Blood is a complex tissue composed of cellular elements suspended within a liquid matrix. This liquid portion transports vital proteins, nutrients, hormones, and waste products throughout the body. When isolated, this liquid component is separated as either plasma or serum. The distinction between them is fundamental to clinical biology and diagnostic testing, and it lies entirely in how the blood sample is handled after collection.
How Plasma is Prepared
The preparation of blood plasma begins by collecting whole blood into a tube that contains a specific anticoagulant chemical. Anticoagulants, such as ethylenediaminetetraacetic acid (EDTA), sodium citrate, or heparin, prevent clotting by interfering with the coagulation cascade.
Since coagulation is actively inhibited, all the proteins involved in clotting remain suspended in the liquid sample. The tube is then subjected to centrifugation, where it is spun at high speeds. This force separates the components by density, causing the heavier red and white blood cells and platelets to settle at the bottom. The straw-colored liquid supernatant, which is the plasma, is then carefully extracted.
How Serum is Prepared
The process for preparing serum is defined by the deliberate absence of an anticoagulant. Whole blood is collected into a plain tube and allowed to sit undisturbed to permit natural clotting. During this time, the body’s natural clotting factors are activated, forming a solid clot composed of blood cells trapped within a fibrin mesh.
After the clot has fully formed, the sample is centrifuged to compress the clotted mass. The liquid that separates from the clot is the serum, which is then removed for analysis. This preparation ensures the final liquid product is free of the cells and the proteins consumed during coagulation.
The Defining Molecular Difference
The difference in preparation results in the defining molecular distinction: the presence or absence of the protein fibrinogen. Plasma contains fibrinogen, a large, soluble protein central to forming a blood clot. Because an anticoagulant was used, fibrinogen remains intact and dissolved in the plasma fluid.
Serum, however, lacks fibrinogen because this protein was converted into its insoluble form, fibrin, to create the clot during preparation. Serum is essentially plasma stripped of its clotting factors. The final serum fluid contains water, electrolytes, antibodies, hormones, and other proteins like albumin, but it is missing coagulation proteins.
The absence of fibrinogen means serum is a purer, more stable fluid for certain types of laboratory assays. Plasma, retaining the clotting proteins, is considered a more complete representation of the blood’s liquid state in vivo.
Why Preparation Affects Medical Use
The choice between plasma or serum depends entirely on the specific substances a laboratory intends to measure. Plasma is mandatory for coagulation studies, such as prothrombin time (PT) or activated partial thromboplastin time (aPTT), because these tests rely on measuring the function of intact clotting factors. Plasma is also necessary for therapeutic use, such as blood transfusions, where the recipient requires the full spectrum of clotting proteins.
Serum is generally the preferred sample for measuring concentrations of various biochemical analytes, including hormones, antibodies, electrolytes, and most proteins. For these tests, the presence of fibrinogen is considered a potential interference that can clog or interfere with automated laboratory equipment. Serum samples offer cleaner results for routine chemistry panels.