25%) with normal WBC and platelet indices. What do you think the diagnosis is ?
Anemia of Prematurity Why does it happen ? Blood loss Shortened RBC lifespan Preterm days Preterm days Inadequate RBC production Suboptimal erythropoiesis in response to hypoxia Suboptimal erythropoiesis in response to hypoxia Switch from hepatic to renal O 2 sensor not till term Switch from hepatic to renal O 2 sensor not till term
Do term infants get anemic ? YES YES Physiologic anemia of infancy happens later in term infants. True or False ? True True Term: Term: 8-12 weeks, Hemoglobin 9-11 g/dL8-12 weeks, Hemoglobin 9-11 g/dL Preterm: Preterm: 3-6 weeks, Hemoglobin 7-9 g/dL3-6 weeks, Hemoglobin 7-9 g/dL
Decreased RBC Production Nutritional Iron Deficiency Iron Deficiency Bone Marrow Suppression Rubella Rubella Parvovirus Parvovirus Aplastic/Hypoplastic Anemia Diamond Blackfan Anemia Diamond Blackfan Anemia Fanconi Anemia Fanconi Anemia
Case 3 You are notified by the state lab that a newborn has Hemoglobin Barts. What does this mean ? Does this relate to Beta or Alpha Thalassemia ?
Alpha Thalassemia % Hgb Bart’s = number of alpha globin genes that are deleted Silent Carrier – 1 abnormal gene Alpha thal trait – 2 abnormal genes Hb H disease – 3 abnormal genes Moderate anemia Moderate anemia Thal Major - 4 abnormal genes Hydrops fetalis Hydrops fetalis Transfusion dependent Transfusion dependent
Beta Thalassemia 2 genes of beta-globin production Silent Carrier: Normal smear and electrophoresis B-thal trait: Frequently misdiagnosed as iron deficiency anemia, mild anemia Thal intermedia: Able to maintain Hgb > 7 without transfusion Thal major: Require regular transfusions
Case 4 3 day old term female presents to your office for first check up. Mom had prenatal care and decided to have the baby at home with a midwife. Uncomplicated pregnancy and delivery. Mom doesn’t believe in immunizations and didn’t want her baby to get any medicines at birth. Baby has been having some mild bleeding around her gums with feeding and mom noticed a small amount of blood in the diaper this morning.
What is her diagnosis ? Hemorrhagic Disease of the Newborn Hemorrhagic Disease of the Newborn How could this have been avoided ? 0.5 to 1 mg IM of vitamin K 0.5 to 1 mg IM of vitamin K
Hemorrhagic Disease of the Newborn Why are Newborns deficient in Vit K ? Placental transfer is poor Placental transfer is poor Breast milk is a poor source Breast milk is a poor source GI tract is sterile at birth GI tract is sterile at birth What lab values are associated ? Platelet Count Platelet Count NormalNormal Fibrinogen Fibrinogen Normal Normal PT PT prolonged prolonged
3 Types of HD of N Early Disease 1 st 24 hours 1 st 24 hours Maternal use of anticoagulant/anticonvulsant Maternal use of anticoagulant/anticonvulsant Severe bleeding/intracranial hemorrhage Severe bleeding/intracranial hemorrhage Classic Disease 1-7 days 1-7 days Cutaneous, GI or circumcision site bleeding Cutaneous, GI or circumcision site bleeding Late-onset Beyond 1 week Beyond 1 week Associated with exclusively breast-fed Associated with exclusively breast-fed
Case 5 Term male infant noted to be bleeding from the umbilical stump in WBN. Physical exam otherwise unremarkable. Family history of maternal uncle with frequent nose bleeds. Labs: Platelet count : 200 Platelet count : 200 PTT : prolonged PTT : prolonged PT : normal PT : normal Bleeding time normal Bleeding time normal Fibrinogen level : normal Fibrinogen level : normal Factor IX and VII : pending Factor IX and VII : pending
Hemophilia A and B X linked disorder Hemophilia A (factor VIII) : 5x more common Hemophilia B (factor IX) : milder Bleeding less common in newborn period Common bleeding sites ? Circumcision, umbilical bleeding, subdural > IVH Circumcision, umbilical bleeding, subdural > IVH
