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Monoclonal antibodies such as daratumumab that target antigens that are also expressed on red blood cells impede blood group typing. The preferred approach to potential transfusion is to do prior extensive antigen typing of patients' red cells; however, this is not always possible. Ehrend et al describe a technique for absorbing the antibodies from serum to allow accurate red cell typing for transfusion.

Pulmonary embolism (PE) due to deep vein thrombosis is a complication with severe morbidity and mortality rates. Neurocritical care patients constitute an inhomogeneous cohort with often strict contraindications to conventional embolism treatment. The aim of the present study is to identify risk factors for pulmonary embolism for intensified risk stratification in this demanding cohort. In this retrospective analysis, 387 neurocritical care patients received computed tomography for clinical suspicion of PE (304 neurosurgical and 83 neurological patients). Analysed parameters included age, gender, disease pattern, the presence of deep vein thrombosis, resuscitation, in-hospital mortality, present anticoagulation, coronary artery disease, diabetes mellitus, smoking status, hypertension and ABO blood type. Computed tomography confirmed 165 cases of pulmonary embolism among 387 patients with clinical suspicion of pulmonary embolism (42%). Younger age (p p p p p

Postoperative thrombotic thrombocytopenic purpura (TTP) shows clinical presentation similar to classical TTP, whereas exact pathophysiological contexts remain unexplained. In this study, we investigated intraoperative and postoperative changes in ADAMTS-13 (a disintegrin and metalloprotease with thrombospondin type 1 motifs, member 13), von Willebrand factor (VWF), large VWF multimers, and interleukin-6 (IL-6) in vascular surgery patients. The objective was to compare the impact of endovascular, peripheral, and aortic surgery on target parameters which are supposed to play a role in surgery-associated TTP. A total of 93 vascular surgery patients were included and divided into 4 groups according to the specific type of intervention they underwent. Blood samples were taken preoperatively, intraoperatively, and postoperatively on days 2 and 4. The ADAMTS-13 activity decreased significantly in 3 of the 4 groups during surgery (from median 81% to 49%, P < .001, in the group undergoing aortoiliacal interventions), whereas the percentage of large VWF multimers increased in all groups of patients. von Willebrand factor antigen increased significantly in all groups on postoperative day 2 and IL-6 increased significantly in the intraoperative and early postoperative period. There was no significant correlation between the intraoperative decrease in ADAMTS-13 and the increase in VWF or IL-6. No patient in this study showed clinical picture of TTP; the precise cause and clinical significance of moderately reduced ADAMTS-13 activity in the perioperative setting have not yet been definitely determined.

Background The INTERCEPT™ Blood System for Red Blood Cells (RBCs) utilizes amustaline (S-303) and glutathione (GSH) to inactivate pathogens and leukocytes in transfused RBCs. Treatment-emergent low titer non-hemolytic antibodies to amustaline/GSH RBC were detected in clinical trials using a prior version of the process. The amustaline/GSH process was re-formulated to decrease S-303 RBC adduct formation. Study design and methods A standard three-cell antibody screening panel was modified to include reagent red cells (RRC) with high (S-303H) or low (S-303L) S-303 adduct density as assessed by flow cytometry, representative of the original and current amustaline/GSH treatment processes, respectively. General hospital and RBC transfusion-dependent patients never exposed, and clinical trial subjects exposed to amustaline/GSH RBC were screened for antibodies to amustaline/GSH RBC using a standardized agglutination assay. Results Twelve (0.1%) of 10,721 general hospital and 5 (0.5%) of 998 repeatedly-transfused patients not previously exposed to amustaline/GSH RBCs expressed natural, low titer (2-32) IgM and/or IgG (non-IgG1 or IgG3 isotype) antibodies with acridine (a structural element of amustaline) (n = 14) or non-acridine (n = 3) specificity. 11 of 17 sera reacted with S-303L panel RRCs. In clinical studies 81 thalassemia and 25 cardiac surgery patients were transfused with a total of 1085 amustaline/GSH RBCs and no natural or treatment-emergent S-303 antibodies were detected. Conclusion Standardized RRC screening panels are sensitive for the detection of natural and acquired S-303-specific antibodies. Natural low titer antibodies to amustaline/GSH RBC are present in 0.15% of naive patients. The clinical relevance of these antibodies appears minimal but is under further investigation.

