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Thrombocytopenia is associated with increased mortality in COVID-19 patients. To determine the association between thrombocytopenia and alterations in host response pathways implicated in disease pathogenesis in patients with severe COVID-19. We studied COVID-19 patients admitted to a general hospital ward included in a national (CovidPredict) cohort derived from 13 hospitals in the Netherlands. In a subgroup, 43 host response biomarkers providing insight in aberrations in distinct pathophysiological domains (coagulation and endothelial cell function; inflammation and damage; cytokines and chemokines) were determined in plasma obtained at a single time point within 48 h after admission. Patients were stratified in those with normal platelet counts (150-400 × 109/L) and those with thrombocytopenia (<150 × 109/L). 6.864 patients were enrolled in the national cohort, of whom 1.348 had thrombocytopenia and 5.516 had normal platelets counts; the biomarker cohort consisted of 429 patients, of whom 85 with thrombocytopenia and 344 with normal platelet counts. Plasma D-dimer levels were not different in thrombocytopenia, although patients with moderate-severe thrombocytopenia (<100 × 109/L) showed higher D-dimer levels, indicating enhanced coagulation activation. Patients with thrombocytopenia had lower plasma levels of many proinflammatory cytokines and chemokines, and antiviral mediators, suggesting involvement of platelets in inflammation and antiviral immunity. Thrombocytopenia was associated with alterations in endothelial cell biomarkers indicative of enhanced activation and a relatively preserved glycocalyx integrity. Thrombocytopenia in hospitalized patients with severe COVID-19 is associated with broad host response changes across several pathophysiological domains. These results suggest a role of platelets in the immune response during severe COVID-19. [Display omitted] • Increased 21-day mortality • Lower plasma levels of many proinflammatory cytokines and chemokines • Lower plasma levels of mediators implicated in antiviral responses • Alterations in endothelial cell biomarkers indicative of enhanced activation [ABSTRACT FROM AUTHOR]

Background: The Netherlands Armed Forces (NLAF) are using −80°C deep‐frozen thrombocyte concentrate (DTC) since 2001. The aim of this study is to investigate the effect of storage duration and alterations in production/measurement techniques on DTC quality. It is expected that DTC quality is unaffected by storage duration and in compliance with the European guidelines for fresh and cryopreserved platelets. Study Design and Methods: Pre‐freeze and post‐thaw product platelet content and recovery were collected to analyze the effects of dimethyl sulfoxide (DMSO) type, duration of frozen storage (DMSO‐1 max 12 years and DMSO‐2 frozen DTC max 4 years at −80°C) and type of plasma used to suspend DTC. Coagulation characteristics of thawed DTC, plasma and supernatant of DTC (2× 2500 G) were measured with Kaolin thromboelastography (TEG) and phospholipid (PPL) activity assay. Results: Platelet content and recovery of DTC is ±10%–15% lower in short‐stored products and remained stable when stored beyond 0.5 years. Thawed DTC (n = 1724) were compliant to the European guidelines (98.1% post‐thaw product recovery ≥50% from original product, 98.3% ≥200 × 109 platelets/unit). Compared to DMSO‐1, products frozen with DMSO‐2 showed ±8% reduced thaw–freeze recovery, a higher TEG clot strength (MA 58 [6] vs. 64 [8] mm) and same ±11 s PPL clotting time. The use of cold‐stored thawed plasma instead of fresh thawed plasma did not influence product recovery or TEG‐MA. Discussion: Regardless of alterations, product quality was in compliance with European guidelines and unaffected by storage duration up to 12 years of −80°C frozen storage. [ABSTRACT FROM AUTHOR]

