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Venous thromboembolism (VTE) is the leading cause of morbidity and death worldwide, after cancer and cardiovascular diseases. VTE is defined to include pulmonary embolism (PE) and/or deep vein thrombosis (DVT). Approximately 25% of PE patients experience sudden death as an initial symptom of VTE, and between 10% and 30% of patients die within the first month after diagnosis. Currently, the only drugs approved for the treatment of both acute and chronic VTE are vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs). However, their effectiveness is limited due to their associated risk of bleeding. Ideally, therapy should be able to treat VTE and limit the risk of VTE recurrence without increasing the risk of bleeding. Several studies have shown that the use of statins during anticoagulation for VTE reduces the risk of death and VTE recurrence. However, to date, there are conflicting data on the impact of statins during anticoagulation for VTE. A biological protective function of statins during anticoagulation has also been reported. Statins affect D-dimer levels; tissue factor (TF) gene expression; and VIII, VII, and Von Willebrand clotting factors—the major clotting factors they are able to affect. However, the usefulness of statins for the treatment and prevention of VTE is currently under debate, and they should not be substituted for guideline-recommended VTE prophylaxis or anticoagulation treatment. In this review of the literature, we illustrate the advances on this topic, including data on the role of statins in primary VTE prevention and secondary VTE prevention, related biological mechanisms, the risk of bleeding during their use, and their ability to reduce the risk of death. [ABSTRACT FROM AUTHOR]

Blood clotting caused by COVID-19 has made this disease much more severe than other respiratory diseases. An alarming number of COVID-19 patients developed blood clots that trigger heart attack, stroke, and other disasters. Currently, blood thinner medicines are the only treatment. While blood thinners lower the blood's ability to clot, they cannot disassemble existing blood clots. Many patients were not helped by them. Here we report our finding: Strong magnetic field can disassemble blood clots safely and effectively. This is attributed to the magnetic property of red cells and their unique disk shape. Hence, we have proposed a new treatment for patients with thrombosis: applying a strong magnetic field along the patients' arm or leg. When the blood clots come to the magnetic field, they are disassembled safely; red cells recover their oxygen function; the blood viscosity along the flow direction is reduced, turbulence in blood circulation is suppressed, and the incidence of heart attack and stroke can be prevented. With thrombosis occurring in COVID-19 patients, the magnetic treatment will resolve this urgent issue and greatly help the patients to recover. [ABSTRACT FROM AUTHOR]

Effective therapies are urgently needed to stabilize patients with marginally compressible junctional hemorrhage long enough to get them to the hospital alive. Herein, we report injectable and rapidly expandable cryogels consisting of polyacrylamide and thrombin (AT cryogels) created by cryo-polymerization for the efficient management of lethal junctional hemorrhage in swine. The produced cryogels have small pore sizes and highly interconnected porous architecture with robust mechanical strength. The cryogels exhibit rapid shape memory properties and prove to be resilient against fatigue. These cryogels also show high water/blood absorption capacity, fast blood clotting effect, and enhanced adhesion of red blood cells and platelets in vitro. Further, in vivo, hemostatic efficacy tests in a lethal swine junctional hemorrhage model suggest that treatment with AT cryogels, especially AT-2 cryogels, achieves the least blood loss and the highest survival rate (100 %) compared to currently employed products such as XStat® and combat gauze. The high hemostatic performance of the cryogels may be attributed to highly interconnected porous architecture with small pore size and the use of thrombin as a pro-coagulant agent. Collectively, injectable and rapidly expandable thrombin-decorated polyacrylamide-based cryogels show significant promise as hemostatic material, offering effective management of marginally compressible junctional hemorrhages in prehospital settings.

