Rh Blood Group System PDF

Chapter 7  PowerPoints are a general overview and are provided to help students take notes over the video lecture ONLY. ◦ PowerPoints DO NOT cover the details needed for the Unit exam  Each student is responsible for READING the TEXTBOOK for details to answer the UNIT...

Chapter 7  PowerPoints are a general overview and are provided to help students take notes over the video lecture ONLY. ◦ PowerPoints DO NOT cover the details needed for the Unit exam  Each student is responsible for READING the TEXTBOOK for details to answer the UNIT OBJECTIVES  Unit Objectives are your study guide (not this PowerPoint)  Test questions cover the details of UNIT OBJECTIVES found only in your Textbook! 1  Over 60 antigenic specificities  After stillborn delivery, mother transfused with husband’s blood of the same ABO type.  Had hemolytic transfusion reaction  Another antibody?  Landsteiner isolated antibody – named “Rh” because of rhesus monkey cells  HDN (erythroblastosis fetalis)  Hemolytic Transfusion Reaction 2  Four sets of nomenclatures  Two based on genetic mechanisms  Third describes only presence or absence of antigen  Fourth is the combined efforts of the International Society of Blood Transfusion (ISBT)  Antigens of system produced by three closely linked sets of alleles  Each gene responsible for producing an antigen on the RBC surface  Each antigen and corresponding gene given the same letter designation ◦ When referring to gene, letter is italicized 3  D, d, C, c, E, e ◦ No “d” has been found – amorph ◦ Codominant expression  Phenotype defined by presence of D, C, c, E, e expression  Inherit a set of Rh genes from each parent (DCe/Dce)  Combination of maternal and paternal forms genotype Gene Com White Black Native Am Asian DCe 42 17 44 70 dce 37 26 11 3 DcE 14 11 34 21 Dce 4 44 2 3 dCe 2 2 2 2 dcE 1 0 6 0 DCE 0 0 6 1 dCE 0 0 0 0 4  d does not represent an antigen, but the absence of the D antigen  C, c, E, e represent actual antigens recognized by specific antibodies  Rare ◦ May not express C, c, E, e ◦ Rhnull (---/---) expresses no antigens  Weiner believed that gene responsible for defining Rh actually produced an agglutinogen that contained a series of blood factors  Rh gene produces at least three factors within the agglutinogen considered to be phenotypic expression of the haplotype 5  Agglutinogen Rh0 Factor Rh0 Rh0 gene hr1 RBC Factor hr1 Surface Factor hr11 hr11 Antibody will recognize each factor within the agglutinogen  Weiner Fisher-Race ◦ R D ◦ r absence of D ◦ Single prime (1) refers to C ◦ Double prime (11) refers to E ◦ r precedes h refers to C or E  (rh1 or rh11 ) ◦ h precedes r refers to c or e  (hr1 or hr11 )  SHORTHAND IS NOW USED (DO NOT MEMORIZE THIS VERSION) 6  Gene Autoag Blood fac. Shorthand Fisher-Race Rh0 Rh0 Rh0hr1hr11 R0 Dce Rh1 Rh1 Rh0rh1hr11 R1 DCe Rh2 Rh2 Rh0hr1rh11 R2 DcE Rhz Rhz Rh0rh1rh11 Rz DCE rh rh hr1hr11 r dce rh1 rh1 rh1hr11 r1 dCe rh11 rh11 hr1rh11 r11 dcE rhy rhy rh1rh11 ry dCE  Assigns a number to each antigen  No genetic basis  A minus sign preceding a number designates the presence or absence of antigens  If not sero-typed – number will not appear  Phenotype is described 7  Rh1 D  Rh2 C  Rh3 E  Rh4 c  Rh5 e  Example: Rh: 1,2,3,-4,-5 ◦ Good for electronic data processing Universal Language – use with computers  Nomenclature both eye and machine readable  Six-digit number for each blood group specificity  First three numbers represent system – 004  Each antigen in Rh system given a unique number  See table 7-4 on page 153-154 8   Be familiar with Fisher-Race, Weiner, Rosenfield, and ISBT nomenclature  Be able to translate among them  Review tables 7-4 and 7-6  Nonglycosylated protein (no carbohydrate)  Transmembrane  Gene products for the Rh system are similar to the H antigen  85% of population is Rh positive – D antigen is present  15% of population is Rh negative – D antigen is absent 9  Rh gene located on chromosome 1  Rh gene inherited as codominant  Two closely linked genes control expression of Rh (crossover rare) ◦ One codes for presence or absence of D ◦ One codes for Ce, cE, ce, or CE  Precursor substances are building blocks Dce/dce DcE/dce Dce/DcE Dce/dce dce/DcE dce/dce 10  Weak D - Du ◦ Rh-positive red cells are expected to give a strong reaction anti-D ◦ Certain RBC’s must be carried through the antiglobulin phase to demonstrate the presence of the D antigen ◦ ALL NEGATIVE D REACTIONS ARE CARRIED THROUGH COOMBS  Inheritance of D genes that code for a weakened expression of D  Seen most frequently in blacks  Rarely found in whites 11  Position effect or gene interaction effect  Allele carrying D is trans to allele carrying C ◦ Dce/dCe ◦ The trans arrangement of D and C appears to interfere with the expression of the D  Weakened D does not occur when D and C are cis  Found only after making anti-D  One or more parts of D is missing ◦ Persons who typed D produced an anti-D that reacted with all D cells ◦ Explained by Wiener  Lack one or more epitopes on D antigen, can make alloantibody to the missing fraction if exposed to RBC’s that have complete D antigen 12   It helps to understand what causes weak D and why some with weak D make anti-D  No differentiation