Serum vs Plasma

Serum has historically been the preferred sample for clinical chemistry tests due to its early adoption and ease of collection. Plasma, on the other hand, was traditionally used only in cases where avoiding in-vitro activation of the coagulation cascade was necessary or when specific preservation techniques were required. Consequently, serum has remained the sample of choice for many laboratories primarily due to tradition.

Using plasma samples for analytes detectable in both plasma and serum offers several advantages:

Time Saving: Plasma can be centrifuged immediately after collection, whereas serum requires at least 30 minutes for coagulation. This quicker processing is crucial in situations where rapid diagnostic results are needed, improving overall healthcare efficiency and patient outcomes.

Higher Yield: Plasma yields 15%-20% more volume than serum, enabling the use of smaller blood draw tubes. This is particularly beneficial for patients with low blood volume, reducing the risk of anemia from frequent collections and lowering waste disposal costs.

Prevention of Coagulation Interferences: Unlike serum, plasma does not contain fibrin strands, which can clog analyzers and cause errors in immunoassays, thereby ensuring more reliable test results.

Avoidance of Clotting-Induced Variations: Clotting alters the concentration of various blood constituents in serum, leading to potential inaccuracies. Plasma avoids these changes, reducing the need for test repetition.

Less Hemolysis: Although still debated, some evidence suggests plasma may reduce hemolysis compared to serum, which is beneficial for sample integrity.

Biobanking: Plasma is recommended for storing metabolites, circulating DNA/RNA, and miRNA, while serum remains preferable for proteomics and lipidology.

Using serum samples for analytes detectable in both serum and plasma offers several advantages:

Less Cell Contamination: In the serum vs plasma comparison, serum is nearly free of cellular components after centrifugation, unlike plasma, which may still contain white and red blood cells, platelets, and debris. This reduces the risk of analyte reduction due to cellular metabolism and prevents issues caused by freezing and thawing, such as increased free hemoglobin.

Better Stability for Some Measurands: Serum provides better stability for certain measurements, such as glucose, when stored at room temperature. In the serum vs plasma debate, serum also avoids issues like pseudohyperkalaemia and pseudohyponatraemia in samples with high white blood cell counts during pneumatic transport.

Absence of Anticoagulants: Serum production does not require anticoagulants, avoiding potential interferences they might cause in tests, which is a known issue with anticoagulants like EDTA and heparin.

Compatibility with Serum Protein Electrophoresis: Serum, lacking fibrinogen, is ideal for serum protein electrophoresis, as it avoids interference from this protein during the procedure. Additionally, the extensive use of serum has led to a broader availability of validated methods for this matrix, ensuring higher traceability and reliability in results.

Vignoli A, et al. Serum or Plasma (and Which Plasma), That Is the Question. J Proteome Res. 2022 Apr 1;21(4):1061–1072. doi:10.1021/acs.jproteome.1c00935

Plebani M, et al. Serum or plasma? An old question looking for new answers. Clin Chem Lab Med (CCLM). 2020;58(2):178–187. doi:10.1515/cclm-2019-0719

Mohamadkhani A, Poustchi H. Repository of Human Blood Derivative Biospecimens in Biobank: Technical Implications. Middle East J Dig Dis. 2015 Apr;7(2):61–8. PMC4430793