Publications by authors named "Hugo Ten Cate"

329 Publications

Antiplatelet Therapy in Patients With COVID-19-More Is Less?

JAMA 2022 01;327(3):223-224

Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jama.2021.23866DOI Listing
January 2022

Unequal prescription of anticoagulants among females and males with atrial fibrillation and similar stroke risk - should we omit sex category from the CHA2DS2-VASc score?

Heart Rhythm 2022 Jan 13. Epub 2022 Jan 13.

Department of Cardiology, Rijnstate, Arnhem, the Netherlands; Department of Cardiology, Radboud University Medical Center, Nijmegen, the Netherlands.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.hrthm.2022.01.014DOI Listing
January 2022

Current and novel biomarkers of thrombotic risk in COVID-19: a Consensus Statement from the International COVID-19 Thrombosis Biomarkers Colloquium.

Nat Rev Cardiol 2022 Jan 13. Epub 2022 Jan 13.

Heart, Lung and Vascular Institute, University of Cincinnati College of Medicine, Cincinnati, OH, USA.

Coronavirus disease 2019 (COVID-19) predisposes patients to thrombotic and thromboembolic events, owing to excessive inflammation, endothelial cell activation and injury, platelet activation and hypercoagulability. Patients with COVID-19 have a prothrombotic or thrombophilic state, with elevations in the levels of several biomarkers of thrombosis, which are associated with disease severity and prognosis. Although some biomarkers of COVID-19-associated coagulopathy, including high levels of fibrinogen and D-dimer, were recognized early during the pandemic, many new biomarkers of thrombotic risk in COVID-19 have emerged. In this Consensus Statement, we delineate the thrombotic signature of COVID-19 and present the latest biomarkers and platforms to assess the risk of thrombosis in these patients, including markers of platelet activation, platelet aggregation, endothelial cell activation or injury, coagulation and fibrinolysis as well as biomarkers of the newly recognized post-vaccine thrombosis with thrombocytopenia syndrome. We then make consensus recommendations for the clinical use of these biomarkers to inform prognosis, assess disease acuity, and predict thrombotic risk and in-hospital mortality. A thorough understanding of these biomarkers might aid risk stratification and prognostication, guide interventions and provide a platform for future research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41569-021-00665-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8757397PMC
January 2022

Rotational Thromboelastometry in High-Risk Patients on Dual Antithrombotic Therapy After Percutaneous Coronary Intervention.

Front Cardiovasc Med 2021 22;8:788137. Epub 2021 Dec 22.

Central Diagnostic Laboratory, Maastricht University Medical Center+, Maastricht, Netherlands.

Patients using antithrombotic drugs after percutaneous coronary intervention (PCI) are at risk for bleeding and recurrent ischemia. We aimed to explore routine and tissue plasminogen activated (tPA) ROTEM results in a post-PCI population on dual antithrombotic treatment. In this prospective cohort, 440 patients treated with double antithrombotic therapy after recent PCI and with ≥3 risk factors for either ischemic or bleeding complications were included and compared with a control group ( = 95) consisting of perioperative patients not using antithrombotic medication. Laboratory assessment, including (tPA) ROTEM, was performed one month post-PCI and bleeding/ischemic complications were collected over a five-month follow-up. Patients were stratified by antithrombotic regimen consisting of a P2Y12 inhibitor with either aspirin (dual antiplatelet therapy; DAPT, = 323), a vitamin K antagonist (VKA, = 69) or a direct oral anticoagulant (DOAC, = 48). All post-PCI patients had elevated ROTEM clot stiffness values, but only the DAPT group additionally presented with a decreased fibrinolytic potential as measured with tPA ROTEM. Patients receiving anticoagulants had prolonged clotting times (CT) when compared to the control and DAPT group; EXTEM and FIBTEM CT could best discriminate between patients (not) using anticoagulants (AUC > 0.97). Furthermore, EXTEM CT was significantly prolonged in DAPT patients with bleeding complications during follow-up (68 [62-70] vs. 62 [57-68], = 0.030). ROTEM CT has high potential for identifying anticoagulants and tPA ROTEM could detect a diminished fibrinolytic potential in patients using DAPT. Furthermore, the ability of EXTEM CT to identify patients at risk for bleeding may be promising and warrants further research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcvm.2021.788137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8727359PMC
December 2021

Platelet Activation Mechanisms and Consequences of Immune Thrombocytopenia.

Cells 2021 12 1;10(12). Epub 2021 Dec 1.

Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, 6200 MD Maastricht, The Netherlands.

Autoimmune disorders are often associated with low platelet count or thrombocytopenia. In immune-induced thrombocytopenia (IIT), a common mechanism is increased platelet activity, which can have an increased risk of thrombosis. In addition, or alternatively, auto-antibodies suppress platelet formation or augment platelet clearance. Effects of the auto-antibodies are linked to the unique structural and functional characteristics of platelets. Conversely, prior platelet activation may contribute to the innate and adaptive immune responses. Extensive interplay between platelets, coagulation and complement activation processes may aggravate the pathology. Here, we present an overview of the reported molecular causes and consequences of IIT in the most common forms of autoimmune disorders. These include idiopathic thrombocytopenic purpura (ITP), systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS), drug-induced thrombocytopenia (DITP), heparin-induced thrombocytopenia (HIT), COVID-19 vaccine-induced thrombosis with thrombocytopenia (VITT), thrombotic thrombocytopenia purpura (TTP), and hemolysis, the elevated liver enzymes and low platelet (HELLP) syndrome. We focus on the platelet receptors that bind auto-antibodies, the immune complexes, damage-associated molecular patterns (DAMPs) and complement factors. In addition, we review how circulating platelets serve as a reservoir of immunomodulatory molecules. By this update on the molecular mechanisms and the roles of platelets in the pathogenesis of autoimmune diseases, we highlight platelet-based pathways that can predispose for thrombocytopenia and are linked thrombotic or bleeding events.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cells10123386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8699996PMC
December 2021

ChAdOx1 vaccination, blood coagulation, and inflammation: No effect on coagulation but increased interleukin-6.

Res Pract Thromb Haemost 2021 Dec 7;5(8):e12630. Epub 2021 Dec 7.

