Dr. Dina Garniasih, SpA, Mkes.

Hematologic physiology of the newborn

Normal development: The physiologic anemia of infancy In utero the fetal aortic O2 saturation is 45%; erythropoietin levels are high, RBC production is rapid, and reticulocyte values are 3 to 7%. After birth the O2 saturation is 95%, and erythropoietin is undetectable. RBC production by day 7 is < 1/10 the level in utero. Reticulocyte counts are low, and the Hb level falls.

normal development: The physiologic anemia of infancy

At 8 to 12 weeks Hb nadir O2 delivery to the tissue is impaired, erythropoietin production is stimulated, and RBC production increases. Active erythropoiesis iron stores are rapidly utilized. The reticuloendothelial system has adequate iron for 15 to 20 weeks in term infants.

Anemia of prematurity
RBC mass is decreased at birth. The Hb nadir is reach earlier, because:

RBC survival is decreased. There is a relatively more rapid rate of

growth. Vit E deficiency is common.

anemia of prematurity

Erythropoietin is produced by:

Term infant at a Hb level of 10-11 g/dL Premature infant at a Hb level of 7 to 9 g/dL.

Iron administration before the age of 10-14 weeks does not increase the nadir of the hemoglobin level or diminish its rate of reduction. Once the nadir is reached RBC production is stimulated an iron stores are rapidly depleted because less iron is stored in premature infant.

Etiology of anemia in the neonate

BLOOD LOSS:
/normal Ht /normal reticulocyte count Normal bilirubin level

Obstetric cause of blood loss, including malformations of plasenta and cord Occult blood loss:

Fetomaternal bleeding Fetoplacental bleeding Twin-to-twin transfusion

etiology of anemia in the neonate

HEMOLYSIS
Ht reticulocyte bilirubin level

Immune hemolysis:

Rh incompatibility ABO incompatibility Minor blood group incompatibility Maternal disease

etiology of anemia in the neonate

Bleeding in the neonatal period:

Intracranial bleeding
Massive cephalhematoma Retroperitoneal bleeding

Ruptured liver or spleen

Adrenal or renal hemorrhage Gastrointestinal bleeding

Bleeding fromumbilicus

Iatrogenic cause

etiology of anemia in the neonate

Hereditary RBC disorders:

RBC membran defects
Metabolic defect Hemoglobinopathies

Acquired hemolysis:
Infection bacterial or virus DIC

Vit E deficiency or other nutritional anemias

Microangiopathic hemolytic anemia

etiology of anemia in the neonate

DIMINISHED RBC PRODUCTION
Ht reticulocyte normal bilirubin level

Diamond-Blackfan syndrome Congenital leukemia or other tumor Infections, especially rubella and parvovirus Osteopetrosis, leading to inadequate erythropoiesis Physiologic anemia or anemia of prematurity

Diagnostic approach to anemia in the newborn

The family history The obstetric history The physical examination:

Acute blood loss Chronic blood loss Chronic hemolysis

Complete blood count Reticulocyte count Blood smear

Diagnostic approach to anemia in the newborn

Coombs test and bilirubin level Apt test on gastrointestinal blood of uncertain origin Kleihauer-Betke preparation of the mothers blood. Ultrasound of abdomen and head Test on parents Studies for infection Bone marrow (rarely used)

Therapy
TRANSFUSION Indications for transfusion:
Infants with significant respiratory disease or

CHD Healthy, asymptomatic newborns will selfcorrect a mild anemia Infants with ABO incompatibility who do not have an exchange transfusion may have protracted hemolysis Premature babies may have be quite comfortable with hemoglobin levels of 6.5 to 7.0 mg/dL

therapy

Blood products and methods of transfusion

Packed RBCs Whole blood

Exchange transfusion with packed RBCs

Irradiated or frozen RBCs Direct-donor transfusion

Transfusing stored red blood cells from a

single unit reserved for an infant.

therapy
PROPHYLAXIS Term infant should be sent home from hospital on iron-fortified formula (2 mg/kg per day) if they are not breastfeeding. Premature infants (preventing or ameliorating the anemia of prematurity).
Iron supplementation in the preterm infant

prevents late iron deficiency.

