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Sample processing and its preanalytical impact on the measurement of circulating matrix metalloproteinases

The significance of the determination of matrix metalloproteinases (MMPs) in serum was recently discussed in two articles of this journal. Thrailkill et al. (1) reported on the age-dependent concentrations of various MMPs, among them MMP-9, during childhood and adolescence and Sfiridaki et al. (2) examined serum MMP-9 concentrations in patients with multiple myeloma. Although I have no special experience in these clinical fields, I think it might be necessary to draw the reader’s attention to the impact of sample processing on the correct determination of circulating MMPs. Numerous studies have already shown the effect of the method of blood collection on the concentrations of MMPs (3–11). Consequently, there are reasonable doubts that serum samples as used by the above-mentioned authors are appropriate samples to measure circulating MMPs (7, 8, 11, 12). To make this aspect clear to the readership of this analytically oriented journal and to complement the conclusions of these two studies, I would like to demonstrate the influence of the blood collection method on circulating MMP-9 and its diagnostic validity by summarizing our own data (4, 13). Serum and plasma samples from eight healthy adults were prepared in plastic tubes (Monovette Systems, Sarstedt GmbH, Nümbrecht, Germany) by centrifugation of blood samples at 1600=g for 15 min within 30 min after venipuncture. Tubes without additives or with kaolin-coated plastic granulate as coagulation accelerator were used to prepare native serum (serum–) and serum after enhanced coagulation (serumq), respectively. Tubes coated with lithium heparin, sodium citrate or potassium EDTA were used to prepare corresponding plasma samples. Heparin plasma and serum (with clot activator) were also collected from 78 healthy adults and 33 patients with localized renal cell carcinoma. The samples were