"Re-evaluation of variants of uncertain significance in patients with hereditary arrhythmogenic disorders".

Background: Genetic diagnostics support the diagnosis of hereditary arrhythmogenic diseases, but variants of uncertain significance (VUS) complicate matters, emphasising the need for regular reassessment. Our study aims to reanalyse rare variants in different genes in order to decrease VUS diagnoses and thus improve risk stratification and personalized treatment for patients with arrhythmogenic disorders.

Methods: Genomic DNA was analysed using Sanger sequencing and next-generation sequencing (NGS).

Concomitant hypofibrinogenemia and factor XI deficiency as rare cause of bleeding during urgent dentistry: case report and short review of the literature.

Hypofibrinogenemia and Factor XI deficiency are rare defects of hemostasis, potentially leading to spontaneous bleeding manifestations and increased bleeding risk during surgery, dentistry, and interventions. Due to the different mode of inheritance, the concomitance of both defects is extremely rare and the clinical management of combined hypofibrinogenemia and factor XI deficiency is not standardized. Here, we report a rare case of concomitant genetically determined hypofibrinogenemia and factor XI deficiency as a cause of increased spontaneous bleeding and bleeding complications during dentistry.

Monitoring the SARS-CoV-2 Pandemic: Prevalence of Antibodies in a Large, Repetitive Cross-Sectional Study of Blood Donors in Germany-Results from the SeBluCo Study 2020-2022.

SARS-CoV-2 serosurveillance is important to adapt infection control measures and estimate the degree of underreporting. Blood donor samples can be used as a proxy for the healthy adult population. In a repeated cross-sectional study from April 2020 to April 2021, September 2021, and April/May 2022, 13 blood establishments collected 134,510 anonymised specimens from blood donors in 28 study regions across Germany.

Liver-related aspects of gene therapy for hemophilia: need for collaborations with hepatologists.

Adeno-associated virus-based gene therapies hemophilia allow long-term transgene expression with reduced annual bleeding rates. Various liver-related aspects are involved in the different phases of gene therapy, such as assessment of liver health in the pretherapy period, patient selection and follow-up, maintenance of liver health after gene therapy, and management of potential short- and long-term adverse events. Increase in alanine aminotransferease is a common adverse event that requires rapid evaluation and an immunosuppressive approach.

Telemedical monitoring in patients with inborn cardiac disease - experience of a tertiary care centre.

Background: The number of cardiologically relevant genetic findings will continue to increase. This is due to the use of high-throughput sequencing techniques and the critical role of incidental findings in cardiac disease genes. Telemedicine can be a useful diagnostic tool to monitor the heart rhythm of patients with inborn cardiac diseases.

Hypofibrinogenemia and miscarriage: report of a first successful pregnancy under fibrinogen substitution and short review of the literature.

Disorders of fibrinogen have been reported to be associated not only with bleeding and thrombosis but also with miscarriage. Here, we report the case of a woman with genetically determined hypofibrinogenemia and recurrent miscarriages who had a first successful pregnancy under fibrinogen substitution. Current knowledge on fibrinogen disorders and recurrent miscarriages is briefly summarized and discussed.

Genetic analysis of sudden unexpected death cases: Evaluation of library preparation methods to handle heterogeneous sample material.

Over the past years, next-generation sequencing (NGS) technologies revolutionized the possibilities in a broad range of application areas. Also in the field of forensic genetics, NGS continuously gained in importance and attentiveness. A significant number of sudden cardiac deaths (SCD) in the young is due to heritable arrhythmia syndromes emphasizing the need of examining the genetic basis in these cases also with regard to the identification of relatives and/or patients being at risk.

Characterization of an N-terminal Na1.5 channel variant - a potential risk factor for arrhythmias and sudden death?

Background: Alterations in the SCN5A gene encoding the cardiac sodium channel Na1.5 have been linked to a number of arrhythmia syndromes and diseases including long-QT syndrome (LQTS), Brugada syndrome (BrS) and dilative cardiomyopathy (DCM), which may predispose to fatal arrhythmias and sudden death. We identified the heterozygous variant c.

Prevalence of natural and acquired antibodies to amustaline/glutathione pathogen reduced red blood cells.

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.

Sudden unexpected death in the young - Value of massive parallel sequencing in postmortem genetic analyses.

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 (aged <45years) by means of a defined gene panel using massive parallel sequencing (MPS).