Background: Autologous stem cell transplantation is considered a standard of care treatment in eligible patients with multiple myeloma, but puts the patient at high risk for infections and bleeding complications. Acquired von-Willebrand's disease (AVWD) and acquired platelet dysfunction are rare bleeding disorders that are associated with lymphoproliferative disorders such as multiple myeloma. Patients with acquired bleeding disorders who are planned for ASCT to treat the underlying condition are considered at highest risk for bleeding complications, and optimal treatment strategies are not known. Materials and Methods: We summarized the diagnostic and therapeutic approach to a patient affected by AVWD and acquired platelet disorder related to multiple myeloma. The patient who was planned for ASCT presented with moderate to severe bleeding symptoms. Results: Acute bleeding episodes were successfully controlled and prevented during induction and consolidation therapy with immunoglobulins, whereas replacement of plasma-derived VW factor showed no clinical improvement. High-dose melphalan-based consolidation therapy supported with autologous stem-cell transplantation led to an immediate and sustainable rise of von-Willebrand antigen and activity and a subsequent normalization of platelet aggregation activity. After a follow-up of 40 weeks, the patient maintained normalized VW levels and platelet aggregation capacity. There were no further signs or symptoms of bleeding. Conclusion: This case report highlights the necessity for combined supportive and causal treatment in patients with AVWD and paraproteinemic PD. High-dose melphalan with autologous stem cell support may function as a treatment option in patients with myeloma-related AVWD.

Background Nucleic acid-targeted pathogen inactivation technology using amustaline (S-303) and glutathione (GSH) was developed to reduce the risk of transfusion-transmitted infectious disease and transfusion-associated graft-versus-host disease with red blood cell (RBC) transfusion. Study design and methods A randomized, double-blind, controlled study was performed to assess the in vitro characteristics of amustaline-treated RBCs (test) compared with conventional (control) RBCs and to evaluate safety and efficacy of transfusion during and after cardiac surgery. The primary device efficacy endpoint was the postproduction hemoglobin (Hb) content of RBCs. Exploratory clinical outcomes included renal and hepatic failure, the 6-minute walk test (a surrogate for cardiopulmonary function), adverse events (AEs), and the immune response to amustaline-treated RBCs. Results A total of 774 RBC unis were produced. Mean treatment difference in Hb content was -2.27 g/unit (95% confidence interval, -2.61 to -1.92 g/unit), within the prespecified equivalence margins (±5 g/unit) to declare noninferiority. Amustaline-treated RBCs met European guidelines for Hb content, hematocrit, and hemolysis. Fifty-one (25 test and 26 control) patients received study RBCs. There were no significant differences in RBC usage or other clinical outcomes. Observed AEs were within the spectrum expected for patients of similar age undergoing cardiovascular surgery requiring RBCs transfusion. No patients exhibited an immune response specific to amustaline-treated RBCs. Conclusion Amustaline-treated RBCs demonstrated equivalence to control RBCs for Hb content, have appropriate characteristics for transfusion, and were well tolerated when transfused in support of acute anemia. Renal impairment was characterized as a potential efficacy endpoint for pivotal studies of RBC transfusion in cardiac surgery.

Objective Rupture of an intracranial aneurysm usually presents with an acute onset and requires multidisciplinary intensive care treatment and the overall death and disability rates are high. The ABO blood type is known to play an important role in hemostasis, thrombosis, and vascular NO response. The aspect of ABO blood type in onset, clinical progress, and outcome after subarachnoid hemorrhage (SAH) is largely unexplored. We conducted this study to elucidate the association of ABO blood type with the occurrence and outcome of aneurysmal SAH. Methods In our retrospective study, 470 patients with aneurysmal SAH treated at our institution were included. We performed a χ2 test for comparison between blood types and World Federation of Neurosurgical Societies admission status, cerebral vasospasm, delayed infarction, associated intracerebral hemorrhage and Fisher grade for analysis for their association with SAH. Results No significant difference between blood type and the reviewed variables for SAH outcome were identified: World Federation of Neurosurgical Societies admission status (odds ratio, 1.12; 95% confidence interval [CI], 0.7–1.6; P = 0.56); SAH-associated intracerebral hemorrhage (odds ratio, 0.81; 95% CI, 0.5–1.3; P = 0.36); cerebral vasospasm (odds ratio, 1.08; 95% CI, 0.7–1.6; P = 0.71); DCI (odds ratio, 1.23; 95% CI, 0.8–1.8; P = 0.30); Fisher grade (odds ratio, 1.13; 95% CI, 0.7–1.6; P = 0.19). Conclusions Although a possible relationship between the ABO blood group and the clinical course of patients with SAH was hypothesized, our study showed no significant influence of patient's ABO blood type on cerebral vasospasm onset, SAH-associated intracerebral hemorrhage, or delayed infarction.

