What Is the Difference Between Plasma and Serum?
Blood is not always used directly for testing in a lab; rather it is the plasma or serum portion of the blood.
When the blood is left in a test tube with an anticoagulant, it sediments. The blood cells having a higher density occupy the lower portion of the test tube and the lighter part that is the plasma occupies the upper portion.
Therefore, one can say that the blood plasma = whole blood - blood cells.
Similarly, when the blood is left undisturbed in a test tube (without an anticoagulant), it clots. Within a few minutes after the clot is formed, it begins to contract and ooze out most of the fluid within 30-45 minutes. The fluid oozed out is called serum.
The blood clot consists of all the blood cells, fibrinogen, and a few other clotting factors. The remaining portion in the test tube is the serum.
Accordingly, serum = whole blood - (blood cells + fibrinogen and clotting factors II, V, VIII)
Summary of the Differences Between Serum and Plasma
- Plasma is blood without cells whereas serum is the remaining plasma after coagulation.
- Anticoagulant is needed for the seperation of plasma, while no anticoagulant are required for the seperation of serum.
- Plasma contains coagulation factors II, V, and VIII and fibrinogen while serum lacks these factors.
- Plasma has comparatively higher concentration of proteins than serum.
- Plasma is obtained within a shorter period of time as the clotting time is eliminated whereas a waiting time of 35-45 minutes before centrifugation is necessary to obtain serum.
- 15-20% more yield of plasma is obtained compared to serum.
- There is a lower risk of haemolysis and thrombolysis in plasma compared to serum.
- Post-centrifugation coagulation can occur in serum whereas it does not occur in plasma.
Apart from these, the two specimens also differ in their usefulness as well as the alnalyte composition. (Refer table 1 and 2 in this article).
Plasma = whole blood - blood cells
Plasma = whole blood - (red blood cells + white blood cells + platelets)
Serum = whole blood - (blood cells + clotting factors)
Serum = whole blood - (red blood cells + white blood cells + platelets + fibrinogen, clotting factors II, V, VIII)
Serum = Plasma - (Fibrinogen + Clotting factors II, V, VIII)
The Coagulation Process Makes Serum Different From Plasma
To understand the differences, you must be aware of how the plasma and serum are seperated from whole blood. The following steps explain what laboratories do to get these specimens.
1. Blood is drawn from the patient.
Blood samples for lab testing may be obtained in several ways. The most common procedure is venipuncture, withdrawal of blood from a vein using a needle and a collecting tube, which contains various additives.
A tourniquet is wrapped around the arm above the venipuncture site, which causes blood to accumulate in the vein. This increased blood volume makes the vein stand out, making venipuncture more successful.
To ensure that there is no confusion on the part of the phlebotomist in identifying the proper tube, the stoppers and closures of collecting tubes are colour-coded. For example, the stopper of collecting tube containing the additive EDTA (an anticoagulant) is lavender. This tube is used when you want to mix the blood with the anticoagulant EDTA to get plasma.
Conversely, if you want to obtain serum you need to have the blood clot so you don't want to use the tube with an anticoagulant. Therefore, the collecting tube to get serum is plain, colour-coded red. Similarly, there are various colour-codes for anticoagulant as well as other additives such as a preservative.
2. The collecting tubes are centrifuged.
The tube with anticoagulants can be spun immediately to obtain plasma. Whereas, the tube for serum must be stored for 30-45 minutes undisturbed, and, preferably, in the dark before centrifugation.
Whole blood in a collecting tube with anticoagulants get you plasma after centrifugation. This is because the coagulability of the blood is inhibited by the addition of anticoagulants.
The heavier portion of the whole blood, the red blood cells settle at the bottom of the test tube. Then, the next layer is the buffy coat consisting of white blood cells and platelets. Plasma is virtually the remaining cell-free supernatant.
Whole blood in a plain collecting tube will give you serum after centrifugation is done 30-40 minutes post-blood collection. The standing time of 40 minutes is given to allow the blood to clot. This clot then contracts to ooze out the serum. Initially, the clot is the whole blood then after some time, it starts to release the fluid portion of it which is plasma except fibrinogen. There is no fibrinogen in the serum because it is converted into fibrin during the formation of the clot.
Laboratories use gel separators to improve the yield of specimens. The gel in a separator tube is a liquid polymer along with an organic or inorganic filler added to achieve the appropriate density of the gel.
3. The specimen is separated for analysis.
Next step after centrifugation is to transfer the samples (plasma or serum) directly to the analyzer. Ideally, the analyzer need does this job by piercing the closed stopper and collecting thereby.
Manually, the plasma or serum is recollected using a transfer pipette. It is done carefully without disturbing the other layers into another labelled tube.
Analytes Concentration in Serum Compared with Plasma
Concentration in serum compared to plasma
Reason for the change
Fibrinogen, platelets and glucose
These analytes are consumed during clotting in the serum.
Potassium, phosphate, ammonia, lactate dehydrogenase
These analytes are released from cells during clotting.
Removal of a large portion of the fibrinogen content of plasma in the form of fibrin clot results in this.
Blood Tests and Specimen Used
Alanine amino transferase (ALT) and aspartate amino transferase (AST)
Cholesterol (total, HDL, LDL)
Blood urea nitrogen
Creatinine Phosphokinase (CPK)
Lipids (total, triglycerides)
Proteins (total, albumin, globulin)
Misconceptions About Serum vs Plasma
1. The serum does not contain clotting factors.
This is false since clotting factors IX, X, XI, and VII/VIIa are found in serum.
2. Plasma is liquid and serum is fluid.
This statement can be true if you are talking about serum as it oozes from the clot. But, to say that the plasma is liquid and serum is fluid is technically wrong considering the definition of fluid and liquid.
- Guder, W. G., Narayanan, S., Wisser, H., & Zawta, B. (2008). Samples: from the patient to the laboratory: the impact of preanalytical variables on the quality of laboratory results. John Wiley & Sons.
- Tortora, G. J., & Derrickson, B. H. (2018). Principles of anatomy and physiology. John Wiley & Sons.
- Issaq, H. J., Xiao, Z., & Veenstra, T. D. (2007). Serum and plasma proteomics. Chemical reviews, 107(8), 3601-3620.
This content is accurate and true to the best of the author’s knowledge and is not meant to substitute for formal and individualized advice from a qualified professional.
© 2020 Sherry Haynes