Kernicterus and Hydrops Fetalis Overview

Kernicterus

• A rare neurological disorder
• Characterized by excessive bilirubin in the blood (hyperbilirubinemia)
• Bilirubin is a breakdown product of hemoglobin
• Normally, unconjugated bilirubin is bound to albumin and processed in the liver
• If not processed, it accumulates in the brain, causing damage
• Unconjugated bilirubin crosses the blood-brain barrier, damaging neuronal membranes
• Symptoms appear 2-5 days after birth
• Can lead to muscle tone problems, respiratory difficulties, and other neurological complications

Hydrops Fetalis

• Caused by fluid accumulation in two or more fetal areas, leading to swelling
• Affected areas can include skin, lungs (pleural effusion), and the heart (pericardial effusion)
• Severe anoxia (lack of oxygen) can result
• Diagnosed using ultrasound

Laboratory Testing for Hemolytic Disease of the Newborn (HDN)

• Maternal Antibody Screening: Check for antibodies; if anemia suspected, proceed to further tests
• Fetal Blood Count (FBC): Assess for low hemoglobin (Hb), low hematocrit, high reticulocytes (immature red blood cells), high Lactate Dehydrogenase (LDH), high unconjugated bilirubin, and low albumin
• ABO and RhD Typing: Type the baby's blood group. If RhD negative, no further action needed. If RhD positive, perform a Kleihauer-Betke test
• Direct Antiglobulin Test (DAT/Direct Coombs Test): Detects maternal antibodies bound to fetal red blood cells (RBCs) – diagnostic for HDN
• Indirect Antiglobulin Test (IAT/Indirect Coombs Test): Detects maternal antibodies in serum; used for prevention of HDN; if antibodies are present, risk of HDN is predicted.

Clinical Presentations of HDN

• Pale yellow skin (jaundice)
• Splenomegaly (enlarged spleen)
• Kernicterus
• Hydrops fetalis

Results of FBC and Blood Film, HDN

• Low HB
• Low hematocrit
• High reticulocytes
• High LDH
• High unconjugated bilirubin
• Low albumin
• Nucleated red blood cells on blood film
• Microcytic cells (small red blood cells)

Coombs Test

• Also known as the antiglobulin test
• Used to detect antibodies attacking red blood cells
• Direct Coombs Test: Diagnoses HDN. Detects maternal anti-D antibodies already bound to fetal RBCs
• Indirect Coombs Test: Used in prevention of HDN. Detects anti-D antibodies in the mother's serum; presence of antibodies indicates risk of HDN.

Kleihauer-Betke Acid Elution Test

• Quantifies fetal hemoglobin (HbF) in maternal blood
• Fetal Hb resists acid elution; adult Hb does not
• Maternal blood sample is analyzed and stained; ratio of fetal to adult red blood cells is calculated.
• Negative results indicate no further testing; positive results trigger confirmatory tests if fetal-maternal hemorrhage exceeds 2 ml.

Fetal-Maternal Hemorrhage Quantification by Flow Cytometry

• Measures RhD+ fetal cells in the maternal circulation
• RhD+ fetal cells fluoresce under a special light
• Used to detect fetal-maternal hemorrhage in Rh-negative mothers with Rh-positive fetuses only

Prevention of HDN

• Anti-D prophylaxis (RhoGAM)
• Administered at 28-30 weeks of pregnancy and after delivery of an Rh-positive baby to prevent mother from developing antibodies against Rh-positive blood cells

ABO Incompatibility, Clinical and Lab Findings

• Mild Clinical Presentation: Normocytic anemia, jaundice
• Laboratory Diagnosis:
  • Complete Blood Count (CBC): Low Hb, low hematocrit, normal Mean Cell Volume (MCV) due to compensatory reticulocyte production
  • Direct Coombs Test: Weakly positive
  • Blood film: Shows spherocytes (spherical red blood cells)

Treatments for HDN

• Treat Anemia: Blood transfusions
• Phototherapy: Treat jaundice by exposing skin to blue-green light, converting unconjugated bilirubin to water-soluble form
• Intravenous Fluids
• Ventilator: To assist breathing

Fetal-Maternal Hemorrhage Mechanism

• Rh-negative mother with Rh-positive father
• Fetal-maternal hemorrhage in the first pregnancy
• Mother becomes sensitized (develops antibodies) to the Rh-positive blood, but IgM antibodies don't cross placenta
• Subsequent pregnancies, IgG antibodies form quickly and attack fetal RBCs, causing hemolysis
• Antibodies diffuse through the placenta, coating fetal RBCs; macrophages phagocytose and lyse these cells, causing hemolysis and release more unconjugated bilirubin
• Extramedullary hematopoiesis (production of blood outside the bone marrow) may occur

Summary of Pathogenesis of HDN

• Antigen-antibody interaction leading to hemolysis
• Anemia limits oxygen delivery to fetal tissues and organs, causing anoxia
• Antibody-coated RBCs (red blood cells) removed from the fetal circulation by macrophages in the spleen and liver

Antibody Absorption Mechanism

• Fetal immunization occurs when maternal antibodies enter fetal circulation via the placenta
• Fetal absorption of maternal IgG towards the end of pregnancy, a protective mechanism, can lead to lysis of fetal red cells

Mechanisms of RhD HDN

• Antibody absorption
• Fetal-Maternal Hemorrhage (FMH)

Causes of HDN

• Antibodies to the ABO system are a frequent cause
• Example: Mother with blood group O, fetus with A, B, or AB blood group
• Rh incompatibility (Rh HDN) is a more severe cause than ABO incompatibility.