Department of Surgery Radboud Institute of Health Sciences (RIHS) Radboud University Medical Center Nijmegen The Netherlands.

Background: Vaccination is the leading approach in combatting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. ChAdOx1 nCoV-19 vaccination (ChAdOx1) has been linked to a higher frequency of rare thrombosis and thromboembolism. This study aimed to explore markers related to the blood coagulation system activation and inflammation, before and after ChAdOx1 vaccination.

Patients And Methods: An observational cohort study including 40 health care workers. Whole blood samples were collected before, and either 1 or 2 days after vaccination. Activated coagulation factors in complex with their natural inhibitors were determined by custom ELISAs, including thrombin:antithrombin (T:AT), kallikrein:C1-esterase-inhibitor (PKa:C1Inh), factor(F)IXa:AT, FXa:AT, FXIaAT, FXIa:alpha-1-antitrypsin (α1AT), FXIa:C1inh, and FVIIa:AT. Plasma concentrations of interleukin (IL)-6 and IL-18 were quantified via ELISA. Analyses were performed using Wilcoxon signed-rank test.

Results: Levels of FVIIa:AT decreased with a median (IQR) of 707 (549-1028) pg/ml versus 598 (471-996) pg/ml,  = 0.01; and levels of IL-6 increased, 4.0 (1.9-6.8) pg/ml versus 6.9 (3.6-12.2) pg/ml,  = 0.02, after vaccination. No changes were observed in T:AT, PKa:C1Inh, FIXa:AT, FXa:AT, FXIaAT, FXIa:α1AT, FXIa:C1inh, and IL-18.

Conclusion: ChAdOx1 leads to an inflammatory response with increased levels of IL-6. We did not observe activation of the blood coagulation system 1-2 days following vaccination.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/rth2.12630DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8652129PMC
December 2021

HEROES V-V-HEmorRhagic cOmplications in Veno-Venous Extracorporeal life Support-Development and internal validation of multivariable prediction model in adult patients.

Artif Organs 2021 Dec 13. Epub 2021 Dec 13.

Division of Cardiothoracic Surgery, University of Utah Health, Salt Lake City, Utah, USA.

Background: During extracorporeal life support (ECLS), bleeding is one of the most frequent complications, associated with high morbidity and increased mortality, despite continuous improvements in devices and patient care. Risk factors for bleeding complications in veno-venous (V-V) ECLS applied for respiratory support have been poorly investigated. We aim to develop and internally validate a prediction model to calculate the risk for bleeding complications in adult patients receiving V-V ECLS support.

Methods: Data from adult patients reported to the extracorporeal life support organization (ELSO) registry between the years 2010 and 2020 were analyzed. The primary outcome was bleeding complications recorded during V-V ECLS. Multivariable logistic regression with backward stepwise elimination was used to develop the predictive model. The performance of the model was tested by discriminative ability and calibration with receiver operating characteristic curves and visual inspection of the calibration plot.

Results: In total, 18 658 adult patients were included, of which 3 933 (21.1%) developed bleeding complications. The prediction model showed a prediction of bleeding complications with an AUC of 0.63. Pre-ECLS arrest, surgical cannulation, lactate, pO , HCO , ventilation rate, mean airway pressure, pre-ECLS cardiopulmonary bypass or renal replacement therapy, pre-ECLS surgical interventions, and different types of diagnosis were included in the prediction model.

Conclusions: The model is based on the largest cohort of V-V ECLS patients and reveals the most favorable predictive value addressing bleeding events given the predictors that are feasible and when compared to the current literature. This model will help identify patients at risk of bleeding complications, and decision making in terms of anticoagulation and hemostatic management.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/aor.14148DOI Listing
December 2021

Thrombin generation by calibrated automated thrombography in goat plasma: Optimization of an assay.

Res Pract Thromb Haemost 2021 Dec 21;5(8):e12620. Epub 2021 Nov 21.

Department of Biochemistry and Internal Medicine Cardiovascular Research Institute Maastricht Maastricht University Medical Center Maastricht The Netherlands.

The goat model of atrial fibrillation (AF) allows investigation of the effect of AF on coagulation. However, assays for goat plasma are not available from commercial sources. Calibrated automated thrombography (CAT) provides a global view of the coagulation profile by assessing thrombin generation (TG). We describe the customization of the CAT assay in goat platelet-poor plasma (PPP) and in factor Xa (FXa)-inhibitor-anticoagulated PPP. TG was initiated in the presence of phospholipids and either (a) PPP reagent, reagent low, or reagent high; (b) goat brain protein extraction (GBP); or (c) Russell's viper venom-factor X activator (RVV-X). Contact activation was assessed by adding corn trypsin inhibitor. Different concentrations of prothrombin complex concentrate (PCC) were used to determine the sensitivity of both the GBP and RVV-X method. To obtain FXa-inhibitor anticoagulated plasma, rivaroxaban was added to plasma. TG settings with human reagents were not suitable for goat plasma. TG triggered with GBP increased peak height and ETP values. Similarly, the RVV-X method produced comparable TG curves and was more sensitive to PCC titration. Finally, both methods were able to detect the decrease in clotting potential induced by FXa inhibition. This is the first study that reports the customization of the CAT assay for goats. The GBP and RVV-X methods were comparable in triggering TG in goat plasma. The RVV-X method seemed to better discriminate changes in TG curves due to increases in clotting potential as well as to FXa inhibition by rivaroxaban in goat plasma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/rth2.12620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8606030PMC
December 2021

Coagulation Factor Xa Induces Proinflammatory Responses in Cardiac Fibroblasts via Activation of Protease-Activated Receptor-1.

Cells 2021 10 30;10(11). Epub 2021 Oct 30.

Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, 6200 MD Maastricht, The Netherlands.

