Presentation on theme: "Neonatal Jaundice and Hematology"— Presentation transcript:
1Neonatal Jaundice and Hematology Raegan Wetzel, M.D.Oct 5, 2010
2Causes of Anemia Accelerated Loss Accelerated Destruction Hemorrhage, Twin-twin transfusion, early umbilical cord clamping, fetal-maternal transfusionAccelerated DestructionImmune hemolytic anemia, hemoglobinopathies, enzyme defects, membrane defects, mechanical destruction, infection, vit E deficiencyDiminished ProductionAnemia of prematurity, Fanconi/Diamond-Blackfan anemia, parvovirus, iron deficiencyThe KB test is the standard method of detecting fetal-maternal hemorrhage (FMH). It takes advantage of the differential resistance of fetal hemoglobin to acid. A standard blood smear is prepared from the mother's blood, and exposed to an acid bath. This removes adult hemoglobin, but not fetal hemoglobin, from the red blood cells. Subsequent staining makes fetal cells (containing fetal hemoglobin) appear rose-pink in color, while adult red blood cells are only seen as 'ghosts'.
3Case 1You 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 ?
4Twin to Twin Transfusion Who is at risk and why ?Monozygotic/monochornic twins13-33% of twin pregnanciesDonorAnemiaRecipientHyperbili, Hyperviscosity
5Blood Loss Fetal-placental Cord abnormalities Placental abnormalities Infant position after deliveryCord abnormalitiesVelamentous insertion, short cords, chord rupture with precipitous delivery or entanglement, nuchal/knotPlacental abnormalitiesAbruption or previaFetal-maternalWhat should you order ?Kleihauer-BetkeThe KB test is the standard method of detecting fetal-maternal hemorrhage (FMH). It takes advantage of the differential resistance of fetal hemoglobin to acid. A standard blood smear is prepared from the mother's blood, and exposed to an acid bath. This removes adult hemoglobin, but not fetal hemoglobin, from the red blood cells. Subsequent staining makes fetal cells (containing fetal hemoglobin) appear rose-pink in color, while adult red blood cells are only seen as 'ghosts'.
6Case 2Ex 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 ?
7Anemia of Prematurity Why does it happen ? Blood loss Shortened RBC lifespanPreterm daysInadequate RBC productionSuboptimal erythropoiesis in response to hypoxiaSwitch from hepatic to renal O2 sensor not till term
8Do term infants get anemic ? YESPhysiologic anemia of infancy happens later in term infants. True or False ?TrueTerm:8-12 weeks, Hemoglobin 9-11 g/dLPreterm:3-6 weeks, Hemoglobin 7-9 g/dLAfter birth blood O2 increases and therefore tissue O2 delivery increases; down regulating epoHgb decreases till O2 demand is greater than O2 delivery capacity, happens at 8-12 wks
11Case 3You are notified by the state lab that a newborn has Hemoglobin Barts. What does this mean ?Does this relate to Beta or Alpha Thalassemia ?Bart’s hemoglobin appears in cord blood when there is a deletion of one or more of the 4alpha goblin genes. The amount of Bart’s hemoglobin reflects the number of genes thatare deleted.The presence of 1-6% Bart’s hemoglobin indicates the deletion of one or two genes. Thisdegree of deletion is clinically insignificant to the infant but may be of genetic significance.The infant may be at risk for having a child with Hydrops Fetalis, if his/her partner carries asimilar deletion. This would be much more likely in an infant of Southeast Asian ancestry.The presence of approximately 20% Bart’s Hemoglobin indicates the deletion of 3 genesand the presence of hemoglobin H disease, which is characterized by mild anemia. Thiscondition would generally be diagnosed during routine pediatric care and does not requireearly intervention.Interpretation
12Alpha Thalassemia% Hgb Bart’s = number of alpha globin genes that are deletedSilent Carrier – 1 abnormal geneAlpha thal trait – 2 abnormal genesHb H disease – 3 abnormal genesModerate anemiaThal Major - 4 abnormal genesHydrops fetalisTransfusion dependentHemoglobin Barts consists of four gamma chains. It is moderately insoluble, and therefore accumulates in the red blood cells. Bart’s hemoglobin appears in cord blood when there is a deletion of one or more of the 4alpha goblin genes. The amount of Bart’s hemoglobin reflects the number of genes thatare deleted.
13Beta Thalassemia 2 genes of beta-globin production Silent Carrier: Normal smear and electrophoresisB-thal trait: Frequently misdiagnosed as iron deficiency anemia, mild anemiaThal intermedia: Able to maintain Hgb > 7 without transfusionThal major: Require regular transfusionsNormal Hgb at birth 2/2 fetal Hgb4 clinical classifications: based on interaction with alpha globin chains and type of genetic defectSilent carrier- usually found thru family history of those with more severe disease
14Case 43 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.
