Proteomic characterization of freeze-dried human plasma: Providing treatment of bleeding disorders without the need for a cold chain

BACKGROUND: Transfusion of human plasma is a basic treatment for severe coagulopathies, especially in major bleeding. The required logistics to provide plasma is challenging because of the need to maintain a cold chain. This disadvantage could be overcome by lyophilized plasma. However, it is unknown to what extent lyophilization alters plasma proteins. Quantitative proteomic technologies were applied to monitor protein changes during production of lyophilized, solvent/detergent (S/D)-treated plasma. MATERIALS AND METHODS: The impact of S/D treatment and lyophilization on the plasma proteome was evaluated by differential in-gel electrophoresis (2D-DIGE), and proteins were characterized by mass spectrometry. Clotting factor activities were determined in lyophilized S/D-treated plasma after 24 months of storage at room temperature. RESULTS: By 2D-DIGE, 600 individual protein spots were compared. Lyophilization did not change any of the 600 spots, whereas pathogen inactivation caused significant changes of 38 spots including α1-antitrypsin, α1-antichymotrypsin, and α2-antiplasmin. Clotting factor activities remained stable over 24 months of storage. CONCLUSION: Lyophilization of human plasma neither alters its protein composition nor impairs its clotting capacity. It does not require cost-intensive logistics for storage and transport and can be quickly reconstituted. It is suggested that lyophilized, pathogen-inactivated plasma is an attractive option to provide the most important basic treatment for severe coagulopathies in areas without cold chain and to provide plasma with reduced time delay in emergency situations

Characterization of the human neutrophil alloantigen-3a

Transfusion-related acute lung injury (TRALI) is a frequent cause of transfusion-associated morbidity and mortality. Severe TRALI is often due to antibodies in blood components directed against the human neutrophil alloantigen-3a (HNA-3a). We show here that the HNA-3a antigen arises from a nucleotide polymorphism in the choline transporter-like protein-2 gene (SLC44A2), with the resulting variation at amino acid position 154 determining the reactivity of the protein with HNA-3a-specific antibodies; the variant with an arginine at this position, rather than a glutamine, constitutes the HNA-3a antigen. The molecular identification of this antigen should facilitate the development of assays for blood donor screening to lower the risk of TRALI

Formate modulated solvothermal synthesis of ZIF-8 investigated using time-resolved in situ X-ray diffraction and scanning electron microscopy

Time-resolved investigations using in situ energy-dispersive X-ray diffraction in tandem with ex situscanning electron microscopy revealed that solvothermal crystallisation of ZIF-8 in methanol solvent and in the presence of sodium formate as a simple monodentate ligand (modulator) is a rapid process yielding big, high-quality single crystals in short time (<4 h). Kinetic analysis of crystallisation curves was performed by applying the Avrami–Erofe'ev and Gualtieri models. The analyses revealed that the weakly basic formate modulator acts as a base in deprotonation equilibria (deprotonation of the bridging 2-methylimidazole ligand) rather than as a competitive ligand in coordination equilibria at the metal (Zn2+) centres. This is in contrast to the coordination modulation function of formate in ZIF-8 synthesis at room temperature. Crystal shape evolves with time in the presence of formate from cubes with truncated edges to rhombic dodecahedra. The latter shape represents most likely the stable equilibrium morphology of ZIF-8