Coagulation factor (F) Xa induces proinflammatory responses through activation of protease-activated receptors (PARs). However, the effect of FXa on cardiac fibroblasts (CFs) and the contribution of PARs in FXa-induced cellular signalling in CF has not been fully characterised. To answer these questions, human and rat CFs were incubated with FXa (or TRAP-14, PAR-1 agonist). Gene expression of pro-fibrotic and proinflammatory markers was determined by qRT-PCR after 4 and 24 h. Gene silencing of (PAR-1) and (PAR-2) was achieved using siRNA. MCP-1 protein levels were measured by ELISA of FXa-conditioned media at 24 h. Cell proliferation was assessed after 24 h of incubation with FXa ± SCH79797 (PAR-1 antagonist). In rat CFs, FXa induced upregulation of (MCP-1; >30-fold at 4 h in atrial and ventricular CF) and (IL-6; ±7-fold at 4 h in ventricular CF). Increased MCP-1 protein levels were detected in FXa-conditioned media at 24 h. In human CF, FXa upregulated the gene expression of (>3-fold) and (>4-fold) at 4 h. Silencing of (PAR-1 gene), but not (PAR-2 gene), downregulated this effect. Selective activation of PAR-1 by TRAP-14 increased and gene expression; this was prevented by (PAR-1 gene) knockdown. Moreover, SCH79797 decreased FXa-induced proliferation after 24 h. In conclusion, our study shows that FXa induces overexpression of proinflammatory genes in human CFs via PAR-1, which was found to be the most abundant PARs isoform in this cell type.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cells10112958DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8616524PMC
October 2021

Variation of platelet function in clinical phenotypes of acute venous thromboembolism - Results from the GMP-VTE project.

J Thromb Haemost 2021 Nov 16. Epub 2021 Nov 16.

Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.

Background: The role of platelets in the pathogenesis of venous thromboembolism (VTE) is receiving increasing attention; however, limited information is available on platelet function in the acute phase of the disease.

Objective: To characterize platelet function according to VTE phenotypes.

Patients/methods: In total, 154 subjects (isolated pulmonary embolism [iPE], n = 28; isolated deep vein thrombosis [iDVT], n = 35; DVT+PE, n = 91) were included. In this study platelet function analyzer (PFA)-200, light transmission aggregometry (LTA), thrombin generation (TG) in presence (PRP) and absence (PFP) of platelets and platelet flow cytometry were investigated. LASSO regression was used to select clinical and platelet biomarkers that distinguish between VTE phenotypes.

Results: PFA-200 results did not differ between VTE phenotypes. LTA from DVT+PE subjects showed lowest maximum aggregation after epinephrine and adenosine diphosphate compared to iPE and iDVT. Lower % of PAC-1-positive platelets after in-vitro trigger were present in DVT+PE and iPE compared to iDVT. TG in PRP had lower peak height and velocity in DVT+PE and iPE against iDVT. The results of LASSO regression for the distinction between DVT+PE vs iDVT identified 18 variables (AUC =0.93) of which 72% were platelet biomarkers. For distinction between iPE and iDVT, 10 variables were selected (AUC = 0.96) of which 50% were platelet-related. Obesity was the only variable weakly discriminating between DVT+PE vs iPE (AUC = 0.66).

Conclusion: This explorative study suggests an important distinction between PE-related phenotypes and iDVT when considering clinical and platelet function data. Lower platelet-dependent TG along with reduced platelet reactivity suggest higher platelet degranulation in PE-dependent phenotypes compared to iDVT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jth.15595DOI Listing
November 2021

Potential value of the calibrated automated thrombogram in patients after a cerebral venous sinus thrombosis; an exploratory study.

Thromb J 2021 Nov 4;19(1):81. Epub 2021 Nov 4.

Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, the Netherlands.

Background: Cerebral venous sinus thrombosis (CVST) is a relatively rare, but potentially lethal condition. In approximately 15% of the patients, the cause of CVST remains unclear. Conventional clotting tests such as prothrombin time and activated partial thromboplastin time are not sensitive enough to detect prothrombotic conditions nor mild haemostatic abnormalities. The calibrated automated thrombogram (CAT) is a physiological function test that might be able to detect minor aberrations in haemostasis. Therefore, we aimed to detect the presence of a prothrombotic state in patients who endured idiopathic CVST with the CAT assay.

Methods: Five adult patients with an idiopathic, radiologically proven CVST that had been admitted during the past 3 years were included in this study. The control group consisted of five age/gender matched healthy volunteers. Exclusion criteria were known haematological disorders, malignancy (current/past) or hormonal and anticoagulant therapy recipients. We obtained venous blood samples from all participants following cessation of anticoagulation. Using the CAT assay, we determined lag time, normalized endogenous thrombin potential (ETP), ETP reduction and normalized peak height. In addition, prothrombin concentrations were determined.

Results: We found no significant differences in lag time (4.7 min [4.5-4.9] vs 5.3 min [3.7-5.7], p = 0.691), normalized ETP (142% [124-148] vs 124% [88-138], p = 0.222), ETP reduction (29% [26-35] vs 28% [24-58], p > 0.999), and normalized peak height (155% [153-175] vs 137 [94-154], p = 0.056) between patients and their age/gender matched controls. In addition, prothrombin concentrations did not significantly differ between patients and controls (120% [105-132] vs 127% [87-139], p > 0.999).

Conclusion: Reasons for absent overt hypercoagulability within this study population may be the small patient sample, long time since the event (e.g. 3 years) and avoidance of acquired risk factors like oral contraception. Given the fact that CVST is a serious condition with a more than negligible risk of venous thrombosis event recurrence, exclusion of clinically relevant hypercoagulability remains a challenging topic to further study at the acute and later time points, particularly in patients with idiopathic CVST.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12959-021-00335-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8567338PMC
November 2021

Using the Functional Resonance Analysis Method to explore how elastic compression therapy is organised and could be improved from a multistakeholder perspective.

BMJ Open 2021 10 12;11(10):e048331. Epub 2021 Oct 12.

Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands.

Objectives: Elastic compression stocking (ECS) therapy is an important treatment for patients with deep venous thrombosis (DVT) and chronic venous insufficiency (CVI). This study aimed to provide insight into the structure and variability of the ECS therapy process, its effects on outcomes, and to elicit improvement themes from a multiple stakeholder perspective.

Design: Thirty semi-structured interviews with professionals and patients were performed. The essential functions for the process of ECS therapy were extracted to create two work-as-done models using the Functional Resonance Analysis Method (FRAM). These findings were used to guide discussion between stakeholders to identify improvement themes.

Setting: Two regions in the Netherlands, region Limburg and region North-Holland, including an academic hospital and a general hospital and their catchment region.