Haemorrhage control during surgery and following traumatic injury remains a critical, life-saving challenge. Cellulose products are already employed in commercially available haemostatic dressings. This work explores sourcing cellulose from sugarcane trash pulp to produce micro- and nanosized fibres with hydroxyl, carboxylic acid, and trimethylamine functional groups, resulting in either positive or negative surface charges. This paper assesses the influence of these fibres on multiple blood clotting parameters in both dispersed solutions and dry gauze applications. In vitro blood clotting studies demonstrated the significant haemostatic potential of cellulose fibres derived from sugarcane waste to initiate clotting. Plasma absorbance assays showed that the 0.25 mg/mL cellulose microfibre dispersion had the highest clotting performance. It was observed that no single property of surface charge, functionality, or fibre morphology exclusively controlled the clotting initiation measured. Instead, a combination of these factors affected clot formation, with negatively charged cellulose microfibres comprising hydroxyl surface groups providing the most promising result, accelerating the coagulation cascade mechanism by 67% compared to the endogenous activity. This difference in clot initiation shows the potential for the non-wood agricultural waste source of cellulose in haemostatic wound healing applications, contributing to the broader understanding of cellulose-based materials' versatility and their applications in biomedicine. [ABSTRACT FROM AUTHOR]

We recently reported the potential application of recombinant prothrombin activator ecarin (RAPClot™) in blood diagnostics. In a new study, we describe RAPClot™ as an additive to develop a novel blood collection prototype tube that produces the highest quality serum for accurate biochemical analyte determination. The drying process of the RAPClot™ tube generated minimal effect on the enzymatic activity of the prothrombin activator. According to the bioassays of thrombin activity and plasma clotting, γ-radiation (>25 kGy) resulted in a 30–40% loss of the enzymatic activity of the RAPClot™ tubes. However, a visual blood clotting assay revealed that the γ-radiation-sterilized RAPClot™ tubes showed a high capacity for clotting high-dose heparinized blood (8 U/mL) within 5 min. This was confirmed using Thrombelastography (TEG), indicating full clotting efficiency under anticoagulant conditions. The storage of the RAPClot™ tubes at room temperature (RT) for greater than 12 months resulted in the retention of efficient and effective clotting activity for heparinized blood in 342 s. Furthermore, the enzymatic activity of the RAPClot™ tubes sterilized with an electron-beam (EB) was significantly greater than that with γ-radiation. The EB-sterilized RAPClot™ tubes stored at RT for 251 days retained over 70% enzyme activity and clotted the heparinized blood in 340 s after 682 days. Preliminary clinical studies revealed in the two trials that 5 common analytes (K, Glu, lactate dehydrogenase (LD), Fe, and Phos) or 33 analytes determined in the second study in the γ-sterilized RAPClot™ tubes were similar to those in commercial tubes. In conclusion, the findings indicate that the novel RAPClot™ blood collection prototype tube has a significant advantage over current serum or lithium heparin plasma tubes for routine use in measuring biochemical analytes, confirming a promising application of RAPClot™ in clinical medicine. [ABSTRACT FROM AUTHOR]

The increase in D-dimer is the most significant change in coagulation parameters in Covid19 patients and can be a marker of poor prognosis. The purpose of this study was to see the average significant D-dimer levels in patients with confirmed Covid-19 with severity. The method used is Retrospective Research with a purposive sampling technique based on the criteria of the severity of Covid-19 disease. Patient data was taken from medical records and D-dimer levels from the Laboratory Information System and then analyzed using a one-way Anova test. The results showed an average Ddimer level of 2.66 mg/L at critical degrees, 2.02 mg/L at severe degrees, 0.30 at moderate degrees and 0.26 at mild degrees. Male patients occupy a larger percentage than female patients with a total of 62.5%. The age of 46-65 years occupies the highest percentage of 55% for the abnormal category because the immune system as a protector of the body does not work as strongly as when it was young. This study showed a significant average difference in the groups of mild severity with severe, mild with critical, moderate with severe, and moderate with critical. For the next researcher, it is expected to be able to analyze other hemostasis examination parameters with variables of disease severity. The increase in D-dimer is the most significant change in coagulation parameters in Covid19 patients and can be a marker of poor prognosis. The purpose of this study was to see the average significant D-dimer levels in patients with confirmed Covid-19 with severity. The method used is Retrospective Research with a purposive sampling technique based on the criteria of the severity of Covid-19 disease. Patient data was taken from medical records and D-dimer levels from the Laboratory Information System and then analyzed using a one-way Anova test. The results showed an average Ddimer level of 2.66 mg/L at critical degrees, 2.02 mg/L at severe degrees, 0.30 at moderate degrees and 0.26 at mild degrees. Male patients occupy a larger percentage than female patients with a total of 62.5%. The age