Higher procoagulatory potential but lower DIC score in COVID-19 ARDS patients compared to non-COVID-19 ARDS patients.

BACKGROUND: COVID-19 is a novel viral disease. Severe courses may present as ARDS. Several publications report a high incidence of coagulation abnormalities in these patients. We aimed to compare coagulation and inflammation parameters in patients with ARDS due to SARS-CoV-2 infection versus patients with ARDS due to other causes. METHODS: This retrospective study included intubated patients admitted with the diagnosis of ARDS to the ICU at Munich university hospital. 22 patients had confirmed SARS-CoV2-infection (COVID-19 group), 14 patients had bacterial or other viral pneumonia (control group). Demographic, clinical parameters and laboratory tests including coagulation parameters and thromboelastometry were analysed. RESULTS: No differences were found in gender ratios, BMI, Horovitz quotients and haemoglobin values. The median SOFA score, serum lactate levels, renal function parameters (creatinine, urea) and all inflammation markers (IL-6, PCT, CRP) were lower in the COVID-19 group (all: p < 0.05). INR (p < 0.001) and antithrombin (p < 0.001) were higher in COVID-19 patients. D-dimer levels (p = 0.004) and consecutively the DIC score (p = 0.003) were lower in this group. In ExTEM®, Time-to-Twenty (TT20) was shorter in the COVID-19 group (p = 0.047), these patients also had higher FibTEM® MCF (p = 0.005). Further, these patients presented with elevated antigen and activity levels of von-Willebrand-Factor (VWF). CONCLUSION: COVID-19 patients presented with higher coagulatory potential (shortened global clotting tests, increased viscoelastic and VWF parameters), while DIC scores were lower. An intensified anticoagulation regimen based on an individual risk assessment is advisable to avoid thromboembolic complications.

The transcriptional landscape of polyploid wheat.

The coordinated expression of highly related homoeologous genes in polyploid species underlies the phenotypes of many of the world's major crops. Here we combine extensive gene expression datasets to produce a comprehensive, genome-wide analysis of homoeolog expression patterns in hexaploid bread wheat. Bias in homoeolog expression varies between tissues, with ~30% of wheat homoeologs showing nonbalanced expression. We found expression asymmetries along wheat chromosomes, with homoeologs showing the largest inter-tissue, inter-cultivar, and coding sequence variation, most often located in high-recombination distal ends of chromosomes. These transcriptionally dynamic genes potentially represent the first steps toward neo- or subfunctionalization of wheat homoeologs. Coexpression networks reveal extensive coordination of homoeologs throughout development and, alongside a detailed expression atlas, provide a framework to target candidate genes underpinning agronomic traits in wheat.

[Bridging anticoagulation in patients receiving vitamin K antagonists : Current status]. / Überbrückende Antikoagulation bei Patienten unter Vitamin-K-Antagonisten : Eine Bestandsaufnahme.

Approximately 30% of patients receiving oral anticoagulation using vitamin K antagonists (VKA) require surgery within 2 years. In this context, a clinical decision on the need and the mode of a peri-interventional bridging with heparin is needed. While a few years ago, bridging was almost considered a standard of care, recent study results triggered a discussion on which patients will need bridging at all. Revisiting the currently available recommendations and study results the conclusion can be drawn that the indications for bridging with heparin must nowadays be taken more narrowly and considering the individual patient risk of bleeding and thromboembolism. Bridging with heparin is only needed in patients with a very high risk of thromboembolism. This overview aims to give guidance for a risk-adapted peri-interventional approach to management of patients with a need for long-term anticoagulation using VKA.

[Bridging anticoagulation in patients receiving vitamin K antagonists : Current status]. / Überbrückende Antikoagulation bei Patienten unter Vitamin-K-Antagonisten : Eine Bestandsaufnahme.

