Rh factor, Rhogam and ABO blood groups

  1. Rhesus blood group system. Named after Rhesus monkey where it was discovered.rho-gam Consists of many antigens, positive/negative refers to D antigen. Incompatibility between mother and fetus causes Rhesus disease. Rh-negative mother produces antibodies that attack rh-positive fetus’s blood
  2. Five isotypes or classes. Each is prefixed with “Ig” meaning immunoglobulin (antibody). IgA, IgD, IgE, IgG, IgM. IgG is the only antibody that can cross the placenta. This confers passive immunity to the fetus during pregnancy and shortly after.
  3. Rhesus disease, RhD Hemolytic Disease of the Newborn. Most common cause of severe hemolytic disease of the newborn. Hemo (blood) + lysis (destruction), i.e. rupturing of erythrocytes (RBC). IgG molecules produces by the mother pass through the placenta and attack fetal RBC’s. HDN: exposure of Rh-negative mother to Rh-positive red blood cells of the fetus, causing production of antibodies which cross the placenta and attack the fetal RBCs.
  4. Occurs by 2 main mechanisms. Most common: Rh-negative pregnant mother is exposed to Rh-positive fetal red blood cells after fetomaternal hemorrhage during pregnancy from abortion, trauma, invasive procedure, or delivery. Rh-positive blood transfusion.
  5. Rh positive fetal blood enters the maternal circulation of an Rh-negative mother. Amount needed to produce incompatibility varies. One study showed that less than 1 mL was needed, other showed that 30% of people never develop incompatibility regardless of volume.Maternal immune system initially produces immunoglobulin M (IgM) antibodies against Rhesus D antigen. (not a problem)

Later, IgG antibodies are produced that can cross the placenta (problem). Takes about one month for these antibodies to equilibrate in the fetal circulation. First child is therefore usually unaffected. Second child is mildly anemic, children after that are seriously affected. Antibodies cross the placenta into the fetal circulation and attach to Rh antigens on RBC’s. Then lysed by lysosomal enzymes released by macrophages and natural killer lymphocytes.

Incidence is sharply reduced when coupled with ABO incompatibility, most likely due to destruction of fetal blood cells before maternal antibodies can develop.

  1. Most frequently caused by child birth (90%). In some cases, can be caused by other event (abortion, trauma, amniocentesis, etc.). There is not always an apparent sensitizing event.
  2. Only 15% of the population are Rh-negative. Sensitization occurs in 1/1000 birth, higher incidence in the Southwest US. Only 17% of pregnant women with Rh-negative blood who are exposed to Rh-positive fetal blood cells develop Rh antibodies. Approximately 15-20% of Caucasians have Rh-negative, 5-10% of African Americans, and less than 5% of Chinese and American Indian descent.
  3. History: – Rh blood type of mother and father. – Previous pregnancies. – Previous administration of Rh IgG (RhoGAM). – Mechanism of injury in case of maternal trauma during pregnancy. – Presence of vaginal bleeding and/or amniotic discharge. – Previous invasive obstetric procedures. – Fetal-maternal hemorrhage may occur without symptoms or evidence of trauma. High index of suspicion, low threshold for treatment
    1. Thorough pelvic examination. If abdominal/pelvic trauma is a consideration, inspect for bruising that may suggest fetomaternal hemorrhage. When infant of Rh-negative mother is delivered, perform thorough physical examination and consult a neonatal clinician immediately. Findings may vary from mild jaundice to extreme pallor and anemia with hydrops fetalis.
    2. Laboratory Studies. Always determine Rh blood type of pregnant female. Ultasonography is limited to pelvic ultrasonography. Fetal ascites, soft tissue edeme are definite signs. Rosette screening test can detect alloimmunization caused by fetomaternal hemorrhage. If positive, Kleihauer-Betke can give a more precise quantification and is used to determine dosage of RhoGAM. Positive direct Coombs test result confirms diagnosis of antibody-induced hemolytic anemia. Elevated serum bilirubin measurerments, low hematocrit, and elevated reticulocyte in neonate can determine if early exchange transfusion is necessary. Required for infants born with erythroblastosis fetalis, hydrops fetalis, or kernicterus.
    3. If mother is Rh-negative and has not been sensitized previously, administer Rh IgG (RhoGAM). If already sensitized, Rh IgG is of no value. When infant with Rh Incompatibility is delivered, needs respiratory and hemodynamic stabilization, possibly emergent exchange transfusion and phototherapy.
  4. Commercial name of Rho(D) immune globulin. Consist of IgG containing a high titer of antibodies against Rh(D) antigen on surface of red blood cells. MOA: Rho(D) immune globulin binds Rho antigens, preventing sensitization. Indicated whenever fetal red blood cells are known to suspected to have netered the circulation of an Rh-negative mother. Given intramuscularly. T1/2 of 21-29 days. Toxicity: injection-site discomfort, low grade fever. Systemic reactions are extremely rare but myalgia, lethargy, and anaphylactic schock have been reported. Very effective, reduces risk from around 17% down to less than 0.1%

Alloimmunization prevention — Women who are Rh(D)-negative and unsensitized should receive Rh(D)-immune globulin following surgical evacuation or upon diagnosis if medical management or EM is planned. A dose of 50 mcg is effective through the 12th week of gestation due to the small volume of red cells in the fetoplacental circulation (mean red cell volume at 8 and 12 weeks is 0.33 mL and 1.5 mL, respectively), although there is no harm in giving the standard 300 microgram dose, which is more readily available

ABO Blood group system:abo-blood-group

  • The four blood types (A, B, AB, and O) and also a Rh +/- distinction
    • Unlike ABO blood types, Rh factor is not determined by a carbohydrate side chain. It is an actual protein.
    • For example, the antigens of the ABO blood group are sugars. They are produced by a series of reactions in which enzymes catalyze the transfer of sugar units. A person’s DNA determines the type of enzymes they have, and, therefore, the type of sugar antigens that end up on their red blood cells.
    • Antigens of the Rh blood group are proteins. A person’s DNA holds the information for producing the protein antigens. The Rh D gene encodes the D antigen, which is a large protein on the red blood cell membrane.
    • ABO alloimmunization occurs in about 15% of all pregnancies and 4% of these are prenatal (prenatal = 0.6% of all pregencies)
    • Hydrops fetalis due to ABO alloimmune is rare and clinically significant hemolysis is uncommon as less than 0.1 percent of infants with evidence of hemolysis will require exchange transfusions.
    • Important to note is that ABO alloimmunization can occur in the first pregnancies because your body develops A and/or B antigens (whichever types they don’t have) through food and bacteria at 3 to 6 months old