Comparative analysis of thrombin generation platforms for patients with coagulation factor deficiencies: A comprehensive assessment.

INTRODUCTION: Thrombin generation assays (TGAs) assess the overall functionality of the hemostatic system and thereby provide a reflection of the hemostatic capacity of patients with disorders in this system. Currently, four (semi-)automated TGA platforms are available: the Calibrated Automated Thrombogram, Nijmegen Hemostasis Assay, ST Genesia and Ceveron s100. In this study, we compared their performance for detecting patients with congenital single coagulation factor deficiencies. MATERIALS AND METHODS: Pooled patient samples, healthy control samples and normal pooled plasma were tested on all four platforms, using the available reagents that vary in tissue factor and phospholipid concentrations. The TGA parameters selected for analysis were peak height and thrombin potential. Results were normalized by using the calculated mean of healthy controls and a correction for between-run variation. Outcomes were presented as relative values, with the mean of healthy controls standardized to 100 %. RESULTS: Across all platforms and reagents used, thrombin potentials and peak heights of samples with coagulation factor deficiencies were lower than those of healthy controls. Reagents designed for bleeding tendencies yielded the lowest values on all platforms (relative median peak height 19-32 %, relative median thrombin potential 19-45 %). Samples representing more severe coagulation factor deficiencies generally exhibited lower relative peak heights and thrombin potentials. CONCLUSIONS: Thrombin generation assays prove effective in differentiating single coagulation factor deficient samples from healthy controls, with modest discrepancies observed between the platforms. Reagents designed for assessing bleeding tendencies, featuring the lowest tissue factor and phospholipid concentrations, emerged as the most suitable option for detecting coagulation factor deficiencies.

Thromboelastometry for assessment of hemostasis and disease severity in 42 dogs with naturally-occurring heatstroke.

BACKGROUND: Thromboelastometry (TEM) provides a comprehensive overview of the entire coagulation process and has not been evaluated in heatstroke-induced coagulopathies in dogs. OBJECTIVES: To determine the diagnostic and prognostic utility of TEM in dogs with heatstroke. ANIMALS: Forty-two client-owned dogs with heatstroke. METHODS: Prospective observational study. Blood samples for intrinsic and extrinsic TEM (INTEM and EXTEM, respectively) were collected at presentation and every 12 to 24 hours for 48 hours. Coagulation phenotype (hypo-, normo-, or hypercoagulable) was defined based on TEM area under the 1st derivative curve (AUC). RESULTS: Case fatality rate was 31%. Median TEM variables associated with death (P < .05 for all) included longer INTEM clotting time, lower AUC at presentation and at 12 to 24 hours postpresentation (PP), lower INTEM alpha angle, maximum clot firmness, and maximum lysis (ML) at 12 to 24 hours PP, and lower EXTEM ML at 12 to 24 hours PP. Most dogs were normo-coagulable on presentation (66% and 63% on EXTEM and INTEM, respectively), but hypo-coagulable 12 to 24 PP (63% for both EXTEM and INTEM). A hypo-coagulable INTEM phenotype was more frequent at presentation and 12 to 24 PP among nonsurvivors compared to survivors (55% vs 15% and 100% vs 50%, P = .045 and .026, respectively). AKI was more frequent (P = .015) in dogs with hypo-coagulable INTEM tracings at 12 to 24 hours. Disseminated intravascular coagulation was more frequent (P < .05) in dogs with a hypo-coagulable INTEM phenotype and in nonsurvivors at all timepoints. CONCLUSIONS AND CLINICAL RELEVANCE: Hypocoagulability, based on INTEM AUC, is predictive of worse prognosis and occurrence of secondary complications.

Assessment of hemostasis in hyperthyroid and euthyroid cats using two viscoelastic assays and platelet aggregometry.