How is this different than Von Willebrand’s disease ? V W is most common heritable bleeding disorder V W is autosomal dominant V W will have prolonged bleeding time What test should you order for diagnosis ? von Willebrand factor activity (ristocetin cofactor von Willebrand factor antigen
Case 6 Newborn male in WBN noted to be oozing from umbilical stump. Physical exam significant for petechiae. Infant born to a primagravida with no prenatal problems. Maternal CBC is normal. Laboratory on baby: Platelet count 20 Platelet count 20 Normal PT,PTT Normal PT,PTT Normal fibrinogen Normal fibrinogen
What is the diagnosis ? Neonatal Alloimmune Thrombocytopenia Neonatal Alloimmune Thrombocytopenia What is the pathophysiology ? Placental transfer of maternal antibodies against paternally inherited antigens on fetal platelets. Placental transfer of maternal antibodies against paternally inherited antigens on fetal platelets. HPA-1a (78%) and HPA-5b alloantigens HPA-1a (78%) and HPA-5b alloantigens Can the disease occur in the first pregnancy ? Yes Yes Antigenic determinants expressed on placental endothelium Antigenic determinants expressed on placental endothelium Extended window of time for sensitization Extended window of time for sensitization
Petechiae Blue Berry Muffin Rash
Case 7 72 hr old infant who was delivered after an uncomplicated 39 WGA appears clinically jaundiced at discharge. Baby is bottle feeding, no family history of jaundice and MBT O+. You get the following lab values: Total bilirubin 11mg/dl Total bilirubin 11mg/dl Direct fraction 0.8 mg/dl Direct fraction 0.8 mg/dl Infant Hct 52% Infant Hct 52% IBT O+ IBT O+ Does this seem physiologic or pathologic ? Physiologic Physiologic
Pathologic Vs. Physiologic What’s the difference ? Physiologic Elevation is universal and transient Mechanisms: Increased RBC destruction Increased RBC destruction Decreased uptake and conjugation Decreased uptake and conjugation Ineffective excretion Ineffective excretion Pathologic Jaundice that varies significantly from physiologic expectations in: Time of appearance Duration Pattern of serially determined concentrations
Pathologic Jaundice Occurs in the first ____ hrs of life 24 hrs of life 24 hrs of life Rate of bilirubin rise > ____ mg/dl/day > 5mg/dl/day > 5mg/dl/day Clinical jaundice > ____ days in duration > 1 week duration > 1 week duration Direct bilirubin > _____ > 2mg/dl or > 15% of total > 2mg/dl or > 15% of total
Natural History Term Infant Peak day Peak day Peak Level Peak Level 8-13 mg/dl8-13 mg/dl Decline day Decline day Preterm Infant Peak day 5-7 Peak level mg/dl Decline day 7-15
Case 8 Term AGA male born to a 35 yo G3P3 without any prenatal/neonatal complications, presents for 2 week check. Mom is exclusively breastfeeding without any difficulty and infant is gaining weight. He looks a little jaundiced. Lab results: H/H and platelet count WNL H/H and platelet count WNL Total Bilirubin 19mg/dl Total Bilirubin 19mg/dl Direct Bilirubin 0.8 mg/dl Direct Bilirubin 0.8 mg/dl
Breast Milk Jaundice % of breast fed infants After first 5 days Peaks at 2 weeks Gradual decline over months Cause ? Progesterone Metabolite Progesterone Metabolite Fatty acids Fatty acids
Breastfeeding Failure Jaundice First few days of life First time moms Poor enteral intake → delayed meconium → increased enterohepatic uptake of bilirubin Prevention: Lactation consultant Lactation consultant At least 8-12 feeds/day At least 8-12 feeds/day Avoid supplements Avoid supplements
Why would these neonates be at risk for hyperbili ?
Case 9 2 week old infant here for routine check. Uncomplicated delivery and WBN stay. Vit K given at birth, discharged at 72 hrs, breastfeeding well. Feeding every 3 hrs, stooling 6 x/day and voiding 9x/day. Exam significant for clinical jaundice. What labs would you order ? What maternal blood type would you be concerned about ?
