A Not So Minor Problem.. Presentor: Angelo Catacutan, MD, MBA Moderator: Dr. Carmela Kasala, MD Reactor: Dr. Joseph Vincent Alba, MD.

A Not So Minor Problem..

Presentor: Angelo Catacutan, MD, MBAModerator: Dr. Carmela Kasala, MDReactor: Dr. Joseph Vincent Alba, MD

Objectives

• To present a case of a newborn who presented with jaundice at <24 HOL

• To discuss the approach to a jaundiced newborn

• To discuss about alloimmune hemolytic anemia in the newborn, its manifestations, approach to diagnosis, treatment, and prevention

Patient Data

• K.M.• Newborn• Female• Filipino• DOB: June 15, 2013• Delivered via emergency CS

– (for repeat CS in labor)• Place of Birth: The Medical City

Chief Complaint

Jaundice

Maternal History

• 42 year old G4P4(4003)• Filipino• College graduate• Office worker• Non-smoker, non-alcoholic beverage

drinker

Maternal History

• Regular prenatal check-ups• OGCT screen normal• HBsAg nonreactive• Denies infection, exposure to viral

exanthems, teratogens, or radiation• Blood type B+

Maternal History

• Complete Blood Count

• Urinalysis

Hgb Hct WBC Neut Lymp Mono Eo Plt115 34 8.8 65 20 10 5 318

RBC WBC Epith CastBacteri

a

13 2 2 0 34

Family History

• (-) hypertension• (-) diabetes• (-) asthma• (-) atopy• (-) hematologic disorders

Obstetric History

• G1 (2000)– Female– Term, NSD at a local hospital– Live, with no problems

Obstetric History

• G2 (2005)– Female– Term, Primary CS for Cephalopelvic

disproportion– Died shortly after birth

• “congenital heart problem”

Obstetric History

• G3 (2006)– Female– Live, Term, Repeat CS – TMC– Diagnosis: Hemolytic Disease of the

Newborn• Underwent phototherapy, double-volume

exchange transfusion and IVIg infusion– No antibody identification done on the

mother

Obstetric History

• G4 (2013)– Present pregnancy

Physical Examination(upon birth)• General Status

– Clear amniotic fluid– No cord coil– Good cry and activity

Physical Examination(upon birth)• Blood Pressures:

– 68/41(right arm), 69/40 (left arm)– 63/48 (right foot), 67/36 (left foot)

• Cardiac rate: 146bpm• Respiratory Rate: 48/min• Temperature: 36.5˚C

Physical Examination(upon birth)• APGAR 9,9• Anthropometrics

– BW: 2850g (50th percentile)– BL: 49cm (40th percentile)– HC: 36cm (90th percentile)– CC: 33cm– AC: 27cm

Physical Examination(upon birth)• HEENT

– Patent nares, formed ears, (-) cleft lip/palate

• Pulmonary– No deformities, no retractions, good air

entry, equal breath sounds• Cardiac

– Adynamic precordium, normal cardiac rate, regular rhythm, (-) murmurs

Physical Examination(upon birth)• Abdominal

– Globular– Soft with no palpable masses– Umbilicus: 2 arteries, 1 vein

• Genitalia– Grossly female, no deformities

• Anus– patent

Physical Examination(upon birth)

18

Physical Examination(upon birth)

20

Physical Examination(upon birth)• Neuromuscular Maturity = 18• Physical Maturity = 20• Total Maturity Raiting = 38

• 39 Weeks• Appropriate for Gestational Age

Admitting Diagnosis

Live, term, baby girl, delivered via emergency repeat CS (for repeat CS

in labor) to a 42 year old G4P4 (4003) at 38 6/7 weeks AOG

BW 2850g BL 49cm HC 36cm CC 33cm AC 27cm. AS 9,9, MT 39 weeks

AGA

COURSE IN THE WARDS

Upon Delivery

• Essential newborn care rendered• Diagnostics:

– Blood typing– Hearing screening (24th – 48th HOL)– Newborn screening (24th – 48th HOL)

Upon Delivery

• Therapeutics: – Vitamin K 0.1mL/IM– Erythromycin eye ointment– Hepatitis B vaccine 0.5mL/IM

• Roomed-in at the 4th HOL• Exclusively breastfed

24th hour of life

Subjective

• Breastfed every 3 hours

• Good suck and activity

• Adequate UO• Meconium passage

Objective

• HR 132bpm, RR 34/min T 36.7C BP 70/40

• Weight: 2880g (+30g)

• Light jaundice to face

• Good air entry• Regular cardiac

rhythm• Soft abdomen• Full pulses

Assessment

• Term baby girl• t/c

Hyperbilirubinemia, unspecfied

35th hour of life

Subjective

• Breastfed every 3 hours


• Adequate UO• Meconium passage

Objective

•HR 135bpm, RR 34/min T 37C BP 70/40•Generalized jaundice•Good air entry•Regular cardiac rhythm•Soft abdomen•Full pulses

