A concerted effort to tackle the global health problem posed by traumatic brain injury (TBI) is long overdue. TBI is a public health challenge of vast, but insufficiently recognised, proportions. Worldwide, more than 50 million people have a TBI each year, and it is estimated that about half the world's population will have one or more TBIs over their lifetime. TBI is the leading cause of mortality in young adults and a major cause of death and disability across all ages in all countries, with a disproportionate burden of disability and death occurring in low-income and middle-income countries (LMICs). It has been estimated that TBI costs the global economy approximately $US400 billion annually. Deficiencies in prevention, care, and research urgently need to be addressed to reduce the huge burden and societal costs of TBI. This Commission highlights priorities and provides expert recommendations for all stakeholders—policy makers, funders, health-care professionals, researchers, and patient representatives—on clinical and research strategies to reduce this growing public health problem and improve the lives of people with TBI.Additional co-authors: Endre Czeiter, Marek Czosnyka, Ramon Diaz-Arrastia, Jens P Dreier, Ann-Christine Duhaime, Ari Ercole, Thomas A van Essen, Valery L Feigin, Guoyi Gao, Joseph Giacino, Laura E Gonzalez-Lara, Russell L Gruen, Deepak Gupta, Jed A Hartings, Sean Hill, Ji-yao Jiang, Naomi Ketharanathan, Erwin J O Kompanje, Linda Lanyon, Steven Laureys, Fiona Lecky, Harvey Levin, Hester F Lingsma, Marc Maegele, Marek Majdan, Geoffrey Manley, Jill Marsteller, Luciana Mascia, Charles McFadyen, Stefania Mondello, Virginia Newcombe, Aarno Palotie, Paul M Parizel, Wilco Peul, James Piercy, Suzanne Polinder, Louis Puybasset, Todd E Rasmussen, Rolf Rossaint, Peter Smielewski, Jeannette Söderberg, Simon J Stanworth, Murray B Stein, Nicole von Steinbüchel, William Stewart, Ewout W Steyerberg, Nino Stocchetti, Anneliese Synnot, Braden Te Ao, Olli Tenovuo, Alice Theadom, Dick Tibboel, Walter Videtta, Kevin K W Wang, W Huw Williams, Kristine Yaffe for the InTBIR Participants and Investigator

The rate of confirmed bacterial contamination of PC units was low. Nevertheless, clinicians must be aware of this risk. The risk of bacterial contamination does not warrant universal preference of APCs. It must be questioned whether routine bacterial screening by a culture method can sufficiently prevent contaminated products from being transfused due to the delay until a positive signal in the culture system and due to false-negative results.

Five blood donors with occult persistent and one donor with an early window phase HBV infection were identified. They were negative in regular HBsAg screening and had low levels of HBV DNA that were probably not detectable by current mini-pool nucleic acid amplification testing. In four donors several mutations were found located in the HBs antigen loop. In three donors the mutations were predominantly outside the ''a'' determinant; one donor had a wild type HBsAg sequence. Fifty-five recipients of donations from the persistently infected donors could be tested for previous or ongoing HBV infection and of them 53% (29/55) were anti-HBc positive. Based on the prevalence of antiHBc in Germany (7%), it was assumed that four of those recipients had already been positive before transfusion. In 22 cases, it was assumed that they acquired infection by the donations, but the infection remained asymptomatic and was resolved. In three cases transmission was proven by the time course of the acute infection and sequence identity The resulting infection was fatal and associated with immunological disorders at the time of transmission: in one case sepsis and in the other two cases immunosuppression. In a further asymptomatic case of proven transmission from the early window phase donation passively administered anti-HBs could not prevent spread of wildtype HBV but antiviral treatment lead to resolution. Surprisingly the typical acute hepatitis B was not observed in a single one of the 26 cases of assumed or proven transmission.

Partial D may be caused by a single-amino-acid deletion in RhD. The altered RhD protein segments in DVL types are adjacent to the extracellular loop 4, which constitutes one of the most immunogenic parts of the D antigen. These RhD protein segments are also altered in all DV, which may explain the similarity in phenotype. At the nucleotide level, the triplet deletions may have resulted from replication slippage. A total of nine amino acid positions in an Rhesus protein may be affected by this mechanism.

The observation of weak D type 1.1 with its distinct phenotype pinpointed to two general problems of current RHD genotyping strategies: Mistyping of alleles with additional mutations and striking geographic variation of the allele distributions.

BackgroundExternal factors following trauma and iatrogenic intervention influence blood coagulation and particularly clot formation. In particular, three external factors (in detail dilution via uncritical volume replacement, acidosis and hypothermia), in combination, referred to as the “lethal triad”, substantially aggravate the hypocoagulative state after trauma. Contribution of these external factors to the resulting hypocoagulative state in trauma and especially their influence on primary haemostasis has still not been investigated systematically.This study aims to assess this contribution to the aggravating hypocoagulative state in trauma-induced coagulopathy (TIC) using an in vitro simulation assay. Emphasis is given to platelet contribution to clot formation and to the investigation of how platelet activation alters under the respective conditions.MethodsTo simulate the conditions of lethal triad in vitro, whole blood samples taken from five healthy volunteers were introduced to the respective conditions. Besides standard coagulation testing, thrombelastometric analysis and differentiated platelet mapping were performed.ResultsAll three simulated conditions induced significant impairments of clot formation (clot formation time, CFT; α -angle) and propagation (maximum clot firmness, MCF; Diameter A5-A25), with the highest impact under hypothermia and dilution. Consistently, lethal triad resulted in an additive effect of all conditions. None of the simulated conditions induced a statistically relevant change in coagulation initiation assessed by EXTEM and FIBTEM thrombelastometry.Platelet contribution to clot formation decreased gradually under the respective conditions, reaching statistical significance for simulated dilution, and attaining its greatest extent under the conditions of lethal triad (Δtrias/baseline 0.59; p = 0.01). Consistent, reduced CD62 expression levels were observed under experimental acidosis (Δacidosis/baseline 0.32; p = 0.006), dilution (Δdilution/baseline 0.34; p = 0.01) and lethal triad (Δlethal triad/baseline 0.24; p = 0.01).ConclusionThe respective external factors of lethal triad play a pivotal role in the development of coagulopathy, essentially influencing the kinetics of clot formation, and to a varying extent clot diameter, as measured by thrombelastometry. Moreover, impairment of platelet function under the conditions of lethal triad plays a key role in the pathophysiology of TIC, resulting in reduced responsiveness to stimulation with ADP that might also be present after trauma. Our data indicate that impairment of primary haemostasis contribute to the hypocoagulative state in TIC after trauma aggravated by external factors of lethal triad.

Fibrinogen concentrates corrected and improved haemodilution-induced changes in blood clotting in vitro. High-dose fibrinogen supplementation was associated with correction and improvement in clot dynamics and stability.

No abstract