To determine whether the implementation of patient blood management (PBM) is effective to decrease the use of red blood cell without impairment of patient's safety.The World Health Organization encouraged all member states to implement PBM programs employing multiple combined strategies to increase and preserve autologous erythrocyte volume to minimize red blood cell transfusions. Data regarding safety issues are not sufficiently available.In this prospective, multicenter study, surgical inpatients from four German University Hospitals were analyzed before (pre-PBM) and after the implementation of PBM. PBM program included multiple measures (ie, preoperative optimization of hemoglobin levels, blood-sparing techniques, and standardization of transfusion practice). Primary aim was to show noninferiority of the PBM cohort with a margin of 0.5%. Secondary endpoints included red blood cell utilization.A total of 129,719 patients discharged between July 2012 and June 2015 with different inclusion periods for pre-PBM (54,513 patients) and PBM (75,206 patients) were analyzed. The primary endpoint was 6.53% in the pre-PBM versus 6.34% in the PBM cohort. The noninferiority aim was achieved (P0.001). Incidence of acute renal failure decreased in the PBM cohort (2.39% vs 1.67%; P0.001, regression model). The mean number of red blood cell transfused per patient was reduced from 1.21 ± 0.05 to 1.00 ± 0.05 (relative change by 17%, P0.001).The data presented show that implementation of PBM with a more conscious handling of transfusion practice can be achieved even in large hospitals without impairment of patient's safety. Further studies should elucidate which PBM measures are most clinically and cost effective.PBM-Study ClinicalTrials.gov, NCT01820949.

Patient Blood Management (PBM) ist ein interdisziplinares Therapiekonzept, welches durch ein umfangreiches praoperatives Anamiemanagement, die Minimierung iatrogener Blutverluste sowie die Ausschopfung der Anamietoleranz zu einer verbesserten Patientenversorgung beitragt. Kostenaspekte von verschiedenen PBM-Masnahmen wurden bislang kaum analysiert. Im Rahmen dieser Arbeit werden die Kosten eines umfassenden PBM-Konzepts und die mit der Einfuhrung assoziierten Projektkosten dargestellt. Es wurden die Sach- und Personalkosten der aus verschiedenen Einzelmasnahmen bestehenden PBM-Saulen sowie der Transfusion von Erythrozytenkonzentraten aus dem Jahr 2013 am Universitatsklinikum Frankfurt analysiert. Zudem wurden die allgemeinen Projektkosten betrachtet. Die patientenbezogenen Mindestkosten einer Erythrozytenkonzentrattransfusion betrugen 147,43 €. Die Kosten von PBM variierten in Abhangigkeit der umgesetzten Einzelmasnahmen. Die Kosten pro Patient betrugen fur die Anamiediagnostik 48,69–123,88 €, Anamietherapie 12,61–127,99 €, Minimierung von Blutverlusten 3,39–1901,81 € und Ausschopfung der Anamietoleranz 28,62 €. Die Projektkosten der Implementierung von PBM beliefen sich auf 24.998,24 €. PBM kombiniert verschiedene Masnahmen, fur deren Realisierung finanzielle Aufwendungen notig sind, wahrend transfusionsassoziierte Kosten durch Ausschopfung der Anamietoleranz gesenkt werden konnen. Im Fokus steht die Optimierung der Patientenversorgung, gleichzeitig spielen gesundheitsokonomische Aspekte eine Rolle, um eine potenzielle Allokation von Ressourcen zu ermoglichen.

Anti-HPA-1a-antibodies are the main cause of fetal and neonatal alloimmune thrombocytopenia (FNAIT) which may result in intracranial hemorrhage (ICH) and death among fetuses and newborns. Advances in understanding the pathogenesis of FNAIT and proof of concept for prophylaxis to prevent immunization suggest that development of hyperimmune anti-HPA-1a IgG aimed at preventing immunization against HPA-1a and FNAIT is feasible. Anti-HPA-1a IgG can be obtained either by isolating immunoglobulin from already-immunized women or by development of monoclonal anti-HPA-1a antibodies. Here we discuss recent advances that may lead to the development of a prenatal and postnatal prophylactic treatment for the prevention of HPA-1a-associated FNAIT and life-threatening FNAIT-induced complications.

Cases of sudden cardiac death (SCD) in young and apparently healthy individuals represent a devastating event in affected families. Hereditary arrhythmia syndromes, which include primary electrical heart disorders as well as cardiomyopathies, are known to contribute to a significant number of these sudden death cases. We performed postmortem genetic analyses in young sudden death cases (aged45years) by means of a defined gene panel using massive parallel sequencing (MPS). The data were evaluated bioinformatically and detected sequence variants were assessed using common databases and applying in silico prediction tools. In this study, we identified variants with likely pathogenic effect in 6 of 9 sudden unexpected death (SUD) cases. Due to the detection of numerous unknown and unclassified variants, interpretation of the results proved to be challenging. However, by means of an appropriate evaluation of the findings, MPS represents an important tool to support the forensic investigation and implies great progress for relatives of young SCD victims facilitating adequate risk stratification and genetic counseling.

Hintergrund Die praoperative Anamie hat in den Industrienationen eine Pravalenz von ungefahr 30 %, ist einer der starksten Pradiktoren fur die perioperative Gabe von Erythrozytenkonzentraten (EK) und zugleich ein eigenstandiger und unabhangiger Risikofaktor fur das Auftreten postoperativer Komplikationen. Im Bereich der Hamotherapie ist weltweit eine breite Variabilitat der Indikationsstellung zum Einsatz von EK auffallend. Vor diesem Hintergrund wird seit 2011 von der Weltgesundheitsorganisation die Implementierung eines Patient-blood-Managements (PBM) gefordert.