Participants: The interviewees were purposely recruited and included 25 healthcare professionals (ie, general practitioners, internists, dermatologists, nurses, doctor's assistants, occupational therapists, home care nurses and medical stocking suppliers) and 5 patients with DVT or CVI.

Results: Two FRAM models were created (one for each region). The variability of the functions and their effect on outcomes, as well as interdependencies between functions, were identified. These were presented in stakeholder meetings to identify the structure of the process and designated variable and uniform parts of the process and its outcomes. Ultimately, six improvement themes were identified: dissemination of knowledge of the entire process; optimising and standardising initial compression therapy; optimising timing to contact the medical stocking supplier (when oedema has disappeared); improving the implementation of assistive devices; harmonising follow-up duration for patients with CVI; personalising follow-up and treatment duration in patients with DVT.

Conclusions: This study provided a detailed understanding of how ECS therapy is delivered in daily practice by describing major functions and variability in performances and elicited six improvement themes from a multistakeholder perspective.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2020-048331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8513256PMC
October 2021

Hemostasis and fibrinolysis in COVID-19 survivors 6 months after intensive care unit discharge.

Res Pract Thromb Haemost 2021 Aug 24;5(6):e12579. Epub 2021 Sep 24.

Central Diagnostic Laboratory Maastricht University Medical Centre+ Maastricht the Netherlands.

Background: The prothrombotic phenotype has been extensively described in patients with acute coronavirus disease 2019 (COVID-19). However, potential long-term hemostatic abnormalities are unknown.

Objective: To evaluate the changes in routine hemostasis laboratory parameters and tissue-type plasminogen activator (tPA) rotational thromboelastometry (ROTEM) 6 months after COVID-19 intensive care unit (ICU) discharge in patients with and without venous thromboembolism (VTE) during admission.

Methods: Patients with COVID-19 of the Maastricht Intensive Care COVID cohort with tPA ROTEM measurement at ICU and 6-month follow-up were included. TPA ROTEM is a whole blood viscoelastic assay that illustrates both clot development and fibrinolysis due to simultaneous addition of tissue factor and tPA. Analyzed ROTEM parameters include clotting time, maximum clot firmness (MCF), lysis onset time (LOT), and lysis time (LT).

Results: Twenty-two patients with COVID-19 were included and showed extensive hemostatic abnormalities before ICU discharge. TPA ROTEM MCF (75 mm [interquartile range, 68-78]-59 mm [49-63];  ≤ .001), LOT (3690 seconds [2963-4418]-1786 seconds [1465-2650];  ≤ .001), and LT (7200 seconds [6144-7200]-3138 seconds [2591-4389];  ≤ .001) normalized 6 months after ICU discharge. Of note, eight and four patients still had elevated fibrinogen and D-dimer concentrations at follow-up, respectively. In general, no difference in median hemostasis parameters at 6-month follow-up was observed between patients with (n=14) and without (n=8) VTE, although fibrinogen appeared to be lower in the VTE group (VTE-, 4.3 g/L [3.7-4.7] vs VTE+, 3.4 g/L [3.2-4.2];  = .05).

Conclusions: Six months after COVID-19 ICU discharge, no persisting hypercoagulable or hypofibrinolytic profile was detected by tPA ROTEM. Nevertheless, increased D-dimer and fibrinogen concentrations persist up to 6 months in some patients, warranting further exploration of the role of hemostasis in long-term morbidity after hospital discharge.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/rth2.12579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8463660PMC
August 2021

Ruling out Pulmonary Embolism in Patients with (Suspected) COVID-19-A Prospective Cohort Study.

TH Open 2021 Jul 15;5(3):e387-e399. Epub 2021 Sep 15.

Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, South-Holland, The Netherlands.

 Diagnostic strategies for suspected pulmonary embolism (PE) have not been prospectively evaluated in COVID-19 patients.  Prospective, multicenter, outcome study in 707 patients with both (suspected) COVID-19 and suspected PE in 14 hospitals. Patients on chronic anticoagulant therapy were excluded. Informed consent was obtained by opt-out approach. Patients were managed by validated diagnostic strategies for suspected PE. We evaluated the safety (3-month failure rate) and efficiency (number of computed tomography pulmonary angiographies [CTPAs] avoided) of the applied strategies.  Overall PE prevalence was 28%. YEARS was applied in 36%, Wells rule in 4.2%, and "CTPA only" in 52%; 7.4% was not tested because of hemodynamic or respiratory instability. Within YEARS, PE was considered excluded without CTPA in 29%, of which one patient developed nonfatal PE during follow-up (failure rate 1.4%, 95% CI 0.04-7.8). One-hundred seventeen patients (46%) managed according to YEARS had a negative CTPA, of whom 10 were diagnosed with nonfatal venous thromboembolism (VTE) during follow-up (failure rate 8.8%, 95% CI 4.3-16). In patients managed by CTPA only, 66% had an initial negative CTPA, of whom eight patients were diagnosed with a nonfatal VTE during follow-up (failure rate 3.6%, 95% CI 1.6-7.0).  Our results underline the applicability of YEARS in (suspected) COVID-19 patients with suspected PE. CTPA could be avoided in 29% of patients managed by YEARS, with a low failure rate. The failure rate after a negative CTPA, used as a sole test or within YEARS, was non-negligible and reflects the high thrombotic risk in these patients, warranting ongoing vigilance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-0041-1735155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8443402PMC
July 2021

Differential Impact of Cytochrome 2C19 Allelic Variants on Three Different Platelet Function Tests in Clopidogrel-Treated Patients.

J Clin Med 2021 Sep 3;10(17). Epub 2021 Sep 3.

Laboratory for Clinical Thrombosis and Haemostasis, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, 6200 MD Maastricht, The Netherlands.

On-treatment platelet reactivity in clopidogrel-treated patients can be measured with several platelet function tests (PFTs). However, the agreement between different PFTs is only slight to moderate. Polymorphisms of the gene have an impact on the metabolization of clopidogrel and, thereby, have an impact on on-treatment platelet reactivity. The aim of the current study is to evaluate the differential effects of the genotype on three different PFTs.