Labs: WBC 9 x 10 3/mm3, Hct 26%, Plt 175k/mm3 WBC 9 x 10 3/mm3, Hct 26%, Plt 175k/mm3 Retic 7% Retic 7% Total Bilirubin 19mg/dl, direct 0.6mg/dl Total Bilirubin 19mg/dl, direct 0.6mg/dl History from the well baby chart Maternal Blood Type O+ Maternal Blood Type O+ Infant Blood Type A + Infant Blood Type A + DAT + DAT +
Immune Mediated Hemolytic Disease Maternal IgG (via placenta) mediated Maternal Coombs (indirect) + Hemolysis of fetal cells Hyperbilirubinemia, anemia Hydrops Fetalis Rh Alloimmunization Rhesus D most common and most severe 28 wks and within 72 hrs of delivery Severity increases ABO Incompatibility Mild to severe Anti-A Anti-B Can occur in 1 st pregnancy
Case 10 4 day old infant presents to office with jaundice. Term male, uncomplicated delivery to a G1 with blood type B+ Prenatal labs unremarkable. Breast feeding well. Jaundiced yesterday with level of 17, home phototherapy initiated and follow up today with bilirubin of 22. PE significant for jaundice and palpable spleen.
Labs Labs Initial Hct 47, now 28 Reticulocyte count 4% Infant blood type B+, coombs – Blood smear What specific test will be positive ? Osmotic Fragility Test
Other Heritable Hemolytic Diseases Pyruvate Kinase Deficiency Inherited as …….. Inherited as …….. Auto recessiveAuto recessive G6PD deficiency Most common in people of what descent ? Most common in people of what descent ? Mediterranean, tropical African, and AsianMediterranean, tropical African, and Asian Inherited as …….. Inherited as …….. X linkedX linked
Case 11 7 day old, full term male comes to office with lethargy. Unremarkable prenatal/nursery course. Exclusively breastfeeding. No stool x 2 days and mom has to wake him up for feeds. Physical exam: lethargic, jaundiced, large head and widely open fontanelles, low tone
Congenital Hypothyroidism Incidence 1:4000 Usually asymptomatic at birth Conjugating enzyme deficiency lasts weeks to months L-thyroxine treatment by 2 weeks Prompt treatment corrects the bilirubin
Case 12 Ex 30 week EGA preemie, now 3 weeks old. Delivered for maternal pre-e, otherwise unremarkable pregnancy with negative maternal labs. Now on RA but with frequent feeding intolerance and multiple periods of NPO. Currently on 5 q3 enteral feeds and had been on TPN since birth. Total bili today 11 mg/dl with a direct component of 5.6mg/dl What are some general causes ? What labs might help narrow your differential ?
Causes of Direct Hyperbilirubinemia Hepatocellular Hepatitis Hepatitis TPN induced TPN induced Alpha-1 antitrypsin Alpha-1 antitrypsin Galacotsemia Galacotsemia Cystic Fibrosis Cystic Fibrosis Biliary Tree Abnormalities Extra-hepatic Biliary Atresia Paucity of bile ducts Choledochal cyst Bile Plug
What tests will be helpful ? Radiology: Abdominal ultrasound Abdominal ultrasound HIDA scan HIDA scan Newborn screen: CF results CF results GALT enzyme activity GALT enzyme activity Infant Labs: Hepatitis panel Hepatitis panel ALT,AST, GGT ALT,AST, GGT Urine for reducing substances Urine for reducing substances
Management When to start Phototherapy
Management When to consider Exchange
Why do we treat ? To prevent …… Kernicterus Kernicterus Which is deposition of unconjugated bilirubin in the ………..Which is deposition of unconjugated bilirubin in the ……….. Basal Ganglia
Phototherapy Photoisomerizes unconjugated bilirubin into more H2O soluble form Excreted rapidly by liver and kidney Excreted rapidly by liver and kidney Does not need glucuronidation Does not need glucuronidation
Exchange Transfusion Double volume exchange Replaces 85% of circulating RBC Replaces 85% of circulating RBC Two neonatal blood volumes Two neonatal blood volumes 160ml/kg160ml/kg Aliquots = 10% of total blood volume Aliquots = 10% of total blood volume