BACKGROUND: Hyperthyroidism in humans is associated with a hypercoagulable state and an increased risk of thromboembolism. OBJECTIVE: To evaluate hemostatic variables in hyperthyroid and euthyroid cats with the hypothesis that hyperthyroid cats will have evidence of altered hemostasis consistent with a potential hypercoagulable state. ANIMALS: Client-owned hyperthyroid (n = 16) and euthyroid (n = 15) cats over 8 years of age. METHODS: Prospective observational study. Hyperthyroid and euthyroid cats were enrolled. Rotational thromboelastometry (ROTEM), whole-blood platelet impedance aggregometry (WBPIA) and a point-of-care viscoelastic coagulation monitor (VCM-Vet) were performed immediately after minimally traumatic venipuncture under sedation. RESULTS: Hyperthyroid cats had significantly higher values for variables as assessed by VCM-Vet: A10 (34 [17-47] vs 25 [17-38], P = .003); A20 (39.5 [23-55] vs 31 [21-45], P = .003); and MCF (41 [24-58] vs 35 [22-49], P = .03). Hyperthyroid cats had significantly different values versus the euthyroid cohort as assessed by different ROTEM channels: increased A10, INTEM (61.5 [39-75] vs 54 [23-66], P = .007) and FIBTEM (18 [10-35] vs 13 [2-27], P = .01); increased A20, INTEM (68 [45-78] vs 61 [30-70], P = .006) and FIBTEM (17 [10-34] vs 11 [2-25], P = .002); increased MCF, EXTEM (72 [65-81] vs 69 [34-78], P = .04), INTEM (70 [45-85] vs 62 [35-71], P = .01) and FIBTEM (18 [13-37] vs 14 [3-27], P = .02); increased alpha angle, EXTEM (80 [68-85] vs 76 [41-84], P = .01); shortened CT, EXTEM (52.5 [29-73] vs 60 [52-92], P = .003) and FIBTEM (52.5 [16-75] vs 65 [53-165], P = .001); and decreased ML, FIBTEM (20 [1-36] vs 33 [19-59], P <.001). No significant differences were found with WBPIA. CONCLUSIONS AND CLINICAL IMPORTANCE: The hyperthyroid cats in this study had evidence of altered hemostasis as assessed by 2 viscoelastic methodologies, and characterized by increased clot amplitude, firmness, and faster coagulation times vs euthyroid controls.

Assessment of hemostatic ability of biomaterial based on chitosan andEclipta prostrataL. extract.

The biomaterials based on chitosan andEclipta prostrataL. extract have been prepared by microemulsion method and solution method (with and without sodium tripolyphosphate (STPP) as a cross-linking agent). The main component inEclipta prostrataL. extract is flavonoid groups. The structure of the chitosan/extract biomaterials was studied by infrared spectroscopy. The chitosan/extract biomaterial using STPP cross-linker appeared an absorption band at 1152 cm-1attributed to the vibrations of C-O-P bonds, which proved that chitosan has crosslinked with STPP. The morphology of the biomaterials was investigated by the dynamic light scattering technique and field emission scanning electron microscopy. The obtained results showed that the particle size of the chitosan/extract biomaterials prepared by microemulsion method and solution method with STPP ranged from 68.06 nm to 1484 nm, with an average particle size of 304.9-1019 nm. The microemulsion method produced biomaterials with much smaller average particle size than the solution method using cross-linkers. The hemostatic ability of the biomaterials was better than that of the control sample based on the time of blood clotting formation and glomerular aggregation ability. The sample with the ratio ofE. prostrataL. extract: chitosan of 1:30 had the lowest hemostasis time (6 min 46 s) and its glomerular aggregation rate after 5 min was 13.05%. This indicated that the biomaterials based on chitosan andE. prostrataL. extract are promising for application in biomedicine as hemostatic materials.

A global assessment of hemostatic function of healthy allogeneic stem cell donors undergoing apheresis by rotational thromboelastometry.

INTRODUCTION: Peripheral blood stem cell (PBSC) collection via apheresis requires the administration of granulocyte colony-stimulating factor (filgrastim) to stem cell donors. Several reports have shown that filgrastim administration and apheresis procedure induce a hypercoagulable state across PBSC collection, which might predispose certain donors to thrombotic complications. METHODS: We evaluated the hemostatic functions of healthy allogeneic stem cell donors by rotational thromboelastometry (ROTEM). Blood samples from healthy donors (n = 30) were collected at defined time points: before filgrastim (baseline), on the day of apheresis before and after the procedure, and 1 week after apheresis. RESULTS: The results indicated that hemostatic changes are temporary since all parameters in both EXTEM and INTEM assays are restored to their initial values 1 week after the apheresis. CONCLUSION: We concluded that stem cell apheresis does not induce a hypercoagulable state in healthy donors. This is the first study evaluating the hemostatic functions of stem cell donors by ROTEM.

Dentistry for patients with haemophilia: Trialling a safe and economical change in management.