Background: The Netherlands Armed Forces have been successfully using deep-frozen (- 80 °C) thrombocyte concentrate (DTC) for the treatment of (massive) bleeding trauma patients in austere environments since 2001. However, high-quality evidence for the effectiveness and safety of DTCs is currently lacking. Therefore, the MAssive transfusion of Frozen bloOD (MAFOD) trial is designed to compare the haemostatic effect of DTCs versus room temperature-stored platelets (RSP) in the treatment of surgical bleeding.Methods: The MAFOD trial is a single-blinded, randomized controlled non-inferiority trial and will be conducted in three level 1 trauma centres in The Netherlands. Patients 12 years or older, alive at hospital presentation, requiring a massive transfusion including platelets and with signed (deferred) consent will be included. The primary outcome is the percentage of patients that have achieved haemostasis within 6 h and show signs of life. Haemostasis is defined as the time in minutes from arrival to the time of the last blood component transfusion (plasma/platelets or red blood cells), followed by a 2-h transfusion-free period. This is the first randomized controlled study investigating DTCs in trauma and vascular surgical bleeding.Discussion: The hypothesis is that the percentage of patients that will achieve haemostasis in the DTC group is at least equal to the RSP group (85%). With a power of 80%, a significance level of 5% and a non-inferiority limit of 15%, a total of 71 patients in each arm are required, thus resulting in a total of 158 patients, including a 10% refusal rate. The data collected during the study could help improve the use of platelets during resuscitation management. If proven non-inferior in civilian settings, frozen platelets may be used in the future to optimize logistics and improve platelet availability in rural or remote areas for the treatment of (massive) bleeding trauma patients in civilian settings.Trial Registration: ClinicalTrials.gov NCT05502809. Registered on 16 August 2022. [ABSTRACT FROM AUTHOR]

Introduction: Transfusion strategy for trauma patients with massive haemorrhage is often incorporated in massive transfusion protocols (MTP). Albeit correct MTP use results in better patient outcome, research regarding the state of MTP knowledge is scarce. The objective of this study is therefore to assess knowledge of local MTP and massive transfusion strategy in the level 1 trauma centres in the Netherlands. Our hypothesis is that actual MTP knowledge is low and transfusion strategy differs.Materials and Methods: Surveys were sent out in January 2020 to all trauma and vascular surgeons, anaesthesiologists, emergency department physicians of the largest level 1 trauma centre (locally, n = 113) and to one trauma surgeon, emergency physician and anaesthesiologist in each of the nine other governmentally assigned level 1 trauma centres in the Netherlands (nationally, n = 27). The respondents were subdivided into a frequent user group (MTP usage ≥ 4 times in 2019) and a non-frequent user group (MTP usage < 4 in 2019). Data are expressed as numbers and percentages.Results: Response rate was (n = 48; 42%) for the local survey and (n = 14; 52%) for the national survey. Locally, (n = 23; 48%) and (n = 25; 52%) respondents were defined frequent and non-frequent users respectively and national respondents all as frequent users. In total, (n = 13; 27%) of local respondents were aware of the current local composition of the MTP. Respondents indicated to transfuse erythrocytes first, followed by plasma and platelets (local non-frequent users n = 23; 92%, local frequent users n = 21; 91% and national frequent users n = 13; 93%). The indication for platelet transfusion was units erythrocytes transfused (local non-frequent users n = 10; 40% frequent users locally n = 11; 48% and nationally n = 5; 36%) and clinical view (local non-frequent users n = 9; 36%, frequent users locally n = 8; 35% and n<5 nationally. Whereas few respondents claimed (n = 5; 21% non-frequent users locally and n <5 nationally) to transfuse platelets based on platelet counts. Viscoelastic haemostatic assays were performed during MTP, but only by frequent users.Conclusion: The majority of physicians dealing with massive transfusion in trauma patients were not aware of the exact composition of the MTP and consensus regarding transfusion strategy and indication for platelet transfusion was low. [ABSTRACT FROM AUTHOR]