in weak D status is made in blood bank  Donors and patients are classified simply as Rh+ or Rh-  Anti-D made by D-mosaic persons can cause HDN and HTR  Once anti-D is identified – Rh negative blood is always used for transfusion  Essential when testing Donor Bloods  Considered Rh positive if D or weak D is positive  All D negative must be taken through the Coombs phase  If Coombs is negative, person is considered to be Rh-  If Coombs is positive, person is considered to be Rh+ 13  Controversial ◦ Recipients with C trans weak D and genetic weak D will have complete D antigen ◦ Recipients with D-mosaic is so low, supply of Rh negative blood so precious that a weak D should be given Rh positive blood ◦ Each transfusion service decides ◦ No regulatory requirements  Critical  All Rh-negative and weak D are candidates for Rh immune globulin  Rh-negative mother with a weak D newborn must be assessed to the need for Rh immune globulin 14  If HDN is suspected in the newborn, it is sometimes difficult to access the Rh type due to a “Blocking Phenomenon” ◦ Newborn’s cells are coated with maternal IgG, anti- D in utero there will be few antigen sites to react with reagent anti-D  Resolve by preforming an Elution and retesting ◦ Elution is the removal of antibody off the red cells and then retest the serum with anti-D. ◦ If positive, it verifies the newborn is D-positive  First recognized in saline (IgM)  Most are IgG ◦ React optimally at 370 C or after AHG  Produced after exposure of immune system to Rh antigen ◦ Pregnancy ◦ Transfusion  Anti-D is the most potent 15  D>c>E>C>e Exposure to less than 1 mL of Rh positive RBC’s can stimulate antibody production in Rh negative person  IgM Rh antibodies formed first  Transition to IgG ◦ IgG1, and IgG3 are greatest significance  Persist for years  Will experience an anamnestic response  Antigen negative blood must be given to patients with history of Rh sensitization 16   Rh antibodies do not bind complement ◦ To bind complement, two IgG molecules must attach to an RBC antigen in close proximity. ◦ Since Rh antigens are not close, when the antibody does attach, intravascular hemolysis does not occur. ◦ RBC destruction resulting from Rh antibodies is extravascular of RBC’s instead  Rh antibodies cross placenta  Rh antigens develop early in fetal life  Coat fetal red cells  Fetal cells are positive for DAT in HDN  Until Rh-immunoglobulin, Rh was most frequent cause of HDN 17   Monoclonal anti-D now available  Usually contain both IgM and IgG to maximize visualization at immediate spin and as well as at Coombs phase  Must be performed with strict adherence to manufacturer’s direction and proper use of controls  Rh Control is always used with anti-D to be sure patient’s cells are not agglutinating any other components of the reagent.  Transfusion reactions ◦ Circulating antibody within 120 days of primary exposure ◦ 2 to 7 days after second exposure  Rh HTR’s result in extravascular destruction of antibody coated RBC ◦ Unexplained fever ◦ Mild bilirubin elevation ◦ Decrease in hemoglobin and haptoglobin  DAT positive – may not have circulating antibodies ◦ Elution studies helpful in defining the antibody specificity 18  Rhnull Syndrome ◦ Demonstrates  mild hemolytic anemia  Reticulocytosis  Stomatocytosis  Decrease in hemoglobin and hematocrit  Increase in Hgb F  Increase in haptoglobin  Elevated bilirubin ◦ Severity is highly variable ◦ Must transfuse with Rhnull cells only  Rhmod ◦ Phenotype exhibit features similar to Rhnull ◦ Clinical symptoms less severe ◦ Other blood group antigen expression may be depressed in both Rhnull and Rhmodl 19  Similar to Rh  Anti LW reacts strongly with most D + cells  Weakly, if at all, with Rh- cells  Two systems are genetically related  Exist but not responsible for mechanisms of LW  Determines the antigens carried on a red blood cell using serologic methods.  The “phenotype” of any blood group refers to the detectable antigens on the RBCs.  Phenotyping is used in blood banking in four main settings: For blood donors, to determine compatibility for a patient with an alloantibody For blood donors, to identify donors with uncommon phenotypes For patients, to determine which antigens the patient lacks in order to prevent future antibody formation For patients, to confirm that the patient is negative for an antigen to which he has formed an antibody 20  See the phenotypic reaction patterns below; determine the possible genotype in Fisher-Race.  Then convert to the Wiener shorthand D C E c e + + - + +  In this example, the patient has D, C, c and e but no E.  To determine the Fisher Race genotype, you will put together the possible sets of antigens (on both sides) that could give this phenotype.  Based on this phenotype, these are the possible genotypes:  Fisher Race: Wiener: 1. DCe/Dce 1. R1R0 2. DCe/dce 2. R1r 3. Dce/dCe 3. R0r’  Do NOT use duplicate sets  For example: Dce/DCe is the same as 1 (just reversed) so it is not counted  READ the TEXTBOOK for the details to answer the UNIT OBJECTIVES.  USE THE UNIT OBJECTIVES AS A STUDY GUIDE  All test questions come from detailed material found in the TEXTBOOK (Not this PowerPoint) and relate back to the Unit Objectives 21