INTRODUCTION: While the dental management of patients with haemophilia has changed considerably in the last decade, haemophiliacs in Western Australia have continued to receive pre-operative factor support for dentistry regardless of the type of dental procedure. AIM: To review the efficacy and safety of established dental protocols that reduce factor use in the dental management of patients with haemophilia and to estimate cost savings. METHODS: Records of 11 patients with haemophilia that were seen in the pilot programme period were reviewed. These were cross-referenced with previous dental and haematology notes that stated the amount and type of pre-operative factor used. Cost savings were estimated using the Australian National Blood Authority's Product List. RESULTS: All study participants were male, and included those with haemophilia A (n = 9), and B (n = 2). Mean age was 45 years (range 22-80). A variety of dental treatments were undertaken, and no pre-operative factor was used. Patients on prophylaxis (n = 6) received dental treatment the same day as their regular factor administration. It was estimated AUD$26,314 was saved by not using pre-operative factor. One patient had bleeding post-extraction and was seen the following day to achieve haemostasis using local measures. The remaining patients had no complaints of post-operative bleeding, and did not require any further haemostatic measures. CONCLUSION: This pilot programme supports data that haemophiliacs can safely receive a variety of dental treatments without the need for pre-operative factor, and the significant cost savings of doing so. Further data is required to support this protocol for invasive dental procedures.

One-pot reaction for the preparation of diatom hemostatic particles with effective hemostasis and economic benefits.

Effective hemostatic materials have been in demand for rapid pre-hospital hemostasis in emergency situations, which can significantly reduce accidental deaths. The development of emergency hemostatic materials with rapid hemostasis, biosafety, and economical preparation is a great challenge. In this study, Ca(OH)2-complexed diatom powder hemostatic particles (Ca(OH)2-Php) were prepared based on a one-pot reaction by directly mixing various raw materials and by rotary granulation. High-temperature calcination was able to carbonate and consume the organic matter in the hemostatic particles. The crosslinked hydrogen bonds in those particles were converted to silica-oxygen bonds, the particles became more stable, and the porous structure of diatom biosilica (DBs) was exposed. Ca(OH)2-Php has high porosity, can quickly adsorb the water in blood (water absorption: 75.85 ± 6.93%), and exhibits rapid hemostasis capacity (clotting time was shortened by 43% compared with that of the control group), good biocompatibility (hemolysis rate <7%, no cytotoxicity), and simplicity of handling (conveniently debride, no residues, no tissue inflammation). This study provides a new idea for the preparation of emergency hemostatic materials, and Ca(OH)2-Php prepared by one-pot reaction has various high-quality characteristics including rapid hemostasis, wide applicability, economical preparation, and potential for large-scale production.

Assessment of Primary Hemostasis by Platelet Function Analyzer-100 and its Relation with TSH and FT4 Levels in Newly Diagnosed Overt and Subclinical Hypothyroid Patients.

Various abnormalities of coagulation such as primary hemostasis, secondary hemostasis and fibrinolysis have been reported in patients with subclinical and overt hypothyroidism. Platelets are major elements of primary hemostasis and endothelial repair. Platelet size, shape and number are the determinant of platelet function. The objective of this study was to assess primary hemostasis by PFA-100 (Platelet Function Analyzer-100) and its relation with TSH and FT4 levels in newly diagnosed overt and subclinical hypothyroid patients. This cross-sectional study was conducted in the Department of Physiology, Dhaka Medical College, Bangladesh from January 2016 to December 2016. Twenty overt and 20 subclinical hypothyroid patients with age ranging from 18 to 55 years were selected as study group and twenty age and sex matched healthy subjects were considered as control group. Patients were selected from Outpatients Department of Endocrinology and Nuclear Medicine & Allied Sciences of Dhaka Medical College Hospital, Dhaka on the basis of exclusion and inclusion criteria. For assessment of primary hemostasis, PFA-100 was analyzed by SIEMENS-INNOVANCE-PFA-200. For statistical analysis Unpaired Student's 't' test, Chi square test and Pearson's correlation co-efficient (r) test were performed. PFA-100 was significantly higher (p<0.001) in overt and subclinical hypothyroid patients as compared to healthy adult subjects. In overt and subclinical hypothyroidism using PFA-100, we found that the existence of a hypocoagulable state is due to a defect in primary hemostasis. Moreover, PFA-100 may replace the in-vivo bleeding time as a screening test for primary hemostasis in routine clinical practice.