Assessment

• Term baby girl• Hyperbilirubinema,

unspecified• R/O Sepsis

35th hour of life

Plan

• Transfer to NICU• Diagnostics:

• Bilirubin levels• CBCPC, Blood culture and sensitivity• CRP• Reticulocyte count• Maternal blood typing

• Therapeutics:• Single Phototherapy• IV fluids (50cc/kg/hr x 6 hours)• Continue oral feeding

• Refer to neonatology

Laboratories

Date Hgb Hct WBC Band Neu Lym Mon Eos Plt

6/16/13 118 35 15.2 02 71 21 4 2 325Macroc

ytic

Peripheral Blood Smear

Smear shows macrocytic RBCs. No abnormal WBCs. Adequate platelet.

CRP (0-0.5 mg/dL)

0.16 mg/dL

Reticulocyte count(0.005 – 0.015)

0.484

Blood Type

B+

42nd Hour of Life

TB mg/dL

DBmg/dL

IBmg/gL

42nd HOL

30.38 1.31 29.57High risk

Plan: Double Phototherapy

42nd Hour of Life

• Persistently jaundiced• Repeat bilirubin levels extracted

42nd Hour of Life

TB mg/dL

DBmg/dL

IBmg/gL

42nd HOL

30.38 1.31 29.57 High risk

Double Phototherapy

48th Hour of Life

Subjective


Objective

• Generalized jaundice

Assessment

• Hyperbilirubinemia• t/c Hemolytic

disease of the newborn

2nd Day of Life

Plan

• Diagnostics:• Coomb’s test (Direct and Indirect)• Repeat bilirubin levels• CBCPC

• Therapeutics:• Maintain Double Phototherapy• IV fluids• Continue oral feeding

Coomb’s test

positive for direct anti-globulinpositive for indirect anti-globulin

TB DB IB

48th HOL 29.27 1.49 28.26High risk

zone


6/17/13 4AM

107 32 14.3 01 69 21 08 01 318Macrocytic

2nd Day of Life

42nd Hour of Life

TB mg/dL

DBmg/dL

IBmg/gL

48th HOL

29.27 1.49 28.26 High risk

Double Phototherapy

2nd Day of Life

Assessment

• Hemolytic Disease of the Newborn

Plan

• Double-volume exchange transfusion

• Human IVIg 1.5g/IV (526.3mg/kg/dose)

• Ampicillin (87.7 mkday) (post-DVET)

• Amikacin (10.52 mkday) (post-DVET)

For Double-VolumeExchange Transfusion• To use: type B whole blood <48

hours old, crossmatched with the mother’s blood– Not available in the blood bank

• Alternative: Reconstitued whole blood– Type O pRBC + type AB FFP,

crossmatched– 5 packs reactive

• IVIg 1.5g IV was started

Double VolumeExchange Transfusion

• Materials:– 3-way stop cock x 2– 500mL sterile bottle– 10mL syringes– Extension tubing– Umbilical catheter