of 46-65 years occupies the highest percentage of 55% for the abnormal category because the immune system as a protector of the body does not work as strongly as when it was young. This study showed a significant average difference in the groups of mild severity with severe, mild with critical, moderate with severe, and moderate with critical. For the next researcher, it is expected to be able to analyze other hemostasis examination parameters with variables of disease severity. The increase in D-dimer is the most significant change in coagulation parameters in Covid19 patients and can be a marker of poor prognosis. The purpose of this study was to see the average significant D-dimer levels in patients with confirmed Covid-19 with severity. The method used is Retrospective Research with a purposive sampling technique based on the criteria of the severity of Covid-19 disease. Patient data was taken from medical records and D-dimer levels from the Laboratory Information System and then analyzed using a one-way Anova test. The results showed an average Ddimer level of 2.66 mg/L at critical degrees, 2.02 mg/L at severe degrees, 0.30 at moderate degrees and 0.26 at mild degrees. Male patients occupy a larger percentage than female patients with a total of 62.5%. The age of 46-65 years occupies the highest percentage of 55% for the abnormal category because the immune system as a protector of the body does not work as strongly as when it was young. This study showed a significant average difference in the groups of mild severity with severe, mild with critical, moderate with severe, and moderate with critical. For the next researcher, it is expected to be able to analyze other hemostasis examination parameters with variables of disease severity. The increase in D-dimer is the most significant change in coagulation parameters in Covid19 patients and can be a marker of poor prognosis. The purpose of this study was to see the average significant D-dimer levels in patients with confirmed Covid-19 with severity. The method used is Retrospective Research with a purposive sampling technique based on the criteria of the severity of Covid-19 disease. Patient data was taken from medical records and D-dimer levels from the Laboratory Information System and then analyzed using a one-way Anova test. The results showed an average Ddimer level of 2.66 mg/L at critical degrees, 2.02 mg/L at severe degrees, 0.30 at moderate degrees and 0.26 at mild degrees. Male patients occupy a larger percentage than female patients with a total of 62.5%. The age of 46-65 years occupies the highest percentage of 55% for the abnormal category because the immune system as a protector of the body does not work as strongly as when it was young. This study showed a significant average difference in the groups of mild severity with severe, mild with critical, moderate with severe, and moderate with critical. For the next researcher, it is expected to be able to analyze other hemostasis examination parameters with variables of disease severity. The increase in D-dimer is the most significant change in coagulation parameters in Covid19 patients and can be a marker of poor prognosis. The purpose of this study was to see the average significant D-dimer levels in patients with confirmed Covid-19 with severity. The method used is Retrospective Research with a purposive sampling technique based on the criteria of the severity of Covid-19 disease. Patient data was taken from medical records and D-dimer levels from the Laboratory Information System and then analyzed using a one-way Anova test. The results showed an average Ddimer level of 2.66 mg/L at critical degrees, 2.02 mg/L at severe degrees, 0.30 at moderate degrees and 0.26 at mild degrees. Male patients occupy a larger percentage than female patients with a total of 62.5%. The age of 46-65 years occupies the highest percentage of 55% for the abnormal category because the immune system as a protector of the body does not work as strongly as when it was young. This study showed a significant average difference in the groups of mild severity with severe, mild with critical, moderate with severe, and moderate with critical. For the next researcher, it is expected to be able to analyze other hemostasis examination parameters with variables of disease severity. The increase in D-dimer is the most significant change in coagulation parameters in Covid19 patients and can be a marker of poor prognosis. The purpose of this study was to see the average significant D-dimer levels in patients with confirmed Covid-19 with severity. The method used is Retrospective Research with a purposive sampling technique based on the criteria of the severity of Covid-19 disease. Patient data was taken from medical records and D-dimer levels from the Laboratory Information System and then analyzed using a one-way Anova test. The results showed an average Ddimer level of 2.66 mg/L at critical degrees, 2.02 mg/L at severe degrees, 0.30 at moderate degrees and 0.26 at mild degrees. Male patients occupy a larger percentage than female patients with a total of 62.5%. The age of 46-65 years occupies the highest percentage of 55% for the abnormal category because the immune system as a protector of the body does not work as strongly as when it was young. This study showed a significant average difference in the groups of mild severity with severe, mild with critical, moderate with severe, and moderate with critical. For the next researcher, it is expected to be able to analyze other hemostasis examination parameters with variables of disease severity. The