Dittadi · The International journal of biological markers 2001 · comparative laboratory validation study · n=30

Validation of blood collection procedures for the determination of circulating vascular endothelial growth factor (VEGF) in different blood compartments.

Cited 82 times in the scientific literature.

Level 4 - case-series / case-control

Comparative laboratory validation study in a single cohort of human subjects

PubMed 11471901 · record verified 2026-08-29

What was done

Authors evaluated blood collection and processing methods for measuring vascular endothelial growth factor (VEGF) across different compartments in 30 subjects. They tested serum clotting durations (comparing centrifugation within 10 minutes against 2 to 4 hours), lysed whole blood, and multiple plasma preparations including Edinburgh anticoagulant mixture (EDTA, PGE1, theophylline), CTAD (citrate, theophylline, adenosine, dipyridamole), and sodium citrate. In vitro platelet activation was assessed by measuring platelet factor 4 (PF4). Both markers were quantified using commercial ELISAs.

What was found

Serum VEGF release increased with clotting time, plateauing between 2 and 4 hours. At 2 hours, VEGF increased by a median of 327% (range: 118% to 4,515%) compared with samples centrifuged within 10 minutes. VEGF levels were equivalent and PF4 was very low or undetectable in Edinburgh and CTAD plasma, whereas sodium citrate plasma showed significantly higher levels of both markers. VEGF in CTAD plasma did not correlate with leukocyte or platelet counts. Serum VEGF correlated significantly with platelet count but not with leukocyte count.

Why it matters

Unstandardized pre-analytical handling and ex vivo platelet degranulation largely explain conflicting results in circulating VEGF literature. Using CTAD plasma for circulating levels and standardized 2-hour clotting for serum enables reproducible quantification across clinical studies.

Limits

The abstract describes a small cohort (n = 30) without detailing participant health status or demographic characteristics. Absolute numerical concentrations for VEGF and PF4 across fractions are not reported in the abstract.

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