neonatal hematology for the primary care physician
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Neonatal Hematology for the Primary Care Physician. Vlad C. Radulescu, M.D. University of Kentucky. Topics. Normal newborn hematologic parameters Common causes of anemia in the newborn Neonatal screening for abnormal hemoglobins Hemostatic abnormalities - PowerPoint PPT PresentationTRANSCRIPT
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Neonatal Hematology for the Primary Care PhysicianVlad C. Radulescu, M.D.University of Kentucky
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TopicsNormal newborn hematologic parametersCommon causes of anemia in the newbornNeonatal screening for abnormal hemoglobins
Hemostatic abnormalitiesCurrent use of umbilical cord blood stem cells
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Case #13 months old infant32 weeks gestation, birth weight : 2100 gSpent two weeks in NICU for respiratory distress, feeding difficulties
Feeding well, thriving, appropriate growthCBC: WBC 10,500 / fl, Hgb 9.5g /dl, MCV 95fl, platelet count 245,000 / fl
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Normal Newborn CBC
HemoglobinRed blood cell indices : Mean Corpuscular VolumePeripheral smear
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Neonatal changes that impact thered blood cell indices
Sudden increase in tissue oxygenation after birthDecrease erythropoietin levelsDecreased hemoglobin production
Transition from fetal hemoglobin to adult hemoglobin
Rapid growth
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Hemoglobin
28 wks
32 wks
term 2 wks
1mo. 2mo. 6mo 1yr 6yrs 12 yrs
02468
101214161820
Hemoglobin
Data extracted from: The Harriet Lane Handbook, 19th edition, table 14-1
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Hemoglobin
Full term
Premature 1200 -2350 gPremature
<1200 g Adapted from:
Nathan and OskiHematology of Infancy and childhood, 7th ed.
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Mean Corpuscular Volume
30 w
ks
32 w
kster
m2 w
ks
1 mon
th
2mon
ths
6 mon
ths 1 yr
6 yrs
12 yr
s0
20
40
60
80
100
120
140
MCV
Data extracted from: The Harriet Lane Handbook, 19th edition, table 14-1
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Normal Adult Blood Smear
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Neonatal Blood Smear
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Hemoglobin, MCV are high at birth and decrease over the first few months of life, more dramatically for the pre-term infant
MCV < 94fl in newborn2/3 had Bart’s HemoglobinSuggestive of alpha thalassemia
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Case #1 : normal infant3 months old infant32 weeks gestation, birth weight : 2100 gSpent two weeks in NICU for respiratory distress, feeding difficulties
Feeding well, thriving, appropriate growthCBC: WBC 10,500 / fl, Hgb 9.5g /dl, MCV 95fl, platelet count 245,000 / fl
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Anemia in the Newborn
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Anemia in the Newborn
Hgb. < 13.5
g/dl
Blood Loss
Hemolysis
Failure of production
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Anemia in the NewbornPresentation
Life threatening event Pallor, difficulty feeding, poor weight gain, tachycardia Incidental finding
Does it require immediate intervention? If a transfusion is indicated should any tests be done prior
to transfusion
Does the newborn have to be referred to a hematologist?
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Evaluation of Anemia in the NewbornCBCRBC indices – MCV (Mean Corpuscular Volume)
Reticulocyte count Elevated – RBC destruction ( hemolysis) or bleed Decreased – decreased RBC production
Coombs ( direct anti-globulin test) Positive in immune hemolysis
Maternal and fetal blood type Identifies mismatched in the ABO and Rh blood types that may
represent set-ups for allo-immunization
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Anemia through blood lossFetal- maternal transfusion
Rupture of the cord
Laceration of the placenta
Internal hemorrhage Intracranial Retroperitoneal Intrathoracic Intraabdominal
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Anemia due to hemolysis
Immune hemolysisMaternal
alloimmunization to fetal RBC antigens
Maternal auto-antibodies ( Lupus)
Non-Immune HemolysisEnzymesG6PD
RBC membrane spherocytosis
HemoglobinThalassemia, Hgb.