therapy
Mothers milk or formulas similar to mothers

milk Vitamin E (15 to 25 IU of water-soluble form) is given daily until the baby is 38 to 40 weeks postconceptional age These infants should be followed carefully Recombinant human erythropoietin (REPO)

RHESUS ISOIMMUNIZATION
Clinical Features Anemia, mild to severe Jaundice (indirect hyperbilirubinemia)
Presents during first 24 hours. May cause kernicterus

(1) Exchange transfusion (2) Factors that predispose to the development of kernicterus at lower levels of bilirubin prematurity, hypoproteinemia, metabolic acidosis, drugs (sulfonamides, caffeine, sodium benzoate), and hypoglycemia.

rhesus isoimmunization
Hepatosplenomegaly; varies with severity. Petechiae (only in severely affected infants). Severe illness with birth of infant with hydrops fetalis, stillbirth, or death in utero and delivery of a macerated fetus. Late hyporegenerative anemia with absent reticulocytes.

rhesus isoimmunization
Laboratory Findings Serologic abnormalities (incompatibility between blood group of infant and mother; direct Coombs test positive in infant; mothers serum has the presence of immune antibodies detected by the indirect Coombs test) Hb level, reticulocyte count, smearincreased nucleated red cells, marked polychromasia, and anisocytosis indirect bilirubin level.

rhesus isoimmunization
Management Antenatal Patients should be screened at their first antenatal visit for Rh and non-Rh antibodies. If an immune antibody is detected in the mothers serum, proper management includes the following:
Obtain past obstetric history and outcome of

previous pregnancies. Determine blood group and conduct indirect Coombs test (to determine the presence and titer of irregular antibodies).

 Determine zygosity of the father

Examination of the amniotic fluid for

spectrophotometric analysis of bilirubin. The following are indications for amniocentesis: a. History of previous Rh disease severe enough to require an exchange transfusion or to cause stillbirth. b. Maternal titer of anti-D, anti-c, or anti-Kell (or other irregular antibodies) of 1:8 to 1:64 or greater by indirect Coombs test or albumin titration and depending on previous history.

Postnatal Hyperbilirubinemia exchange transfusion. phototherapy

In hydropic infant at birth:

Adequate ventilation. Partial exchange transfusion. Double-volume exchange transfusion.

Clinical signs suggesting kernicterus at any time at any bilirubin level are an indication for exchange transfusion.

Prevention of Rh Hemolytic Disease

Rh hemolytic disease can be prevented by the use of Rh Ig at a dose of 300 mg, which is indicated in the following circumstances: For all Rh-negative, Rh0 (Du)-negative mothers who are unimmunized to the Rh factor. For all unimmunized Rh-negative mothers who have undergone spontaneous or induced abortion. After ruptured tubal pregnancies in unimmunized Rh-negative mothers Following any event during pregnancy that may lead to transplacental hemorrhage or antepartum hemorrhage in unimmunized Rh-negative women Following tubal ligation or hysterotomy after the birth of an Rhpositive child in unimmunized Rh-negative women. Following chorionic villus sampling at 1012 weeks gestation. In these patients 50 mg of Rh immunoglobulin should be given.

ABO Isoimmunization
Clinical Features Jaundice (indirect hyperbilirubinemia) usually within first 24 hours; may be of sufficient severity to cause kernicterus Anemia Hepatosplenomegaly.

ABO Isoimmunization
Diagnosis Hemoglobin decreased Smear: spherocytosis in 80% of infants, reticulocytosis, marked polychromasia Elevated indirect bilirubin level Demonstration of incompatible blood group
Group O mother may have an infant who is group A

or B. Rarely, mother may be A and baby B or AB or mother may be B and baby A or AB.

Direct Coombs test on infants red cells usually positive

ABO Isoimmunization

Demonstration of antibody in infants serum

These antibodies can be demonstrated by

the indirect Coombs test in the infants serum using adult erythrocytes possessing the corresponding A or B antigen. Antibody can be eluted from the infants red cells and identified.

Demonstration of antibodies in maternal serum.

ABO Isoimmunization
Treatment Antenatal management or premature delivery is not required. After delivery controlling the hyperbilirubinemia by frequent determination of unconjugated bilirubin levels, with a view to the need for phototherapy or exchange transfusion. Whole blood.