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• Her serum also reacted from 80 out of 104 ABO-compatible donors
• Dr. Philip Levine and Rufus Stetson described an HTR on an obstetrical patient after delivering a stillborn infant which then father had something in common that the mother lacked


  1939
• The concern on blood types were only limited to ABO

  1930’s (Before 1939)
• Dr. Levine found in over 90% of erythroblastosis fetalis cases, that the mother was Rh-negative, and the father was Rh-positive

  1941
• “Fisher-Race” or “DCE term” was proposed by Sir Fisher in 1941, where he suggested that Antigens of the system were produced by 3 closely linked set of alleles, each gene responsible for producing an antigen on the RBC surface
• The name “Rh” was retained for the human-made antibody, while the anti-Rhesus produced by animals was renamed “anti-LW” in honor of Dr. Landsteiner and Dr. Wiener
• It was then thought that the fetus and the

  mother had different blood types
• The plus and/or minus beside the blood groups indicates that it is an Rh Positive and/or Negative
• A mother required transfusion and had her husband be the donor because they have the same ABO blood type
• Dr. Karl Landsteiner and Dr. Alexander S. Wiener reported an antibody made by a guinea pig and rabbits when transfused with the Rhesus macaque monkey RBC’s

  1940
• It was at this time also when they correctly concluded that the mother from the previous case they encountered had been immunized by the fetus, which carried an antigen inherited from the father
• Despite correct ABO match, people were wondering there are still mortality and morbidity problems
• An antibody was isolated from the mother’s serum that reacts on both 37C and 20C with the father’s RBC
• Reports about Hemolytic Transfusion Reactions (HTR) and Hemolytic Disease of Fetus and Newborn (HDN) were present during this time
• HDN was first described by a French midwife in a set of twins where one was hydropic and stillborn, while the other twin was jaundiced and died of kernicterus
• The antibody reacted also on 85% of humans RBC’s and then the antigen that caused the formation of the newly found antibody was named, “Rh” after the Rhesus monkey
• It was the maternal antibody that caused the erythroblastosis fetalis
• Terminologies related to Rh blood group

  • Sir Ronald Aylmer Fisher and Dr. Robert Russell race
• Antigens of the Rh system were produced by 3 closely linked set of alleles. Each gene was responsible for producing an antigen on the RBC surface
• Rh phenotype was reported in order of "DCE" because Dr. Fisher thought the C/c locus lies between D/d and E/e loci


  1946
• Dr. Alexander Weiner believed there was 1 gene responsible for defining Rh that produced an agglutinogen containing a series of blood factors
• The "Alphanumeric Terminology" assigns a number to each antigen of the Rh system in order of its discovery or recognized relationship to the Rh system
• In 1941, Fisher named C and c antigens based on the reactivity of two antibodies, and used D and E to define the antigens recognized by two additional antibodies
• Antigens defining Rh phenotype

  • D
  • C
  • c
  • E
  • e
  • d
• Placing parenthesis around (D), (C), and (e) indicates a weakened antigen expression
• Dr. Weiner's Rh-hr Terminology includes factors R, r, 1, 2, 0, Z, y, ', and "
• Fisher-Race terminology was followed for written communication
• Each person inherits a set of Rh genes from each parent (One D or d, one C or c, and one E or e) because the Rh genes were once thought to be codominant
• The "Alphanumeric Terminology" simply demonstrates the presence or absence of the antigen on the RBC
• Gene frequencies of common Rh antigens in Caucasians

  • D = 85%
  • d = 15%
  • C = 70%
  • E = 30%
  • c = 80%
  • e = 98%
• Richard Rosenfield and Coworkers introduced a new "Alphanumeric Terminology" for Rh group in 1962
• A minus sign preceding the number designates absence, and the number is omitted if the antigen was not tested
• In 1943, Sir Fisher proposed that each gene was responsible for producing an antigen on the RBC surface
• RHAG gene codes for “Rh-associated glycoprotein” (Rh50 glycoprotein)
• The ISBT terminology is not commonly used due to the need to memorize a lot of numbers
• Patricia Tippett (1997) based Rh on two Rh genes – “RHD” and “RHCE”
• One reason Richard Rosenfield and his coworkers developed the “Alphanumeric Terminology” and the ISBT is that when using the Weiner Terminology, more antigens will be discovered in the future
• The International Society of Blood Transfusion Committee (ISBT) formed a committee on terminology for Red Cell surface antigens to establish a uniform nomenclature that is both eye and machine-readable and in keeping with the genetic basis of blood groups
• Two theories on Rh genetic control were initially given: Wiener theory and Fisher-Race theory
• During blood cell maturation, the least known ancestor of our cells is identified by the CD34+ marker