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Background: Nanoparticles play a crucial role in nanodiagnostics, radiation therapy of cancer, and they are now widely used to effectively deliver drugs to specific sites, targeting whole organs and down to single cells, in a controlled manner. Therapeutic efficiency of nanoparticles greatly depends on their clustering distribution inside cells. Our purpose is to find the cluster density using Smoluchowski’s coagulation equation with injections. Results: We obtain an exact cluster density of nanoparticles as the steady-state solution of Smoluchowski’s equation describing clustering due to the fusion of endosomes. We also analyze the unsteady cluster distribution and compare it with the experimental data for time evolution of gold nanoparticle clusters in living cells. Conclusions: We show the steady cluster density is in good agreement with experimental data on gold nanoparticle distribution inside endosomes. We find that for clusters containing between 1 and 20 nanoparticles, the exact cluster density provides a better description of the existing experimental data than the well-known approximate asymptotic power-law distribution x- 3 / 2 © 2022, The Author(s).

Hypercytokinemia, or cytokine storm, is one of the severe complications of viral and bacterial infections, involving the release of abnormal amounts of cytokines, resulting in a massive inflammatory response. Cytokine storm is associated with COVID-19 and sepsis high mortality rate by developing epithelial dysfunction and coagulopathy, leading to thromboembolism and multiple organ dysfunction syndrome. Anticoagulant therapy is an important tactic to prevent thrombosis in sepsis and COVID-19, but recent data show the incompatibility of modern direct oral anticoagulants and antiviral agents. It seems relevant to develop dual-action drugs with antiviral and anticoagulant properties. At the same time, it was shown that azolo[1,5-a]pyrimidines are heterocycles with a broad spectrum of antiviral activity. We have synthesized a new family of azolo[1,5-a]pyrimidines and their condensed polycyclic analogs by cyclocondensation reactions and direct CH-functionalization and studied their anticoagulant properties. Five compounds among 1,2,4-triazolo[1,5-a]pyrimidin-7-ones and 5-alkyl-1,3,4-thiadiazolo[3,2-a]purin-8-ones demonstrated higher anticoagulant activity than the reference drug, dabigatran etexilate. Antithrombin activity of most active compounds was confirmed using lipopolysaccharide (LPS)-treated blood to mimic the conditions of cytokine release syndrome. The studied compounds affected only the thrombin time value, reliably increasing it 6.5–15.2 times as compared to LPS-treated blood. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Calcium ions are used in the development of biomaterials for the promotion of coagulation, bone regeneration, and implant osseointegration. Upon implantation, the time-dependent release of calcium ions from titanium implant surfaces modifies the physicochemical characteristics at the implant-tissue interface and thus, the biological responses. The aim of this study is to examine how the dynamics of protein adsorption on these surfaces change over time. Titanium discs with and without Ca were incubated with human serum for 2 min, 180 min, and 960 min. The layer of proteins attached to the surface was characterised using nLC-MS/MS. The adsorption kinetics was different between materials, revealing an increased adsorption of proteins associated with coagulation and immune responses prior to Ca release. Implant-blood contact experiments confirmed the strong coagulatory effect for Ca surfaces. We employed primary human alveolar osteoblasts and THP-1 monocytes to study the osteogenic and inflammatory responses. In agreement with the proteomic results, Ca-enriched surfaces showed a significant initial inflammation that disappeared once the calcium was released. The distinct protein adsorption/desorption dynamics found in this work demonstrated to be useful to explain the differential biological responses between the titanium and Ca-ion modified implant surfaces. Graphic abstract

Background: Left ventricular thrombus (LVT) has a 5% incidence after anterior ST-elevation myocardial infarction (STEMI). Multiple risk factors predispose to LVT formation, including left ventricular systolic dysfunction and infarct size, however measurable predictors during index left heart catheterization (LHC) have not been determined. Method(s): We performed a retrospective analysis of patients presenting between January 2010 and September 2017 with anterior STEMI who had in-hospital transthoracic echocardiography (TTE). LHC variables that were assessed included coronary anatomy, location of culprit stenosis, presence of diffuse stenosis, number of severely diseased vessels, apical akinesis on left ventriculogram (LVG), left ventricular end diastolic pressure, and success of percutaneous coronary intervention (PCI). Result(s): Of 598 consecutive anterior STEMI patients, records and inpatient TTE results were available in 425 patients. The incidence of LVT was 6.8% (n = 29). After multivariate adjustment, severe triple vessel coronary disease (OR = 8.27, CI = 2.97-23.00, p <=0.001), apical akinesis on LVG (OR = 6.74, CI = 1.48-30.73, p = 0.014), wrap-around left anterior descending (LAD) anatomy (OR = 5.10, CI = 1.97-13.23, p = 0.001), and failure of recanalization after PCI (OR = 3.94, CI = 1.06-14.66, p = 0.04) were predictors for LVT formation. The combined negative predictive value (NPV) for the absence of these four indices was 99.2%. Conclusion(s): Severe triple vessel disease, apical akinesis on LVG during index admission, wrap-around LAD, and failure of recanalization after PCI are associated with increased risk of LVT formation after anterior STEMI. The high NPV for the absence of these indices could serve as a risk stratification tool for LVT risk to guide early TTE utilization.Copyright © 2021 Elsevier Inc.

[EN] Calcium ions are used in the development of biomaterials for the promotion of coagulation, bone regeneration, and implant osseointegration. Upon implantation, the time-dependent release of calcium ions from titanium implant surfaces modifies the physicochemical characteristics at the implant-tissue interface and thus, the biological responses. The aim of this study is to examine how the dynamics of protein adsorption on these surfaces change over time. Titanium discs with and without Ca were incubated with human serum for 2 min, 180 min, and 960 min. The layer of proteins attached to the surface was characterised using nLC-MS/MS. The adsorption kinetics was different between materials, revealing an increased adsorption of proteins associated with coagulation and immune responses prior to Ca release. Implant-blood contact experiments confirmed the strong coagulatory effect for Ca surfaces. We employed primary human alveolar osteoblasts and THP-1 monocytes to study the osteogenic and inflammatory responses. In agreement with the proteomic results, Ca-enriched surfaces showed a significant initial inflammation that disappeared once the calcium was released. The distinct protein adsorption/desorption dynamics found in this work demonstrated to be useful to explain the differential biological responses between the titanium and Ca-ion modified implant surfaces.

