What Is It, Purpose, and More

Author:Anna Hernández, MD

Editors:Alyssa Haag,Emily Miao, PharmD,Kelsey LaFayette, DNP, ARNP, FNP-C

Illustrator:Jessica Reynolds, MS

Copyeditor:Stacy M. Johnson, LMSW

What is agglutination?

Agglutination, which refers to the clumping of particles together, is an antigen-antibody reaction that occurs when an antigen (i.e., a molecule capable of triggering the adaptive immune response) is mixed with its corresponding antibody at a suitable pH and temperature. These antibodies are called agglutinins because they bind multiple antigens together and form a lattice-like structure seen as clumping by the naked eye. 

The first step in the agglutination process is the attachment of the specific antibody to the corresponding antigen. IgM antibodies react best at cold temperatures, usually between 4 to 22ºC, whereas IgG antibodies react best at warm temperatures, typically around 37ºC. Their preference for differing temperatures is why IgM is also called “cold agglutinins” and IgG “warm agglutinins.” For agglutination to occur, the ratio of antigen to antibody must be similar; otherwise, clumping will not happen. Excessive amounts of antigens or antibodies in the solution may prevent agglutination; a phenomenon called prozone and postzone effect, respectively.

Clumping blood in a test tube.

What is the purpose of agglutination?

The purpose of agglutination is to detect the presence of specific antigens or antibodies in samples of bodily fluids, such as blood, saliva, urine, or cerebrospinal fluid (CSF); as well as to identify specific strains of bacteria in microbiological cultures. One of the most common applications of agglutination in clinical practice is blood typing, where the donor and recipient’s blood is typed and crossmatched to prevent hemolytic transfusion reactions, which often occur in ABO blood group incompatibility. In this situation, the recipient’s preformed antibodies attack the donor red blood cells, resulting in their destruction or hemolysis

During blood typing, serum with known anti-A and anti-B antibodies is mixed with an individual’s red blood cells. If an agglutination reaction occurs, the red blood cells tested have that specific antigen—the A or B glycoprotein—on their surface. For example, if the anti-A serum is mixed with an individual’s red blood cells and an agglutination reaction occurs but does not when mixed with anti-B serum, that person has blood type A. Similarly, if an agglutination reaction occurs when mixed with anti-A and anti-B serum, that person has blood type AB. The same process can be done with anti-Rh (D) serum to determine the person’s Rh status.

Agglutination tests are also commonly used in the serological diagnosis of several infections and to type specific strains of bacteria that may be causing an infection.

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What is the difference between agglutination and aggregation?

The difference between agglutination and aggregation is that agglutination occurs due to an antigen-antibody reaction, whereas aggregation involves clumping due to platelet-to-platelet interaction. Platelet aggregation allows platelets to rapidly aggregate at the site of injury to form a platelet plug that can help stop the bleeding in case of injury.

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Related links

Blood groups and transfusions
Warm autoimmune hemolytic anemia and cold agglutinin (NORD)
ELISA (Enzyme-linked immunosorbent assay)

Resources for research and reference

Fischbach, F. T., Fischbach, M., & Stout, K. (2021). Fischbach’s A manual of laboratory and diagnostic tests (11th ed.). Wolters Kluwer Health.

Ryan, K. J., Ray, C. G., Ahmad, N., Drew, W. L., & Plorde, J. J. (2010). Sherris Medical Microbiology (5th ed.). McGraw-Hill Medical.

Sue Katz, D. (2011). Bacterial Agglutination Protocol.