Approximately 30% of patients receiving oral anticoagulation using vitamin K antagonists (VKA) require surgery within 2 years. In this context, a clinical decision on the need and the mode of a peri-interventional bridging with heparin is needed. While a few years ago, bridging was almost considered a standard of care, recent study results triggered a discussion on which patients will need bridging at all. Revisiting the currently available recommendations and study results the conclusion can be drawn that the indications for bridging with heparin must nowadays be taken more narrowly and considering the individual patient risk of bleeding and thromboembolism. Bridging with heparin is only needed in patients with a very high risk of thromboembolism. This overview aims to give guidance for a risk-adapted peri-interventional approach to management of patients with a need for long-term anticoagulation using VKA.

Target plasma factor levels for personalized treatment in haemophilia: a Delphi consensus statement.

BACKGROUND: Prophylactic replacement with factor concentrate is the optimal treatment for persons with severe haemophilia to avoid or minimize bleeding. This ultimately prevents or reduces joint disease and improves life expectancy and quality of life towards values matching those in the normal population. However, uncertainty still exists around the optimal regimens to be prescribed for prophylaxis. An increasing number of treating physicians and patients are showing interest in patient-tailored approaches to prophylaxis, which aim to harmonize the prophylaxis regimen with the patients' bleeding phenotype, levels of physical activity and a variety of other variables. METHODS: A modified Delphi technique was adopted to generate consensus. The expert panel met in person to set the objectives, be trained on the Delphi technique and agree on the desired level of consensus. Three iterations were used to identify the targets, the scenarios and their combinations. RESULTS: Twenty-eight scenarios and eight target levels were identified and used to issue recommendations. The panel reached the desired level of consensus on positive or negative recommendations. Areas where consensus was not reached were identified and proposed as areas for future research. Prospective assessment of the validity of most of the proposed targets is recommended. CONCLUSIONS: We have generated, by expert consensus, target plasma levels of factor concentrate to be used to tailor treatment for persons with haemophilia.

[Bleeding in patients receiving dual antiplatelet therapy after acute coronary syndrome - significance, prevention and interdisciplinary management]. / Interdisziplinäres Management von Blutungen unter dualer antithrombozytärer Therapie nach akutem Koronarsyndrom.

For secondary prevention of acute coronary syndrome, guidelines recommend dual antiplatelet therapy with acetylsalicylic acid and a P2Y12 receptor antagonist such as clopidogrel, prasugrel or ticagrelor for a period of 12 months. Premature discontinuation of dual antiplatelet therapy is associated with an increased risk of ischaemic events. However, antiplatelet therapy is also associated with an increased risk of bleeding that should not be under- or overestimated. To ensure an optimal care of patients receiving dual antiplatelet therapy after an acute coronary syndrome, an interdisciplinary group of experienced experts in the fields of cardiology, cardiac surgery, gastroenterology, anaesthesiology, intensive care and haemostaseology gathered bleeding-related information and developed recommendations relevant to daily clinical practice. These include the significance of bleeding events in the course of treatment, measures for bleeding prevention and the adequate care of patients with bleedings.

Climbing therapy under PK-tailored prophylaxis.

UNLABELLED: Climbing has a low risk of injury and strengthens the entire musculature. Due to its benefits in physical and mental health as well as its high fun factor climbing is an established way of therapy. So far, the usefulness of climbing therapy has not been shown for people with haemophilia (PWH). A crucial requirement for physical activity in PWH is regular prophylaxis. As the patient's individual pharmacokinetic (PK) response varies significantly, PK-tailored prophylaxis may decrease bleeding frequency. CASE REPORT: We describe a man (age 25 years) with severe haemophilia A who took part in an 8.5-month weekly climbing program under PK-tailored prophylaxis. Bleeding frequency, factor consumption, joint health (Haemophilia Joint Health Score, HJHS), quality of life (Haemo-QoL-A) and climbing performance (UIAA scale) were assessed before and after the training. Prior to the study, the patient was on demand treatment. The patient was started on standard prophylaxis for a 2 months period and then observed for 6.5 months under PK-tailored prophylaxis. PK-tailored prophylaxis was targeted to a trough level of 1-3%. For high-impact activities a factor activity >15%, for low-impact activities a factor activity >5% was suggested. RESULTS: Climbing therapy was safe. The bleeding rate decreased from 14 (2012) to 1 (during the study period of 8.5 months). The one bleeding event was due to a missed infusion and was not triggered by physical activity. The elimination half-life using Bayesian statistics was determined to be 16h. Using this half-life for PK-tailored prophylaxis reduced the factor VIII consumption in comparison to standard prophylaxis. Joint health was particularly improved in the categories range of motion and swelling. Quality of life scores stayed at a high level. Climbing performance improved by 1 grade. CONCLUSION: The combination of PK-tailored prophylaxis with therapeutic climbing improved clinical outcome in this young adult with severe haemophilia. The tailored concept for high- and low-impact activities appeared to be safe.

