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Blood type is determined by the presence or absence of specific antigens on the surface of red blood cells. The ABO system — the most important for transfusion compatibility — is governed by three alleles (Iᴬ, Iᴮ, i) at a single locus, producing four blood types: A, B, AB, and O. The Rh blood group system adds the D antigen, creating Rh-positive (D antigen present) or Rh-negative (D antigen absent) designations. Incompatible blood transfusions trigger severe and potentially fatal hemolytic reactions mediated by pre-formed antibodies (for ABO) or antibodies developed after sensitization (for Rh).

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The ABO Blood Group System

The ABO gene encodes a glycosyltransferase enzyme that adds specific sugar residues to the H antigen on red blood cell surfaces. Type A: Iᴬ allele adds N-acetylgalactosamine → A antigen; anti-B antibodies in plasma. Type B: Iᴮ allele adds galactose → B antigen; anti-A antibodies in plasma. Type AB: Both antigens; no ABO antibodies. Type O: Non-functional enzyme; only H antigen; both anti-A and anti-B antibodies.

ABO Inheritance

Iᴬ and Iᴮ are codominant; both are dominant over i (recessive). Genotypes: AA or Ai → Type A; BB or Bi → Type B; AB → Type AB; ii → Type O. ABO blood typing is used in paternity testing, forensics, and organ transplant matching.

The Rh Blood Group

The Rh(D) antigen is encoded by the RHD gene. Rh+ individuals (about 85% of the population) carry at least one functional RHD allele. Rh− individuals lack functional RHD. Unlike ABO, Rh antibodies are not naturally present — they form only after Rh+ red cell exposure (transfusion or pregnancy).

Hemolytic Disease of the Newborn (HDN)

An Rh− mother carrying an Rh+ fetus may develop anti-D antibodies after exposure to fetal blood during delivery. In subsequent Rh+ pregnancies, these antibodies cross the placenta and destroy fetal RBCs, causing hemolytic disease. RhoGAM (anti-D immunoglobulin) given at 28 weeks and delivery prevents maternal sensitization.

Glossary

ABO Blood Group System
A classification of blood types based on the presence or absence of A and B antigens on red blood cell surfaces, determined by codominant Iᴬ and Iᴮ alleles and a recessive i allele.
Rh(D) Antigen
A red blood cell surface protein encoded by the RHD gene; individuals carrying this antigen are Rh-positive; its absence (Rh-negative) can cause immune sensitization after exposure to Rh+ blood.
Hemolytic Disease of the Newborn (HDN)
A condition caused by maternal antibodies crossing the placenta and destroying fetal red blood cells; most commonly due to Rh(D) or ABO incompatibility between mother and fetus.

Frequently Asked Questions

ABO blood type is determined by which version (allele) of the ABO gene you inherit from each parent. The Iᴬ allele codes for an enzyme that adds the A antigen to red blood cells; Iᴮ adds the B antigen; the i allele produces a nonfunctional enzyme (no A or B antigen). Type A = Iᴬ Iᴬ or Iᴬ i; Type B = Iᴮ Iᴮ or Iᴮ i; Type AB = Iᴬ Iᴮ; Type O = ii.

The Rh factor refers to the RhD antigen on red blood cells. Rh-positive individuals (about 85% of the population) have this antigen; Rh-negative individuals lack it. Rh compatibility matters for blood transfusions — giving Rh+ blood to an Rh− recipient triggers anti-D antibody formation. In pregnancy, Rh incompatibility between an Rh− mother and Rh+ fetus can cause hemolytic disease of the newborn in subsequent pregnancies.

Type O negative blood is the universal donor for red blood cells — it lacks A, B, and D antigens, so it cannot trigger ABO or Rh hemolytic reactions in most recipients. In emergencies when the patient's blood type is unknown, O negative is used. Type AB positive is the universal recipient — AB patients have no ABO antibodies and can receive A, B, or O blood, and being Rh+ means they can receive Rh+ blood without risk.

Type B patients have anti-A antibodies naturally present in their plasma. Transfusing type A red cells (which carry A antigens) would trigger an acute hemolytic transfusion reaction — the anti-A antibodies bind to the donated red cells, activating complement and causing rapid intravascular hemolysis. This can cause kidney failure, disseminated intravascular coagulation (DIC), and death. ABO compatibility is the first check in blood banking.