SS
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Hemolytic Disease of the NewbornThe mother becomes sensitized to antigens
present on fetal red blood cells Fetal- maternal hemorrhage Prior maternal transfusion
Antigens Rh ABO Kell, Duffy, Kidd
Maternal antibodies cross the placenta IgG can cross, IgM, IgA can not cross Transport increases in the 3rd trimester
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Hemolytic Disease of the Newborn
Maternal antibodies bind to fetal RBC and sometimes other tissues
AB, Duffy, Kidd, Kell antigens are expressed on erythroid and non erythroid tissues
Rh, MN, SS antigens expressed only on erythroid tissues
Antibodies bound to RBC induce hemolysis if they can activate complement promote cell mediated cytotoxicity
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Hemolytic Disease of the Newborn
RhD Most commonly identified antigenic stimulus Mother is Rh negative, fetus Rh positive The incidence has dropped with the use of anti-D antibodies
to decrease maternal sensitization
ABO Mother is type O, fetus is type A, B
Kell, Duffy, Kidd Maternal sensitization may be due to prior maternal blood
transfusions mismatched in the minor blood types
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Hemolytic Disease of the NewbornDiagnosis:
Mismatch between maternal and newborn blood types
History of prior maternal transfusions
Combs ( Direct Antiglobulin Test) positive
Neonatal Hyperbilirubinemia
Managemnt Anemia simple or exchange
transfusion
Hyperbilirubinemia Phototherapy Exchange transfusions
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Anemia through decreased production
Physiologic anemia
Anemia of prematurity
Late anemia of the hemolytic disease of the newborn
Bone marrow failure syndromes Diamond Blackfan sdr. Fanconi sdr.
Nutritional deficiencies
Infections
Infiltrative processes Leukemia Neuroblastoma
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Anemia of prematurity
Causes Low erythropoietin levels Small circulating blood
volumes Blood loss Hemolysis
Minimize blood lossPRBC transfusions
Hgb < 7 g/dl Apnea & bradycardia Tachycardia Tachypnea Poor weight gain Respiratory distress
Erythropoietin Iron supplements
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Hemoglobin Screening in Newborns
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Hemoglobin Screening in Newborns
Goal: early diagnosis of sickle cell disease
The first manifestations of sickle cell disease in infants may be life-threatening complications:Pneumococcal sepsisSplenic sequestration
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Methodology
High performance liquid chromatography
Identifies different types of hemoglobin
Relevant for sickle cell disease: Hgb S , Hgb C
Incidental findings: Hgb H , Hgb Bart’s, Hgb E, D, etc.
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HemoglobinNormal variants
Embrionic Fetal a2 g2 Adult 1 a2 b2 Adult 2 a2 d2
Abnormal variants S, D, C, E : abn. b chain Barts: g4 H: b4
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Hemoglobin Switching during development
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Normal newborn
Screening test: FA
Hemoglobin electrophoresis: Hgb F 60-90% Hgb A1 10-40% Hgb A2 < 1 %
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Sickle Cell SyndromesScreening test
Diagnostic possibilities
FS Hgb SSHgb S B0 thalassemia
FSCFSD
Hgb SCHgb SD
FSA Hgb S B+ thal.Sickle Cell Trait
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Sickle Cell Syndromes: Interventions
Refer to Pediatric Hematology/ repeat testingEvaluate infant for splenomegaly.Educate parents/caregivers regarding
risk of sepsis , aggressive management of fevers splenic sequestration in Sickle Cell disease
Pen V K 125 mg po bid until repeat testing confirms or rules out a sickle cell syndrome
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Thalassemia Syndromes
Screening test
Diagnosis Implications
F bThalasemia majorPremature infant
Severe anemia, may need transfusionsRepeat screening
FAB a Thallsemia
Variable manifestations depending on the number of affected genes
Genetic implications
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Globin Genes
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Alpha Thalassemia
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Alpha ThalassemiaFollow-up tests:
CBC, Hemoglobin electrophoresis Consider alpha globin gene mutation analysis
Family history Ethnic origin: common in SE Asia History of anemia or microcytosis
Genetic counseling
Consider Pediatric Hematology referral
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Non- Sickle HemoglobinopathiesScreening test
Diagnosis Implications
FE Hemoglobin EEHgb E b0 Thal.
Mild anemiaModerate to severe anemia
FC Hemoglobin CCHgb C b0 Thal.