increase in D-dimer is the most significant change in coagulation parameters in Covid19 patients and can be a marker of poor prognosis. The purpose of this study was to see the average significant D-dimer levels in patients with confirmed Covid-19 with severity. The method used is Retrospective Research with a purposive sampling technique based on the criteria of the severity of Covid-19 disease. Patient data was taken from medical records and D-dimer levels from the Laboratory Information System and then analyzed using a one-way Anova test. The results showed an average Ddimer level of 2.66 mg/L at critical degrees, 2.02 mg/L at severe degrees, 0.30 at moderate degrees and 0.26 at mild degrees. Male patients occupy a larger percentage than female patients with a total of 62.5%. The age of 46-65 years occupies the highest percentage of 55% for the abnormal category because the immune system as a protector of the body does not work as strongly as when it was young. This study showed a significant average difference in the groups of mild severity with severe, mild with critical, moderate with severe, and moderate with critical. For the next researcher, it is expected to be able to analyze other hemostasis examination parameters with variables of disease severity. The increase in D-dimer is the most significant change in coagulation parameters in Covid19 patients and can be a marker of poor prognosis. The purpose of this study was to see the average significant D-dimer levels in patients with confirmed Covid-19 with severity. The method used is Retrospective Research with a purposive sampling technique based on the criteria of the severity of Covid-19 disease. Patient data was taken from medical records and D-dimer levels from the Laboratory Information System and then analyzed using a one-way Anova test. The results showed an average Ddimer level of 2.66 mg/L at critical degrees, 2.02 mg/L at severe degrees, 0.30 at moderate degrees and 0.26 at mild degrees. Male patients occupy a larger percentage than female patients with a total of 62.5%. The age of 46-65 years occupies the highest percentage of 55% for the abnormal category because the immune system as a protector of the body does not work as strongly as when it was young. This study showed a significant average difference in the groups of mild severity with severe, mild with critical, moderate with severe, and moderate with critical. For the next researcher, it is expected to be able to analyze other hemostasis examination parameters with variables of disease severity. The increase in D-dimer is the most significant change in coagulation parameters in Covid19 patients and can be a marker of poor prognosis. The purpose of this study was to see the average significant D-dimer levels in patients with confirmed Covid-19 with severity. The method used is Retrospective Research with a purposive sampling technique based on the criteria of the severity of Covid-19 disease. Patient data was taken from medical records and D-dimer levels from the Laboratory Information System and then analyzed using a one-way Anova test. The results showed an average Ddimer level of 2.66 mg/L at critical degrees, 2.02 mg/L at severe degrees, 0.30 at moderate degrees and 0.26 at mild degrees. Male patients occupy a larger percentage than female patients with a total of 62.5%. The age of 46-65 years occupies the highest percentage of 55% for the abnormal category because the immune system as a protector of the body does not work as strongly as when it was young. This study showed a significant average difference in the groups of mild severity with severe, mild with critical, moderate with severe, and moderate with critical. For the next researcher, it is expected to be able to analyze other hemostasis examination parameters with variables of disease severity. The increase in D-dimer is the most significant change in coagulation parameters in Covid19 patients and can be a marker of poor prognosis. The purpose of this study was to see the average significant D-dimer levels in patients with confirmed Covid-19 with severity. The method used is Retrospective Research with a purposive sampling technique based on the criteria of the severity of Covid-19 disease. Patient data was taken from medical records and D-dimer levels from the Laboratory Information System and then analyzed using a one-way Anova test. The results showed an average Ddimer level of 2.66 mg/L at critical degrees, 2.02 mg/L at severe degrees, 0.30 at moderate degrees and 0.26 at mild degrees. Male patients occupy a larger percentage than female patients with a total of 62.5%. The age of 46-65 years occupies the highest percentage of 55% for the abnormal category because the immune system as a protector of the body does not work as strongly as when it was young. This study showed a significant average difference in the groups of mild severity with severe, mild with critical, moderate with severe, and moderate with critical. For the next researcher, it is expected to be able to analyze other hemostasis examination parameters with variables of disease severity. The increase in D-dimer is the most significant change in coagulation parameters in Covid19 patients and can be a marker of poor prognosis. The purpose of this study was to see the average significant D-dimer levels in patients with confirmed Covid-19 with severity. The method used is Retrospective Research with a purposive sampling technique based on the criteria of the severity of Covid-19 disease. Patient data was taken from medical records and D-dimer levels from the Laboratory