Plasma and serum are two related but distinct components derived from whole blood, and they are often confused because both represent the liquid fraction remaining after blood cells are removed. They share most components, including water, electrolytes, antibodies, hormones, and proteins like albumin. However, the exact composition of the two fluids differs due to the methods used to obtain them, which dictates their unique applications in medicine and research.
The Preparation of Plasma
To isolate plasma, whole blood is collected into a tube that contains a chemical called an anticoagulant. The purpose of an anticoagulant, such as heparin, EDTA, or citrate, is to chemically bind to or inhibit specific molecules required for the blood clotting cascade. The treated blood is then placed in a centrifuge, which spins the sample at high speeds. This force separates the components based on their density, pushing the heavier blood cells to the bottom of the tube. The clear, yellowish liquid that remains at the top is the plasma.
The Preparation of Serum
The process for obtaining serum is fundamentally different because it relies on natural blood coagulation. To prepare serum, whole blood is collected into a plain tube or one containing a clot activator, but importantly, no anticoagulant is added. The blood is allowed to sit undisturbed, typically for 15 to 30 minutes, giving the coagulation cascade time to run its course. During this time, the blood naturally forms a solid clot containing the blood cells and a mesh-like protein network. Once the clot has formed, the sample is centrifuged to compress the solid clot to the bottom of the tube. The pale yellow fluid that is separated from the mass is the serum.
The Definitive Difference: Clotting Factors
The single compositional distinction between plasma and serum is the presence or absence of specific coagulation factors. Plasma contains all the proteins required for blood clotting because its preparation actively prevented them from being consumed. The most notable of these proteins is fibrinogen, a large protein that converts into an insoluble mesh called fibrin during coagulation. Therefore, plasma retains fibrinogen and other factors. Serum, by contrast, is essentially plasma minus the clotting factors. Since the blood was allowed to clot to obtain the serum sample, the fibrinogen and other coagulation factors were activated and used up to form the solid clot.
Distinct Roles in Health and Medicine
The presence of clotting factors in plasma makes it an irreplaceable product for transfusion medicine. Fresh Frozen Plasma (FFP) is administered to patients who have severe bleeding, liver failure, or certain clotting deficiencies to replace lost fluid volume and supply the necessary coagulation proteins. Plasma is also used to manufacture life-saving therapies, such as immunoglobulins and specific factor concentrates for hemophilia treatment.
Serum, because it is free of clotting factors, is the preferred sample type for the vast majority of diagnostic laboratory tests. The absence of fibrinogen means the sample will not clot in the testing equipment, which could interfere with accurate measurement. Clinicians rely on serum analysis to check concentrations of hormones, antibodies, electrolytes, and drug levels. This makes serum the standard medium for chemistry, immunology, and toxicology testing.