Background Patient blood management (PBM) concepts aim to identify patients with anemia and optimize their treatment including use of preoperative iron substitution, blood-sparing techniques and adequate transfusion practice. PBM concepts thus have great potential to increase patient safety and clinical outcome. Nevertheless, up to now, structured PBM programmes have only been implemented in very few hospitals in Germany and safety data regarding clinical outcome parameters is rare. Methods The German PBM network was founded in January 2014 and joined by 24 hospitals different hospitals of varying sizes and levels of patient care. An evidence-based PBM programme will be applied in these hospitals reforming the care of adult patients undergoing surgery, and data will be monitored prospectively. This PBM programme includes the following three main pillars: (1) preoperative optimization of hemoglobin levels in high-risk patients suffering from anemia, (2) standardization of transfusion practice according to evidence-based guidelines and (3) wide implementation of alternatives to transfusion of allogeneic red blood cell (RBC) concentrates including blood-sparing techniques. Primary endpoints are the following composite endpoints: (1) in-hospital myocardial infarction, (2) stroke, (3) acute renal failure, (4) death of any cause, (5) pneumonia and (6) sepsis until hospital discharge in patients before and after the implementation of the PBM programme. Conclusions This trial will determine whether the implementation of a PBM programme is safe and effective in terms of clinical outcome. Data will be compared to data prior to implementation of PBM in (the same?) 20 Germany hospitals.

In patients with non-aneurysmal subarachnoid hemorrhage (NA-SAH), the etiology is unknown and the bleeding source remains unidentified. However, the ABO blood type system has a profound role in patient’s hemostasis and thrombosis. To date, the aspect of ABO blood type in incidence, clinical course, and outcome after NA-SAH has not been investigated. In this retrospective analysis, 81 patients with non-traumatic and non-aneurysmal subarachnoid hemorrhage treated between 2010 and 2014 at the author’s institution were included. WFNS admission status, cerebral vasospasm, delayed infarction, ventriculoperitoneal shunt necessity, the Fisher grade, and the modified Rankin Scale were analyzed for their association with ABO blood type. Four hundred seventy patients with aneurysmal subarachnoid hemorrhage served as a control group. The AB blood type is more frequent in NA-SAH compared to aneurysmal patients and the German population (OR 2.45, p ≤ 0.05). Furthermore, NA-SAH with AB blood type showed a similar sequelae compared to aneurysmal patients in terms of shunt necessity (OR 2.00, p ≥ 0.05), cerebral vasospasm (OR 1.66, p ≥ 0.05), and delayed infarctions (OR 1.07, p ≥ 0.05). The clinical course of NA-SAH AB blood type patients shows similar severity as of aneurysmal subarachnoid hemorrhage. Therefore, patients with AB blood type should be under intensified observation.

Patient Blood Management (PBM) als ein multidisziplinares, evidenzbasiertes Behandlungskonzept zur Reduktion von Anamie und Blutverlust muss am einzelnen Krankenhaus einrichtungsadaptiert verwirklicht werden. Die Implementierung eines PBM-Programms in einer klinischen Einrichtung wird eine herausfordernde, in jedem Fall aber eine lohnende Aufgabe sein. Die Ausstattung zur Erfullung der Schulungsanforderungen fur eine grose Gruppe unterschiedlicher Mitarbeiter kann unzureichend sein. Deshalb ist die nachhaltige Unterstutzung durch die Krankenhausleitung mit Bereitstellung der notwendigen Ressourcen fur Personal und Material unabdingbar. Die Bildung eines PBM-Kernteams, bei uns zu Anfang bestehend aus Anasthesisten, Chirurgen, Internisten und Transfusionsmedizinern sowie – besonders wichtig – aus motivierten Pflegekraften, ist eine der vordringlichen und primaren Aufgaben bei der Etablierung eines PBM-Projekts. Ebenso wichtig ist es, das PBM-Projekt dauerhaft im Krankenhaus zu verankern. Mogliche Schritte und Details hierzu werden anhand aktueller Erfahrungen der Autoren am Universitatsklinikum Frankfurt vorgestellt und in ihrer Wertigkeit diskutiert.

Das multimodale Konzept des Patient Blood Managements tangiert zahlreiche Aspekte der Krankenhausbehandlung eines Patienten. Hauptaugenmerk liegt darauf, patienteneigene Ressourcen zu schonen und zu starken. Dies kann v.a. durch akribische Minimierung des perioperativen Blutverlusts und den Ausbau und die Ausschopfung der individuellen Anamietoleranz erreicht werden. Blutprodukte sollen erst nach Optimierung aller anderen Aspekte leitliniengerecht zur Anwendung kommen, um die mit allogenen Bluttransfusionen verbundenen Risiken zu vermeiden. Das vorgeschlagene Masnahmenbundel besitzt groses Potenzial zur Steigerung der Patientensicherheit!

