Rh Negative History

The rhesus blood type named after the rhesus monkey was first discovered in 1937 by Karl Landsteiner and Alexander S. Wiener. The significance of the discovery was not immediately apparent and was only realized in 1940, after subsequent findings by Philip Levine and Rufus Stetson. This serum that led to the discovery was produced by immunizing rabbits with red blood cells from a rhesus macaque. The antigen that induced this immunization was designated by them as Rh factor to indicate that rhesus blood had been used for the production of the serum.

In 1939, Phillip Levine and Rufus Stetson published in a first case report the clinical consequences of non-recognized Rh factor, hemolytic transfusion reaction and hemolytic disease of the newborn in its most severe form. It was recognized that the serum of the reported woman agglutinated with red blood cells of about 80% of the people although the then known blood groups, in particular ABO were matched. No name was given to this agglutinin when described. In 1940, Karl Landsteiner and Alexander S. Wiener made the connection to their earlier discovery, reporting a serum that also reacted with about 85% of different human red blood cells.

Based on the serologic similarities Rh factor was later also used for antigens, and anti-Rh for antibodies, found in humans such as the previously described by Levine and Stetson. Although differences between these two sera were shown already in 1942 and clearly demonstrated in 1963, the already widely used term “Rh” was kept for the clinically described human antibodies which are different from the ones related to the rhesus monkey. This real factor found in rhesus macaque was classified in the Landsteiner-Wiener antigen system (antigen LW, antibody anti-LW) in honor of the discoverers. It was recognized that the Rh factor was just one in a system of various antigens. Based on different models of genetic inheritance, two different terminologies were developed; both of them are still in use.

The clinical significance of this highly immunizing D antigen (i.e. Rh factor) was soon realized. Some keystones were to recognize its importance for blood transfusion including reliable diagnostic tests, and hemolytic disease of the newborn including exchange transfusion and very importantly the prevention of it by screening and prophylaxis.

The discovery of fetal cell-free DNA in maternal circulation by Holzgrieve et al. led to the noninvasive genotyping of fetal Rh genes in many countries.

More to come …


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