Blood Group Systems

There are 29 blood group systems, among which the ABO group is the most important. Blood groups are determined by antigens that are surface markers on the RBC and consist of proteins and carbohydrates. Antigens are also found on platelets, leukocytes, and tissue cells and also exist in soluble form in body secretions such as breast milk, seminal fluid, saliva, sweat, gastric secretions, urine, and amniotic fluid. Individuals will naturally develop antibodies (Abs) against the ABO antigens they do not have. For this reason, determining an individual’s blood group is important prior to any blood product transfusion and prior to donating or receiving an organ transplant. If appropriate matching does not happen, a massive activation of the immune system and coagulation cascade will ensue, leading to shock, organ failure, and even death.

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ABO Blood Group

Antigens

There are 4 common blood groups in the ABO system: A, B, AB, and O.

  • These blood groups are defined by the presence of specific antigens on RBCs.
    • Blood group A: antigen A
    • Blood group B: antigen B
    • Blood group AB: antigens A and B
    • Blood group O: no antigens
  • A and B antigens consist of specific carbohydrate sugars:
    • N-acetylgalactosamine for the A antigen 
    • D-galactose for the B antigen 
    • Both of these sugars bind to and modify the H antigen on the surface of RBCs.
    • If the H antigen is left unmodified, the resulting blood group is O. 
  • There are over 80 ABO alleles: The most common are A1, A2, B1, O1, O1v, and O2.
Blood groups - antigens

Diagram showing the carbohydrate chains that determine the ABO blood group

Image: “ABO blood group system”. License: CC BY-SA 4.0

Inheritance

Blood-type frequencies vary in different racial/ethnic groups. The ABO blood type is inherited in an autosomal codominant fashion:

  • The A and B alleles are codominant.
  • The O allele is recessive.
Table: Inheritance pattern for ABO blood group
Mother A Mother B Mother O
Father A AA AB AO
Father B BA BB BO
Father O OA OB OO
Table: Alleles and blood types
Alleles Blood type
A + A A
A + O A
A + B AB
B + B B
B + O B
O + O O
The dominant alleles are A and B; when both of them are present, the individual has the blood type AB. The recessive allele is O.

Antibodies

Individuals will naturally develop antibodies (Abs) against the ABO antigens they do not have:

  • Individuals with blood group A have anti-B Ab.
  • Individuals with blood group B have anti-A Ab.
  • Individuals with blood group O will have both anti-A and anti-B Abs.

These Abs can elicit a hemolytic response upon encountering their respective antigen:

  • An ABO-incompatible blood transfusion can be fatal.
  • A universal RBC donor has type O blood.
  • A universal plasma donor has type AB blood.

Associated risks

Blood groups are associated with differential risk to certain diseases. Blood group O may have ↓ risk for: 

  • Pancreatic cancer 
  • Thromboembolic disease
  • Malaria
Blood-type antigens

Diagram showing that a person may express A, B, AB, or no antigen at all:
The diagram also describes the type of antibody produced by the carrier.

Image: “ABO blood group antigens present on red blood cells and IgM antibodies present in the serum” by InvictaHOG. License: Public Domain

Rh Factor

Definition

Rh factor (Rhesus factor) is an RBC surface antigen.

  • Encoded by the 2 genes RHD and RHCE:
    • ↑ Polymorphism: Numerous genetic rearrangements produce distinct Rh antigens.
    • 50 Rh group antigens (5 are important)
  • 85% of people carry the D allele: They are Rh+. 
  • 15% do not carry it: They are Rh–.
  • Rh– persons do not carry anti-Rh Ab unless they are exposed to Rh+ RBCs.

Rh incompatibility

Anti-Rh Abs occur when:

  • Rh– blood is transfused into Rh+ person:
    • Causes an acute hemolytic reaction
    • Results in a mild hemolytic anemia
  • Rh– pregnant mother is exposed to Rh+ fetal RBCs:
    • Secondary to fetomaternal hemorrhage from abortion, trauma, invasive obstetric procedures, or normal delivery
    • Mother produces Abs against the baby’s RBCs. 
    • Abs are IgG and cross the placenta. 
    • Abs can cause hemolysis to the fetus (also called hemolytic disease of the newborn or erythroblastosis fetalis).
    • Anti-D Ig is administered to sensitized women after pregnancy to avoid this reaction.

If fetus is Rh+ and the mother Rh–, serial monitoring during pregnancy is needed and is accomplished by:

  • Serial indirect Coombs test in mother
  • Measurement of fetal blood flow velocity in middle cerebral artery by Doppler
Hemolytic reaction symptoms

Signs and symptoms of acute hemolytic transfusion reactions

Image: “Main symptoms of acute hemolytic reaction” by Mikael Häggström. License: Public Domain, edited by Lecturio.

Other Blood Groups

Kell system

  • 3rd most potent immunogenic antigen after ABO and Rh system
  • 25 Kell antigens have been discovered.
  • Defined by the immune Ab anti-K
  • Anti-K Ab causes:
    • Severe hemolytic disease of the fetus and newborn
    • Hemolytic transfusion reactions

Duffy system

  • Duffy antigen was 1st isolated from a patient with hemophilia.
  • Also known as Fy glycoprotein
  • 2 alleles exist: 
    • Fya
    • Fyb
  • There are 4 possible phenotypes: 
    • Fy(a+b–)
    • Fy(a+b+)
    • Fy(a–b+)
    • Fy(a–b–)
  • Nonspecific receptor for chemokines and the malaria parasite Plasmodium vivax
  • Associated Abs are IgG and can cause hemolytic transfusion reactions.