Methods: From a prospective cohort study, we included patients treated with clopidogrel following percutaneous coronary intervention (PCI). One month after PCI, we simultaneously performed three different PFTs; light transmission aggregometry (LTA), VerifyNow P2Y12, and Multiplate. In whole EDTA blood, genotyping of the polymorphisms was performed.

Results: We included 308 patients treated with clopidogrel in combination with aspirin (69.5%) and/or anticoagulants (33.8%) and, based on genotyping, classified them as either extensive (36.4%), rapid (34.7%), intermediate (26.0%), or poor metabolizers (2.9%). On-treatment platelet reactivity as measured by LTA and VerifyNow is significantly affected by metabolizer status ( < 0.01); as metabolizer status changes from rapid, via extensive and intermediate, to poor, the mean platelet reactivity increases accordingly ( < 0.01). On the contrary, for Multiplate, no such ordering of metabolizer groups was found ( = 0.10).

Conclusions: For VerifyNow and LTA, the on-treatment platelet reactivity in clopidogrel-treated patients correlates well with the underlying polymorphism. For Multiplate, no major effect of genetic background could be shown, and effects of other (patient-related) variables prevail. Thus, besides differences in test principles and the influence of patient-related factors, the disagreement between PFTs is partly explained by differential effects of the genotype.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm10173992DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8432532PMC
September 2021

Special Issue: "The Latest Clinical Advances in Thrombocytopenia".

J Clin Med 2021 Aug 5;10(16). Epub 2021 Aug 5.

Center for Thrombosis and Hemostasis, University Medical Center Mainz, Johannes Gutenberg University, 55131 Mainz, Germany.

Platelets are critical elements in the blood stream, supporting hemostasis as well as performing even more complex tasks within networks of biological (immunity) and pathophysiological processes, such as cancer and ischemia/reperfusion injury [...].
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm10163463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8397007PMC
August 2021

A known unknown? Pharmacological prevention of venous thromboembolism in nursing home residents.

J Am Geriatr Soc 2021 11 23;69(11):3338-3343. Epub 2021 Aug 23.

Department of Internal Medicine, Section Vascular Medicine and Thrombosis Expert Center, Maastricht University Medical Center+, Maastricht, The Netherlands.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jgs.17422DOI Listing
November 2021

Surviving Covid-19 with Heparin?

Authors:
Hugo Ten Cate

N Engl J Med 2021 08 4;385(9):845-846. Epub 2021 Aug 4.

From the Thrombosis Expertise Center, Department of Internal Medicine, Maastricht University Medical Center and Cardiovascular Research Institute Maastricht, Maastricht, the Netherlands, and the Center for Thrombosis and Hemostasis, Gutenberg University Medical Center, Mainz, Germany.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1056/NEJMe2111151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8362589PMC
August 2021

Different circulating biomarkers in women and men with paroxysmal atrial fibrillation: results from the AF-RISK and RACE V studies.

Europace 2021 07 30. Epub 2021 Jul 30.

Department of Cardiology, University of Groningen, University Medical Centre Groningen, Groningen, Hanzeplein 1, 9713 GZ, The Netherlands.

Aims: The clinical risk profile of atrial fibrillation (AF) patients is different in men and women. Our aim was to identify sex differences in blood biomarkers in patients with paroxysmal AF.

Methods And Results: Sex differences in 92 blood biomarkers were measured in 364 patients included in our discovery cohort, the identification of a risk profile to guide atrial fibrillation therapy (AF-RISK) study, assessed by multivariable logistic regression and enrichment pathway analysis. Findings were subsequently confirmed in 213 patients included in our validation cohort, the Reappraisal of Atrial Fibrillation: Interaction between HyperCoagulability, Electrical remodelling, and Vascular Destabilisation in the Progression of AF (RACE V) study. In the discovery cohort, mean age was 59 ± 12 years, 41% were women. CHA2DS2-VASc-score was 1.6 ± 1.4. A total of 46% had hypertension, 10% diabetes, and 50% had heart failure, predominantly with preserved ejection fraction (47%). In women, activated leucocyte cell adhesion molecule (ALCAM) and fatty acid binding protein-4 (FABP-4) were higher. In men, matrix metalloproteinase-3 (MMP-3), C-C motif chemokine-16 (CCL-16), and myoglobin were higher. In the validation cohort, four out of five biomarkers could be confirmed: levels of ALCAM (P = 1.73 × 10-4) and FABP-4 (P = 2.46 × 10-7) and adhesion biological pathways [false discovery rate (FDR) = 1.23 × 10-8] were higher in women. In men, levels of MMP-3 (P = 4.31 × 10-8) and myoglobin (P = 2.10 × 10-4) and markers for extracellular matrix degradation biological pathways (FDR = 3.59 × 10-9) were higher.

Conclusion: In women with paroxysmal AF, inflammatory biomarkers were more often higher, while in men with paroxysmal AF, biomarkers for vascular remodelling were higher. Our data support the clinical notion that pathophysiological mechanisms in women and men with AF may differ.

Trial Registration: Clinicaltrials.gov identifier NCT01510210 for AF-RISK; Clinicaltrials.gov NCT02726698 for RACE V.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/europace/euab179DOI Listing
July 2021

Quality of life in patients with pulmonary embolism treated with edoxaban versus warfarin.

Res Pract Thromb Haemost 2021 Jul 14;5(5):e12566. Epub 2021 Jul 14.

Daiichi Sankyo Pharma Development Basking Ridge NJ USA.

Background: Long-term sequelae of acute pulmonary embolism (PE) include decreased quality of life (QoL). Evidence suggests that adequacy of initial anticoagulant treatment in the acute phase of venous thrombosis has a key impact on late postthrombotic complications. We hypothesize that patients with acute PE treated with edoxaban for acute PE experience have improved QoL compared to those treated with warfarin.

Methods: Patients with PE who participated in the Hokusai-VTE trial were contacted between June 2017 and September 2020 for a single long-term follow-up visit. Main outcomes were the generic and disease-specific QoL measured by the 36-Item Short Form Health Survey (SF-36) and Pulmonary Embolism Quality of Life questionnaire.

