OBJECTIVE: To derive systematic review informed, modified Delphi consensus regarding monitoring and replacement of specific coagulation factors during pediatric extracorporeal membrane oxygenation (ECMO) support for the Pediatric ECMO Anticoagulation CollaborativE.
METHODS: A structured literature search was performed using PubMed, Embase, and Cochrane Library (CENTRAL) databases from January 1988 to May 2020, with an update in May 2021.
METHODS: Included studies assessed monitoring and replacement of antithrombin, fibrinogen, and von Willebrand factor in pediatric ECMO support.
METHODS: Two authors reviewed all citations independently, with conflicts resolved by a third reviewer if required. Twenty-nine references were used for data extraction and informed recommendations. Evidence tables were constructed using a standardized data extraction form.
RESULTS: Risk of bias was assessed using the Quality in Prognosis Studies tool. The evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation system. A panel of 48 experts met over 2 years to develop evidence-based recommendations and, when evidence was lacking, expert-based consensus statements. A web-based modified Delphi process was used to build consensus via the Research And Development/University of California Appropriateness Method. Consensus was defined as greater than 80% agreement. We developed one weak recommendation and four expert consensus statements.
CONCLUSIONS: There is insufficient evidence to formulate recommendations on monitoring and replacement of antithrombin, fibrinogen, and von Willebrand factor in pediatric patients on ECMO. Optimal monitoring and parameters for replacement of key hemostasis parameters is largely unknown.

Background: Chronic inflammation is a constant phenomenon which accompanies the heart failure pathophysiology. In all phenotypes of heart failure, irrespective of the ejection fraction, there is a permanent low-grade activation and synthesis of proinflammatory cytokines. Many classes of anti-remodelling medication used in the treatment of chronic heart failure have been postulated to have an anti-inflammatory effect. Methods: This retrospective study enrolled 220 patients and focused on evaluating the effect of the most used active substances from these classes in reducing the level of inflammatory biomarkers (C reactive protein, erythrocyte sedimentation rate and fibrinogen) after initiation or up-titration. Our research is evaluating if this anti-inflammatory effect intensifies while raising the dose. The evaluation was performed at two visits with an interval between them of 6 months. Results: From the beta-blockers class, carvedilol showed a reduction in erythrocyte sedimentation rate (ESR), in low (6.25 mg, bi daily) and medium (12.5 mg, bi daily) doses. At the same time, sacubitril/valsartan showed a reduction in CRP levels. This effect was obtained only in the medium (49/51 mg, bi daily) and high (97/103 mg, bi daily) doses, with the maximum reduction being observed in the high dose. Conclusions: From the classes of medication evaluated, the study showed a significant reduction in ESR levels in the low and medium doses of carvedilol and a reduction in CRP values in the cases of medium and high doses of ARNI.

BACKGROUND: Congenital dysfibrinogenemia (CD) is characterized by dysfunction induced by an abnormal fibrinogen molecule structure that results in blood coagulation dysfunction. The clinical manifestations of CD patients are asymptomatic, bleeding and thrombosis. The majority of patient are asymptomatic. However, the single fibrinogen detection method is easy to cause missed diagnosis or misdiagnosis of CD patients. The treatment strategies of CD patients with different clinical manifestations are also different.
METHODS: Combing the existing experimental diagnosis technology, literature and our research results, a simple and practical CD diagnostic criteria was proposed. And based on the relevant literature and existing treatment guidelines, more comprehensive treatment recommendations are summarized.
RESULTS: In this new criteria, combination Clauss method and PT derived method was proposed to detect fibrinogen and its ratio was used to diagnose for CD. Diagnosis also needs to be combined the clinical manifestations, family investigation and genetic testing. According to different clinical manifestation (bleeding, thrombosis or asymptomatic), treatment methods and strategies are different. The treatment of CD patients should consider the patient\'s personal and family history of bleeding or thrombosis. Treatment of thrombosis and pregnancy may be more challenging. The risk of bleeding and thrombosis should be evaluated and balanced at all times during clinical treatment. These detailed treatment recommendations can provide reference for patients with different clinical manifestations of CD.
CONCLUSIONS: The new CD diagnosis criteria and comprehensive treatment recommendations can effectively improve the diagnosis and treatment of CD.