SummaryMutations in the antithrombin (AT) gene can impair the capacity of AT to bind heparin (AT deficiency type IIHBS), its target proteases such as thrombin (type IIRS), or both (type IIPE). Type II AT deficiencies are almost exclusively caused by missense mutations, whereas type I AT deficiency can originate from missense or null mutations. In a retrospective cohort study, we investigated the impact of the type of mutation and type of AT deficiency on the manifestation of thromboembolic events in 377 patients with hereditary AT deficiencies (133 from our own cohort, 244 reported in the literature). Carriers of missense mutations showed a lower risk of venous thromboembolism (VTE) than those of null mutations (adjusted hazard ratio [HR] 0.39, 95% confidence interval [CI] 0.27–0.58, p

Hamotherapie ist ein integraler Bestandteil der modernen Hochleistungsmedizin. Ohne die Transfusion von Erythrozyten- und Thrombozytenkonzentraten sowie Plasma waren Hochdosis-Chemotherapien bei hamatologischen und soliden Tumoren, die Transplantation hamatopoetischer Stammzellen, Organtransplantationen, grose operative Eingriffe sowie ein modernes Traumamanagement nicht denkbar. In diesem Beitrag wird der aktuelle Stand der Hamotherapie, das Risiko unverwunschter Wirkungen sowie Masnahmen zur Risikovermeidung dargestellt. Auf die hamolytischen Transfusionsreaktionen (HTR), die transfusionsassoziierte akute Lungeninsuffizienz (TRALI) und transfusionsassoziierte Infektionen wird im Besonderen eingegangen. Mit der Einfuhrung von Nukleinsaure-Amplifikations-Testen (NAT) fur HIV-1 und Hepatitis-C-Virus (HCV) kann heute die HIV- und HCV-Transmission uber Blutprodukte in Deutschland nahezu vollstandig verhindert werden. Aktuelle Restinfektionsrisiken werden bezogen auf Blutpraparate des Deutschen Roten Kreuzes mit 1:10,8 Millionen fur HCV, 1:4,3 Millionen fur HIV-1 und 1:360.000 fur Hepatitis-B-Viren (HBV) angegeben.

Summary. Female carriers of haemophilia might suffer from increased bleeding tendency therefore the assessment of the bleeding risk is very important for improving care. This single-centre study documents the occurrence of bleedings in 46 carriers of haemophilia A including bleeding after tooth extraction (77%), easy bruising (67%), postsurgical bleeding (61%), menorrhagia (50%) or prolonged postpartum bleeding (43%). The F8 gene mutation of all 46 carriers (median age: 36.5 years, 15–80 years; mean FVIII:C activity: 59 ± 24.45%; normal range: 64–167%) was determined, and family history of haemophilia was recorded. For analysis, the bleeding tendency of the carriers was differentiated by severity into three groups. There was no statistically significant difference of FVIII:C between these groups. However, a correlation was found between the severity of bleeding tendency and the type of F8 gene mutation (P

BACKGROUND: The modulation of Factor (F)VIII activity (FVIII : C), von Willebrand factor antigen (VWF : Ag), and von Willebrand factor ristocetin cofactor (VWF : RCo) by the ABO(H) blood group is well established in adults. Expression of ABH antigens on N-linked glycans of VWF protects plasma VWF from proteolysis and clearance. Protection by H antigens is less effective than by AB antigens, resulting in approximately 25% lower VWF plasma levels in adults with blood group O compared to non-O. Given the reduced branching of ABO(H) bearing structures (I blood group system) with lower numbers of H, A, and B antigen sites during the first 18 months of life, we reasoned that if the relationship between ABO(H) blood group and VWF levels were causal, the difference of ABO(H) blood group–dependent VWF levels should be marginal or not be observed in the first months of life. STUDY DESIGN AND METHODS: We undertook quantification of FVIII : C and VWF in 574 presumably healthy children aged 1 to 210 months and correlated the values with ABO(H) blood type. Moreover, we establish reference intervals for common coagulation variables for several pediatric age groups. RESULTS: Significant differences between blood group O versus non-O values of FVIII : C, VWF : Ag, and VWF : RCo were not observed in the first months of life, started to develop during childhood, and in adolescence reached adult values. CONCLUSION: In comparison to the levels for adults and adolescents, we report fundamental differences of VWF levels in the first year of life, which may be associated with the physiologic development of the ABO(H) and I blood group system.