Results: We included 251 patients from 26 centers in eight countries, of which 129 (51%) had been assigned to edoxaban and 122 (49%) to warfarin. Patient- and thrombus-specific characteristics were similar in both groups. Mean time since randomization in the Hokusai-VTE trial was 7.0 years (standard deviation, 1.0). No relevant or statistical differences were observed in the QoL for patients treated with edoxaban compared to patients treated with warfarin. The mean difference between patients treated with edoxaban and patients with PE treated with warfarin was 0.8 (95% confidence interval [CI]. -1.6 to 3.2) for the SF-36 summary mental score and 1.6 (95% CI, -0.9 to 4.1) for summary physical score.

Conclusion: Our findings indicate that patients with an index PE treated with edoxaban or warfarin have a similar long-term QoL. Since our study was a follow-up study from a well-controlled clinical trial setting, future studies should be designed in a daily clinical practice setting. We suggest a longitudinal design for investigation of changes in QoL over time.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/rth2.12566DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8279124PMC
July 2021

Soluble Platelet Release Factors as Biomarkers for Cardiovascular Disease.

Front Cardiovasc Med 2021 21;8:684920. Epub 2021 Jun 21.

Departments of Biochemistry and Internal Medicine, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, Netherlands.

Platelets are the main players in thrombotic diseases, where activated platelets not only mediate thrombus formation but also are involved in multiple interactions with vascular cells, inflammatory components, and the coagulation system. Although reactivity of platelets provides information on the function of circulating platelets, it is not a full reflection of the activation state, which may be relevant for thrombotic risk assessment in various disease conditions. Therefore, studying release markers of activated platelets in plasma is of interest. While this type of study has been done for decades, there are several new discoveries that highlight the need for a critical assessment of the available tests and indications for platelet release products. First, new insights have shown that platelets are not only prominent players in arterial vascular disease, but also in venous thromboembolism and atrial fibrillation. Second, knowledge of the platelet proteome has dramatically expanded over the past years, which contributed to an increasing array of tests for proteins released and shed from platelets upon activation. Identification of changes in the level of plasma biomarkers associated with upcoming thromboembolic events allows timely and individualized adjustment of the treatment strategy to prevent disease aggravation. Therefore, biomarkers of platelet activation may become a valuable instrument for acute event prognosis. In this narrative review based on a systematic search of the literature, we summarize the process of platelet activation and release products, discuss the clinical context in which platelet release products have been measured as well as the potential clinical relevance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcvm.2021.684920DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255615PMC
June 2021

Sex-Specific Relationship Between Parathyroid Hormone and Platelet Indices in Phenotypes of Heart Failure-Results From the MyoVasc Study.

Front Cardiovasc Med 2021 16;8:682521. Epub 2021 Jun 16.

DZHK (German Center for Cardiovascular Research), Partner Site Rhine Main, Mainz, Germany.

Heart failure (HF) is a multifactorial syndrome with pathophysiological complexities still not fully understood. Higher mean platelet volume (MPV), a potential marker of platelet activation, and high concentrations of parathyroid hormone (PTH) have been implicated in the pathogenesis of HF. This study aims to investigate sex-specifically the association between PTH concentrations and platelet indices in phenotypes of HF. PTH and platelet indices (MPV and platelet count) were available in 1,896 participants from the MyoVasc study in Mainz, Germany. Multivariable linear regression models, adjusted for age, sex, season, vitamin D status, cardiovascular risk factors, comorbidities, estimated glomerular filtration rate, and medication, were used to assess the associations between platelet indices and PTH. The results showed distinct sex-specific associations between PTH and platelet indices. A positive association between PTH and MPV was found in females with symptomatic HF with reduced ejection fraction (HFrEF) only [β = 0.60 (0.19; 1.00)]. Platelet count was inversely associated with PTH in male HFrEF individuals [β = -7.6 (-15; -0.30)] and in both males and females with HF with preserved ejection fraction (HFpEF). This study reports differential, sex-specific relationships between PTH and platelet indices in HF individuals independent of vitamin D status and clinical profile. Particularly in phenotypes of symptomatic HF, distinct associations were observed, suggesting a sex-specific mechanism involved in the interaction between PTH and platelets.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcvm.2021.682521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245004PMC
June 2021

Activated factor XI-antithrombin complex presenting as an independent predictor of 30-days mortality in out-of-hospital cardiac arrest patients.

Thromb Res 2021 08 29;204:1-8. Epub 2021 May 29.

Stavanger University Hospital, Department of Cardiology, Stavanger, Norway; University of Bergen, Department of Clinical Science, Bergen, Norway.

Background: Cardiac arrest and cardiopulmonary resuscitation (CPR) are associated with activated coagulation and microvascular fibrin deposition with subsequent multiorgan failure and adverse outcome.

Objectives: Activated Factor XI-antithrombin (FXIa-AT) complex, activated Factor IX-antithrombin (FIXa-AT) complex and thrombin-antithrombin (TAT) complex were measured as markers of coagulation activation, and evaluated as independent prognostic indicators in out-of-hospital cardiac arrest (OHCA) patients.

Methods: From February 2007 until December 2010 blood samples were collected in close approximation to CPR from patients with OHCA of assumed cardiac origin. Follow-up samples in survivors were drawn 8-12 h and 24-48 h after hospital admission. All measurements were determined by ELISA.

Results: Thirty-seven patients presented with asystole and 77 with ventricular fibrillation as first recorded heart rhythm. At 30-days follow-up, 70 patients (61.4%) had died. All patients had elevated levels of FXIa-AT complex, FIXa-AT complex and TAT. Initial levels were significantly higher in non-survivors compared to 30-days survivors. A significant increase in risk of 30-days all-cause mortality was observed through increasing quartiles of all three biomarkers in univariate Cox regression analysis. Compared to the lowest quartile (Q1), only FXIa-AT complex levels in Q3 (HR 3.17, p = 0.011) and Q2 (HR 3.02, p = 0.016) were independently associated with all-cause mortality in the multivariable analysis. FIXa-AT complex and TAT-complex did not behave as independent predictors.

Conclusions: Complexes of FXIa-AT were independently associated with 30-days survival in OHCA-patients.

Clinical Trial Registration: ClinicalTrials. gov, NCT02886273.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.thromres.2021.05.014DOI Listing
August 2021

Serial markers of coagulation and inflammation and the occurrence of clinical pulmonary thromboembolism in mechanically ventilated patients with SARS-CoV-2 infection; the prospective Maastricht intensive care COVID cohort.