Information System and then analyzed using a one-way Anova test. The results showed an average Ddimer level of 2.66 mg/L at critical degrees, 2.02 mg/L at severe degrees, 0.30 at moderate degrees and 0.26 at mild degrees. Male patients occupy a larger percentage than female patients with a total of 62.5%. The age of 46-65 years occupies the highest percentage of 55% for the abnormal category because the immune system as a protector of the body does not work as strongly as when it was young. This study showed a significant average difference in the groups of mild severity with severe, mild with critical, moderate with severe, and moderate with critical. For the next researcher, it is expected to be able to analyze other hemostasis examination parameters with variables of disease severity. The increase in D-dimer is the most significant change in coagulation parameters in Covid19 patients and can be a marker of poor prognosis. The purpose of this study was to see the average significant D-dimer levels in patients with confirmed Covid-19 with severity. The method used is Retrospective Research with a purposive sampling technique based on the criteria of the severity of Covid-19 disease. Patient data was taken from medical records and D-dimer levels from the Laboratory Information System and then analyzed using a one-way Anova test. The results showed an average Ddimer level of 2.66 mg/L at critical degrees, 2.02 mg/L at severe degrees, 0.30 at moderate degrees and 0.26 at mild degrees. Male patients occupy a larger percentage than female patients with a total of 62.5%. The age of 46-65 years occupies the highest percentage of 55% for the abnormal category because the immune system as a protector of the body does not work as strongly as when it was young. This study showed a significant average difference in the groups of mild severity with severe, mild with critical, moderate with severe, and moderate with critical. For the next researcher, it is expected to be able to analyze other hemostasis examination parameters with variables of disease severity. The increase in D-dimer is the most significant change in coagulation parameters in Covid19 patients and can be a marker of poor prognosis. The purpose of this study was to see the average significant D-dimer levels in patients with confirmed Covid-19 with severity. The method used is Retrospective Research with a purposive sampling technique based on the criteria of the severity of Covid-19 disease. Patient data was taken from medical records and D-dimer levels from the Laboratory Information System and then analyzed using a one-way Anova test. The results showed an average Ddimer level of 2.66 mg/L at critical degrees, 2.02 mg/L at severe degrees, 0.30 at moderate degrees and 0.26 at mild degrees. Male patients occupy a larger percentage than female patients with a total of 62.5%. The age of 46-65 years occupies the highest percentage of 55% for the abnormal category because the immune system as a protector of the body does not work as strongly as when it was young. This study showed a significant average difference in the groups of mild severity with severe, mild with critical, moderate with severe, and moderate with critical. For the next researcher, it is expected to be able to analyze other hemostasis examination parameters with variables of disease severity. The increase in D-dimer is the most significant change in coagulation parameters in Covid19 patients and can be a marker of poor prognosis. The purpose of this study was to see the average significant D-dimer levels in patients with confirmed Covid-19 with severity. The method used is Retrospective Research with a purposive sampling technique based on the criteria of the severity of Covid-19 disease. Patient data was taken from medical records and D-dimer levels from the Laboratory Information System and then analyzed using a one-way Anova test. The results showed an average Ddimer level of 2.66 mg/L at critical degrees, 2.02 mg/L at severe degrees, 0.30 at moderate degrees and 0.26 at mild degrees. Male patients occupy a larger percentage than female patients with a total of 62.5%. The age of 46-65 years occupies the highest percentage of 55% for the abnormal category because the immune system as a protector of the body does not work as strongly as when it was young. This study showed a significant average difference in the groups of mild severity with severe, mild with critical, moderate with severe, and moderate with critical. For the next researcher, it is expected to be able to analyze other hemostasis examination parameters with variables of disease severity. The increase in D-dimer is the most significant change in coagulation parameters in Covid19 patients and can be a marker of poor prognosis. The purpose of this study was to see the average significant D-dimer levels in patients with confirmed Covid-19 with severity. The method used is Retrospective Research with a purposive sampling technique based on the criteria of the severity of Covid-19 disease. Patient data was taken from medical records and D-dimer levels from the Laboratory Information System and then analyzed using a one-way Anova test. The results showed an average Ddimer level of 2.66 mg/L at critical degrees, 2.02 mg/L at severe degrees, 0.30 at moderate degrees and 0.26 at mild degrees. Male patients occupy a larger percentage than female patients with a total of 62.5%. The age of 46-65 years occupies the highest percentage of 55% for the abnormal category because the immune system as a protector of the body does not work as strongly as