Background: Vitamin K deficiency is the major cause of coagulopathy-induced intracranial bleeding in term neonates and is considered first in any term neonate with severe hemorrhage. The most common manifestation of hereditary prothrombotic disorders during the neonatal period is thrombosis of the A. cerebri media or sinus thrombosis. Case Report: A 4-day-old newborn was admitted with seizures and hemorrhagic shock. Ultrasound revealed a left-sided intraparenchymatous bleeding. MRI findings supported a subarachnoidal and intracerebral mass bleeding. Vitamin K deficiency-related bleeding or hemophiliac diseases were excluded; however, homozygous protein S deficiency with a new mutation in the protein S (PROS1) gene (c.701A>G, p.Tyr234Cys) was found. The patient experienced an additional thrombosis of the A. abdominalis and expired. Conclusion: Congenital prothrombotic disorders have to be considered in the differential diagnosis of neonatal intracranial hemorrhage. This newly described mutation in the PROS1 gene (c.701A>G, p.Tyr234Cys) appears to be of clinical relevance.

BACKGROUND AND OBJECTIVES: Patient Blood Management (PBM) in Europe is a working group of the European Blood Alliance with the initial objective to identify the starting position of the participating hospitals regarding PBM for benchmarking purposes, and to derive good practices in PBM from the experience and expertise in the participating teams with the further aim of implementing and strengthening these practices in the participating hospitals.METHODS: We conducted two surveys in seven university hospitals in Europe: Survey on top indications for red blood cell use regarding usage of red blood cells during 1 week and Survey on PBM organization and activities.RESULTS: A total of 3320 units of red blood cells were transfused in 1 week at the seven hospitals. Overall, 61% of red cell units were transfused to medical patients and 36% to surgical patients, although there was much variation between hospitals. The organization and activities of PBM in the seven hospitals were variable, but there was a common focus on optimizing the treatment of bleeding patients, monitoring the use of blood components and treatment of preoperative anaemia.CONCLUSION: Although the seven hospitals provide a similar range of clinical services, there was variation in transfusion rates between them. Further, there was variable implementation of PBM activities and monitoring of transfusion practice. These findings provide a baseline to develop joint action plans to further implement and strengthen PBM across a number of hospitals in Europe.

Background Ebola virus disease is a public health emergency of international concern, and enormous efforts are being made in the development of vaccines and therapies. Ebola virus convalescent plasma is a promising anti-infective treatment of Ebola virus disease. Therefore, we developed and implemented a pathogen-reduced Ebola virus convalescent plasma concept in accordance with national, European and global regulatory framework. Materials and Methods Ebola virus convalescent plasma manufacture and distribution was managed by a collection centre, two medical centres and an expert group from the European Blood Alliance. Ebola virus convalescent plasma was collected twice with an interval of 61 days from a donor recovering from Ebola virus disease in Germany. After pathogen reduction, the plasma was analysed for Ebola virus-specific immunoglobulin G (IgG) antibodies and its Ebola virus neutralizing activity. Results Convalescent plasma could be collected without adverse events. Anti-Ebola virus IgG titres and Ebola-specific neutralizing antibodies in convalescent plasma were only slightly reduced after pathogen reduction treatment with S59 amotosalen/UVA. A patient in Italy with Ebola virus disease was treated with convalescent plasma without apparent adverse effects. Discussion As proof of principle, we describe a concept and practical implementation of pathogen-reduced Ebola virus convalescent plasma manufacture, quality control and its clinical application to an Ebola virus disease patient.

The risk of viral transmission via transfusion of packed red blood cells in Germany has reached an all-time low. The reasons comprise the selection of donors and the screening for pathogens such as hepatitis C virus (HCV) or human immunodeficiency virus (HIV) by molecular and serological methods. Transmission of transfusion-relevant viruses via blood products is nowadays a rare event, found only in isolated cases (1). For example, since the introduction of mandatory HCV-PCR (polymerase chain reaction) in Germany in 1999, there has been one single case of transfusion-related HCV transmission in 16 years. At an annual rate of about 4 million units of packed red cells, over 60 million units were transfused in this period (1). Modern production methods using closed blood bag systems and “inline” leukocyte depletion also contribute towards the safety of modern blood products. All steps of production are subject to quality controls to ensure good manufacturing practice (GMP). The use of blood preparations is closely regulated by: European Union directives The German Transfusion Act (TFG; [2]) The German Medical Association (GMA) guidelines on collection of blood and blood components and use of blood products (hemotherapy) (3) The “Cross-Sectional Guidelines for Therapy with Blood Components and Plasma Derivatives“ of the Scientific Advisory Board of the GMA (4). Safety The risk of viral transmission via transfusion of packed red cells in Germany has reached an all-time low. Transmission of transfusion-relevant viruses via blood products is nowadays a rare event. Germany as well as other member states of the European Union have carried EU directives over into their own laws and guidelines, so that these regulations and recommendations are largely similar in EU member states. Nevertheless, in English-speaking countries, for example, the bedside test and certain laboratory tests are not mandatory, but there is a compulsory ID check by means of the patient’s wrist band.