This document is an update of the multidisciplinary document HEMOMAS, published in 2016 with the endorsement of the Spanish Scientific Societies of Anaesthesiology (SEDAR), Intensive Care (SEMICYUC) and Thrombosis and Haemostasis (SETH). The aim of this document was to review and update existing recommendations on the management of massive haemorrhage. The methodology of the update was based on several elements of the ADAPTE method by searching and adapting guidelines published in the specific field of massive bleeding since 2014, plus a literature search performed in PubMed and EMBASE from January 2014 to June 2021. Based on the review of 9 guidelines and 207 selected articles, the 47 recommendations in the original article were reviewed, maintaining, deleting, or modifying each of them and the accompanying grades of recommendation and evidence. Following a consensus process, the final wording of the article and the resulting 41 recommendations were approved by all authors.

This document is an update of the multidisciplinary document HEMOMAS, published in 2016 with the endorsement of the Spanish Scientific Societies of Anaesthesiology (SEDAR), Intensive Care (SEMICYUC) and Thrombosis and Haemostasis (SETH). The aim of this document was to review and update existing recommendations on the management of massive haemorrhage. The methodology of the update was based on several elements of the ADAPTE method by searching and adapting guidelines published in the specific field of massive bleeding since 2014, plus a literature search performed in PubMed and EMBASE from January 2014 to June 2021. Based on the review of 9 guidelines and 207 selected articles, the 47 recommendations in the original article were reviewed, maintaining, deleting, or modifying each of them and the accompanying grades of recommendation and evidence. Following a consensus process, the final wording of the article and the resulting 41 recommendations were approved by all authors.

Previous criteria for coagulation dysfunction in critically ill children were based mainly on expert opinion.
To evaluate current evidence regarding coagulation tests associated with adverse outcomes in children to inform criteria for coagulation dysfunction during critical illness.
Electronic searches of PubMed and Embase were conducted from January 1992 to January 2020 by using a combination of medical subject heading terms and text words to define concepts of coagulation dysfunction, pediatric critical illness, and outcomes of interest.
Studies were included if critically ill children with coagulation dysfunction were evaluated, if performance characteristics of assessment and/or scoring tools to screen for coagulation dysfunction were evaluated, and if outcomes related to mortality or functional status, organ-specific outcomes, or other patient-centered outcomes were assessed.
Data were abstracted from each eligible study into a standard data extraction form, along with risk of bias assessment, by a task force member.
The systematic review supports the presence of at least 2 of the following criteria reflecting coagulation dysfunction in the absence of liver dysfunction: platelet count <100 000 cells per μL, international normalized ratio >1.5, fibrinogen level <150 mg/dL, and D-dimer value above 10 times the upper limit of normal, or above the assay\'s upper limit of detection if this limit is below 10 times the upper limit of normal.
The proposed criteria for coagulation dysfunction are limited by the available evidence and will require future validation.
Validation of the proposed criteria and identified scientific priorities will enhance our understanding of coagulation dysfunction in critically ill children.

To date, data regarding the efficacy and safety of administering fibrinogen concentrate in cardiac surgery are limited. Studies are limited by their low sample size and large heterogeneity with regard to the patient population, by the timing of fibrinogen concentrate administration, and by the definition of transfusion trigger and target levels. Assessment of fibrinogen activity using viscoelastic point-of-care testing shortly before or after weaning from cardiopulmonary bypass in patients and procedures with a high risk of bleeding appears to be a rational strategy. In contrast, the use of Clauss fibrinogen test for determination of plasma fibrinogen level can no longer be recommended without restrictions due to its long turnaround time, high inter-assay variability and interference with high heparin levels and fibrin degradation products. Administration of fibrinogen concentrate for maintaining physiological fibrinogen activity in the case of microvascular post-cardiopulmonary bypass bleeding appears to be indicated. The available evidence does not suggest aiming for supranormal levels, however. Use of cryoprecipitate as an alternative to fibrinogen concentrate might be considered to increase plasma fibrinogen levels. Although conclusive evidence is lacking, fibrinogen concentrate does not seem to increase adverse outcomes (i.e., thromboembolic events). Large prospective multi-centre studies are needed to better define the optimal perioperative monitoring tool, transfusion trigger and target levels for fibrinogen replacement in cardiac surgery.