when it was young. This study showed a significant average difference in the groups of mild severity with severe, mild with critical, moderate with severe, and moderate with critical. For the next researcher, it is expected to be able to analyze other hemostasis examination parameters with variables of disease severity. The increase in D-dimer is the most significant change in coagulation parameters in Covid19 patients and can be a marker of poor prognosis. The purpose of this study was to see the average significant D-dimer levels in patients with confirmed Covid-19 with severity. The method used is Retrospective Research with a purposive sampling technique based on the criteria of the severity of Covid-19 disease. Patient data was taken from medical records and D-dimer levels from the Laboratory Information System and then analyzed using a one-way Anova test. The results showed an average Ddimer level of 2.66 mg/L at critical degrees, 2.02 mg/L at severe degrees, 0.30 at moderate degrees and 0.26 at mild degrees. Male patients occupy a larger percentage than female patients with a total of 62.5%. The age of 46-65 years occupies the highest percentage of 55% for the abnormal category because the immune system as a protector of the body does not work as strongly as when it was young. This study showed a significant average difference in the groups of mild severity with severe, mild with critical, moderate with severe, and moderate with critical. For the next researcher, it is expected to be able to analyze other hemostasis examination parameters with variables of disease severity. The increase in D-dimer is the most significant change in coagulation parameters in Covid19 patients and can be a marker of poor prognosis. The purpose of this study was to see the average significant D-dimer levels in patients with confirmed Covid-19 with severity. The method used is Retrospective Research with a purposive sampling technique based on the criteria of the severity of Covid-19 disease. Patient data was taken from medical records and D-dimer levels from the Laboratory Information System and then analyzed using a one-way Anova test. The results showed an average Ddimer level of 2.66 mg/L at critical degrees, 2.02 mg/L at severe degrees, 0.30 at moderate degrees and 0.26 at mild degrees. Male patients occupy a larger percentage than female patients with a total of 62.5%. The age of 46-65 years occupies the highest percentage of 55% for the abnormal category because the immune system as a protector of the body does not work as strongly as when it was young. This study showed a significant average difference in the groups of mild severity with severe, mild with critical, moderate with severe, and moderate with critical. For the next researcher, it is expected to be able to analyze other hemostasis examination parameters with variables of disease severity. The increase in D-dimer is the most significant change in coagulation parameters in Covid19 patients and can be a marker of poor prognosis. The purpose of this study was to see the average significant D-dimer levels in patients with confirmed Covid-19 with severity. The method used is Retrospective Research with a purposive sampling technique based on the criteria of the severity of Covid-19 disease. Patient data was taken from medical records and D-dimer levels from the Laboratory Information System and then analyzed using a one-way Anova test. The results showed an average Ddimer level of 2.66 mg/L at critical degrees, 2.02 mg/L at severe degrees, 0.30 at moderate degrees and 0.26 at mild degrees. Male patients occupy a larger percentage than female patients with a total of 62.5%. The age of 46-65 years occupies the highest percentage of 55% for the abnormal category because the immune system as a protector of the body does not work as strongly as when it was young. This study showed a significant average difference in the groups of mild severity with severe, mild with critical, moderate with severe, and moderate with critical. For the next researcher, it is expected to be able to analyze other hemostasis examination parameters with variables of disease severity. The increase in D-dimer is the most significant change in coagulation parameters in Covid19 patients and can be a marker of poor prognosis. The purpose of this study was to see the average significant D-dimer levels in patients with confirmed Covid-19 with severity. The method used is Retrospective Research with a purposive sampling technique based on the criteria of the severity of Covid-19 disease. Patient data was taken from medical records and D-dimer levels from the Laboratory Information System and then analyzed using a one-way Anova test. The results showed an average Ddimer level of 2.66 mg/L at critical degrees, 2.02 mg/L at severe degrees, 0.30 at moderate degrees and 0.26 at mild degrees. Male patients occupy a larger percentage than female patients with a total of 62.5%. The age of 46-65 years occupies the highest percentage of 55% for the abnormal category because the immune system as a protector of the body does not work as strongly as when it was young. This study showed a significant average difference in the groups of mild severity with severe, mild with critical, moderate with severe, and moderate with critical. For the next researcher, it is expected to be able to analyze other hemostasis examination parameters with variables of disease severity. The increase in D-dimer is the most significant change in coagulation parameters in Covid19 patients and can be a marker of poor prognosis. The purpose of this study