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Hemolytic disease of the newborn, (also known as HDN) is an alloimmune condition that develops in a fetus when the IgG antibodies produced by the mother and passing through the placenta include ones which attack the red blood cells in the fetal circulation. The red cells are broken down and the fetus can develop reticulocytosis and anemia. The fetal disease ranges from mild to very severe and fetal death from heart failure - hydrops fetalis - can occur. When the disease is moderate or severe many erythroblasts are present in the fetal blood and so these forms of the disease can be called erythroblastosis fetalis (or erythroblastosis foetalis),
Symptoms
After delivery bilirubin is no longer cleared (via the placenta) from the neonates blood and the symptom of jaundice (yellowish skin and yellow discolouration of the whites of the eyes) increase within 24 hours after birth. Pallor, enlarged liver and/or spleen, generalized swelling, respiratory distress, petechiae and purpura may be present in a severe form of hydrops fetalis. The infant may be stillborn or die shortly after birth.
Causes
There are three ways in which a woman becomes sensitised toward (i.e., able to produce IgG antibodies against) a particular blood type:
- Fetal-maternal hemorrhage can occur due to ruptures in the placenta during pregnancy, childbirth, medical procedures carried out during pregnancy that breach the uterine wall, abortion or trauma. On subsequent pregnancies, if there is a similar incompatibility in the fetus these antibodies are then able to cross the placenta into the fetal bloodstream to attach to the red blood cells and cause hemolysis. In other words, if a mother has anti-RhD (D being the major Rhesus antigen) IgG antibodies as a result of previously carrying a RhD positive fetus, this antibody will only affect a fetus with RhD positive blood.
- Therapeutic blood transfusion with an incompatible blood type. Suggestions have been made that women of child bearing age or young girls should not be given a transfusion with Rhc positive blood or Kell1 positive blood to avoid possible sensitization. This would require a lot of extra work in blood transfusion departments and it is currently considered uneconomical to screen for these blood groups.
- The third sensitisation model can occur in women of blood type O. The immune response to A and B antigens, that are widespread in the environment, usually leads to the production of IgM anti-A and IgM anti-B antibodies early in life, but sometimes IgG (as opposed to the usual IgM) antibodes are produced. In contrast, Rhesus antibodies are generally not produced from exposure to environmental antigens.
Examples of serological diagnosis
- ABO system
- ABO hemolytic disease of the newborn can range from mild to severe, but generally it is a mild disease.
- anti-A antibodies
- anti-B antibodies
- ABO hemolytic disease of the newborn can range from mild to severe, but generally it is a mild disease.
- Rhesus system
- rhesus D hemolytic disease of the newborn (often called Rh disease) is the commonest form of severe HDN. The disease varies from mild to severe.
- rhesus E hemolytic disease of the newborn is a mild disease
- rhesus c hemolytic disease of the newborn can range from a mild to severe disease - is the third most common form of severe HDN
- rhesus e hemolytic disease of the newborn - rare
- rhesus C hemolytic disease of the newborn - rare
- antibody combinations (ie anti-Rhc and anti-RhE antibodies occurring together) - can be severe
- (the Rh d antigen and Rh d antibodies do not exist)
- Kell system
- anti-Kell hemolytic disease of the newborn
- anti-K 1 antibodies - disease ranges from mild to severe - over half of the cases are caused by multiple blood transfusions - is the second most common form of severe HDN
- anti-K 2 ,anti-K 3 and anti-K 4 antibodies - rare
- anti-Kell hemolytic disease of the newborn
- Other blood group antibodies (Kidd, Lewis, Duffy, MN, P and others).
Diagnosis
The diagnosis of HDN is based on history and laboratory findings:
Blood tests done on the newborn baby
- Biochemistry tests for Jaundice
- Peripheral blood morphology shows increased reticulocytes. Erythroblasts (also known as nucleated red blood cells) occur in moderate and severe disease.
- Positive direct Coombs test (may be negative after fetal interuterine blood transfusion)
- Positive indirect Coombs test
Treatment
Before birth, options for treatment include intrauterine transfusion or early induction of labor when pulmonary maturity has been attained, fetal distress is present, or 35 to 37 weeks of gestation have passed. The mother may also undergo plasma exchange to reduce the circulating levels of antibody by as much as 75%. After birth, treatment depends on the severity of the condition, but could include temperature stabilization and monitoring, phototherapy, transfusion with compatible packed red blood, exchange transfusion with a blood type compatible with both the infant and the mother, sodium bicarbonate for correction of acidosis and/or assisted ventilation. Rhesus negative mothers who have had a pregnancy with/are pregnant with a rhesus-positive infant are given Rh immune globulin (RhIG) during pregnancy and after delivery to prevent sensitisation to the D antigen. It works by binding any fetal red cells with the D antigen before the mother is able to produce an immune response and form anti-D IgG. A drawback to pre-partum administration of RhIG is that it causes a positive antibody screen when the mother is tested which is indistinguishable from immune reasons for antibody production.
Complications
Complications of HDN could include kernicterus, hepatosplenomegaly, inspissated (thickened or dried) bile syndrome and/or greenish staining of the teeth, hemolytic anemia and damage to the liver due to excess bilirubin.
Similar Conditions
Similar conditions include acquired hemolytic anemia, congenital toxoplasma and syphilis infection, congenital obstruction of the bile duct and cytomegalovirus infection.
References
- Geifman-Holtzman O, Wojtowycz M, Kosmas E, and Artal R. Female allo-immunization with antibodies known to cause hemolytic disease. Obstetrics and Gynecology 1997 89, 272-275
- Mollison PL, Engelfriet CP and Contreras M. Blood Transfusion in Clinical Medicine. 1997. 10th edition. Blackwell Science, Oxford, UK.
See also
External links
Hematology Transfusion medicine | Blood disorders Pediatrics Obstetrics
"Hemolytic disease of the newborn"