[EN] Calcium ions are used in the development of biomaterials for the promotion of coagulation, bone regeneration, and implant osseointegration. Upon implantation, the time-dependent release of calcium ions from titanium implant surfaces modifies the physicochemical characteristics at the implant-tissue interface and thus, the biological responses. The aim of this study is to examine how the dynamics of protein adsorption on these surfaces change over time. Titanium discs with and without Ca were incubated with human serum for 2 min, 180 min, and 960 min. The layer of proteins attached to the surface was characterised using nLC-MS/MS. The adsorption kinetics was different between materials, revealing an increased adsorption of proteins associated with coagulation and immune responses prior to Ca release. Implant-blood contact experiments confirmed the strong coagulatory effect for Ca surfaces. We employed primary human alveolar osteoblasts and THP-1 monocytes to study the osteogenic and inflammatory responses. In agreement with the proteomic results, Ca-enriched surfaces showed a significant initial inflammation that disappeared once the calcium was released. The distinct protein adsorption/desorption dynamics found in this work demonstrated to be useful to explain the differential biological responses between the titanium and Ca-ion modified implant surfaces.

Background: Left ventricular thrombus (LVT) has a 5% incidence after anterior ST-elevation myocardial infarction (STEMI). Multiple risk factors predispose to LVT formation, including left ventricular systolic dysfunction and infarct size, however measurable predictors during index left heart catheterization (LHC) have not been determined. Method(s): We performed a retrospective analysis of patients presenting between January 2010 and September 2017 with anterior STEMI who had in-hospital transthoracic echocardiography (TTE). LHC variables that were assessed included coronary anatomy, location of culprit stenosis, presence of diffuse stenosis, number of severely diseased vessels, apical akinesis on left ventriculogram (LVG), left ventricular end diastolic pressure, and success of percutaneous coronary intervention (PCI). Result(s): Of 598 consecutive anterior STEMI patients, records and inpatient TTE results were available in 425 patients. The incidence of LVT was 6.8% (n = 29). After multivariate adjustment, severe triple vessel coronary disease (OR = 8.27, CI = 2.97-23.00, p <=0.001), apical akinesis on LVG (OR = 6.74, CI = 1.48-30.73, p = 0.014), wrap-around left anterior descending (LAD) anatomy (OR = 5.10, CI = 1.97-13.23, p = 0.001), and failure of recanalization after PCI (OR = 3.94, CI = 1.06-14.66, p = 0.04) were predictors for LVT formation. The combined negative predictive value (NPV) for the absence of these four indices was 99.2%. Conclusion(s): Severe triple vessel disease, apical akinesis on LVG during index admission, wrap-around LAD, and failure of recanalization after PCI are associated with increased risk of LVT formation after anterior STEMI. The high NPV for the absence of these indices could serve as a risk stratification tool for LVT risk to guide early TTE utilization.Copyright © 2021 Elsevier Inc.

Calcium ions are used in the development of biomaterials for the promotion of coagulation, bone regeneration, and implant osseointegration. Upon implantation, the time-dependent release of calcium ions from titanium implant surfaces modifies the physicochemical characteristics at the implant-tissue interface and thus, the biological responses. The aim of this study is to examine how the dynamics of protein adsorption on these surfaces change over time. Titanium discs with and without Ca were incubated with human serum for 2 min, 180 min, and 960 min. The layer of proteins attached to the surface was characterised using nLC-MS/MS. The adsorption kinetics was different between materials, revealing an increased adsorption of proteins associated with coagulation and immune responses prior to Ca release. Implant-blood contact experiments confirmed the strong coagulatory effect for Ca surfaces. We employed primary human alveolar osteoblasts and THP-1 monocytes to study the osteogenic and inflammatory responses. In agreement with the proteomic results, Ca-enriched surfaces showed a significant initial inflammation that disappeared once the calcium was released. The distinct protein adsorption/desorption dynamics found in this work demonstrated to be useful to explain the differential biological responses between the titanium and Ca-ion modified implant surfaces. Graphic abstract

Calcium ions are used in the development of biomaterials for the promotion of coagulation, bone regeneration, and implant osseointegration. Upon implantation, the time-dependent release of calcium ions from titanium implant surfaces modifies the physicochemical characteristics at the implant-tissue interface and thus, the biological responses. The aim of this study is to examine how the dynamics of protein adsorption on these surfaces change over time. Titanium discs with and without Ca were incubated with human serum for 2 min, 180 min, and 960 min. The layer of proteins attached to the surface was characterised using nLC-MS/MS. The adsorption kinetics was different between materials, revealing an increased adsorption of proteins associated with coagulation and immune responses prior to Ca release. Implant-blood contact experiments confirmed the strong coagulatory effect for Ca surfaces. We employed primary human alveolar osteoblasts and THP-1 monocytes to study the osteogenic and inflammatory responses. In agreement with the proteomic results, Ca-enriched surfaces showed a significant initial inflammation that disappeared once the calcium was released. The distinct protein adsorption/desorption dynamics found in this work demonstrated to be useful to explain the differential biological responses between the titanium and Ca-ion modified implant surfaces. Graphic abstract

An important component of severe COVID-19 disease is virus-induced endothelilitis. This leads to disruption of normal endothelial function, initiating a state of failing normal clotting physiology. Massively increased levels of von Willebrand Factor (VWF) lead to overwhelming platelet activation, as well as activation of the enzymatic (intrinsic) clotting pathway. In addition, there is an impaired fibrinolysis, caused by, amongst others, increased levels of alpha-(2) antiplasmin. The end result is hypercoagulation (proven by thromboelastography® (TEG®)) and reduced fibrinolysis, inevitably leading to a difficult-to-overcome hypercoagulated physiological state. Platelets in circulation also plays a significant role in clot formation, but they themselves may also drive hypercoagulation when they are overactivated due to the interactions of their receptors with the endothelium, immune cells or circulating inflammatory molecules. From the literature it is clear that the role of platelets in severely ill COVID-19 patients has been markedly underestimated or even ignored. We here highlight the value of early management of severe COVID-19 coagulopathy as guided by TEG®, microclot and platelet mapping. We also argue that the failure of clinical trials, where the efficacy of prophylactic versus therapeutic clexane (low molecular weight heparin (LMWH)) were not always successful, which may be because the significant role of platelet activation was not taken into account during the planning of the trial. We conclude that, because of the overwhelming alteration of clotting, the outcome of any trial evaluating an any single anticoagulant, including thrombolytic, would be negative. Here we suggest the use of the degree of platelet dysfunction and presence of microclots in circulation, together with TEG®, might be used as a guideline for disease severity. A multi-pronged approach, guided by TEG® and platelet mapping, would be required to maintain normal clotting physiology in s