Kidd system

  • Kidd antigen (Jk antigen) acts as an urea transporter in RBC and renal endothelium.
  • 3 antigens have been identified to date: 
    • Jka
    • Jkb
    • JK3
  • Kidd Ab can cause severe transfusion reactions.

Complications of Blood Transfusion

Complications of blood transfusion can be acute (minutes to hours) or delayed (days to months).

Acute

  • Hemolytic reaction:
    • Immediate: 
      • Due to IgM antibodies against RBCs
      • Typically of the ABO group
    • Delayed: IgG antibodies are not present during transfusion but develop later. 
    • Nonimmune: 
      • Due to aged RBCs
      • Improper storage
      • Transfusion along noncompatible medications 
      • Transfusion through small-bore IV tubes
  • Infection:
    • Bacterial
    • Viral: HIV, hepatitis C virus, hepatitis B virus, human T-lymphotropic virus 1 or 2
  • Allergic reaction:
    • Mild: hives, pruritus
    • Severe, leading to anaphylaxis:
      • Hypotension
      • Bronchospasm 
      • GI symptoms
      • Systemic organ failure
    • Due to sensitization to antigens in the donor unit, especially plasma proteins
  • Transfusion-related acute lung injury (TRALI):
    • Within 6 hours after transfusion 
    • Causes noncardiogenic pulmonary edema with severe hypoxemia
    • Diagnosis requires no other risk factors for acute lung injury.
    • Due to activation of recipient’s immune system by anti-HLA or anti-neutrophil Ab
  • Acute febrile nonhemolytic reaction: 
    • ↑ Body temperature by 1°F (-17°C) within 24 hours after blood transfusion
    • More frequent with: 
      • Repeated transfusions
      • Pregnancy
    • Due to release of Ab-mediated endogenous pyrogens and cytokines
  • Circulatory overload: 
    • Due to rapid transfusion of large volume of blood products
    • ↑ Risk:
      • Underlying cardiopulmonary disease
      • Renal failure
      • Chronic anemia
      • Elderly patients 
    • Signs and symptoms include:
      • ↑ HR, dyspnea, cough 
      • ↑ Central venous pressure, widened pulse pressure 
      • Chest radiography shows cardiomegaly and pulmonary edema.

Delayed

  • Iron overload:
    • In patients who receive blood long term and regularly
    • 1 unit of RBC = 200 mg of iron
    • Iron accumulation can occur and is toxic for tissues and organs.
    • Management: iron chelation
  • Graft-versus-host disease:
    • Due to proliferation of donor’s lymphocytes, which attack recipient’s tissues and organs
    • Symptoms include: 
      • Rash, fever, diarrhea, liver dysfunction, and pancytopenia 
      • Symptoms occur 1–6 weeks after transfusion
    • Fatal in > 90% of cases
    • ↑ Risk in: 
      • Immunocompromised 
      • History of Hodgkin disease
      • History of stem cell transplantation
      • History of solid tumors treated with cytotoxic drugs
      • Intensive chemotherapy
      • Blood transfusion from relative (shared HLA haplotypes)

References

  1. Avent, N. D., & Reid, M. E. (2000). The Rh blood group system: a review. Blood, 95(2), 375–387. Retrieved August 31, 2021, from https://pubmed.ncbi.nlm.nih.gov/10627438/
  2. Mitra, R., Mishra, N., & Rath, G. P. (2014). Blood groups systems. Indian journal of anaesthesia, 58(5), 524–528. Retrieved August 31, 2021, from https://pubmed.ncbi.nlm.nih.gov/25535412/
  3. Moise KJ. (2021). RhD alloimmunization in pregnancy: Management. UptoDate. Retrieved August 31, 2021, from https://www.uptodate.com/contents/rhd-alloimmunization-in-pregnancy-management
  4. Sharma, S., Sharma, P., & Tyler, L. N. (2011). Transfusion of blood and blood products: indications and complications. American family physician, 83(6), 719–724. Retrieved August 31, 2021, from https://pubmed.ncbi.nlm.nih.gov/21404983/
  5. Seltsam A., et al. (2003). The nature of diversity and diversification at the ABO locus. Blood 102(8), 3035–3042. Retrieved August 31, 2021, from https://pubmed.ncbi.nlm.nih.gov/12829588/
  6. Salem, L. (2017). Rh Incompatibility. Emedicine. Accessed August 31, 2021, from: https://emedicine.medscape.com/article/797150-overview
  7. Baur, A. (2018). Erythrocyte alloimmunization and pregnancy. Emedicine. Retrieved August 31, 2021, from https://emedicine.medscape.com/article/273995-overview
  8. Sandler, G. (2021). Transfusion reactions. Emedicine. Retrieved August 31, 2021, from https://emedicine.medscape.com/article/206885-overview#:~:text=significant%20clinical%20symptoms.-,Nonhemolytic%20febrile%20reactions,1%C2%BA%20C%20or%202%C2%BA%20F.

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