Serum and plasma are the pale yellow, liquid portions of blood, but they are fundamentally different substances used for distinct purposes in medicine and research. Both are derived directly from whole blood, a composite fluid made up of cellular components suspended in a liquid matrix. Understanding the difference requires focusing on how each liquid is separated from the cellular parts of the blood.
Defining Whole Blood and Plasma
Whole blood is composed of approximately 55% liquid and 45% blood cells, including red blood cells, white blood cells, and platelets. The liquid portion of this circulating blood is known as plasma. Plasma is a complex fluid made mostly of water, carrying dissolved proteins, hormones, nutrients, electrolytes, and waste products.
To isolate plasma in a laboratory setting, blood must be collected into a tube containing an anticoagulant chemical, such as ethylenediaminetetraacetic acid (EDTA) or heparin. This chemical prevents the blood from clotting immediately after it is drawn. The treated sample is then spun at high speed in a centrifuge, which separates the components by density.
The heavier blood cells settle at the bottom of the tube, while the lighter, straw-colored plasma rises to the top. Crucially, because clotting was prevented, plasma retains all proteins involved in the coagulation cascade. This includes a large protein called fibrinogen, which is necessary for the formation of a stable blood clot.
Defining Serum: The Key Difference
Serum is the liquid component that remains after whole blood has been allowed to clot naturally. Unlike the process for plasma, blood collected for serum separation is placed in a plain tube or one containing a clot-activating substance. The collected sample is left undisturbed for a period, typically 30 to 60 minutes, allowing the natural coagulation process to occur.
During this clotting time, the fibrinogen protein transforms into an insoluble mesh of fibrin, which traps the blood cells and forms a solid clot. This process effectively consumes the fibrinogen and several other clotting factors from the liquid portion. The clot is then separated from the liquid using a centrifuge.
The resulting liquid is serum, which is essentially plasma that has had its clotting factors removed and consumed by the coagulation process. This difference is the sole compositional distinction between the two liquids. While plasma contains fibrinogen, serum does not, making serum a cleaner sample for certain types of laboratory analysis. This process is analogous to how milk separates into solid curds and liquid whey.
Practical Applications in Testing
The presence or absence of clotting factors dictates whether a laboratory chooses serum or plasma for a diagnostic test. Plasma is required for any test that needs to analyze the blood’s ability to clot, such as coagulation studies that measure prothrombin time (PT) or activated partial thromboplastin time (aPTT). The intact clotting factors in the plasma sample are necessary to accurately measure the function of the coagulation cascade. Plasma is also often preferred for genetic testing because the use of anticoagulants ensures the sample is processed quickly without the time delay required for clotting.
Conversely, serum is the preferred sample type for the vast majority of routine clinical chemistry tests, including measuring electrolytes, glucose, cholesterol, and kidney function markers. Since the clotting factors have been removed, the sample is less likely to interfere with the sensitive chemical reactions used in these assays. Serum is also widely used in serology and immunology testing, which focuses on detecting antibodies and other immune proteins in the blood. The absence of fibrinogen provides a cleaner liquid sample that is less prone to causing instrumentation errors in automated laboratory analyzers.