Background: High convection volume hemodiafiltration may improve survival compared to high-flux hemodialysis, however there is significant variation in its use. Clinician attitudes towards hemodiafiltration are poorly understood but may explain differences in practice patterns. Method(s): A 17-question online survey was administered from February 2017 to January 2018. Clinicians involved in the care of hemodialysis patients were invited to participate via the Australian and New Zealand Society of Nephrology. The survey addressed domains of clinician knowledge; hemodiafiltration prescription; perceived benefits, harms, and barriers to use; and indications and contraindications. Result(s): Eighty-two responses were received from clinicians affiliated with 49 of 81 hemodialysis units (60 unit response rate). Hemodiafiltration was prescribed by 87 of respondents, but generally to less than 25 of patients. The percentage of respondents prescribing hemodiafiltration to most of their patients was greater for those in privately funded (60) than publicly funded units (28). Only 26 of respondents considered the level of evidence supporting the superiority of hemodiafiltration over high-flux hemodialysis to be high. Its key benefits were perceived to be superior middle molecule clearance, hemodynamic stability, phosphate clearance, and amyloid prevention. Common indications included frequent intradialytic symptoms, intradialytic hypotension, and uremic polyneuropathy. Few respondents (14) agreed hemodiafiltration conveyed harm to patients, however 25 considered frequent circuit clotting to be a relative contraindication. Although most respondents (63) believed hemodiafiltration was more expensive than high-flux hemodialysis, this was not a barrier to its use. Three-quarters of respondents prescribed post-dilution hemodiafiltration, but only 55 targeted a convection volume greater than 20L. Conclusion(s): Most clinicians in Australia and New Zealand prescribe hemodiafiltration

Left ventricular thrombus (LVT) has a 5% incidence after anterior ST elevation myocardial infarction (aSTEMI) in the primary percutaneous coronary intervention (PCI) era. Numerous risk factors predispose to LVT formation, including history of left ventricular dysfunction and infarct size, however measurable predictors during left heart catheterisation (LHC) have not been determined. We sought to investigate the predictive utility of LHC indices for LVT formation. We performed a dual-centre retrospective analysis of patients presenting between January 2010 and September 2017 with aSTEMI who had inpatient transthoracic echocardiography (TTE). LHC indices that were assessed on index LHC included location of culprit stenosis, presence of focal or diffuse stenosis, number of severely diseased vessels, presence of apical akinesis on left ventriculogram, left ventricular end diastolic pressure (LVEDP), and whether PCI was performed. Analysis was performed using multivariate analysis with results reported as odds ratios (OR) with 95% confidence intervals (CI). Of 514 consecutive aSTEMI patients, TTE results were available in 425 patients. The incidence of LVT was 6.8% (n=29). After multivariate adjustment, severe triple vessel disease (OR=6.82, CI=2.73-17.02, p=<0.001), apical akinesis (OR=4.58, CI=1.31-16.08, p=0.02), and LVEDP >20mmHg (OR=2.88, CI=1.03-8.05, p=0.04) were predictors of LVT formation. Negative predictive values for triple vessel disease, apical akinesis and LVEDP >20mmHg were 95.3%, 97.7%, and 97% respectively. Triple vessel disease, apical akinesis, and LVEDP >20mmHg are associated with increased risk of LVT in patients with aSTEMI. The high NPV for these indices could serve as a stratification tool for LVT risk to guide inpatient TTE utilisation.Copyright © 2020

This interactive session will include a number of interesting real-life cases encountered by the specialty coagulation lab.Copyright © 2020

Background: High convection volume hemodiafiltration may improve survival compared to high-flux hemodialysis, however there is significant variation in its use. Clinician attitudes towards hemodiafiltration are poorly understood but may explain differences in practice patterns. Method(s): A 17-question online survey was administered from February 2017 to January 2018. Clinicians involved in the care of hemodialysis patients were invited to participate via the Australian and New Zealand Society of Nephrology. The survey addressed domains of clinician knowledge; hemodiafiltration prescription; perceived benefits, harms, and barriers to use; and indications and contraindications. Result(s): Eighty-two responses were received from clinicians affiliated with 49 of 81 hemodialysis units (60 unit response rate). Hemodiafiltration was prescribed by 87 of respondents, but generally to less than 25 of patients. The percentage of respondents prescribing hemodiafiltration to most of their patients was greater for those in privately funded (60) than publicly funded units (28). Only 26 of respondents considered the level of evidence supporting the superiority of hemodiafiltration over high-flux hemodialysis to be high. Its key benefits were perceived to be superior middle molecule clearance, hemodynamic stability, phosphate clearance, and amyloid prevention. Common indications included frequent intradialytic symptoms, intradialytic hypotension, and uremic polyneuropathy. Few respondents (14) agreed hemodiafiltration conveyed harm to patients, however 25 considered frequent circuit clotting to be a relative contraindication. Although most respondents (63) believed hemodiafiltration was more expensive than high-flux hemodialysis, this was not a barrier to its use. Three-quarters of respondents prescribed post-dilution hemodiafiltration, but only 55 targeted a convection volume greater than 20L. Conclusion(s): Most clinicians in Australia and New Zealand prescribe hemodiafiltration

Left ventricular thrombus (LVT) has a 5% incidence after anterior ST elevation myocardial infarction (aSTEMI) in the primary percutaneous coronary intervention (PCI) era. Numerous risk factors predispose to LVT formation, including history of left ventricular dysfunction and infarct size, however measurable predictors during left heart catheterisation (LHC) have not been determined. We sought to investigate the predictive utility of LHC indices for LVT formation. We performed a dual-centre retrospective analysis of patients presenting between January 2010 and September 2017 with aSTEMI who had inpatient transthoracic echocardiography (TTE). LHC indices that were assessed on index LHC included location of culprit stenosis, presence of focal or diffuse stenosis, number of severely diseased vessels, presence of apical akinesis on left ventriculogram, left ventricular end diastolic pressure (LVEDP), and whether PCI was performed. Analysis was performed using multivariate analysis with results reported as odds ratios (OR) with 95% confidence intervals (CI). Of 514 consecutive aSTEMI patients, TTE results were available in 425 patients. The incidence of LVT was 6.8% (n=29). After multivariate adjustment, severe triple vessel disease (OR=6.82, CI=2.73-17.02, p=<0.001), apical akinesis (OR=4.58, CI=1.31-16.08, p=0.02), and LVEDP >20mmHg (OR=2.88, CI=1.03-8.05, p=0.04) were predictors of LVT formation. Negative predictive values for triple vessel disease, apical akinesis and LVEDP >20mmHg were 95.3%, 97.7%, and 97% respectively. Triple vessel disease, apical akinesis, and LVEDP >20mmHg are associated with increased risk of LVT in patients with aSTEMI. The high NPV for these indices could serve as a stratification tool for LVT risk to guide inpatient TTE utilisation.Copyright © 2020

This interactive session will include a number of interesting real-life cases encountered by the specialty coagulation lab.Copyright © 2020