Introduction: A multicomponent, evidence-based and interdisciplinary Patient Blood Management (PBM) program was introduced at the University Hospital Frankfurt in July 2013. The implementation strategy included practical and tactical components aimed to increase knowledge on the risks of preoperative anemia, to standardize hemotherapy, and to facilitate PBM components. Methods: This article analyzes barriers to PBM implementation and outlines a strategy to introduce and manifest PBM. The effects in Frankfurt were measured in a before and after questionnaire study distributed among groups of physicians immediately before and 1 year after PBM implementation. Results: 142 clinicians completed the questionnaire in July 2013 and 101 clinicians in August 2014. Absolute certainty that the treatment of preoperative anemia favorably influences morbidity and mortality rose from 25 to 37%. Transfusion behavior seems to have been affected: In 2014, 56% of clinicians stated that they clinically reassess the patient and analyze hemoglobin following each single red blood cell unit compared to only 38% stating this in 2013. Conclusion: These results show that our implementation strategy was effective in changing physicians' risk perception, attitude, and knowledge on PBM principles. Our experience highlights key success factors for the implementation of a comprehensive PBM program.

Die praoperative Anamie ist ein unabhangiger Risikofaktor fur eine erhohte perioperative Morbiditat und Mortalitat. Im Rahmen des Patient Blood Managements (PBM) sollen Patienten mit Anamie zum fruhestmoglichen Zeitpunkt vor elektiven Eingriffen erfasst, die Ursachen der Anamie abgeklart und bei behandelbaren Ursachen der Anamie eine spezifische Behandlung eingeleitet werden. Dabei muss ein multidisziplinares Team mittels spezifischer Anamnese und korperlicher, Labor- sowie apparativer Untersuchung haufige und behandelbare Anamieursachen wie Eisenmangel, Blutungen oder (Autoimmun-)Hamolysen erkennen und praoperativ soweit wie moglich beheben bzw. therapieren. Das gelingt nur, wenn praoperativ Anasthesisten, Chirurgen, Hamatologen, Gastroenterologen, Gynakologen, Labor- und Transfusionsmediziner in einem PBM-Team mit einem gemeinsamen PBM-Plan zusammenarbeiten und die Kommunikation untereinander und mit den zuweisenden Kollegen reibungslos funktioniert.

Factitious anticoagulant-resistance as a cause of recurrent arterial bypass graft occlusions

Prospective validation of two algorithms for the initiation of phenprocoumon treatment.; Inpatients with new-onset anticoagulation were randomised to one of two computer assisted dosing algorithms, or to a control arm. The primary outcome measure was the time to achieve therapeutic anticoagulation without overshooting (INR

Transfusion of the 'wrong' stem cell product would almost inevitably be lethal, yet assays to confirm the contents of the product bag, except by checking labels and paperwork, are lacking. To increase the likelihood that a product mix-up would be detected in the transplant center, we developed a simple protocol for extended blood typing and hence, for confirmation of donor/product identity, on a tube segment. Apheresis samples were applied, directly or after erythrocyte enrichment, to commercially available blood typing assays, including lateral flow cards and gel agglutination cards. Without sample modification, low hematocrit and high leukocyte count obviated definitive blood typing. Using the most simple erythrocyte enrichment protocol, that is, centrifugation, reliable blood group analysis became possible with either assay. Other, more cumbersome pre-analytical protocols were also successful but provided no advantage. The preferred method was validated on 100 samples; ABD was correctly identified in 100% of cases. Of the other Rh Ags, all except two 'small e', in both cases in heterozygous individuals, were detected; there were no false positives. A simple, inexpensive point-of-care assay for extended blood typing of apheresis products is available, which can reduce the fatal risk of administering the wrong stem cell product.

SummaryCompared to warfarin, little is known about the effect of pharmacogenomics on the inter-individual variability of phenprocoumon therapy. In a retrospective cohort study, we investigated the impact of VKORC1 c.-1639G>A; CYP2C9*2, CYP2C9*3; GGCX c.214+597G>A; CALU c.*4A>G; EPHX1 c.337T>C; F7 c.-402G>A, and F7 c.-401G>T on the initiation (n=54) and maintenance phases (n=91) of phenprocoumon therapy. We assessed the following outcome parameters: time to stable international normalised ratio (INR), time to first supra-therapeutic INR, time out of INR range, probability of over-anticoagulation, number of anticoagulation clinic visits. During the initiation phase, homozygotes for the VKORC1 c.-1639 A and G alleles achieved stable INRs later (p

Background Our aim was to understand why some sera from patients with a broad spectrum of autoimmune diseases or non-autoimmune diseases involving enhanced apoptosis, cell lysis and/or putative secondary autoimmune processes show reactions in the tissue transglutaminase (TGc) ELISA used for diagnosis of gluten-sensitive disease. Methods Sera were compared from groups of patients with autoimmune diseases, diseases involving organ specific enhanced cell death, celiac disease or dermatitis herpetiformis, diseases of non-autoimmune origin, and a group without known disease. IgA antibodies against TGc were detected using human antigen (produced recombinantly in bacterial or human cells) in different systems (non-commercial ELISA with buffers of differing NaCl concentrations, and anti-TGc sandwich ELISA). Anti-gliadin and anti-endomysium antibodies were also determined. Results Many sera from patients with autoimmune disorders gave a positive signal in the human TGc ELISAs. The signal appeared related to minor impurities in the recombinant human TGc used and to raised serum IgA antibody levels rather than to the occurrence of TGc specific antibodies in these patients. Conclusions No association of anti-TGc Abs and autoimmune conditions independent of gluten-sensitive disease could be shown. Care should be taken to exclude copurification of chaperones, like heat shock protein 70, where preparing antigens for TGc ELISAs. Keywords: Tissue transglutaminase; Celiac disease; Gluten-sensitive disease; Autoimmunity; ELISA