Light transmission aggregometry (LTA) is considered the gold standard method for evaluation of platelet function. However, there are a lot of variation in protocols (pre-analytical procedures and agonist concentrations) and results. The aim of our study was to establish a national LTA protocol, to investigate the effect of standardization and to define national reference values for LTA. The SSC guideline was used as base for a national procedure. Almost all recommendations of the SSC were followed e.g. no adjustment of PRP, citrate concentration of 109 mM, 21 needle gauge, fasting, resting time for whole blood and PRP, centrifugation time, speed and agonists concentrations. LTA of healthy volunteers was measured in a total of 16 hospitals with 5 hospitals before and after standardization. Results of more than 120 healthy volunteers (maximum aggregation %) were collected, with participating laboratories using 4 different analyzers with different reagents. Use of low agonist concentrations showed high variation before and after standardization, with the exception of collagen. For most high agonist concentrations (ADP, collagen, ristocetin, epinephrine and arachidonic acid) variability in healthy subjects decreased after standardization. We can conclude that a standardized Dutch protocol for LTA, based on the SSC guideline, does not result in smaller variability in healthy volunteers for all agonist concentrations. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to evaluate the incidence of transfusions, including red blood cells (RBC), platelets, and fresh frozen plasma (FFP) during and after coronary artery bypass grafting (CABG) in the Netherlands. Furthermore, the authors aimed to identify the impact of sex on blood product transfusion., Design: A retrospective multicenter cohort study. Data were collected from January 2013 to December 2021 from the Netherlands Heart Registration (NHR) database., Setting: The NHR receives its data from 16 heart centers in the Netherlands., Participants: Patients older than 18 years who underwent CABG in the Netherlands., Interventions: Coronary artery bypass grafting with extracorporeal circulation or off-pump coronary artery bypass grafting., Measurements and Main Results: The incidence of blood transfusion, defined as transfusions intraoperatively and during the length of the hospital admission after CABG. In addition, a differentiation was made according to the type of transfusion (packed RBC, platelets, and FFP). In the overall cohort (N = 42,388), the number of patients who received a transfusion of any type was 27.0% (n = 11,428). Women received more often RBC transfusions compared with men (45.4% v 15.6%, respectively, p < 0.001). There was a significant difference between the 2 sexes regarding platelet transfusion (women 10.0% v men 11.1%, p = 0.005) but not in FFP transfusion. Female sex was independently associated with RBC transfusion, using the multivariate logistic regression analysis., Conclusions: The incidence of any blood transfusion was 27.0%, and was higher in women than in men. The female sex was independently associated with receiving RBC during and after CABG., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Anaemia and coagulopathy are common issues in critically ill patients. Transfusion can be lifesaving, however, is associated with potential life threatening adverse events. As an international transfusion guideline for this specific patient population is lacking, we hypothesize that a high heterogeneity in transfusion practices exists. In this pilot-study we assessed transfusion practice in a university hospital in the Netherlands and tested the feasibility of this protocol for an international multi-centre study. A prospective single centre cohort study was conducted. For seven days all consecutive non-readmitted patients to the adult Intensive Care Unit (ICU) were included and followed for 28 days. Patients were prospectively followed until ICU discharge or up to day 28. Patient outcome data was collected at day 28. Workload for this study protocol was scored in hours and missing data. In total, 48 patients were included, needed in total three hours patient to include and collect all data, with 1.6% missing data showing the feasibility of the data acquisition. Six (12.5%) patients received red blood cells (RBCs), three patients (6.3%) received platelet concentrates, and two (4.2%) patients received plasma units. In total eight (16.7%) patients were transfused with one or more blood products. Median pre- and post-transfusion haemoglobin (Hb) levels were 7.6 (6.7–7.7) g/dL and 8.1 (7.6–8.7) g/dL, respectively. In this pilot-study we proved the feasibility of our protocol and observed in this small population a restrictive transfusion practice for all blood products. [ABSTRACT FROM AUTHOR]

The objective of this study is to estimate cost-effectiveness of pathogen inactivation for platelet transfusions in the Netherlands. We used decision tree analysis to evaluate the cost-effectiveness of the addition of pathogen inactivation of pooled platelets to standard procedures for platelet transfusion safety (such as, donor recruitment and screening). Data on transfusions were derived from the University Medical Centre Groningen (the Netherlands) for 1997. Characteristics of platelet recipients (patient group, age, gender and survival) and data/assumptions on viral and bacterial risks were linked to direct and indirect costs/benefits of pathogen inactivation. Post-transfusion survival was simulated with a Markov model. Standard methods for cost-effectiveness were used. Cost-effectiveness was expressed in net costs per life-year gained (LYG) and estimated in baseline- and sensitivity analysis. Sensitivity was analysed with respect to various assumptions including sepsis risk, reduction of the discard rate and discounting. Stochastic analysis to derive 90% simulation intervals (SIs) was performed on sepsis risk. Net costs per LYG for pathogen inactivation were estimated €554 000 in the baseline-weighted average over the three patient groups (90% SI: €354 000–1092 500). Sensitivity analysis revealed that cost-effectiveness was insensitive to viral risks and indirect costing, but highly sensitive to the assumed excess transfusions required and discounting of LYG. Given relatively high net costs per LYG that are internationally accepted for blood transfusion safety interventions, our estimated cost-effectiveness figures for pathogen inactivation may reflect acceptable cost-effectiveness in this specific area. Two main assumptions of our model were that the pathogen inactivation was 100% effective in preventing transmission of the pathogens considered and was not associated with major and/or costly adverse reactions. Validation of several crucial parameters is required, in particular the Dutch risk for acquiring and dying of transfusion-related sepsis. [ABSTRACT FROM AUTHOR]