Assessment of Hemostatic Profile in Neonates with Intrauterine Growth Restriction: A Systematic Review of Literature.

Intrauterine growth restriction (IUGR) affects nearly 10 to 15% of pregnancies and is responsible for many short- and long-term adverse consequences, including hemostatic derangement. Both thrombotic and hemorrhagic events are described in the perinatal period in these neonates. The aim of this study was to systematically review the literature on the laboratory studies used to evaluate the hemostatic system of the IUGR small for gestational age neonate. We reviewed the current literature via PubMed and Scopus until September 2022. Following our inclusion/exclusion criteria, we finally included 60 studies in our review. Thrombocytopenia, characterized as hyporegenerative and a kinetic upshot of reduced platelet production due to in utero chronic hypoxia, was the main finding of most studies focusing on growth-restricted neonates, in most cases is mild and usually resolves spontaneously with the first 2 weeks of life. In regard to coagulation, growth-restricted newborns present with prolonged standard coagulation tests. Data regarding coagulation factors, fibrinolytic system, and anticoagulant proteins are scarce and conflicting, mainly due to confounding factors. As thromboelastography/rotational thromboelastometry (TEG/ROTEM) provides a more precise evaluation of the in vivo coagulation process compared with standard coagulation tests, its use in transfusion guidance is fundamental. Only one study regarding TEG/ROTEM was retrieved from this population, where no difference in ROTEM parameters compared with appropriate for gestational age neonates was found. Despite the laboratory aberrations, no correlation could be achieved with clinical manifestations of bleeding or thrombosis in the studies included. More studies are needed to assess hemostasis in IUGR neonates and guide targeted therapeutic interventions.

Assessment of coagulation assays on Roche Cobas t711 analyzer: performance and clinical implications.

OBJECTIVES: We performed an analytical assessment of five coagulation tests [i.e. prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, thrombin time (TT) and D-dimer] on the Roche Cobas t711 analyzer and a comparison study with the methodology in use at our laboratory (i.e. Werfen ACL Top 750 analyzer), expanding the analysis to the clinical implications of Cobas t711 implementation. METHODS: Imprecision studies were performed following the Clinical and Laboratory Standards Institute (CLSI) H57 A:2008 guideline. Linearity of D-dimer and fibrinogen tests was analysed according to the CLSI EP06-A: 2003 recommendations. For method comparison, the results were analyzed using the Bland-Altman plot and Passing-Bablok regression. RESULTS: Imprecision met manufacturer claims for PT, aPTT and TT. D-dimer and fibrinogen tests showed a coefficient of variation (CV)% over manufacturer claims at certain concentration levels. Linearity ranges could not be verified. Comparison study revealed that results are not interchangeable for any test, a lower correlation for aPTT test and lower D-dimer results from Roche Cobas t711. CONCLUSION: The strength of this study relies on the analysis of the clinical implications of reporting Cobas t711 results compared to those obtained with the methodology in use at our laboratory. Different sensibility to factor deficiency, anticoagulant therapy and interferences might explain lower correlation rates obtained for the aPTT test. Different monoclonal antibodies used for D-dimer determination might explain the lower results obtained with the Cobas t711 analyzer. This aspect needs further studies given the relevance of D-dimer test to exclude thrombotic events and reinforces the need of harmonization in the haemostasis laboratory.

Clinical Assessment of Primary Hemostasis: A Review.

Primary hemostatic disorders such as thrombocytopenia and thrombocytopathia are commonly encountered in small animal practice. The key stages of primary hemostasis include platelet adhesion, activation, and aggregation. Understanding the interaction between tissues, platelets, and signaling molecules not only helps clinicians comprehend clot formation but also better recognize thrombocytopathias. Although congenital thrombocytopathia is rare, commercially available platelet function tests allow veterinarians to narrow differentials in many clinical settings. Thrombocytopenia can be easily diagnosed in any clinical setting. In this paper, we review the current understanding of primary hemostasis in veterinary medicine, including the clinical presentation and available diagnostics to identify platelet abnormalities.

Platelet function analyzer-200 closure curve analysis and assessment of flow-obstructed samples.