BackgroundSevere injury initiates a complex physiologic response encompassing multiple systems and varies phenotypically between patients. Trauma-induced coagulopathy may be an early warning of a poorly coordinated response at the molecular level, including a deleterious immunologic response and worsening of shock states. The onset of trauma-induced coagulopathy (TIC) may be subtle however. In previous work, we identified an early warning sign of coagulopathy from the admission thromboelastogram, called the MAR ratio. We hypothesized that a low MAR ratio would be associated with specific derangements in the inflammatory response.MethodsIn this prospective, observational study, 88 blunt trauma patients admitted to the intensive care unit (ICU) were identified. Concentrations of inflammatory mediators were recorded serially over the course of a week and the MAR ratio was calculated from the admission thromboelastogram. Correlation analysis was used to assess the relationship between MAR and inflammatory mediators. Dynamic network analysis was used to assess coordination of immunologic response.ResultsSeventy-nine percent of patients were male and mean age was 37 years (SD 12). The mean ISS was 30.2 (SD 12) and mortality was 7.2%. CRITICAL patients (MAR ratio ≤14.2) had statistically higher shock volumes at three time points in the first day compared to NORMAL patients (MAR ratio >14.2). CRITICAL patients had significant differences in IL-6 (P=0.0065), IL-8 (P=0.0115), IL-10 (P=0.0316) and MCP-1 (P=0.0039) concentrations compared to NORMAL. Differences in degree of expression and discoordination of immune response continued in CRITICAL patients throughout the first day.ConclusionsThe admission MAR ratio may be the earliest warning signal of a pathologic inflammatory response associated with hypoperfusion and TIC. A low MAR ratio is an early indication of complicated dysfunction of multiple molecular processes following trauma.

Left ventricular thrombus (LVT) is a well-described complication of anterior ST elevation myocardial infarction (aSTEMI), with a 9% incidence in the primary percutaneous coronary intervention era. Numerous risk factors predispose to LVT formation, including infarct size and apical akinesis, however measurable predictors during coronary angiography remain elusive. This study aimed to investigate left ventricular end diastolic pressure (LVEDP), a surrogate marker for left ventricular dysfunction, as a predictor for LVT formation. We performed a dual-centre retrospective analysis of patients presenting between January 2010 and September 2017 with aSTEMI. Patients thought to be at high risk for LVT were evaluated via transthoracic echocardiogram (TTE) during index admission. LVEDP measurements were obtained from index coronary angiography. Landmark analysis was performed at LVEDP of 20 mmHg using multivariable logistic regression. Results were reported as odds ratio (OR) with 95% confidence intervals (CI). Of 514 aSTEMI patients, TTE results confirming presence or absence of LVT were available in 240 patients. The incidence of LVT was 12.1% (n = 29). 70.8% of patients had LVEDP of >=20 mmHg. Patients with LVEDP of >=20 mmHg were found to have an increased risk of LVT formation (OR = 4.03, CI = 1.18-13.79, p = 0.03). Similar findings were found after adjusting for age and sex (OR = 4.24, CI = 1.23-14.65, p = 0.02). For each 1 mmHg increase in LVEDP above 20 mmHg, risk of LVT formation also increased (OR = 1.12, CI = 1.03-1.21, p = 0.01). LVEDP of >=20 mmHg after aSTEMI is associated with an increased risk of LVT formation. This finding highlights the importance of routine TTE during index admission for aSTEMI patients with LVEDP >=20 mmHg.Copyright © 2019

Left ventricular thrombus (LVT) is a well-described complication of anterior ST elevation myocardial infarction (aSTEMI), with a 9% incidence in the primary percutaneous coronary intervention era. Numerous risk factors predispose to LVT formation, including infarct size and apical akinesis, however measurable predictors during coronary angiography remain elusive. This study aimed to investigate left ventricular end diastolic pressure (LVEDP), a surrogate marker for left ventricular dysfunction, as a predictor for LVT formation. We performed a dual-centre retrospective analysis of patients presenting between January 2010 and September 2017 with aSTEMI. Patients thought to be at high risk for LVT were evaluated via transthoracic echocardiogram (TTE) during index admission. LVEDP measurements were obtained from index coronary angiography. Landmark analysis was performed at LVEDP of 20 mmHg using multivariable logistic regression. Results were reported as odds ratio (OR) with 95% confidence intervals (CI). Of 514 aSTEMI patients, TTE results confirming presence or absence of LVT were available in 240 patients. The incidence of LVT was 12.1% (n = 29). 70.8% of patients had LVEDP of >=20 mmHg. Patients with LVEDP of >=20 mmHg were found to have an increased risk of LVT formation (OR = 4.03, CI = 1.18-13.79, p = 0.03). Similar findings were found after adjusting for age and sex (OR = 4.24, CI = 1.23-14.65, p = 0.02). For each 1 mmHg increase in LVEDP above 20 mmHg, risk of LVT formation also increased (OR = 1.12, CI = 1.03-1.21, p = 0.01). LVEDP of >=20 mmHg after aSTEMI is associated with an increased risk of LVT formation. This finding highlights the importance of routine TTE during index admission for aSTEMI patients with LVEDP >=20 mmHg.Copyright © 2019

[EN] Calcium is an element widely used in the development of biomaterials for bone tissue engineering as it plays important roles in bone metabolism and blood coagulation. The Ca ions can condition the microenvironment at the tissue-material interface, affecting the protein deposition process and cell responses. The aim of this study was to analyze the changes in the patterns of protein adsorption on the silica hybrid biomaterials supplemented with different amounts of CaCl2, which can function as release vehicles. This characterization was carried out by incubating the Ca-biomaterials with human serum. LC-MS/MS analysis was used to characterize the adsorbed protein layers and compile a list of proteins whose affinity for the surfaces might depend on the CaCl2 content. The attachment of pro- and anti-clotting proteins, such as THRB, ANT3, and PROC, increased significantly on the Ca-materials. Similarly, VTNC and APOE, proteins directly involved on osteogenic processes, attached preferentially to these surfaces. To assess correlations with the proteomic data, these formulations were tested in vitro regarding their osteogenic and inflammatory potential, employing MC3T3-E1 and RAW 264.7 cell lines, respectively. The results confirmed a Ca dose-dependent osteogenic and inflammatory behavior of the materials employed, in accordance with the protein attachment patterns.

[EN] Calcium is an element widely used in the development of biomaterials for bone tissue engineering as it plays important roles in bone metabolism and blood coagulation. The Ca ions can condition the microenvironment at the tissue-material interface, affecting the protein deposition process and cell responses. The aim of this study was to analyze the changes in the patterns of protein adsorption on the silica hybrid biomaterials supplemented with different amounts of CaCl2, which can function as release vehicles. This characterization was carried out by incubating the Ca-biomaterials with human serum. LC-MS/MS analysis was used to characterize the adsorbed protein layers and compile a list of proteins whose affinity for the surfaces might depend on the CaCl2 content. The attachment of pro- and anti-clotting proteins, such as THRB, ANT3, and PROC, increased significantly on the Ca-materials. Similarly, VTNC and APOE, proteins directly involved on osteogenic processes, attached preferentially to these surfaces. To assess correlations with the proteomic data, these formulations were tested in vitro regarding their osteogenic and inflammatory potential, employing MC3T3-E1 and RAW 264.7 cell lines, respectively. The results confirmed a Ca dose-dependent osteogenic and inflammatory behavior of the materials employed, in accordance with the protein attachment patterns.