Fr 5– 460mL

reconstituted blood

Double VolumeExchange Transfusion

• Procedure– Umbilical vein

catheterization– 46 cycles, 10mL

per aliquot– VS every 15

minutes

Waste Blood Donor Blood

Post-Transfusion Plans

• To start Ampicillin and Amikacin for antibiotic coverage

• For repeat bilirubin levels 6 hrs post-transfusion

• Send maternal blood for antibody identification

6 Hours Post-Transfusion

TB DB IB

6/17/13 11pm67th HOL

16.41 mg/dL 0.93 15.75 High risk zone

Na mmol/L130 - 145

K mmol/L3.7 – 5.9

iCal mg/dL3.9 – 6.0

6/17/13 11pm 135 3.70 3.72


6/17 11pm

164 50 9 0 78 13 8 1 188

42nd Hour of Life

TB mg/dL

DBmg/dL

IBmg/gL

67th

HOL16.41 0.93 15.75

High risk zone

Double Phototherapy

DVET

3rd Day of Life

Subjective

• 20-40mL of milk


Objective

• Jaundice to upper chest

• Mild bipedal edema

Assessment

• Hemolytic disease of the newborn

• s/p DVET

Plan

• Maternal antibody screening

• Repeat bilirubin levels

• 2nd dose of IVIG

• Continue Phototherapy

3rd Day of Life

TB DB IB

6/18/13 11am 79th HOL

15.94 mg/dL 0.88 15.32 HIRZ

Maternal antibody identification

Allo-anti EAllo anti-c

42nd Hour of Life

TB mg/dL

DBmg/dL

IBmg/gL

79th

HOL15.94 0.88 15.32

High inter-

mediate

Double Phototherapy

DVET

Double Phototherapy

42nd Hour of Life

TB mg/dL

DBmg/dL

IBmg/gL

122nd

HOL8.64 0.71 8.07

Low Risk Zone

d/c Phototherapy

Double Phototherapy

5th Day of Life

Subjective

• Tolerates 30-60mL of milk


• UO 2.8mL/kg/hr

• (+)BM

Objective

• Light jaundice to flexural areas

Assessment

• Hemolytic disease of the newborn

Plan

• Discharged

Final Diagnosis

Live, term, baby girl, delivered via emergency repeat CS (for repeat CS in labor) to a 42 year

old G4P4 (4003) at 38 6/7 weeks AOGBW 2850g BL 49cm HC 36cm CC 33cm AC

27cm. AS 9,9, MT 39 weeks AGA

Hemolytic Disesase of the Newborn secondary to Minor Rh Incompatibility

s/p Double-Volume Exchange Transfusions/p IVIg infusion

DISCUSSION

Salient Features

• Term, baby girl• Generalized jaundice before 24th HOL• Serum bilirubin levels of 34mg/dL• History of a sibling with history of

jaundice, underwent phototherapy, IVIg infusion, and exchange transfusion

JAUNDICE IN THE NEWBORN

Jaundice andHyperbilirubinemia• Yellow discoloration

of the skin secondary to deposition of bilirubin

Jaundice andHyperbilirubinemia• Etiology

– Increased bilirubin load / heme catabolism

– Decreased enzyme activity• Genetic predisposition• Competitive inhibition(drugs)

Nelson’s Textbook of Pediatrics 19th ed

Jaundice andHyperbilirubinemia

Jaundice

Physiologic Pathologic

Jaundice andHyperbilirubinemia

Physiologic• Appears at 2nd or 3rd

day of life

• Peaks at 2nd to 4th day of life

• Rises at a rate of <5mg/dL/day

Pathologic• Appears at the 24th

HOL or earlier– >12mg/dL in a term

infant– >10-14mg/dL in a

preterm infant• Persists to 10th-14th

day of life• Rises at a rate of

>5mg/dL/day

Nelson Textbook of Pediatrics, 19th ed,

AAP Guidelines. 2004

Approach to a Jaundiced Newborn

AAP Guidelines. 2004

Laboratory Evaluation


Alloimmune HemolyticDisease of the Newborn• “Erythroblastosis Fetalis”• Destruction of RBC by maternal IgG

against RBC antigens that access the fetal circulation transplacentally– ABO, Rhesus (Rh factor), other blood

group antigens


RBC Antigens

• Transmembrane proteins• Either synthesized by the RBC or

adsorbed from the plasma• 29 blood group systems• 250 antigens

Wintrobe’s Clinical Hematology, 12e. 2009

Rh Blood Group

• Discovered by Landsteiner and Weiner in 1940 from the rhesus monkey

• Has 3 nomenclature systems– Weiner system (Rh1, Rh2…)– Fisher-Race (Cc, Dd, Ee)– Rosenfield (Rho, rh’, rh’’…)


Rh Blood Group

• Highly immunogenic (70%)• An individual is Rh+ if the RBC

expresses the D antigen• 50-70% of antibody response to Rh

antigens are due to the D antigen


Rh Blood Group

AntigenCaucasian

sBlacks Asians

D 85% 92% 99%

C 68% 27% 93%

E 29% 22% 39%

c (little c) 80% 96% 47%

e (little e) 98% 98% 96%

Dean. Blood Groups and Red Cell Antigens. 2005

Prevalence of Rh Antigens in Racial Groups

HDN Caused byRh Incompatibility• Antibody formation when an Rh-

woman receives Rh+ blood (>1mL)• Once sensitization occurs, small

doses of Rh+ blood can increase titers (IgM and IgG)


Pathophysiology of HDN

Pathophysiology of HDN

Rh and ABOIncompatibility• Concomitant ABO incompatibility is

protective against Rh sensitization– Confers almost ninefold protection– Rapid removal of fetal Rh+ from