Measurement procedure for glucose in serum using liquid chromatography isotope dilution--tandem mass spectrometry (LC-ID-MS/MS).

BACKGROUND: We developed and validated a measurement procedure for glucose using liquid chromatography-isotope dilution tandem mass spectrometry. The proposed method is intended to be used for setting target values in EQAS samples and for certification of glucose reference materials, including those in biological matrices. METHODS: Serum samples were spiked with internal standard 13C6 D-glucose. Protein precipitation was performed with ethanol. The samples were vortexed and centrifuged. An aliquot of the supernatant was evaporated to dryness, the residue dissolved in elution buffer and injected into the LC-MS/MS system. Measurements were performed in the positive ion mode monitoring the Cs+ adducts for glucose at m/z 313 --> 132.9 and m/z 319 --> 132.9 for the internal standard. RESULTS: The coefficient of variation (CV) of the measurement procedure for lyophilized, liquid, and fresh serum samples was between 0.27 and 1.77%. The bias from certified target values for NIST reference materials was < or = 0.62%. A Deming regression comparison demonstrated a good correlation of results obtained with the proposed LC-ID-MS/MS method and target values obtained in the internationally accepted IFCC-RELA ring trial using JCTLM-recognized reference measurement procedures. CONCLUSIONS: The proposed LC-ID-MS/MS measurement procedure with traceability to SI units shows excellent accuracy and precision and is suitable for use as reference measurement procedure for certification of target values in lyophilized and fresh serum samples.

[Coagulation disorders in the intensive care station]. / Gerinnungsstörungen auf der Intensivstation.

Coagulation disorders are frequently encountered in the intensive care unit (ICU) and are challenging due to a variety of potential etiologies. Critically ill patients with coagulation abnormalities may present with an increased risk of bleeding, show coagulation activation resulting in thromboembolism, or have no specific symptoms. Hemostatic abnormalities observed in ICU patients range from isolated thrombocytopenia or prolonged global clotting tests to complex and life-threatening coagulation defects. Successful management of coagulation disorders requires prompt and accurate identification of the underlying cause. This review describes the most frequently occurring diagnoses found in intensive care patients with thrombocytopenia and coagulation test abnormalities and summarizes appropriate diagnostic interventions and current approaches to differential diagnosis.

[Perioperative management of patients with hemophilia]. / Perioperatives Management bei Patienten mit Hämophilie.

Hemophilia A and hemophilia B are X chromosome-linked congenital bleeding disorders caused by a deficiency or absence of activity of coagulation factor VIII (hemophilia A) or factor IX (hemophilia B), which are graded in different degrees of severity (mild, moderate, severe). Depending on the severity patients may experience spontaneous bleeding episodes or will develop excessive bleeding in the context of injuries or surgery. Hemophilia should not be a contraindication for an invasive procedure; however, a number of conditions are required to provide successful surgery and an uncomplicated and safe postoperative course. This review provides an overview of hemophilia and the key biochemical laboratory and clinical aspects as well as possible specific and non-specific treatment options and addresses the special needs for the perioperative care of these patients.

