What substances are present in both serum and plasma?

Substances Present in Both Serum and Plasma

Both serum and plasma contain the same core substances including water, soluble proteins, lipoproteins, electrolytes, metabolites, glucose, and extracellular vesicles, with the critical distinction being that plasma retains clotting factors (particularly fibrinogen) while serum does not. 1

Key Shared Components

Water and Soluble Proteins

• Both matrices consist primarily of water with high concentrations of soluble proteins 1
• Plasma contains approximately 11% higher water concentration per unit volume compared to whole blood due to the absence of cellular components 1

Metabolites and Small Molecules

• The vast majority of metabolites are present in both serum and plasma, though concentrations differ 2, 3
• Glucose is measurable in both matrices, though plasma glucose concentrations are approximately 0.9-2% higher than serum 1
• Of 163 metabolites analyzed, 122 showed similar patterns between plasma and serum, with high correlation (mean r = 0.81±0.10) despite absolute concentration differences 3

Lipoproteins

• Chylomicrons, VLDL, LDL, and HDL are present in both serum and plasma 1
• These particles overlap in size with extracellular vesicles and must be considered as potential confounders in biomarker studies 1

Extracellular Vesicles (EVs)

• Both matrices contain EVs originating from blood cells (erythrocytes, leukocytes, platelets) and endothelial cells 1
• Leukocyte-derived EVs (CD45+) and erythrocyte-derived EVs (CD235a+) are present in comparable concentrations in both matrices 1
• Critical caveat: Platelet-derived EVs (CD61+) are significantly more concentrated in serum than plasma due to platelet activation during the clotting process 1

Important Concentration Differences

Higher in Serum

• 104 out of 163 metabolites show significantly higher concentrations in serum, with 9 metabolites showing >20% relative concentration differences 3
• Platelet-derived EVs are markedly elevated in serum due to thrombin-induced platelet activation during clotting 1
• Growth factors, cytokines, and anti-microbial compounds released from platelet granules during coagulation 1

Clotting Factors (Plasma Only)

• Fibrinogen and other coagulation factors (II, VII, IX, X) are present only in plasma 1
• During serum preparation, fibrinogen is converted to insoluble fibrin and removed with the clot 1

Clinical Implications and Pitfalls

Matrix Selection Considerations

• For most analytes, either matrix generates similar results as long as the same preparation procedure is used consistently 3
• Plasma demonstrates better measurement stability (mean correlation r = 0.83 vs 0.80 for serum duplicates, p = 0.01) 3
• Serum provides higher metabolite concentrations, potentially offering more sensitive biomarker detection 3

Common Confounders

• Hemolysis (disruption of red blood cells) can occur in both matrices from poor venipuncture technique, causing orange or red discoloration 1
• Lipemia (elevated lipoproteins in postprandial state) causes milky appearance in both matrices 1
• Residual platelets in plasma can fragment during storage and freeze-thaw cycles, creating particles indistinguishable from native EVs 1

Standardization Requirements

• The anticoagulant type in plasma collection significantly affects results - EDTA, heparin, and citrate have different effects on protein binding, stability, and assay interference 4
• Pre-centrifugation delay time, centrifugation conditions, and temperature during processing affect both matrices differently 1
• Serum clotting time (30-60 minutes recommended) must be standardized to prevent either residual fibrin formation or cell lysis contamination 1