15How could this have been avoided ? What is her diagnosis ?Hemorrhagic Disease of the NewbornHow could this have been avoided ?0.5 to 1 mg IM of vitamin K
16Hemorrhagic Disease of the Newborn Why are Newborns deficient in Vit K ?Placental transfer is poorBreast milk is a poor sourceGI tract is sterile at birthWhat lab values are associated ?Platelet CountNormalFibrinogenPTprolonged
173 Types of HD of N Early Disease Classic Disease Late-onset 1st 24 hoursMaternal use of anticoagulant/anticonvulsantSevere bleeding/intracranial hemorrhageClassic Disease1-7 daysCutaneous, GI or circumcision site bleedingLate-onsetBeyond 1 weekAssociated with exclusively breast-fed
18Case 5Term 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 : 200PTT : prolongedPT : normalBleeding time normalFibrinogen level : normalFactor IX and VII : pending
19Hemophilia A and B X linked disorder Hemophilia A (factor VIII) : 5x more commonHemophilia B (factor IX) : milderBleeding less common in newborn periodCommon bleeding sites ?Circumcision, umbilical bleeding, subdural > IVHContrast with VWD: Newborn bleeding is rare. Auto dom, Prolonged bleeding time. Test: VWF activity, antigen. Most common heritable bleeding disorder
20How is this different than Von Willebrand’s disease ? V W is most common heritable bleeding disorderV W is autosomal dominantV W will have prolonged bleeding timeWhat test should you order for diagnosis ?von Willebrand factor activity (ristocetin cofactorvon Willebrand factor antigen
21Case 6Newborn 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 20Normal PT,PTTNormal fibrinogen
22What is the pathophysiology ? What is the diagnosis ?Neonatal Alloimmune ThrombocytopeniaWhat is the pathophysiology ?Placental transfer of maternal antibodies against paternally inherited antigens on fetal platelets.HPA-1a (78%) and HPA-5b alloantigensCan the disease occur in the first pregnancy ?YesAntigenic determinants expressed on placental endotheliumExtended window of time for sensitization
25Case 772 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/dlDirect fraction 0.8 mg/dlInfant Hct 52%IBT O+Does this seem physiologic or pathologic ?Physiologic
26Pathologic Vs. Physiologic What’s the difference ? Elevation is universal and transientMechanisms:Increased RBC destructionDecreased uptake and conjugationIneffective excretionPathologicJaundice that varies significantly from physiologic expectations in:Time of appearanceDurationPattern of serially determined concentrationsNewborn rbc lifespan days
27Pathologic Jaundice Occurs in the first ____ hrs of life Rate of bilirubin rise > ____ mg/dl/day> 5mg/dl/dayClinical jaundice > ____ days in duration> 1 week durationDirect bilirubin > _____> 2mg/dl or > 15% of total
28Natural History Term Infant Preterm Infant Peak day Peak Level 3-5Peak Level8-13 mg/dlDecline day5-10Preterm InfantPeak day5-7Peak level12-15 mg/dlDecline day7-15
29Case 8Term 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 WNLTotal Bilirubin 19mg/dlDirect Bilirubin 0.8 mg/dl
30Breast Milk Jaundice 10-30 % of breast fed infants After first 5 days Peaks at 2 weeksGradual decline over monthsCause ?Progesterone MetaboliteFatty acidsProgesterone and fatty acids inhibit conjugation
31Breastfeeding Failure Jaundice First few days of lifeFirst time momsPoor enteral intake → delayed meconium → increased enterohepatic uptake of bilirubinPrevention:Lactation consultantAt least 8-12 feeds/dayAvoid supplements
32Why would these neonates be at risk for hyperbili ?
33Case 92 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 ?
34History from the well baby chart Labs:WBC 9 x 10 3/mm3, Hct 26%, Plt 175k/mm3Retic 7%Total Bilirubin 19mg/dl, direct 0.6mg/dlHistory from the well baby chartMaternal Blood Type O+Infant Blood Type A +DAT +
35Immune Mediated Hemolytic Disease Maternal IgG (via placenta) mediatedMaternal Coombs (indirect) +Hemolysis of fetal cellsHyperbilirubinemia, anemiaHydrops FetalisRh AlloimmunizationRhesus D most common and most severe28 wks and within 72 hrs of deliverySeverity increasesABO IncompatibilityMild to severeAnti-AAnti-BCan occur in 1st pregnancyIndirect coombs checks for antibodies in mom’s plasma, direct coombs detects antibodies that are bound to red blood cells
36Case 104 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.
37Labs Initial Hct 47, now 28 Reticulocyte count 4% Infant blood type B+, coombs –Blood smearWhat specific test will be positive ?Osmotic Fragility Test
38Hereditary Spherocytosis Autosomal DominantNorthern European descentAnemiaJaundiceSplenomegaly
39Other Heritable Hemolytic Diseases Pyruvate Kinase DeficiencyInherited as ……..Auto recessiveG6PD deficiencyMost common in people of what descent ?Mediterranean, tropical African, and AsianX linkedPK- diagnosed with decreased PK activity
40Case 117 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
41Congenital Hypothyroidism Incidence 1:4000Usually asymptomatic at birthConjugating enzyme deficiency lasts weeks to monthsL-thyroxine treatment by 2 weeksPrompt treatment corrects the bilirubin
42Case 12Ex 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/dlWhat are some general causes ?What labs might help narrow your differential ?
43Causes of Direct Hyperbilirubinemia HepatocellularHepatitisTPN inducedAlpha-1 antitrypsinGalacotsemiaCystic FibrosisBiliary Tree AbnormalitiesExtra-hepatic Biliary AtresiaPaucity of bile ductsCholedochal cystBile Plug
44What tests will be helpful ? Radiology:Abdominal ultrasoundHIDA scanNewborn screen:CF resultsGALT enzyme activityInfant Labs:Hepatitis panelALT,AST, GGTUrine for reducing substances