BACKGROUND: The Platelet function analyzer-200 can determine the effect of clopidogrel in cats. Flow obstruction is an error that causes uninterpretable results. Closure curves and parameters initial flow rate (IF) and total volume (TV) are displayed by the PFA-200 and may allow interpretation of results in cases of flow obstruction. The primary hemostasis components (PHC) are calculated values that normalize these parameters. OBJECTIVES: To determine if closure curves and research parameters allow detecting the effect of clopidogrel in cases of flow obstruction. METHODS: A review of closure curves identified those with flow obstruction and paired analysis that did not. Non-flow-obstructed curves were used to categorize curves with respect to clopidogrel effects. IF, TV, PHC(1), and PHC(2) were evaluated to determine if these could be used to categorize if a sample exhibited the effects of clopidogrel. Curves were visually analyzed, and characteristics identified that were more common with or without the effect of clopidogrel. Visual analysis of curves was performed by blinded observers to determine if a visual analysis was able to predict the effect of clopidogrel. RESULTS: Analysis of parameters was able to predict closure or non-closure in flow-obstructed curves. TV, PHC(1), and PHC(2) had area under the curve of the receiver operating characteristics of 0.79, 0.79, and 0.87. Visual curve analysis was unable to predict closure, with an average accuracy of only 55%, among three reviewers. Agreement between reviewers was poor (Fleiss' Kappa 0.06). CONCLUSIONS: Visual curve analysis was unable to determine the effect of clopidogrel in flow-obstructed samples. Numerical parameters were able to detect the effect of clopidogrel with a high degree of accuracy in flow-obstructed samples.

Invited Commentary: Achieving Post-Bypass Hemostasis in Young Children: At What Cost?

Young children requiring bypass often develop coagulopathy resulting in major postoperative blood loss. Increased post-bypass bleeding and donor exposures are independently associated with adverse outcomes. When transfusion of hemostatic blood products fails to reduce bleeding to an acceptable level, rescue therapies including prothrombin complex concentrates (PCCs), and/or recombinant activated factor VII are being given "off-label" with increasing frequency. A number of studies attempting to determine the safety and efficacy of PCCs in neonates and young children are being published. These studies are most commonly retrospective, observational, performed in a single center with varying doses, indications for, and timing of administration in a small number of patients with varying results. The results of these individual studies are questionable and are not to be generalized to other center's patients. Because factor VIII inhibitor bypassing activity (FEIBA) contains the activated form of factor VII and factor X there are concerns regarding the potential for thrombotic events in a population with a known risk of postoperative thromboembolism. Currently, there is no validated assay with which to measure the efficacy of FEIBA in vivo to determine dose titration. Well-designed multicenter randomized control trials are needed to determine the optimal dose and risk-benefit of PCCs after pediatric cardiac surgery. Until such data are available the decision to give a procoagulant to neonates and young children after bypass needs to be made when the consequences of blood loss and replacement pose more risk than the risk of thrombotic complications from the drug.

Advanced in vitro hemocompatibility assessment of biomaterials using a new flow incubation system.

Physiologically relevant in vitro hemocompatibility assessment of biomaterials remains challenging. We present a new setup that enables standardized whole blood incubation of biomedical materials under flow. A blood volume of 2 mL is recirculated over test surfaces in a custom-made parallel plate incubation system to determine the activation of hemostasis and inflammation. Controlled physiological shear rates between 125 s-1 and 1250 s-1 and minimized contact to air are combined with a natural-like pumping process. A unique feature of this setup allows tracing adhesion of blood cells to test surfaces microscopically in situ. Validation testing was performed in comparison to previously applied whole blood incubation methodologies. Experiments with the newly developed setup showed that even small obstacles to blood flow activate blood (independent of materials-induced blood activation levels); that adhesion of blood cells to biomaterials equilibrates within 5 to 10 min; that high shear rates (1250 compared to 375 s-1) induce platelet activation; and that hemolysis, platelet factor 4 (PF4) release and platelet loss - but not thrombin formation - depend on shear rate (within the range investigated, 125 to 1250 s-1).

Assessment of joint bleeding and target joints in patients with severe or moderately severe hemophilia B (factor IX ≤2%) receiving prophylaxis with rIX-FP in the PROLONG-9FP clinical trial program.

