Marleen Straat

Transfusion of fresh-frozen plasma in critically ill patients with a coagulopathy before invasive procedures: a randomized clinical trial (CME).

Prophylactic use of fresh‐frozen plasma (FFP) is common practice in patients with a coagulopathy undergoing an invasive procedure. Evidence that FFP prevents bleeding is lacking, while risks of transfusion‐related morbidity after FFP have been well demonstrated. We aimed to assess whether omitting prophylactic FFP transfusion in nonbleeding critically ill patients with a coagulopathy who undergo an intervention is noninferior to a prophylactic transfusion of FFP.

Red Blood Cell Clearance in Inflammation

Anemia is a frequently encountered problem in the critically ill patient. The inability to compensate for anemia includes several mechanisms, collectively referred to as anemia of inflammation: reduced production of erythropoietin, impaired bone marrow response to erythropoietin, reduced iron availability, and increased red blood cell (RBC) clearance. This review focuses on mechanisms of RBC clearance during inflammation. We state that phosphatidylserine (PS) expression in inflammation is mainly enhanced due to an increase in ceramide, caused by an increase in sphingomyelinase activity due to either platelet activating factor, tumor necrosis factorα, or direct production by bacteria. Phagocytosis of RBCs during inflammation is mediated via RBC membrane protein band 3. Reduced deformability of RBCs seems an important feature in inflammation, also mediated by band 3 as well as by nitric oxide, reactive oxygen species, and sialic acid residues. Also, adherence of RBCs to the endothelium is increased during inflammation, most likely due to increased expression of endothelial adhesion molecules as well as PS on the RBC membrane, in combination with decreased capillary blood flow. Thereby, clearance of RBCs during inflammation shows similarities to clearance of senescent RBCs, but also has distinct entities, including increased adhesion to the endothelium.

Extracellular Vesicles from Red Blood Cell Products Induce a Strong Pro-Inflammatory Host Response, Dependent on Both Numbers and Storage Duration

Background: Transfusion of red blood cells (RBCs) is associated with adverse outcome, but the causative factor is unknown. Extracellular vesicles (EVs) have pro-inflammatory properties. We hypothesized that EVs released from both fresh and stored RBC products can induce a host inflammatory response in a dose-dependent manner. Methods: Whole blood was incubated with supernatant from RBC units stored for different time periods, either containing (different numbers of) EVs or depleted from EVs. Results: Incubation with both fresh and stored supernatant containing EVs induced a strong host response with production of TNF, IL-6 and IL-8. In supernatant depleted from EVs, this host response was completely abrogated. IL-10 levels were not affected. EV-induced host response was both dependent on the number of EVs as well as on storage time. Conclusions: EVs from both fresh and stored RBC units illicit a strong inflammatory host response in recipients and may therefore contribute to adverse outcome of RBC transfusion.

Monocyte‐mediated activation of endothelial cells occurs only after binding to extracellular vesicles from red blood cell products, a process mediated by β‐integrin

Red blood cell (RBC) transfusion is associated with organ failure. The mechanism remains unknown, but may include adherence of blood cells to the microvasculature. We hypothesized that RBC‐derived extracellular vesicles (EVs) interact with monocytes to activate endothelial cells.

Thomas Montag-Lessing †

On May 18, 2012, Dr. med. Thomas Montag-Lessing (MD) died at the age of 61. Despite his health problems, which had persisted for several years, he worked ceaselessly for the safety of patients with great enthusiasm and commitment. He particularly contributed to the establishment and introduction of effective methods against bacterial contamination of biological medicinal products. Dr. Montag-Lessing supported the Advisory Committee Blood of the Federal Ministry of Health for many years and enriched the committee by several essential contributions. He was the head of the subgroup ‘Bacterial Safety’ and contributed actively to the subgroup ‘Assessment of Pathogens Transmissible by Blood’. Dr. Montag-Lessing started his scientific career in 1974 as assistant doctor at the Institute for Medical Microbiology and Hygiene of the Charité at the Humboldt University of Berlin. In 1980, he became the head of the research group ‘Molecular Biology’. During the 10 years that followed, he worked in the fields of immunology, biochemistry, and molecular biology of microorganisms as well as in microbiological diagnostics. In 1990, he became the head of a research group at the Paul-Ehrlich-Institut which devoted itself to the area of immune modulation by bacteria and parasites, and was trusted with the marketing authorization and batch release of diagnostic devices for blood groups. In 1994, the function as acting head of the Division of Hematology/Transfusion Medicine was assigned to him, a division which had to be newly established. In this very difficult phase of crisis management with an initially relatively small team, he showed a great deal of skill and prudence. In 1995, he assumed the responsibility as head of the Section Microbial Safety at the Paul-EhrlichInstitut where he was able to continue his intensive research activities and regulatory work for the microbial safety of biological medicinal products. Focuses of his work which were particularly important for transfusion medicine included the elaboration of strategies for the microbiological control and verification of methods for pathogen inactivation of blood products. Thanks to his profound and focussed scientific and regulatory work, Dr. Montag-Lessing was highly appreciated at a national and international level. He was a member of various scientific organizations, for example the International Society of Blood Transfusion (ISBT), in which he was the head of the sub-group for bacteria of the Working Party TransfusionTransmitted Infectious Diseases. He initiated and supervised an international study for the characterization and establishment of suitable bacteria strains in order to provide blood donation services and manufacturers of diagnostic medical devices with a tool for the development and validation of methods of microbiological control of blood components. These reference strains were recognized as First Repository for Transfusion-Relevant Bacteria Reference Strains by the Expert Committee for Biological Standardization of the WHO. We will gratefully remember Dr. Montag-Lessing as an excellent scientist, who always discussed scientific matters with high commitment and good perception, partly also expressing unorthodox ideas, and defended his concepts and convictions perseveringly.