Mild anemiaMild Anemia
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Carriers of Hemoglobin VariantsScreening test
Diagnostic possibilities
Implications
FAS Sickle Cell Trait
Generally AsymptomaticGenetic implications
FAC Hemoglobin C trait
AsymptomaticGenetic implications
FAE Hemoglobin E trait
Asymptomatic / mild anemiaGenetic implications
FAV Variant Hemoglobin
Most likely clinically insignificant
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Carriers of Hemoglobin Variants In general, no medical intervention is needed for
the patient
Genetic counseling : asses the risk of having a child with sickle cell disease or thalassemia major
For the patient future children
For the patient’s parents Evaluation of the carrier state : CBC, Hgb electrophoresis
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Hemostatic abnormalities in the newborn
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Case # 2
FT newborn Covered in petechiae at
birth Birthweight : 3.4kg Apgar scores: 9, 9
Case # 3
FT male newborn Birthweight : 3.5kg Apgar scores: 8, 9 Oozing for 4 hrs. at the site
of the heel-stick Develops unexpected
bleeding after circumcision
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Hemostatic abnormalities:presentation
Petechial rash EcchymosesCephalohematomaSmall but prolonged bleeding at the heel-stick siteHematoma at the IM injection siteOozing form the umbilicus Bleeding with circumcision Intracranial bleeding
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Laboratory evaluation
CBCPTPTTFibrinogen
Platelet Function Analysis
Normal values*1 day 1
month1 year
PT 14-16s 11-15s 11-14s
PTT 34-44s 35-46s 28-38s
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Neonatal Thrombocytopenia
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Neonatal ThrombocytopeniaPrevalence
Common in the sick newborn 20-40% of NICU admissions 70-80% of very low birth weight premature newborns
Uncommon in the healthy newborn (1-2%)
Timing <72 hrs – due to prenatal or perinatal factors >72 hrs - due to postnatal factors Sepsis Necrotizing enterocolitis
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Thrombocytopenia in the sick newbornFrequently associated with:
Infection Asphyxia Meconium aspiration Respiratory distress syndrome Necrotizing enterocolitis Presence of indwelling catheters
Predictor of poor prognosis Mortality Intestinal gangrene in NEC
Frequently leads to bleeding complications
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Thrombocytopenia in the well -looking newborn
Maternal historyDrug ingestion Sulphonamides, valproic acid, carbamazepine, quinindine
Hypertension / Pre-eclampsia
Infections during pregnancy
Maternal ITP/ low maternal platelet count
Previous newborn with thrombocytopenia Neonatal Allo-immune Thrombocytopenia (NAIT)
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Thrombocytopenia in the well -looking newbornNewborn exam
Normal NAIT Maternal ITP Maternal drug exposure
Congenital abnormalities Thrombocytopenia absent radii syndrome (TAR) Fanconi anemia
Hepatosplenomegaly Infection Leukemia
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Neonatal Allo-Immune Thrombocytopenia ( NAIT)Mechanism
The mother is exposed to a Platelet antigen they do not posses The mother produces an IgG. antibody that crosses the placenta Induces thrombocytopenia in the newborn
Incidence 1:5000- 10,000 birth
May occur with the first pregnancy, more severe with subsequent pregnancies
Manifestations Thrombocytopenia Purpura Internal hemorrhage including intracranial hemorrhage
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Neonatal Allo-Immune Thrombocytopenia ( NAIT)Diagnosis
Identification of maternal and paternal platelet antigens Maternal and paternal genotyping
Management Platelet transfusions IV Immunoglobulins
Subsequent pregnancies Close monitoring IV Ig. Steroids Cord blood sampling and in utero platelet transfusions
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Case # 2
FT newborn Covered in petechiae at birth Birthweight : 3.4kg Apgar scores: 9, 9 Platelet count 10,000 Older brother had thrombocytopenia Maternal CBC is normal
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Abnormal PT and or PTTCoagulation abnormalities:
History
Did the child receive the Vitamin K injection at birth?
Any family history of bleeding disorders?Von Willebrand diseaseFactor VIII or factor IX deficiency
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Hemophilia A and B
X linked disorders Females are carriers Males have the bleeding
disorder
1/3 of cases of Factor VIII deficiency are due to new mutations, thus no family history
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Hemophilia A and B
ManifestationsProlonged bleeding at the heel-stick siteCephalhematomaExcessive or prolonged bleeding with
circumcisionHematomas at the IM injection sites
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Hemophilia A and B
Laboratory PT- normal PTT- prolonged Mixing studies PTT corrects with
addition of normal plasma
Factor VIII or IX level is low
Management No arterial sticks No IM injections No procedures Pressure at the site of
bleeding
Hematology consult ASAP
Factor concentrates
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Case # 3
FT male newbornBirthweight : 3.5kgApgar scores: 8, 9Oozing for 4 hrs. at the site of the heel-stickDevelops unexpected bleeding after circumcisionPT 60 s , corrects to 29 s on mixing studiesMaternal great-uncle was a “free bleeder”Fct. VIII level 4%
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Umbilical Cord Blood Stem Cell Transplantation
Cord blood stem cells may be used for a bone marrow transplant
Less likely to cause graft versus host diseaseDoes not need to be fully HLA matched for a
successful transplantCan be collected without any risk for the donor
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Private Cord Blood Banking Service offered to parents by several for profit companies
Autologous transplant Malignant disorders rare in children no graft vs. leukemia/ tumor effect
Allogeneic transplant First degree relatives with Malignancies treatable with stem cell transplant Hemoglobinopathies ( Sickle Cell Disease, Thalassemia) Congenital Immunodeficiency Disorders Bone marrow Failure Disorders
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Newborns have distinct Blood count values Hemostatic parameters
Differential diagnosis Disorders of the feto-maternal unit Immunologic responses of the mother to fetal antigens Congenital / genetic abnormalities
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