Intravenous infusion of alteplase is used for thrombolysis before endovascular thrombectomy for ischemic stroke. Tenecteplase, which is more fibrin-specific and has longer activity than alteplase, is given as a bolus and may increase the incidence of vascular reperfusion. METHODS We randomly assigned patients with ischemic stroke who had occlusion of the internal carotid, basilar, or middle cerebral artery and who were eligible to undergo thrombectomy to receive tenecteplase (at a dose of 0.25 mg per kilogram of body weight; maximum dose, 25 mg) or alteplase (at a dose of 0.9 mg per kilogram; maximum dose, 90 mg) within 4.5 hours after symptom onset. The primary outcome was reperfusion of greater than 50% of the involved ischemic territory or an absence of retrievable thrombus at the time of the initial angiographic assessment. Noninferiority of tenecteplase was tested, followed by superiority. Secondary outcomes included the modified Rankin scale score (on a scale from 0 [no neurologic deficit] to 6 [death]) at 90 days. Safety outcomes were death and symptomatic intracerebral hemorrhage. RESULTS Of 202 patients enrolled, 101 were assigned to receive tenecteplase and 101 to receive alteplase. The primary outcome occurred in 22% of the patients treated with tenecteplase versus 10% of those treated with alteplase (incidence difference, 12 percentage points; 95% confidence interval [CI], 2 to 21; incidence ratio, 2.2; 95% CI, 1.1 to 4.4; P=0.002 for noninferiority; P=0.03 for superiority). Tenecteplase resulted in a better 90-day functional outcome than alteplase (median modified Rankin scale score, 2 vs. 3; common odds ratio, 1.7; 95% CI, 1.0 to 2.8; P=0.04). Symptomatic intracerebral hemorrhage occurred in 1% of the patients in each group. CONCLUSIONS Tenecteplase before thrombectomy was associated with a higher incidence of reperfusion and better functional outcome than alteplase among patients with ischemic stroke treated within 4.5 hours after symptom onset.Copyri

Intravenous infusion of alteplase is used for thrombolysis before endovascular thrombectomy for ischemic stroke. Tenecteplase, which is more fibrin-specific and has longer activity than alteplase, is given as a bolus and may increase the incidence of vascular reperfusion. METHODS We randomly assigned patients with ischemic stroke who had occlusion of the internal carotid, basilar, or middle cerebral artery and who were eligible to undergo thrombectomy to receive tenecteplase (at a dose of 0.25 mg per kilogram of body weight; maximum dose, 25 mg) or alteplase (at a dose of 0.9 mg per kilogram; maximum dose, 90 mg) within 4.5 hours after symptom onset. The primary outcome was reperfusion of greater than 50% of the involved ischemic territory or an absence of retrievable thrombus at the time of the initial angiographic assessment. Noninferiority of tenecteplase was tested, followed by superiority. Secondary outcomes included the modified Rankin scale score (on a scale from 0 [no neurologic deficit] to 6 [death]) at 90 days. Safety outcomes were death and symptomatic intracerebral hemorrhage. RESULTS Of 202 patients enrolled, 101 were assigned to receive tenecteplase and 101 to receive alteplase. The primary outcome occurred in 22% of the patients treated with tenecteplase versus 10% of those treated with alteplase (incidence difference, 12 percentage points; 95% confidence interval [CI], 2 to 21; incidence ratio, 2.2; 95% CI, 1.1 to 4.4; P=0.002 for noninferiority; P=0.03 for superiority). Tenecteplase resulted in a better 90-day functional outcome than alteplase (median modified Rankin scale score, 2 vs. 3; common odds ratio, 1.7; 95% CI, 1.0 to 2.8; P=0.04). Symptomatic intracerebral hemorrhage occurred in 1% of the patients in each group. CONCLUSIONS Tenecteplase before thrombectomy was associated with a higher incidence of reperfusion and better functional outcome than alteplase among patients with ischemic stroke treated within 4.5 hours after symptom onset.Copyri

Purpose : This study investigated the relationship between blood clotting in the circuit soon after initiating cardiopulmonary bypass (CPB) and echinocytes that appear with alkalemia, using a recirculation circuit filled with heparinized bovine blood. Methods : Alkalemic conditions in the recirculation circuit were prepared by adding various concentrations of NaHCO3 to the priming fluid. Albumin was also added to confirm its inhibitory effect on blood clotting. Blood pH, hold-up, the pressure gradient, and red blood cell (RBC) reduction rate were monitored. Blood clots were examined microscopically. Results : Although blood pH was elevated under all experimental conditions, clotting in the circuit increased with increased concentrations of HCO3-. Albumin inhibited the clotting under the same alkalemic conditions. Microscopic findings revealed echinocytes in the blood clots. Conclusions : The shape of echinocytes was transformed by a reduction in the Donnan equilibrium ratio because of changes in pH inside and outside the RBC membrane. Blood clotting in the circuit soon after initiating CPB may be caused by echinocytes that appear under alkalemic conditions. This was inhibited by albumin, suggesting that the addition of albumin to the priming fluid may prevent such clotting in the circuit after initiating CPB., 博士（医学）・甲第664号・平成29年3月15日, Copyright © 2016 Japanese Journal of Extra-Corporeal Technology（日本体外循環技術医学会）, This is a non-final version of an article published in final form in "http://doi.org/10.7130/jject.43.339"

Purpose : This study investigated the relationship between blood clotting in the circuit soon after initiating cardiopulmonary bypass (CPB) and echinocytes that appear with alkalemia, using a recirculation circuit filled with heparinized bovine blood. Methods : Alkalemic conditions in the recirculation circuit were prepared by adding various concentrations of NaHCO3 to the priming fluid. Albumin was also added to confirm its inhibitory effect on blood clotting. Blood pH, hold-up, the pressure gradient, and red blood cell (RBC) reduction rate were monitored. Blood clots were examined microscopically. Results : Although blood pH was elevated under all experimental conditions, clotting in the circuit increased with increased concentrations of HCO3-. Albumin inhibited the clotting under the same alkalemic conditions. Microscopic findings revealed echinocytes in the blood clots. Conclusions : The shape of echinocytes was transformed by a reduction in the Donnan equilibrium ratio because of changes in pH inside and outside the RBC membrane. Blood clotting in the circuit soon after initiating CPB may be caused by echinocytes that appear under alkalemic conditions. This was inhibited by albumin, suggesting that the addition of albumin to the priming fluid may prevent such clotting in the circuit after initiating CPB., 博士（医学）・甲第664号・平成29年3月15日, Copyright © 2016 Japanese Journal of Extra-Corporeal Technology（日本体外循環技術医学会）, This is a non-final version of an article published in final form in "http://doi.org/10.7130/jject.43.339"