OBJECTIVE: To assess the impact of prophylaxis with rIX-FP, a fusion protein linking recombinant factor IX (FIX) with human albumin, on joint outcomes. METHODS: Joint outcomes were assessed in pediatric (<12 years) and adult/adolescent (≥12 years) patients receiving rIX-FP prophylaxis every 7, 10, or 14 days; patients (>18 years) well-controlled on a 14-day regimen could switch to a 21-day regimen. Target joints were defined as ≥3 spontaneous bleeds into a single joint within a 6-month period. RESULTS: For adult/adolescent (n = 63) and pediatric (n = 27) patients, median (Q1, Q3) annualized joint bleeding rate was 0.39 (0.00, 2.31), 0.80 (0.00, 2.85), 0.20 (0.00, 2.58), and 0.00 (0.00, 1.78) when treated with 7-, 10-, 14-, or 21-day prophylaxis. 50.0%, 38.9%, 45.5%, and 63.6% of adult/adolescent patients had no joint bleeds when treated with 7-, 10-, 14-, or 21-day prophylaxis, respectively, and 40.7%, 37.5%, and 37.5% of pediatric patients had no joint bleeds when treated with 7-, 10-, or 14-day prophylaxis. Ten adult and two pediatric patients developed target joints; all resolved by the end of the study. CONCLUSION: Prophylaxis with rIX-FP produced low joint bleeding rates and provided excellent hemostatic efficacy in the treatment of joint bleeds. All target joints reported resolved with rIX-FP prophylaxis.

Prospective assessment of platelet function in patients undergoing elective resection of glioblastoma multiforme.

This prospective study was aimed to test changes in hemostasis in patients with GBM, occurring at baseline (before surgery, time 0, T0) and 2 (T2), 24 (T24), and 48-hour (T48) after surgery. We enrolled consecutive patients subjected to GBM resection (GBR group; N = 60), laparoscopic colon cancer resection (comparative CCR group; N = 40), and healthy blood donors (HBD group; N = 40). We performed 1. conventional coagulation tests 2. ROTEM (rotational thromboelastometry) parameters and 3. platelet function tests, including PFA-200 closure time when stimulated by collagen/epinephrine (COL-EPI) and ROTEM platelet, using three different activators (arachnoid acid in ARATEM, adenosine diphosphate in ADPTEM, and thrombin receptor-activating peptide-6 in TRAPTEM). Variables associated with unfavorable 1-year clinical outcome were investigated, too. We observed in GBR patients that platelet aggregometry, as assessed by ROTEM platelet parameters, was significantly impaired along with a shortened closure time. These changes were evident from T0 to T48. A decreased area under the aggregation curve in TRAPTEM was associated with improved survival (adjusted odd ratio (95% CI), 1.03 (1.01-1.06)). This study suggests that patients with GBM presented a decreased platelet aggregation from before surgery and thorough the postoperative period. Decreased platelet aggregation improved clinical outcome.

What is the context? Glioblastoma has an impact on the platelet number and the functional state of platelets. Platelets can be activated by tumor cells, and platelets count and function may impact patient survival. It has been showed an association between thrombocytosis and a decreased overall survival, with a small reduction in glioma risk associated with the long-term use of low-dose aspirin.Platelet function before and during the perioperative period in patients with glioblastoma has not been systematically investigated. Limited data suggest that platelet function may be impaired before and throughout the perioperative period, and that impaired platelet function affects clinical outcome.What is new? In this prospective study, we systematically investigated how glioblastoma provokes systemic alterations of hemostasis. We enrolled 60 consecutive patients (sample size calculated) subjected to resection of glioblastoma multiforme, and other 40 consecutive patients undergoing laparoscopic resection of colon cancer, as a comparative group, in order to differentiate hemostasis and coagulation profiles of two tumors (glioblastoma and colon adenocarcinoma) with high prothrombotic power. Forty healthy volunteers were also included to establish local reference values.We performed 1. conventional coagulation tests 2. ROTEM (rotational thromboelastometry) parameters and 3. platelet function tests, including PFA-200 closure time when stimulated by collagen/epinephrine (COL-EPI) and ROTEM platelet, using three different activators (arachnoid acid in ARATEM, adenosine diphosphate in ADPTEM, and thrombin receptor-activating peptide-6 in TRAPTEM). Variables associated with unfavorable 1-year clinical outcome were investigated, too. All these analyses were carried out at baseline (T0, time 0, before surgery) and 2 (T2), 24(T24) and 48-hour (T48) after surgery.We observed in GBR patients that platelet aggregometry, as assessed by ROTEM platelet parameters, was significantly impaired along with a shortened closure time. These changes were evident from T0 to T48. A decreased area under the aggregation curve in TRAPTEM was associated with improved survival (adjusted odd ratio (95% CI), 1.03 (1.01­1.06)).What is the impact? This study provides further evidence that patients with GBM presented a decreased platelet aggregation from before surgery and thorough the postoperative period. Decreased platelet aggregation improved clinical outcome.The cut-offs obtained can potentially to provide risk stratification for clinical outcome and to be hypothesis generating research to be confirmed by RCTs.