Thromb J 2021 May 31;19(1):35. Epub 2021 May 31.

Department of Intensive Care Medicine, Maastricht University Medical Centre+, Maastricht, The Netherlands.

Background: The incidence of pulmonary thromboembolism is high in SARS-CoV-2 patients admitted to the Intensive Care. Elevated biomarkers of coagulation (fibrinogen and D-dimer) and inflammation (c-reactive protein (CRP) and ferritin) are associated with poor outcome in SARS-CoV-2. Whether the time-course of fibrinogen, D-dimer, CRP and ferritin is associated with the occurrence of pulmonary thromboembolism in SARS-CoV-2 patients is unknown. We hypothesise that patients on mechanical ventilation with SARS-CoV-2 infection and clinical pulmonary thromboembolism have lower concentrations of fibrinogen and higher D-dimer, CRP, and ferritin concentrations over time compared to patients without a clinical pulmonary thromboembolism.

Methods: In a prospective study, fibrinogen, D-dimer, CRP and ferritin were measured daily. Clinical suspected pulmonary thromboembolism was either confirmed or excluded based on computed tomography pulmonary angiography (CTPA) or by transthoracic ultrasound (TTU) (i.e., right-sided cardiac thrombus). In addition, patients who received therapy with recombinant tissue plasminogen activator were included when clinical instability in suspected pulmonary thromboembolism did not allow CTPA. Serial data were analysed using a mixed-effects linear regression model, and models were adjusted for known risk factors (age, sex, APACHE-II score, body mass index), biomarkers of coagulation and inflammation, and anticoagulants.

Results: Thirty-one patients were considered to suffer from pulmonary thromboembolism ((positive CTPA (n = 27), TTU positive (n = 1), therapy with recombinant tissue plasminogen activator (n = 3)), and eight patients with negative CTPA were included. After adjustment for known risk factors and anticoagulants, patients with, compared to those without, clinical pulmonary thromboembolism had lower average fibrinogen concentration of - 0.9 g/L (95% CI: - 1.6 - - 0.1) and lower average ferritin concentration of - 1045 μg/L (95% CI: - 1983 - - 106) over time. D-dimer and CRP average concentration did not significantly differ, 561 μg/L (- 6212-7334) and 27 mg/L (- 32-86) respectively. Ferritin lost statistical significance, both in sensitivity analysis and after adjustment for fibrinogen and D-dimer.

Conclusion: Lower average concentrations of fibrinogen over time were associated with the presence of clinical pulmonary thromboembolism in patients at the Intensive Care, whereas D-dimer, CRP and ferritin were not. Lower concentrations over time may indicate the consumption of fibrinogen related to thrombus formation in the pulmonary vessels.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12959-021-00286-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165953PMC
May 2021

CAVA (Ultrasound-Accelerated Catheter-Directed Thrombolysis on Preventing Post-Thrombotic Syndrome) Trial: Long-Term Follow-Up Results.

J Am Heart Assoc 2021 06 25;10(11):e018973. Epub 2021 May 25.

CARIM Cardiovascular Research Institute MaastrichtSchool for Cardiovascular DiseasesMaastricht University Medical Centre Maastricht the Netherlands.

Background The CAVA (Ultrasound-Accelerated Catheter-Directed Thrombolysis Versus Anticoagulation for the Prevention of Post-Thrombotic Syndrome) trial did not show a reduction of post-thrombotic syndrome (PTS) after additional ultrasound-accelerated catheter-directed thrombolysis in patients with acute iliofemoral deep vein thrombosis at 1-year follow-up. This prespecified analysis of the CAVA trial aimed to determine the impact of additional thrombolysis on outcomes of PTS at long-term follow-up. Methods and Results Patients aged 18 to 85 years with a first-time acute iliofemoral deep vein thrombosis were included and randomly assigned (1:1) to either standard treatment plus ultrasound-accelerated catheter-directed thrombolysis or standard treatment alone. The primary outcome was the proportion of PTS (Villalta score ≥5 on 2 occasions ≥3 months apart or venous ulceration) at the final follow-up visit. Additionally, PTS according to the International Society on Thrombosis and Haemostasis (ISTH) consensus definition was assessed to allow external comparability. Major bleedings were the main safety outcome. At a median follow-up of 39.0 months (interquartile range, 23.3-63.8), 120 patients (79.8%) participated in the final follow-up visit: 62 from the intervention group and 58 from the standard treatment group. PTS developed in 19 (30.6%) versus 26 (44.8%) patients, respectively (odds ratio [OR], 0.54; 95% CI, 0.26 to 1.15 [=0.11]), with an absolute difference between groups of -14.2% (95% CI, -32.0% to 4.8%). Using the ISTH consensus definition, a significant reduction in PTS was observed (29 [46.8%] versus 40 [69.0%]) (OR, 0.40; 95% CI, 0.19-0.84 [=0.01]) with an absolute difference between groups of -22.2% (95% CI, -39.8% to -2.8%). No new major bleedings occurred following the 12-month follow-up. Conclusions The impact of additional ultrasound-accelerated catheter-directed thrombolysis on the prevention of PTS was found to increase with time. Although this study was limited by its sample size, the overall findings indicate a reduction of mild PTS without impact on quality of life. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00970619.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/JAHA.120.018973DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8483549PMC
June 2021

Thrombosis: Grand Challenges Ahead!

Authors:
Hugo Ten Cate

Front Cardiovasc Med 2021 4;8:637005. Epub 2021 May 4.

Thrombosis Expertise Center, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, Netherlands.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcvm.2021.637005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129168PMC
May 2021

Serial EXTEM, FIBTEM, and tPA Rotational Thromboelastometry Observations in the Maastricht Intensive Care COVID Cohort-Persistence of Hypercoagulability and Hypofibrinolysis Despite Anticoagulation.

Front Cardiovasc Med 2021 26;8:654174. Epub 2021 Apr 26.

Central Diagnostic Laboratory, Maastricht University Medical Centre+, Maastricht, Netherlands.