SummaryIn order to elucidate the role of VCORC1 sequence variants in warfarin sensitivity, we established a complete SNP map of the VKORC1 gene locus in 200 blood donors from Western Germany. Nearly all of the genetic variability of the VKORC1 gene in Europeans is reflected by three main haplotypes. Recently described polymorphisms associated with low warfarin dose requirement (dbSNP:rs9934438; dbSNP:rs17878363) were found in complete linkage disequilibrium with the VKORC1*2 haplotype. In two patient cohorts of European origin with either increased coumarin sensitivity (n=14) or partial coumarin resistance (n=36) the VKORC1*2 frequency varied highly significant between the two groups and also when compared to 200 blood donor controls (coumarin sensitive 96%, coumarin resistant 7%, controls 42%) thus demonstrating a strong association between these two phenotypes and the VKORC1 haplotype (p = 1.6 x 10−8 for coumarin sensitive and p = 1.9 x 10−8 for coumarin resistant). Analysis of database derived VKORC1 genotypes of African Americans and Chinese revealed that haplotype frequencies in these populations differ significantly from the European sample (for VKORC1*2: Europeans 42%, Chinese 95%, African Americans 14%). These observations suggest VKORC1 as principal genetic modulator of the ethnic differences in warfarin response. Since hereditary pharmacodynamic (VKORC1) and pharmacokinetic (CYP2C9) factors account for up to 50% of the inter-individual variability of the warfarin response, these genetic markers may serve as clinically relevant predictors of warfarin dosing in future studies.

Background Hydroxyethyl starch (HES) 130/0.4 may impair blood coagulation less than other HES solutions and, thus, may be used at larger doses without increasing the risk of postoperative bleeding. This study tested the hypothesis that volume replacement with 6% HES 130/0.4 at a dose of up to 50 ml/kg does not increase blood loss and transfusion requirements in elective coronary artery bypass surgery compared with 6% HES 200/0.5 at a dose of up to 33 ml/kg. Methods One hundred twenty adult patients scheduled for elective coronary artery bypass surgery were randomized to receive up to 50 ml/kg of 6% HES 130/0.4 or up to 33 ml/kg of 6% HES 200/0.5 for volume replacement during surgery and until 24 h thereafter. Volume requirements in excess of the respective maximum dose of HES were treated with gelatin. Colloid use was at the discretion of the attending physicians and not dictated by protocol. The primary outcome variable was chest tube drainage volume during the first 24 h after surgery. Results The data from 117 patients (HES 130/0.4, 59 patients; HES 200/0.5, 58 patients) who completed the study according to protocol were analyzed. The median volumes of HES administered were 49 and 33 ml/kg in the HES 130/0.4 and HES 200/0.5 groups, respectively (P < 0.001). Consequently, patients in the HES 130/0.4 group required less gelatin in addition to HES than those in the HES 200/0.5 group (medians: 7 ml/kg vs. 20 ml/kg, P < 0.001). The combined volumes of HES and gelatin were similar for both groups (P = 0.21). The 24-h chest tube drainage (medians: 660 ml vs. 705 ml, P = 0.60) did not differ significantly between the groups, nor did transfusion outcome. Conclusion Six percent HES 130/0.4 at a median dose of 49 ml/kg did not increase blood loss and transfusion requirements in coronary artery bypass surgery compared with 6% HES 200/0.5 at a median dose of 33 ml/kg.

A Novel Point Mutation in the 3’ Region of the Prothrombin Gene at Position 20221 in a Lebanese/Syrian Family

Background Preoperative and hospital-acquired anaemia is common among surgical patients. It is associated with an increased risk of morbidity and mortality and a strong risk factor for allogeneic blood transfusions with their own inherent risks. Patient Blood Management (PBM) concepts aim to increase and preserve autologous erythrocyte volume and to optimise haemotherapy. They thus have great potential to benefit patients. Methods/Design This prospective, multi-centre clinical trial tests the hypothesis that PBM programs are safe and effective in the care of adult surgical patients. Primary outcome is a composite endpoint of adverse events and in-hospital mortality. Discussion This trial will determine whether the implementation of a PBM program is safe and effective in terms of clinical outcome compared to a pre-implementation cohort. This trial is registered at www.clinicaltrials.gov (NCT01820949).