The terms plasma and serum are often used interchangeably, leading to confusion. Both are yellowish liquid portions derived from blood, but they are fundamentally distinct in their composition. The difference between these two substances is determined entirely by one biological process: blood clotting. Understanding this distinction is important for medical diagnostics and therapeutic applications.
Whole Blood: The Shared Source Material
Whole blood is a complex fluid that circulates throughout the body and is the source material for both plasma and serum. It is a mixture of formed elements suspended in a liquid matrix, consisting of roughly 55% liquid and 45% cellular components. The formed elements include red blood cells (for oxygen transport), white blood cells (for immune defense), and platelets (which initiate clotting).
The liquid matrix suspending these cellular components is plasma. This straw-colored fluid is mostly water, carrying dissolved proteins, electrolytes, hormones, and nutrients. To obtain a sample for analysis, the cellular components must be separated from this liquid portion.
Plasma vs. Serum: Understanding the Key Difference
The core difference between plasma and serum lies in the presence of specific proteins involved in coagulation. Plasma is the liquid component collected when clotting is actively prevented. This requires adding an anticoagulant chemical, such as EDTA or heparin, immediately after the blood sample is drawn. The sample is then spun down in a centrifuge, separating the cellular components and leaving the liquid plasma layer on top.
Because clotting was prevented, plasma retains all coagulation factors, including fibrinogen. Fibrinogen is a protein converted into fibrin, which forms the structure of a blood clot. Plasma is defined as the liquid portion of blood that contains all clotting factors intact.
In contrast, serum is the liquid portion that remains after the blood has been allowed to clot naturally. No anticoagulant is added, allowing the clotting cascade to activate and consume fibrinogen and other clotting proteins. These proteins become trapped within the solid clot mass alongside the blood cells.
When this clotted sample is centrifuged, the solid clot settles at the bottom, and the resulting liquid layer is serum. Serum is essentially plasma with the fibrinogen and other clotting factors removed during coagulation. This absence of clotting proteins makes serum a cleaner, more stable sample for many types of laboratory tests.
Practical Applications: When Labs Choose One Over the Other
The presence or absence of clotting factors dictates the utility of plasma and serum in clinical and research settings. Plasma is the required sample type when a laboratory needs to analyze the body’s ability to stop bleeding. Coagulation studies, such as Prothrombin Time (PT) and Partial Thromboplastin Time (PTT), must use plasma because they measure the activity of the clotting factors.
Plasma is also a direct therapeutic product, used in transfusions for patients suffering from severe burns, trauma, or certain liver diseases where they cannot produce sufficient clotting factors. Plasma is often preferred when analyzing certain analytes that are rapidly released from blood cells upon clotting, as the anticoagulant helps preserve their natural state.
Serum, lacking interfering clotting proteins, is the preferred sample for the majority of routine diagnostic testing. Most chemistry panels, which measure substances like glucose, cholesterol, electrolytes, and liver enzymes, use serum. Hormone level tests and therapeutic drug monitoring also rely on serum for its stable composition and reduced likelihood of forming fibrin strands. The use of serum is standard for serology, which involves the detection and measurement of antibodies for immunology and infectious disease testing.