Assessment of Platelet Function by Automated Light Transmission Aggregometry.

Light transmission aggregometry (LTA) has long been the historical "gold standard" of platelet function testing and is typically performed in specialized hemostasis laboratories due to its manual and labor intensive process. However, newer automated testing provides a means of standardization and ability to perform the testing in routine laboratories. Here we describe the measurement of platelet aggregation in the CS-Series™ (Sysmex Corporation, Kobe, Japan) and CN-Series™ (Sysmex Corporation, Kobe, Japan) routine blood coagulation analyzers. Differences in the methods for both analyzers are further described. For the CS-5100™ analyzer, the final diluted concentrations of the agonists are prepared by manual pipetting from reconstituted agonist solutions. These prepared dilutions are eight times concentrated with respect to the final working concentration of the agonists and appropriately diluted within the analyzer to achieve the desired concentration of agonists prior to testing. For the CN-6000™ analyzer, the dilutions of agonists and the final working concentrations are automatically prepared by the auto-dilution feature in the analyzer.

Targeted Blood Plasma Proteomics and Hemostasis Assessment of Post COVID-19 Patients with Acute Myocardial Infarction.

The molecular mechanisms underlying cardiovascular complications after the SARS-CoV-2 infection remain unknown. The goal of our study was to analyze the features of blood coagulation, platelet aggregation, and plasma proteomics in COVID-19 convalescents with AMI. The study included 66 AMI patients and 58 healthy volunteers. The groups were divided according to the anti-N IgG levels (AMI post-COVID (n = 44), AMI control (n = 22), control post-COVID (n = 31), and control (n = 27)). All participants underwent rotational thromboelastometry, thrombodynamics, impedance aggregometry, and blood plasma proteomics analysis. Both AMI groups of patients demonstrated higher values of clot growth rates, thrombus size and density, as well as the elevated levels of components of the complement system, proteins modifying the state of endothelium, acute-phase and procoagulant proteins. In comparison with AMI control, AMI post-COVID patients demonstrated decreased levels of proteins connected to inflammation and hemostasis (lipopolysaccharide-binding protein, C4b-binding protein alpha-chain, plasma protease C1 inhibitor, fibrinogen beta-chain, vitamin K-dependent protein S), and altered correlations between inflammation and fibrinolysis. A new finding is that AMI post-COVID patients opposite the AMI control group, are characterized by a less noticeable growth of acute-phase proteins and hemostatic markers that could be explained by prolonged immune system alteration after COVID-19.

Evaluation of adolescents with heavy menstrual bleeding using the International Society of Thrombosis Haemostasis- Bleeding Assessment Tool and The Pediatric Bleeding Questionnaire scores.

BACKGROUND: Heavy menstrual bleeding (HMB) is a common condition in adolescents. However, bleeding disorders are known to be one of the causes of HMB in adolescent girls, so they should be considered. Simple methods that can be used in primary health care are needed to determine whether patients have bleeding disorders. The aim of this study was to evaluate the bleeding score of patients admitted with HMB and to determine the diagnostic value of patients who were symptomatic but whose initial hemostatic tests were normal. METHODS: A total of 113 adolescents with HMB and 20 healthy adolescent girls were included in the study. The Pediatric Bleeding Questionnaire (PBQ) and the International Society of Thrombosis Haemostasis-Bleeding Assessment Tool (ISTH-BAT) were used for evaluation. RESULTS: Overall, approximately 18% (n= 20) of the adolescents in the study were diagnosed with a bleeding disorder. The cut off value for the `clinically significant bleeding score` was found to be 3.5. CONCLUSIONS: The PBQ and ISTH-BAT can help distinguish a significant bleeding history from an otherwise trivial bleeding and can be included in the algorithm for the primary care of adolescents with HMB with suspected bleeding disorders.