в статье обсуждаются вопросы целесообразности применения метода герудотерапии для сохранения и укрепления здоровья человека. Использование герудотерапии в сочетании с лекарственной терапией дает более высокий и быстрый эффект лечения. На основании клинических данных и опроса 162 пациентов с различными заболеваниями было проанализировано влияние герудотерапии на динамику улучшения состояния больных и их излечивания. Анализ показал, что лечение герудотерапией в комплексе с другими методами приводит к более быстрому купированию болевого синдрома, улучшению микроциркуляции крови и положительной динамики лечения. Герудотерапия снимает воспалительные процессы и восстанавливает иммунитет., The article discusses the usefulness of the application of the method of girudo-therapy for preserving and strengthening of human health. The use of girudothera-py in combination with drug therapy provides higher and more rapid effect of treatment. On the basis of clinical and survey data of 162 patients with different diseases the influence of girudotherapy on the dynamics of the improvement of the condition of the patients and their curing was analyzed. The analysis showed that treatment with girudotherapy in combination with other methods leads to more rapid relief of pain, improvement of blood microcirculation and the positive dy-namics of treatment. Gerudotherapy relieves inflammation and restores the immune system.

The mechanical properties determine to a large extent the functioning of a blood clot. These properties depend on the composition of the clot and have been related to many diseases. However, the various involved components and their complex interactions make it difficult at this stage to fully understand and predict properties as a function of the components. Therefore, in this study, a constitutive model is developed that describes the viscoelastic behavior of blood clots with various compositions. Hereto, clots are formed from whole blood, platelet-rich plasma and platelet-poor plasma to study the influence of red blood cells, platelets and fibrin, respectively. Rheological experiments are performed to probe the mechanical behavior of the clots during their formation. The nonlinear viscoelastic behavior of the mature clots is characterized using a large amplitude oscillatory shear deformation. The model is based on a generalized Maxwell model that accurately describes the results for the different rheological experiments by making the moduli and viscosities a function of time and the past and current deformation. Using the same model with different parameter values enables a description of clots with different compositions. A sensitivity analysis is applied to study the influence of parameter variations on the model output. The relative simplicity and flexibility make the model suitable for numerical simulations of blood clots and other materials showing similar behavior.

The mechanical properties determine to a large extent the functioning of a blood clot. These properties depend on the composition of the clot and have been related to many diseases. However, the various involved components and their complex interactions make it difficult at this stage to fully understand and predict properties as a function of the components. Therefore, in this study, a constitutive model is developed that describes the viscoelastic behavior of blood clots with various compositions. Hereto, clots are formed from whole blood, platelet-rich plasma and platelet-poor plasma to study the influence of red blood cells, platelets and fibrin, respectively. Rheological experiments are performed to probe the mechanical behavior of the clots during their formation. The nonlinear viscoelastic behavior of the mature clots is characterized using a large amplitude oscillatory shear deformation. The model is based on a generalized Maxwell model that accurately describes the results for the different rheological experiments by making the moduli and viscosities a function of time and the past and current deformation. Using the same model with different parameter values enables a description of clots with different compositions. A sensitivity analysis is applied to study the influence of parameter variations on the model output. The relative simplicity and flexibility make the model suitable for numerical simulations of blood clots and other materials showing similar behavior.

Lampreys and hagfish are the earliest diverging of extant vertebrates and are obvious targets for investigating the origins of complex biochemical systems found in mammals. Currently, the simplest approach for such inquiries is to search for the presence of relevant genes in whole genome sequence (WGS) assemblies. Unhappily, in the past a high-quality complete genome sequence has not been available for either lampreys or hagfish, precluding the possibility of proving gene absence. Recently, improved but still incomplete genome assemblies for two species of lamprey have been posted, and, taken together with an extensive collection of short sequences in the NCBI trace archive, they have made it possible to make reliable counts for specific gene families. Particularly, a multi-source tactic has been used to study the lamprey blood clotting system with regard to the presence and absence of genes known to occur in higher vertebrates. As was suggested in earlier studies, lampreys lack genes for coagulation factors VIII and IX, both of which are critical for the "intrinsic" clotting system and responsible for hemophilia in humans. On the other hand, they have three each of genes for factors VII and X, participants in the "extrinsic" clotting system. The strategy of using raw trace sequence "reads" together with partial WGS assemblies for lampreys can be used in studies on the early evolution of other biochemical systems in vertebrates.

Venous thromboembolism that cause blood clotting in blood vessels, prevent blood circulation, depending on changes in one or more of the coagulation factors II, VII, IX and X. Patients who have had a blood clot or cardiovascular diseases are treated with oral anti-vitamin K (Warfarin®) to reducing and prevent relapse. Warfarin is also used as a preventive treatment before the disease. An overdose of Warfarin® may cause bleeding-complications and low dose cause blood clotting. The dosage of the drug is controlled by measuring prothrombin in plasma. The aim of this study was to investigate if prothrombin-complex value changes due to re-spinning and re-analysis after six hours. Fitty whole blood samples from warfarin-treated patients were divided into three subgroups, those with protrombinkomplex-values of 2-4 (n=20), >4 (n=15) and <2 (n=15). The samples were centrifugated and measured (Method A), re-centrifugated and measured (Method B) or re-analysed after six hours (Method C). All results were compared in a Bland-Altman plot as follows: Method B vs. Method A and Method C vs. Method A. The scatter graph yielded a strong correlation between Method A and Method B (R2=0.9984) and Method A and Methods C (R2=0.9977). The results from t-test showed a significance level (p<0.001) for both analyses (statistical significance=p<0.05). In this study we showed that prothrombin complex value ware stable after re-centrifugation and re-measurement after six hours. Statistical calculations yielded a strong correlation between the methods (A, B, C), and there was no significance difference between the methods.

Blood clot formation is important to prevent blood loss in case of a vascular injury but disastrous when it occludes the vessel. As the mechanical properties of the clot are reported to be related to many diseases, it is important to have a good understanding of their characteristics. In this study, a constitutive model is presented that describes the nonlinear viscoelastic properties of the fibrin network, the main structural component of blood clots. The model is developed using results of experiments in which the fibrin network is subjected to a large amplitude oscillatory shear (LAOS) deformation. The results show three dominating nonlinear features: softening over multiple deformation cycles, strain stiffening and increasing viscous dissipation during a deformation cycle. These features are incorporated in a constitutive model based on the Kelvin–Voigt model. A network state parameter is introduced that takes into account the influence of the deformation history of the network. Furthermore, in the period following the LAOS deformation, the stiffness of the networks increases which is also incorporated in the model. The influence of cross-links created by factor XIII is investigated by comparing fibrin networks that have polymerized for 1 and 2 h. A sensitivity analysis provides insights into the influence of the eight fit parameters. The model developed is able to describe the rich, time-dependent, nonlinear behavior of the fibrin network. The model is relatively simple which makes it suitable for computational simulations of blood clot formation and is general enough to be used for other materials showing similar behavior.