Elevated lipoprotein (a) levels are an independent risk factor for retinal vein occlusion.

Purpose: To investigate the prevalence of lipoprotein (a) [Lp(a)] and other thrombophilic disorders among retinal vein occlusion (RVO) patients with regard to age and various risk factors.

Methods: We retrospectively reviewed the medical records of 100 patients with central, hemicentral or branch RVO who had undergone routine thrombophilia screening. Data were compared with 100 controls.

Patient Blood Management in Europe: surveys on top indications for red blood cell use and Patient Blood Management organization and activities in seven European university hospitals.

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.

Prediction of the pathogenicity of antithrombin sequence variations by in silico methods.

Computational prediction tools have been developed to aid in the interpretation of novel sequence variations, but their utility within the diagnostic setting of antithrombin (AT) deficiency has not been evaluated to date. The aim of our study was to test the performance of different bioinformatic tools (Meta-SNP, MutPred, nsSNPAnalyzer, PANTHER, PhD-SNP, PMut, SIFT, SNAP, SNPs&Go, PolyPhen-2, PON-P2, and PredictSNP) in predicting the pathogenicity of AT sequence variations. We analysed all naturally occurring SERPINC1 missense mutations that have been previously characterised to be damaging with regard to the secretion or function of the AT molecule.

Bleeding and non-bleeding phenotypes in patients with GGCX gene mutations.

Functional limitations for the vitamin K cycle, caused either by mutations in gamma-glutamyl carboxylase or vitamin K epoxide reductase genes, result in hereditary deficiency of vitamin K-dependent coagulation factors (VKCFD1 and VKCFD2, respectively). Patients suffering from VKCFD often share several other anatomical irregularities which are not related to haemostasis. Here we report on nine patients, eight of them previously unreported, who presented with VKCFD1.

Travel habits and complications in patients treated with vitamin K antagonists: a cross sectional analysis.

Background: Travel-related conditions have impact on the quality of oral anticoagulation therapy (OAT) with vitamin K-antagonists. No predictors for travel activity and for travel-associated haemorrhage or thromboembolic complications of patients on OAT are known.

Methods: A standardised questionnaire was sent to 2500 patients on long-term OAT in Austria, Switzerland and Germany.

Impact of the type of SERPINC1 mutation and subtype of antithrombin deficiency on the thrombotic phenotype in hereditary antithrombin deficiency.

Mutations 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).

Performance of five D-dimer assays for the exclusion of symptomatic distal leg vein thrombosis.

The diagnostic value of D-dimer (DD) in the exclusion of proximal deep-vein thrombosis (DVT) is well-established but is less well-known in the exclusion of distal (infrapopliteal) DVT. Therefore, we evaluated the diagnostic abilities of five DD assays (Vidas-DD, Liatest-DD, HemosIL-DD, HemosIL-DDHS, Innovance-DD) for excluding symptomatic proximal and distal leg DVT. A total of 243 outpatients whose symptoms were suggestive of DVT received complete compression ultrasonography (cCUS) of the symptomatic leg(s).

Prediction of phenprocoumon maintenance dose and phenprocoumon plasma concentration by genetic and non-genetic parameters.

Purpose: The anticoagulation response to vitamin K antagonists is characterised by high inter-individual variability. The impact of single nucleotide polymorphisms (SNPs) in several genes of enzymes involved in the vitamin K cycle on phenprocoumon dose variability and phenprocoumon plasma concentrations is still under investigation.

Methods: We assessed the influence of VKORC1 c.

Impact of pharmacokinetic (CYP2C9) and pharmacodynamic (VKORC1, F7, GGCX, CALU, EPHX1) gene variants on the initiation and maintenance phases of phenprocoumon therapy.

Compared 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.

VKORC1 haplotypes and their impact on the inter-individual and inter-ethnical variability of oral anticoagulation.

In 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.

Evaluation of an automated high-volume extraction method for viral nucleic acids in comparison to a manual procedure with preceding enrichment.

Background And Objectives: Nucleic acid extraction still harbours the potential for improvements in automation and sensitivity of nucleic acid amplification technology (NAT) testing. This study evaluates the feasibility of a novel automated high-volume extraction protocol for NAT minipool testing in a blood bank setting.

Materials And Methods: The chemagic Viral DNA/RNA Kit special for automated purification of viral nucleic acids from 9.