In the current study, we have developed predictive quantitative structure-activity relationship (QSAR) models for cellular response (foetal rate lung fibroblast proliferation) and protein adsorption (fibrinogen adsorption (FA)) on the surface of tyrosine-derived biodegradable polymers designed for tissue engineering purpose using a dataset of 66 and 40 biodegradable polymers, respectively, employing two-dimensional molecular descriptors. Best four individual models have been selected for each of the endpoints. These models are developed using partial least squares regression with a unique combination of six and four descriptors for cellular response and protein adsorption, respectively. The generated models were strictly validated using internal and external metrics to determine the predictive ability and robustness of proposed models. Subsequently, the validated individual models for each response endpoints were used for the generation of \'intelligent\' consensus models ( http://teqip.jdvu.ac.in/QSAR_Tools/DTCLab/ ) to improve the quality of predictions for the external data set. These models may help in prediction of virtual polymer libraries for rational design/optimization for properties relevant to biomedical applications prior to their synthesis.

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To evaluate the level of agreement between hematologists and emergency medicine physicians regarding the best clinical practices for managing bleeding and anticoagulant reversal.
Nationwide Spanish multicenter Delphi method study with a panel of experts on anticoagulation and the management of bleeding. Two survey rounds were carried out between April and September 2015. Consensus was reached when more than 75% of the panelists scored items in the same tertile.
Fifteen hematologists and 17 emergency medicine specialists from 14 Spanish autonomous communities participated. Consensus was reached on the use of both hemodialysis and an activated prothrombin complex concentrate (PCC) to antagonize significant/major bleeding in patients taking dabigatran. Use of an activated PCC was considered sufficient for patients on rivaroxaban or apixaban. The panel did not consider any PCC to be both effective and safe. Tests for activated partial thromboplastin, thrombin, diluted thrombin, and ecarin clotting times were considered useful in patients treated with dabigatran. A specific anti-Xa activity assay was suggested for patients who developed bleeds while treated with rivaroxaban or apixaban. Specific antidotes for direct-acting oral anticoagulants would be useful when severe bleeding occurs according to 97% of the panelists. Such antidotes would substantially change current treatment algorithms.
The points of consensus were generally in line with clinical practice guidelines, but the Delphi process revealed that there are aspects of the clinical management of bleeding that require unified criteria. The need for specific antidotes for direct-acting oral anticoagulants was emphasized.
Evaluar el grado de acuerdo entre hematólogos y urgenciólogos respecto a las mejores prácticas para el manejo de hemorragias y la reversión de la anticoagulación oral.
Estudio Delphi multicéntrico español con médicos expertos en anticoagulación y manejo de hemorragias. Se realizaron dos rondas de preguntas entre abril y septiembre de 2015. Se obtenía consenso cuando el 75% o más de los panelistas puntuaban en el mismo tercil.
Se encuestó a 15 hematólogos y 17 urgenciólogos de 14 comunidades autónomas. La hemodiálisis y la administración de concentrados de complejo protrombínico (CCP) activado fueron tratamientos consensuados para antagonizar una hemorragia relevante/mayor en pacientes tratados con dabigatrán. Para rivaroxabán y apixabán solo se consideró el CCP. El panel no valoró ningún CCP como eficaz y seguro a la vez. Los tiempos de tromboplastina parcial activado, trombina, ecarina y de trombina diluido se indicaron para pacientes tratados con dabigatrán y la actividad anti-Xa específica para los tratados con rivaroxabán y apixabán cuando presentan una hemorragia. Disponer de un antídoto específico para el tratamiento de los anticoagulantes orales de acción directa (ACOD) sería útil en caso de hemorragia grave (97%) y supondría un cambio sustancial en el algoritmo de tratamiento actual (97%).
Los resultados estuvieron en general alineados con las guías de práctica clínica, pero mostraron que existen áreas de mejora en la unificación de criterios sobre el manejo de los pacientes con hemorragias, y destacan la necesidad de disponer de antídotos específicos para ACOD.