Lampreys and hagfish are the earliest diverging of extant vertebrates and are obvious targets for investigating the origins of complex biochemical systems found in mammals. Currently, the simplest approach for such inquiries is to search for the presence of relevant genes in whole genome sequence (WGS) assemblies. Unhappily, in the past a high-quality complete genome sequence has not been available for either lampreys or hagfish, precluding the possibility of proving gene absence. Recently, improved but still incomplete genome assemblies for two species of lamprey have been posted, and, taken together with an extensive collection of short sequences in the NCBI trace archive, they have made it possible to make reliable counts for specific gene families. Particularly, a multi-source tactic has been used to study the lamprey blood clotting system with regard to the presence and absence of genes known to occur in higher vertebrates. As was suggested in earlier studies, lampreys lack genes for coagulation factors VIII and IX, both of which are critical for the "intrinsic" clotting system and responsible for hemophilia in humans. On the other hand, they have three each of genes for factors VII and X, participants in the "extrinsic" clotting system. The strategy of using raw trace sequence "reads" together with partial WGS assemblies for lampreys can be used in studies on the early evolution of other biochemical systems in vertebrates.

Venous thromboembolism that cause blood clotting in blood vessels, prevent blood circulation, depending on changes in one or more of the coagulation factors II, VII, IX and X. Patients who have had a blood clot or cardiovascular diseases are treated with oral anti-vitamin K (Warfarin®) to reducing and prevent relapse. Warfarin is also used as a preventive treatment before the disease. An overdose of Warfarin® may cause bleeding-complications and low dose cause blood clotting. The dosage of the drug is controlled by measuring prothrombin in plasma. The aim of this study was to investigate if prothrombin-complex value changes due to re-spinning and re-analysis after six hours. Fitty whole blood samples from warfarin-treated patients were divided into three subgroups, those with protrombinkomplex-values of 2-4 (n=20), >4 (n=15) and <2 (n=15). The samples were centrifugated and measured (Method A), re-centrifugated and measured (Method B) or re-analysed after six hours (Method C). All results were compared in a Bland-Altman plot as follows: Method B vs. Method A and Method C vs. Method A. The scatter graph yielded a strong correlation between Method A and Method B (R2=0.9984) and Method A and Methods C (R2=0.9977). The results from t-test showed a significance level (p<0.001) for both analyses (statistical significance=p<0.05). In this study we showed that prothrombin complex value ware stable after re-centrifugation and re-measurement after six hours. Statistical calculations yielded a strong correlation between the methods (A, B, C), and there was no significance difference between the methods.

Blood clot formation is important to prevent blood loss in case of a vascular injury but disastrous when it occludes the vessel. As the mechanical properties of the clot are reported to be related to many diseases, it is important to have a good understanding of their characteristics. In this study, a constitutive model is presented that describes the nonlinear viscoelastic properties of the fibrin network, the main structural component of blood clots. The model is developed using results of experiments in which the fibrin network is subjected to a large amplitude oscillatory shear (LAOS) deformation. The results show three dominating nonlinear features: softening over multiple deformation cycles, strain stiffening and increasing viscous dissipation during a deformation cycle. These features are incorporated in a constitutive model based on the Kelvin–Voigt model. A network state parameter is introduced that takes into account the influence of the deformation history of the network. Furthermore, in the period following the LAOS deformation, the stiffness of the networks increases which is also incorporated in the model. The influence of cross-links created by factor XIII is investigated by comparing fibrin networks that have polymerized for 1 and 2 h. A sensitivity analysis provides insights into the influence of the eight fit parameters. The model developed is able to describe the rich, time-dependent, nonlinear behavior of the fibrin network. The model is relatively simple which makes it suitable for computational simulations of blood clot formation and is general enough to be used for other materials showing similar behavior.

Les PCCs ou concentrés du complexe prothrombinique (Prothrombin Complex Concentrates ou PCCs) sont des dérivés plasmatiques contenant les facteurs de la coagulation dont la synthèse est dépendante de la vitamine K. Il s’agit des facteurs II, VII, IX et X ainsi que certains inhibiteurs de la coagulation (protéines C et S). De nombreux concentrés commerciaux contiennent également de l’héparine exogène rajoutée pour réduire le risque thrombotique. Administrés par voie intraveineuse après une reconstitution rapide, les PCCs permettent en quelques minutes de corriger l’hypocoagulation excessive induite par les agents anti-vitamine K (AVKs) lors d’un surdosage ou de restaurer une coagulation normale avant un geste invasif potentiellement hémorragique chez les patients traités par AVKs. Même si divers PCCs sont disponibles, le PPSB (PPSB solvent detergent CAF-DCF) était jusqu’il y a peu le complexe le mieux connu et maîtrisé par le corps médical belge qui a pu apprécier l’efficacité de cet agent thérapeutique, sa sécurité et sa facilité d’utilisation. Le remplacement récent du PPSB par le COFACT offre l’opportunité de revoir les propriétés uniques de ce concentré de facteurs caractérisé par une composition équilibrée des facteurs et inhibiteurs de la coagulation et surtout par l’absence d’addition d’héparine. Cette absence d’héparine confère au COFACT un potentiel hémostatique favorable tout en évitant l’exposition des patients à de l’héparine potentiellement responsable de réactions d’intolérance graves., [Cofact, continuity and specificity of an antidote to AVKs] Prothrombin complex concentrates (PCCs) are plasma-derived concentrates of vitamin K-dependent clotting factors (Factors II, VII, IX and X as well as proteins C and S). Most commercial PCCs also contain exogenous heparin aimed to reduce the risk of thrombosis. Following intravenous administration, all PCCs correct within a few minutes the excessive hypocoagulation induced by overdosing of vitamin K antagonists (VKAs) or restore normal coagulation prior to potentially hemorrhagic invasive procedures in VKA-treated patients. Until very recently, among the currently available PCCs, PPSB® (CAF-DCF) was the best known, and the most widely used by Belgian practitioners who were well aware of its effectiveness and safely. The recent substitution of PPSB ® by Cofact® has offered us the opportunity to review this PCC's unique properties, namely its balanced composition of coagulation factors and inhibitors, along with the absence of exogenous heparin, which contribute to Cofact®'s favorable hemostatic profile while avoiding possible intolerance and serious adverse reactions.

