Blood Groups & Typing

Antigens and Antibodies

Blood group antigens and antibodies are essential for distinguishing self from non-self and play a critical role in transfusion medicine and immune responses.

• Antigens (agglutinogens): Unique molecules on the surface of red blood cells (RBCs) that are recognized by the immune system. Foreign antigens can trigger an immune response.

• Antibodies (agglutinins): Proteins secreted by immune cells in response to foreign antigens. They bind specifically to antigens and can cause agglutination (clumping) of RBCs.

• Agglutination: The process where antibodies bind to antigens on RBCs, causing them to clump together. This is the basis for blood typing and transfusion reactions.

Blood Group Antigens

The specific antigens present on the surface of RBCs determine an individual's blood type. The most clinically significant blood group systems are the ABO and Rh systems.

• Type O: Most common blood type; lacks both A and B antigens.

• Type AB: Rarest blood type; has both A and B antigens.

ABO Blood Typing

The ABO system classifies blood based on the presence or absence of A and B antigens on RBCs and corresponding antibodies in plasma.

Blood Typing Procedure

Blood typing involves mixing a blood sample with anti-A and anti-B sera to observe agglutination, which indicates the presence of specific antigens.

Transfusion Reaction

If incompatible blood is transfused, antibodies in the recipient's plasma bind to donor RBC antigens, causing agglutination and hemolysis. This can block blood vessels and lead to kidney failure or death.

Clinical Case Example

Errors in blood typing or organ matching can have fatal consequences, as illustrated by the tragic case of Jesica Santillan, who received mismatched organs (Type O recipient, Type A donor).

Other Blood Groups

There are over 100 other blood group antigens (e.g., MN, Duffy, Kell, Kidd, Lewis), but these rarely cause transfusion reactions compared to ABO and Rh systems.

Rh Group

The Rh (D) antigen is another major blood group antigen. Individuals with the antigen are Rh positive (Rh+); those without are Rh negative (Rh-). Rh antibodies are not naturally present but can form after exposure to Rh+ blood.

• 85% of white Americans are Rh+; 99% of Asians are Rh+.

• Rh- individuals can develop anti-D antibodies after exposure (e.g., transfusion or pregnancy).

Hemolytic Disease of the Newborn (HDN)

HDN occurs when an Rh- mother develops anti-D antibodies after exposure to Rh+ fetal blood, which can attack the RBCs of a subsequent Rh+ fetus, causing anemia and neurological damage. Prevention involves administering RhoGAM to Rh- mothers.

Universal Donors and Recipients

• Universal donor: Type O- (lacks A, B, and Rh antigens).

• Universal recipient: Type AB+ (lacks anti-A, anti-B, and anti-Rh antibodies).

Leukocytes (White Blood Cells, WBCs)

General Features

Leukocytes are immune cells that protect the body against pathogens. They have a conspicuous nucleus, mature in lymphoid organs, and migrate from blood to connective tissues. Normal count: 5,000–10,000/μL.

Classification of Leukocytes

Leukocytes are classified as granulocytes or agranulocytes based on the presence of cytoplasmic granules.

Agranulocytes

• Lymphocytes: Round, dark blue nucleus; produce antibodies; include B cells, T cells, and natural killer cells.

• Monocytes: Large, kidney-shaped nucleus; differentiate into macrophages; increase in viral infections and inflammation.

Granulocytes

• Neutrophils: Pale lilac granules, 3–5 lobed nucleus; increase during bacterial infections.

• Eosinophils: Red-orange granules, bilobed nucleus; increase with allergies and parasitic diseases.

• Basophils: Large, dark violet granules, S-shaped nucleus; granules contain heparin and histamine.

Leukopoiesis and Leukocyte Disorders

Leukopoiesis

Leukopoiesis is the process of white blood cell formation from hematopoietic stem cells in the bone marrow.

Leukocyte Disorders

• Leukopenia: Low WBC count (<5,000/μL); increases risk of infection.

• Leukocytosis: High WBC count (>10,000/μL); often due to infection, allergy, or disease.

• Leukemia: Cancer of hematopoietic tissue; uncontrolled WBC production disrupts normal cell percentages and impairs clotting.

Platelets and Hemostasis

Platelets

Platelets are small cell fragments (2–4 μm) derived from megakaryocytes. They play a vital role in hemostasis and have a lifespan of 5–9 days. Normal count: 130,000–400,000/μL.

Platelet Functions

• Plug small injuries to blood vessels

• Secrete clotting factors

• Release serotonin (vasoconstriction)

• Dissolve old clots

• Attract WBCs

• Phagocytize bacteria

Thrombopoiesis (Platelet Production)

Platelets are produced from megakaryocytes in the bone marrow. Stem cells differentiate into megakaryoblasts, which become megakaryocytes. Cytoplasmic fragments of megakaryocytes enter the bloodstream as platelets.

Hemostasis

Hemostasis is the process of stopping bleeding. It involves three main steps:

1. Vascular spasm: Vasoconstriction reduces blood flow.

2. Platelet plug formation: Platelets adhere to exposed collagen and aggregate.

3. Coagulation: Fibrin forms a mesh that traps blood cells, forming a stable clot.

Coagulation Pathways

Blood coagulation occurs via two pathways:

• Extrinsic pathway: Triggered by external trauma; rapid (12–15 seconds).

• Intrinsic pathway: Triggered by internal vessel damage; slower (30–45 seconds).

• Both pathways require calcium ions (Ca2+).

Completion of Coagulation

The final steps of coagulation involve the conversion of prothrombin to thrombin, which then converts fibrinogen to fibrin, forming the clot. Thrombin also accelerates its own formation (positive feedback).

Fate of Blood Clots

After clot formation, clot retraction occurs within 30 minutes. Fibrinolysis (clot dissolution) is mediated by plasmin, a fibrin-dissolving enzyme. This process is also regulated by positive feedback.

Prevention of Inappropriate Clotting

• Platelet repulsion: Platelets do not adhere to undamaged endothelium.

• Thrombin dilution: Rapid blood flow prevents clot formation; slow flow (e.g., in shock) increases risk.

• Natural anticoagulants: Heparin inhibits thrombin formation.

Coagulation Disorders

• Embolus: A clot traveling in a vessel.

• Thrombosis: Abnormal clotting in unbroken vessels, often in leg veins of inactive people.

• Pulmonary embolism: A clot that travels to the lungs.

• Infarction: Tissue death due to blocked blood supply (e.g., myocardial infarction, stroke).

• Prevention: Aspirin, heparin, and warfarin (Coumadin) are used to reduce clot risk.

Disseminated Intravascular Coagulation (DIC)

DIC is a pathological process involving widespread clotting and bleeding due to consumption of clotting factors and platelets. Causes include pregnancy, cancers, and septicemia.

Hemophilia

Hemophilia is a genetic disorder (often X-linked recessive) characterized by a deficiency of clotting factors, leading to excessive bleeding and pain. Treatment involves transfusion of plasma or purified clotting factors.