Group-specific amplification of HLA-DQA1 revealed a number of genomic full-length sequences including the novel HLA alleles DQA1*01:10 and DQA1*01:11.

In this article, we describe a subgroup-specific amplification assay for HLA-DQA1 that encompasses the whole coding region and allows us to sequence full-length HLA-DQA1 genes. We introduce the novel alleles HLA-DQA1*01:10 and HLA-DQA1*01:11. Moreover, we were able to confirm the full-length genomic sequence data of the alleles HLA-DQA1*01:07, HLA-DQA1*03:01:01, HLA-DQA1*03:02, HLA-DQA1*04:01:02, HLA-DQA1*04:02, HLA-DQA1*05:03, HLA-DQA1*05:05:01:02 and HLA-DQA1*06:01:01. A complete genomic overview of all six HLA-DQA1 allele groups is now available from the submission of our data to the IMGT/HLA database. Because our approach facilitates the analysis of all HLA-DQA1 allele sequences, HLA-DQA1 may become the first HLA locus from which all subgroup members will be known in detail in the near future.

Direct oral anticoagulants and antiplatelet agents. Clinical relevance and options for laboratory testing.

Oral anticoagulants and platelet receptor blockers are widely used in clinical practice with the aim of reducing the risk of thrombotic complications in patients with cardiovascular diseases. Their regular intake and adequate antithrombotic action is vital and this is way numerous assays have been developed for laboratory testing and monitoring of these agents. Available assays can be stratified into pharmacokinetic and pharmacodynamic assays. Such assays are increasingly used in clinical routine and their daily use is triggered by the advent of the novel direct oral anticoagulants (DOACs) as an alternative for vitamin K antagonist (VKA) treatment, which are dabigatran, rivaroxaban and apixaban, and by the advent of prasugrel or ticagrelor as an alternative for clopidogrel with regard to platelet P2Y12 receptor inhibition. In this review the most important and most commonly used laboratory assays are summarized as well as their clinical implications with the focus on DOACs as an alternative for VKAs and the different P2Y12 receptor blockers for antiplatelet treatment.

Candidate reference measurement procedures for chloride, potassium, sodium, calcium, magnesium, and lithium by inductively coupled plasma (isotope dilution) sector field mass spectrometry (ICP-(ID) SFMS) in serum.

BACKGROUND: Standardization of the measurement of electrolyte concentrations in serum is of considerable interest for quality assurance in patient care. To promote the ongoing process of standardization we developed candidate reference measurement procedures of highest metrological order for Cl, K, Na, Ca, Mg, and Li using ICP-(ID) SFMS. METHODS: Serum samples were diluted with 4 mmol/L nitric acid and were spiked with the internal standard for quantification, separately for each analyte. The samples were introduced in the ICP-SFMS device by continuous infusion using a peristaltic pump. The measurement results were compared with reference measurement procedure values obtained by atom absorption spectroscopy, flame emission spectroscopy, and coulometry. The measurement accuracy and precision was calculated by analyzing certified reference materials and EQAS samples. RESULTS: The mean coefficient of variation (CV) of the ICP-MS procedures for the serum samples was 0.65% for Cl, 0.46% for K, 0.51% for Na, 0.77% for Ca, 0.78% for Mg, and 0.58% for Li. The mean bias from target values of NIST certified reference materials was +0.85% for Cl, -0.46% for K, +0.68% for Na, -0.21% for Ca, +0.27% for Mg, and -0.39% for Li. CONCLUSIONS: Candidate reference measurement procedures for 6 electrolytes were developed by high performance magnetic sector field ICP-MS fulfilling the requirements of ISO 15193:2009 for reference measurement procedures with traceability to SI according to ISO 17511:2003 and can be used for setting target values in EQAS and for certification of reference materials.

The novel allele DRB1*07:23 was revealed by LABType HD DRB1 typing test and confirmed by sequence-based HLA typing.

The novel allele HLA-DRB1*07:23 shows a single nucleotide change in comparison to DRB1*07:01:01:01.