Les PCCs ou concentrés du complexe prothrombinique (Prothrombin Complex Concentrates ou PCCs) sont des dérivés plasmatiques contenant les facteurs de la coagulation dont la synthèse est dépendante de la vitamine K. Il s’agit des facteurs II, VII, IX et X ainsi que certains inhibiteurs de la coagulation (protéines C et S). De nombreux concentrés commerciaux contiennent également de l’héparine exogène rajoutée pour réduire le risque thrombotique. Administrés par voie intraveineuse après une reconstitution rapide, les PCCs permettent en quelques minutes de corriger l’hypocoagulation excessive induite par les agents anti-vitamine K (AVKs) lors d’un surdosage ou de restaurer une coagulation normale avant un geste invasif potentiellement hémorragique chez les patients traités par AVKs. Même si divers PCCs sont disponibles, le PPSB (PPSB solvent detergent CAF-DCF) était jusqu’il y a peu le complexe le mieux connu et maîtrisé par le corps médical belge qui a pu apprécier l’efficacité de cet agent thérapeutique, sa sécurité et sa facilité d’utilisation. Le remplacement récent du PPSB par le COFACT offre l’opportunité de revoir les propriétés uniques de ce concentré de facteurs caractérisé par une composition équilibrée des facteurs et inhibiteurs de la coagulation et surtout par l’absence d’addition d’héparine. Cette absence d’héparine confère au COFACT un potentiel hémostatique favorable tout en évitant l’exposition des patients à de l’héparine potentiellement responsable de réactions d’intolérance graves., [Cofact, continuity and specificity of an antidote to AVKs] Prothrombin complex concentrates (PCCs) are plasma-derived concentrates of vitamin K-dependent clotting factors (Factors II, VII, IX and X as well as proteins C and S). Most commercial PCCs also contain exogenous heparin aimed to reduce the risk of thrombosis. Following intravenous administration, all PCCs correct within a few minutes the excessive hypocoagulation induced by overdosing of vitamin K antagonists (VKAs) or restore normal coagulation prior to potentially hemorrhagic invasive procedures in VKA-treated patients. Until very recently, among the currently available PCCs, PPSB® (CAF-DCF) was the best known, and the most widely used by Belgian practitioners who were well aware of its effectiveness and safely. The recent substitution of PPSB ® by Cofact® has offered us the opportunity to review this PCC's unique properties, namely its balanced composition of coagulation factors and inhibitors, along with the absence of exogenous heparin, which contribute to Cofact®'s favorable hemostatic profile while avoiding possible intolerance and serious adverse reactions.

NADPH oxidases (NOXs) are reactive oxygen species (ROS)-generating enzymes implicated in the pathophysiology of vascular diseases such as hypertension and stroke. Endothelial cells express four NOX isoforms including the superoxide-generating enzymes NOX1, NOX2, and NOX5 and the hydrogen peroxide-generating enzyme NOX4. Studies on arteries from patients with coronary artery disease, and in animals with experimentally induced hypertension, diabetes, or atherosclerosis, suggest that NOX1, NOX2, and NOX5 promote endothelial dysfunction, inflammation, and apoptosis in the vessel wall, whereas NOX4 is by contrast vasoprotective in increasing nitric oxide bioavailability and suppressing cell death pathways. Based on these findings and promising preclinical studies with the NOX1/NOX2 antagonist, apocynin, we suggest that the field is poised for clinical evaluation of NOX inhibitors as therapeutics for cardiovascular disease. © 2014 Elsevier Ltd.

Introduction: Coagulation-free dialysis, also commonly known as "heparin-free" dialysis, can be a challenging procedure as it increases the risk of clotting the dialysis circuit. Utilizing a better saline flushing technique can lead to improved patient outcomes as well as huge financial benefits to the health institution. The purpose of this study was to compare the effectiveness of continuous saline infusion (CSI) and intermittent saline flushing (ISF) in preventing clotting of the dialysis extracorporeal circuit (ECC). Method(s): Fifty heparin-free treatments were randomized into two treatment arms, namely CSI and ISF. Predialysis full blood count and coagulation studies were performed for all patients. During ISF, 100 mL saline was infused via the arterial line every 30 minutes while occluding the blood inlet line. Normal saline was infused into the ECC at a rate of 200 mL/hour throughout the duration of dialysis under CSI. The ECC was inspected for clotting and graded accordingly post-dialysis. Result(s): Seventy-six percent of the CSI treatments were completed without losing the ECC while 52% of the ISF treatments were also successful. Patients who were treated with CSI were less likely to have clotted ECCs (odds ratio 3.4, 95% CI, 1.04 to 11.2; P = 0.04). No significant differences existed between the two groups' hematological factors that could influence clotting, such as hemoglobin and platelets. Conclusion(s): This study demonstrates that, when heparin-free dialysis is indicated, CSI might be a better method of preventing the ECC from clotting. There is a greater chance of realizing long-term benefits to patients and the health service with the CSI method since there is a likelihood of a reduction in the use of erythropoietin-stimulating agents and blood transfusions with the CSI method. © 2013 Zimbudzi, publisher and licensee Dove Medical Press Ltd.

Dabigatran is an oral direct thrombin inhibitor that does not require routine laboratory monitoring. However, an assessment of its anticoagulant effect in certain clinical settings is desirable. We examined the relationship between dabigatran levels, as determined by the Hemoclot thrombin inhibitor assay (HTI), the thrombin time (TT) and the activated partial thromboplastin time (aPTT) using different reagents. We describe these parameters with the clinical outcomes of patients receiving dabigatran. Seventy-five plasma samples from 47 patients were analysed. The HTI assay was established to measure dabigatran level. aPTTs were performed using TriniCLOT aPTT S reagent (TC) and three additional aPTT reagents. From linear regression lines, we established the aPTT ranges corresponding to the therapeutic drug levels for dabigatran (90-180 ng/ml). The aPTT demonstrated a modest correlation with the dabigatran level (r= 0.80) but the correlation be came less reliable at higher dabigatran levels. The therapeutic aPTT ranges for reagents were clinically and statistically different compared with our reference reagent (46-54 s (TC) vs 51-60 s (SP), 54-64 s (SS) and 61-71 s (Actin FS) (p<0.05)). The TT was sensitive to the presence of dabigatran with a level of 60 ng/ml resulting in a TT > 300 s. In conclusion, the aPTT demonstrated a modest correlation with the dabigatran level and was less responsive with supra-therapeutic levels. aPTT reagents differed in their responsiveness, suggesting individual laboratories must determine their own therapeutic range for their aPTT reagent. The TT is too sensitive to quantify dabigatran levels, but a normal TT suggests minimal or no plasma dabigatran. © Schattauer 2013.