When a blood sample is drawn, it is whole blood—a mix of cellular components and a liquid matrix. To analyze the body’s chemistry and function, laboratories must first separate this fluid component from the red blood cells, white blood cells, and platelets. This separation process yields one of two distinct liquid matrices: plasma or serum. While both liquids are used extensively in diagnostics, their preparation methods result in fundamental compositional differences. Understanding these differences is necessary for accurate interpretation of diagnostic results.
Defining Serum and Plasma
Plasma is the clear, straw-colored liquid portion of blood that remains when clotting is prevented in a collected sample. It is the natural, circulating fluid that makes up approximately 55% of the total blood volume in the body. Plasma acts as the primary transport system, carrying substances like dissolved proteins, electrolytes, hormones, nutrients, and metabolic waste products. Its general composition includes about 90% water.
Serum, in contrast, is the liquid that separates from the blood after the clotting process has naturally occurred. It is essentially plasma minus the components that were consumed and trapped in the resulting blood clot. Consequently, serum contains the same water, electrolytes, and non-clotting proteins as plasma, such as albumin and globulins. This slight difference in composition gives serum a pale yellow or clear transparent appearance.
How Preparation Determines Composition
The method used to manage the blood’s natural clotting cascade immediately following collection dictates whether a sample yields plasma or serum. Samples intended for plasma preparation are collected in specialized tubes containing a specific anticoagulant agent. These agents, which include ethylenediaminetetraacetic acid (EDTA), heparin, or citrate, work to prevent the formation of a clot. For example, EDTA and citrate prevent clotting by binding to the calcium ions necessary for the cascade to initiate.
Since the clotting cascade is chemically inhibited, all proteins and factors involved remain suspended in the liquid portion of the blood. Plasma thus retains all coagulation factors, most notably the protein fibrinogen. Fibrinogen is a large protein circulating in the blood, making up about 3% of the total plasma protein content. When anticoagulated whole blood is spun in a centrifuge, the cells settle, leaving the plasma layer with all clotting factors intact at the top.
Preparation of a serum sample requires the blood to be collected in a plain tube without an anticoagulant. The sample is then allowed to sit, typically for around 30 minutes, during which the clotting factors activate. During this natural process, soluble fibrinogen is converted into an insoluble mesh of fibrin strands. This fibrin mesh traps the blood cells and other clotting factors, forming the clot matrix at the bottom of the tube.
The liquid that separates from this solid clot is serum, which is therefore devoid of fibrinogen and other consumed clotting proteins. The absence of this specific protein is the most significant structural difference between the two liquids. Serum represents the remaining fluid after clotting components have been utilized and removed by the clotting process.
Diagnostic Utility and Specific Tests
The compositional difference between plasma and serum dictates which sample type is used for specific diagnostic tests. Plasma is required for any test measuring the function or concentration of clotting factors that serum lacks. Coagulation studies, such as the Prothrombin Time (PT) and Activated Partial Thromboplastin Time (aPTT), rely on these intact factors to assess a patient’s ability to clot. Citrate is the preferred anticoagulant for collecting plasma for these precise measurements.
Plasma is also favored for urgent analysis because it can be separated immediately following collection, bypassing the 30-minute waiting time required for serum to clot. This rapid processing is useful in emergency settings where time-sensitive results are necessary for patient care. Furthermore, specialized tests, such as those for circulating DNA or RNA, utilize plasma because the clotting process can alter the concentration of these analytes.
Serum is the preferred sample for most routine chemistry panels, metabolic screens, and hormone level testing. The absence of fibrinogen is advantageous because this protein can interfere with testing equipment, potentially clogging automated analyzers or causing errors in immunoassays. Tests commonly run on serum include measurements of blood sugar, cholesterol, electrolytes, and kidney function markers like creatinine.
The stability of certain analytes also makes serum the choice for long-term monitoring and testing for antibodies and other immune factors. While some analytes can be tested on either sample, diagnostic standards often mandate a specific sample type for accuracy and consistency. The decision between using plasma or serum ultimately depends on the specific substance being measured and the need to avoid interference from the clotting cascade or the anticoagulants used.