TABLE 2

Examples of Markers Artificially Altered by Coagulation, Anticoagulants, or Collection Techniques

Sample TypeExamples of Biomarkers Affected
Serum (due to coagulation process)• VEGF is highly expressed in serum due to platelet secretion during clotting in both healthy patients9294 and in those with disease95–99
• MMPs increase with clot accelerators due to amorphous silica or silicate salts (components of clot activators)100
• α-2 Macroglobulin, BDNF, EGF, ENA-78, IL-8, PAI-1, and TIMP-1 are higher in serum samples from healthy patients compared with plasma samples using EDTA, sodium citrate, or heparin as anticoagulant101
• Lysophosphatidylcholines are higher in serum from healthy patients due to platelet release of phospholipases activated by thrombin102
Plasma (due to the use of different anticoagulants or collection techniques)• MMP-1, MMP-2, MMP-13, IL-4, IL-10, and growth factors increase in plasma isolated with EDTA63
• Neutrophil elastase, MMP-2, and MMP-9 increase due to isolation-dependent activation of neutrophils and mononuclear phagocytes33,65
• Troponin-I and troponin-T decrease in tubes with heparin due to binding103
• Glucose is lower due to fluid shifting from erythrocytes to plasma caused by anticoagulants,104 as compared with serum102
• Total cholesterol is lower due to fluid shifting from erythrocytes to plasma with EDTA, as compared with serum105
• HDL-C is higher in plasma due to EDTA, as compared with serum105
• Lysophosphatidylcholines are higher due to the storage of plasma sample at RTa106
• FVIII levels decrease due to storage at RT before blood processing107
• VEGF levels increase with EDTA as anticoagulant108
• VEGF, MCP-1, eotaxin, and factor VII are increased in citrate and heparin plasma samples from healthy patients101
  • BDNF, brain-derived neurotrophic factor; EGF, epidermal growth factor; ENA-78, epithelial neutrophil-activating peptide 78; FVIII, factor VIII; HDL-C, high-density lipoprotein cholesterol; IL, interleukin; MCP-1, monocyte chemotactic protein 1; MMP, matrix metalloproteinase; PAI-1, plasminogen activator inhibitor 1; TIMP-1, tissue inhibitor of metalloproteinase 1; VEGF, vascular endothelial growth factor.

  • a RT = 20–25°C.