Hemolytic disease of the newborn (anti-Kell)

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Synonyms and keywords: Anti-Kell1

Overview

Hemolytic disease of the newborn is the second most common cause of severe hemolytic diseases of newborns (HDN) after Rh disease. Anti-Kell1 is becoming relatively more important as prevention of Rh disease is becoming more and more effective.

Pathophysiology

Hemolytic disease of the newborn (anti-Kell1 is caused by a mis-match between the Kell antigens of the mother and fetus. About 91% of the population are Kell1 negative and about 9% are Kell1 positive. A fraction of a percentage are homozygous for Kell 1. Therefore, about 4.5% of babies of a Kell1 negative mother are Kell1 positive.

The disease results when maternal antibodies to Kell1 are transferred to the fetus across the placental barrier. These antibodies can cause severe anemia by interfering with the early proliferation of red blood cells as well as causing alloimmune hemolysis. Very severe disease can occur as early as 20 weeks gestation. Hydrops fetalis can also occur early. The finding of anti-Kell antibodies in an antenatal screening blood test (indirect Coombs test) is an indication for early referral to a specialist service for assessment, management and treatment.

Anti-Kell2, anti-Kell3 and anti-Kell4 antibodies

Hemolytic disease of the newborn can also be caused by anti-Kell2, anti-Kell3 and anti-Kell4 IgG antibodies. These are rarer and generally the disease is milder.

Causes

Mothers who are negative for the Kell1 antigen develop antibodies after being exposed to red blood cells that are positive for Kell1. Over half of the cases of hemolytic disease of the newborn owing the anti-Kell antibodies are caused by multiple blood transfusions, with the remainder due to a previous pregnancy with a Kell1 positive baby.

Medical Therapy

It can be detected by routine antenatal antibody screening blood tests (indirect Coombs test) in a similar way to Rh disease. The treatment of hemolytic disease of the newborn (anti-Rhc) is similar to the management of Rh disease.

Primary Prevention

Suggestions have been made that women of child bearing age or young girls should not be given a transfusion with Kell1 positive blood. Donated blood is not currently screened (in the U.S.A.) for the Kell blood group antigens as it is not considered cost effective at this time.

It has been hypothesized that IgG anti-Kell1 antibody injections would prevent sensitization to RBC surface Kell1 antigens in a similar way that IgG anti-D antibodies (Rho(D) Immune Globulin) are used to prevent Rh disease, but the methods for IgG anti-Kell 1 antbodies have not been developed at the present time.

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
  • Wiener CP, and Widness JA. Decreased fetal erythropoiesis and hemolysis in Kell hemolytic anemia. American Journal of Obstetrics and Gynecology. 1996 174: 547-55

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