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Proteomics as a tool for assessment of therapeutics in transfusion medicine: evaluation of prothrombin complex
Matthias Brigulla1, Thomas Thiele, Christian Scharf
1Institute for Immunology and Transfusion Medicine, the Laboratory for Functional Genomics, Ernst-Moritz-Arndt University, Greifswald, Germany.
Background:
Proteomic technologies are evolving tools to analyze complex protein patterns that to date have been rarely applied to transfusion medicine. The analysis of prothrombin complex concentrates (PCCs) was used as a model to evaluate to what extent these technologies can detect differences in blood-derived therapeutics beyond that of standard quality control.
Study Design And Methods:
Three PCCs (two batches each) were individually analyzed for differences in protein content by functional assays, two-dimensional gel electrophoresis, and mass spectrometry. The results were compared to a pool of 72 normal plasma samples.
Results:
A highly complex protein pattern was found that varied considerably among the three PCCs: 192 spots comprising 40 different proteins were identified. Factor (F) IX activities of the three PCCs were comparable, but their F IX protein contents differed considerably. Many proteins were present in multiple spots (e.g. FII, FX, protein C, vitronectin), indicating a high degree of posttranslational modifications. In comparison with untreated pooled plasma, PCCs displayed several low-molecular-weight variants of proteins that likely constitute potential degradation products.
Conclusion:
Proteomic technologies allow the identification of potentially modified proteins in clotting factor concentrates, indicating that they could become a useful tool for transfusion medicine to assess the impact of processing on the integrity of blood-derived therapeutics.