maternal circulation


Alloimmune HemolyticDisease of the Newborn• Manifestations

– Anemia– Fluid accumulation – “hydrops fetalis”– Jaundice and kernicterus

HDN with Rh antigens

Antigen HDN Severity

Anti-D Severe

Anti-C Mild to moderate

Anti-c (little c) Severe

Anti-E Mild to moderate

Anti-e (little e) Mild to moderate

Dean. Blood Groups and Red Cell Antigens. 2005

Alloimmune HemolyticDisease of the Newborn• Laboratory Evaluation

– Total serum bilirubin– CBC– Reticulocyte count– Direct Coomb’s test

Coomb’s Test

Alloimmune HemolyticDisease of the Newborn• Antenatal Diagnosis

– Percutaneous umbilical blood sampling– Ultrasonography

• Definitive Diagnosis– Demonstration of blood incompatibility

antibody identification

Alloimmune HemolyticDisease of the Newborn• Treatment Goals

– Avoid intrauterine and extrauterine death from anemia and hypoxia

– Avoid neurotoxicity from hyperbilirubinemia

Treatment for HDN

• For unborn infants– Intravascular fetal transfusion

• For liveborn infants– Exchange Transfusion– Phototherapy– IV Immunoglobulins

Management ofJaundice and HDN• Phototherapy

– Exposure to high-intensity light to reduce indirect bilirubin levels

– Maximal at blue range (420-470nm)• 15-20cm from infant

– Photo-isomerization• 4Z,15Z-bili 4Z, 15E-bili

Management ofJaundice and HDN

Management ofJaundice and HDN• Complications of phototherapy

– Loose stools and rash due to porphyrinemia

– Dehydration– Retinal damage– Bronze baby syndrome – skin

discoloration

Management ofJaundice and HDN• Intravenous Immunoglobulin

– For isoimmune hemolytic disease– Recommended when

• serum bilirubin levels are increasing despite phototherapy

• Serum levels become close to exchange levels

– Dose: 0.5-1.0 g/kg/dose– Shown to have decreased the need for

exchange transfusion

Mechanism of Actionof IVIg

Management ofJaundice and HDN• Double-Volume Exchange Transfusion

– If intensive phototherapy fails to reduce bilirubin levels to non-ET requiring range

– removes about 60% of bilirubin from the plasma, • clearance of about 30 -40 % of the total

bilirubin

Gomella. Neonatology: Management, Procedures, On-Call Problems, Diseases, and Drugs

Management ofJaundice and HDN• Other indications of ET

– Sepsis– DIC– Metabolic disorders leading to severe

acidosis– Severe fluid or electrolyte imbalance– Polycythemia

Management ofJaundice and HDN• Double-Volume Exchange Transfusion

– RBC units should be O, Rh-, or ABO/Rh type specific blood, compatible with the mother’s serum

Management ofJaundice and HDN• Complications

• metabolic acidosis• electrolyte imbalance• Hypoglycemia• infection

6 Hours Post-Transfusion

TB DB IB

6/17/13 11pm67th HOL

16.41 mg/dL 0.93 15.75 High risk zone

Na mmol/L130 - 145

K mmol/L3.7 – 5.9

iCal mg/dL3.9 – 6.0

6/17/13 11pm 135 3.70 3.72


6/17 11pm

164 50 9 0 78 13 8 1 188

Management ofJaundice and HDN

Prevention of HDN fromRH Incompatibility• Early identification

– Pre-/Antenatal identification of antigens (i.e. Blood typing)

• Avoid further sensitization– Indirect Coomb’s test– Anti-D immunoglobulin (RhoGAM)– Family Planning

Prevention ofRh Sensitization• Human anti-D globulin (RhoGAM)

– eliminate ≈ 10 mL of potentially antigenic fetal cells from the maternal circulation

Prevention ofRh Sensitization (ACOG)• Antenatal

– 300µg RhIG IM at 28 wks AOG (unless father is known to be RhD-

• Postpartum– 300µg after delivery

Prevention ofRh Sensitization (RCOG)• Antenatal

– 100µg RhIG IM at 28 wks AOG (unless father is known to be RhD-

– 100µg at 34 wks AOG• Postpartum

– 100µg after delivery

• Same protective rates but more visits

What is our Role?

The Role of theGeneral Pediatrician• Advise regular follow-up• Repeat blood typing

– Especially on the 90-120th day post-transfusion

• Vaccinations– May be given– Measles or MMRV may have to be

delayed

Blood Transfusion, IVIg,and VaccinationsRecommended intervals between administration of immune globulin preparations and measles- or varicella-containing vaccine

CDC “Pink Book” Epidemiology and Prevention of Vaccine-Preventable Diseases 12th ed. 2012

Patient Updates

• 4 months old – ~7kg• Has regular check-ups with her

attending pediatrician• Developmentally at par with age• No reports of recurrent jaundice or

anemia• Vaccinations are up-to-date

Summary

• Presented a case of a newborn who had early jaundice

• Discussed the approach on a jaundiced newborn

• Tackled on alloimmune hemolytic in the newborn, its manifestations, approach to diagnosis, treatment, and prevention

Thank You!

A Not So Minor Problem.. Presentor: Angelo Catacutan, MD, MBA Moderator: Dr. Carmela Kasala, MD Reactor: Dr. Joseph Vincent Alba, MD.

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