Simple Summary: To define a healthy animal in an experimental setting or to differentiate and backup a diagnosis in cattle practice, reference intervals (RIs) in haematology diagnostics are necessary. The RIs in calves for blood cell counts, such as platelets and white blood cells, differ from RIs in adult cattle and are not widely studied. Blood results from dairy calves in the Netherlands were used to study the variation in platelet counts in young calves and to calculate an RI for platelet and white blood cell counts. In new-born calves up to six days of age, platelet counts were lower than in calves older than five days. From six days of age until 60 days of age we propose an RI platelet count of 287–1372 × 109/L and for the first 60 days of life an RI for leukocyte count of 4.0–18.9 × 109/L. Platelet and leukocyte count reference intervals (RIs) for cattle differ by age and while adult RIs are known, RIs for calves are studied less. The aims of this observational study are to evaluate variation of platelet counts of Holstein Friesian calves over the first 14 days of life and to propose RIs for platelet and leukocyte counts of Holstein Friesian calves aged 0–60 days. In a longitudinal study, 19 calves were blood sampled 17 times, in the first 14 days of their lives. Blood was collected in a citrate blood tube and platelet counts were determined. We assessed the course of platelet counts. In a field study, 457 healthy calves were blood sampled once. Blood was collected in an EDTA blood tube and platelet and leukocyte counts were determined. The RIs were calculated by the 2.5 and 97.5 percentiles. Platelet counts started to increase 24 h after birth (mean platelet count 381 × 109/L ± 138 × 109/L) and stabilized after five days (mean platelet count 642 × 109/L ± 265 × 109/L). In calves up to six days of age, platelet counts were lower than in calves older than five days. In conclusion, the RIs of platelet and leukocyte counts in calves were wider in range than the RIs for adult cattle, therefore, calf specific RIs for platelet and leukocyte counts should be used. From 6 until 60 days of age, we propose an RI for platelet counts of 287–1372 × 109/L and for the first 60 days of life an RI for leukocyte counts of 4.0–18.9 × 109/L. [ABSTRACT FROM AUTHOR]

Objectives: Massive transfusion protocols (MTPs) may improve survival in patients with uncontrolled haemorrhage. An MTP was introduced into the Dutch transfusion guidelines in 2011, the ninth edition of the advanced trauma life support course in 2012 and the third version of the European guideline in 2013. This is the first survey of MTPs in Dutch trauma centres., Methods: The aim of the study was to compare MTP strategies in level 1 trauma centres in The Netherlands, and with (inter)national guidelines. A contact in each government assigned level 1 trauma centre in The Netherlands and the Dutch Ministry of Defence was approached to share their MTPs and elucidate their protocol in a survey and oral follow-up interview., Results: All 11 level 1 trauma centres responded. The content of the packages and transfusion ratios (red blood cells/plasma/platelets) were 3:3:1, 5:5:1, 5:3:1, 2:3:1, 4:4:1, 5:2:1, 2:2:1 and 4:3:1. Tranexamic acid was used in all centres and an additional dose was administered in eight centres. Fibrinogen was given directly (n=4), with persistent bleeding (n=3), based on Clauss fibrinogen (n=3) or rotational thromboelastometry (n=1). All centres used additional medication in patients in the form of anticoagulants, but their use was ambiguous., Conclusion: MTPs differed between institutes and guidelines. The discrepancies in transfusion ratios can be explained by (inter)national differences in preparation and volume of blood components and/or interpretation of the '1:1:1' guideline. We recommend updating MTPs every year using the latest guidelines and evaluating the level of evidence for treatment during massive transfusion., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)