Coronavirus Disease 2019 (COVID-19) patients often present with thromboembolic events. In COVID-19 patients, routine hemostatic assays cannot correctly identify patients at risk for thromboembolic events. Viscoelastic testing with rotational thromboelastometry (ROTEM) might improve the characterization of COVID-19-associated coagulopathy. To unravel underlying coagulopathy and fibrinolysis over time as measured by serial assessment heparin-independent (FIBTEM and EXTEM) and fibrinolysis illustrating (tissue plasminogen activator; tPA) ROTEM assays. Between April 23 and June 12, consecutive adult patients enrolled within the Maastricht Intensive Care COVID (MaastrICCht) cohort were included, and a comprehensive set of clinical, physiological, pharmaceutical, and laboratory variables were collected daily. Twice per week, EXTEM, FIBTEM, and tPA ROTEM were performed. Clotting time (CT), clot formation time (CFT), maximum clot firmness (MCF), lysis onset time (LOT), and lysis time (LT) were determined to assess clot development and breakdown and were compared to routine hemostatic assays. In 36 patients, 96 EXTEM/FIBTEM and 87 tPA ROTEM tests were performed during a 6-week follow-up. CT prolongation was present in 54% of EXTEM measurements, which were not matched by prothrombin time (PT) in 37%. Respectively, 81 and 99% of all EXTEM and FIBTEM MCF values were above the reference range, and median MCF remained elevated during follow-up. The ROTEM fibrinolysis parameters remained prolonged with median LOT consequently >49 min and unmeasurable LT in 56% of measurements, suggesting a severe hypofibrinolytic phenotype. ROTEM tests in COVID-19 ICU patients show hypercoagulability and severe hypofibrinolysis persisting over at least 6 weeks.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcvm.2021.654174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107372PMC
April 2021

Systematic review and meta-analysis of the clinical effectiveness of point-of-care testing for anticoagulation management during ECMO.

J Clin Anesth 2021 Oct 4;73:110330. Epub 2021 May 4.

Cardiac Surgery Unit, Dept. Experimental and Clinical Medicine, University "Magna Graecia" of Catanzaro, Catanzaro, Italy.

Study Objective: Viscoelastic point-of-care (POC) tests are commonly used to provide prompt diagnosis of coagulopathy and allow targeted treatments in bleeding patients on ECMO. We evaluated the clinical effectiveness of point-of-care (POC) testing for anticoagulation management in patients on extracorporeal membrane oxygenation (ECMO).

Design: Systematic review and meta-analysis. Eligible studies evaluating the use of thromboelastography- or thromboelastometry-guided algorithms, anti-factor Xa and platelet function testing were selected after screening the literature from July 1975 to January 2020.

Setting: Patients on ECMO support.

Patients: Anticoagulation management on ECMO patients.

Interventions: Rotational thromboelastometry, thromboelastography, alone or combined with platelet function testing. Trials monitoring the anticoagulation effects during ECMO using an anti-factor Xa assay were included in the systematic review.

Measurements: The primary outcomes were bleeding events, surgical revisions, thrombosis events and ECMO circuit change/failure. Secondary outcomes were blood-product transfusions, cerebrovascular accidents, mortality on ECMO, ECMO duration, intensive care unit and hospital discharge rates, and in-hospital mortality.

Main Results: Thirty-one trials enrolling 1684 participants were included in the systematic review. Four trials enrolling 547 subjects were included in the meta-analysis. The use of a POC testing device resulted in improved detection of surgical bleeding (RR: 0.68, 95% CI 0.49 to 0.94, I = 0%; χ test for heterogeneity, P = 0.02). The use of POC-guided algorithms did not affect bleeding (RR:0.78, 95% CI 0.58 to 1.04, I = 47%; χ test for heterogeneity, P = 0.09), thrombosis events (RR:1.35, 95% CI 0.86 to 2.12, I = 37%; χ test for heterogeneity, P = 0.19), or ECMO circuit/change (RR:0.90, 95% CI 0.48 to 1.71, I = 28%; χ test for heterogeneity, P = 0.75).

Conclusion: Routine use of POC tests did not improve the main clinical outcomes beyond suggesting a diagnosis of surgical bleeding in ECMO patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jclinane.2021.110330DOI Listing
October 2021

Evaluation of the analytical performance of the PC100 platelet counter.

Thromb J 2021 May 4;19(1):29. Epub 2021 May 4.

Departments of Internal Medicine and Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre+, Universiteitssingel 50, Maastricht, 6229 ER, The Netherlands.

Introduction: Platelet count can be altered in various diseases and treatments and measuring it may provide better insight into the expected outcome. So far, quantification of platelet count is done within laboratory conditions by using established hematology analyzers, whereas a point-of-care device could be used for this purpose outside of the clinical laboratories.

Aim: Our aim was to assess the closeness of agreement between a newly developed point-of-care PC100 platelet counter and two reference methods (Sysmex® XP-300, Sysmex® XN-9000) in measuring platelet counts in whole blood and platelet-rich-plasma (PRP).

Method: Whole blood was obtained from 119 individuals, of which 74 were used to prepare PRP samples. Whole blood platelet count was measured by the two reference methods and the PC100 platelet counter. PRP was prepared from the whole blood and platelet count was adjusted to the range of 250-3600 × 10/μl and measured with the PC100 platelet counter and Sysmex® XP-300.

Results: A median difference of - 1.35% and - 2.98% occurred in whole blood platelet count between the PC100 platelet counter and the Sysmex® XP-300 and Sysmex® XN-9000, respectively. A strong linear correlation (r ≥ 0.98) was seen in both cases and regression equations indicated neither a constant nor a proportional bias between the methods. Direct comparison of the two reference methods revealed a median difference of - 1.15% and a strongly linear relationship (r = 0.99). Platelet count in PRP resulted in a median difference of 1.42% between the PC100 platelet counter and the reference method, Sysmex® XP-300. While the difference between two methods increased with concentration of platelets in PRP, a strong linear relationship remained throughout the whole measuring interval indicated by the high correlation coefficient (r = 0.99). Assessment of the predicted bias at predefined platelet counts showed that the bias in platelet counts falls within the acceptance criterion for both whole blood and PRP measurements.

Conclusions: Our results show that the PC100 platelet counter can be used interchangeably with the reference methods for determining platelet counts.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12959-021-00283-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8094460PMC
May 2021
-->