was to see the average significant D-dimer levels in patients with confirmed Covid-19 with severity. The method used is Retrospective Research with a purposive sampling technique based on the criteria of the severity of Covid-19 disease. Patient data was taken from medical records and D-dimer levels from the Laboratory Information System and then analyzed using a one-way Anova test. The results showed an average Ddimer level of 2.66 mg/L at critical degrees, 2.02 mg/L at severe degrees, 0.30 at moderate degrees and 0.26 at mild degrees. Male patients occupy a larger percentage than female patients with a total of 62.5%. The age of 46-65 years occupies the highest percentage of 55% for the abnormal category because the immune system as a protector of the body does not work as strongly as when it was young. This study showed a significant average difference in the groups of mild severity with severe, mild with critical, moderate with severe, and moderate with critical. For the next researcher, it is expected to be able to analyze other hemostasis examination parameters with variables of disease severity. [ABSTRACT FROM AUTHOR]

Background and Objectives Uncontrolled post-operative bleeding can lead to several problems and tissue repair disorder indentistry. This study has been conducted to compare the effect of Chitohem and natural silk on the onset of clot formations. Materials and Methods This laboratory study was carried out with a dependent parallel design. Three drops of blood were taken from each of 32 participants in the study. Fifty milligram Chitohem and natural silk powder were poured on two blood drops, respectively. The clot formation time was measured for all three groups simultaneously. Duration between pouring powder and starting of clot formation was recorded. Data analysis was performed using paired t-test and repeated measure ANOVA methods using SPSS 17 software. Results Participants composed of 20 (62.5%) women and 12 (37.5%) men. The average age of the participants was 43.33 ± 4.08 years. The average time periods of the onset of blood clot formation in Chitohem group, natural silk and control group were 90.97 ± 29.99, 141.97 ± 49.10, and 195.44 ± 58.70 second, respectively. Paired t-test showed the mean time of clot formation was significantly different among groups (p = 0.0001). Conclusions Based on the obtained results, it seems that although effect of “organic natural silk” on coagulation time was less than “Chitohem”, but silk has an acceptable hemostatic effect. The simultaneous use of natural silk and Chitohem can have a synergistic effect. [ABSTRACT FROM AUTHOR]

Venous thromboembolism (VTE) is the leading cause of morbidity and death worldwide, after cancer and cardiovascular diseases. VTE is defined to include pulmonary embolism (PE) and/or deep vein thrombosis (DVT). Approximately 25% of PE patients experience sudden death as an initial symptom of VTE, and between 10% and 30% of patients die within the first month after diagnosis. Currently, the only drugs approved for the treatment of both acute and chronic VTE are vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs). However, their effectiveness is limited due to their associated risk of bleeding. Ideally, therapy should be able to treat VTE and limit the risk of VTE recurrence without increasing the risk of bleeding. Several studies have shown that the use of statins during anticoagulation for VTE reduces the risk of death and VTE recurrence. However, to date, there are conflicting data on the impact of statins during anticoagulation for VTE. A biological protective function of statins during anticoagulation has also been reported. Statins affect D-dimer levels; tissue factor (TF) gene expression; and VIII, VII, and Von Willebrand clotting factors—the major clotting factors they are able to affect. However, the usefulness of statins for the treatment and prevention of VTE is currently under debate, and they should not be substituted for guideline-recommended VTE prophylaxis or anticoagulation treatment. In this review of the literature, we illustrate the advances on this topic, including data on the role of statins in primary VTE prevention and secondary VTE prevention, related biological mechanisms, the risk of bleeding during their use, and their ability to reduce the risk of death.

Proteolytic reactions on the phospholipid membrane surface, so‐called "membrane‐dependent" reactions, play central role in the process of blood clotting. One particularly important example is FX activation by the extrinsic tenase (VIIa/TF). Here we constructed three mathematical models of FX activation by VIIa/TF: (A) a homogeneous "well‐mixed" model, (B) a two‐compartment "well‐mixed" model, (C) a heterogeneous model with diffusion, to investigate the impact and importance of inclusion of each complexity level. All models provided good description of the reported experimental data and were equivalently applicable for <40 μM of phospholipids. Model C provided better predictions than A, B in the presence of TF‐negative phospholipid microparticles. Models predicted that for high TF surface density (STF) and FX deficiency the FX activation rate was limited by the rate of FX binding to the membrane. For low STF and excess of FX the reaction rate was limited by the tenase formation rate. The analysis of the substrate delivery pathways revealed that FX bound to VIIa/TF predominantly from solution for STF >2.8 × 10−3 nmol/cm2 and from the membrane for lower STF. We proposed the experimental setting to distinguish between the collision‐limited and non‐collision‐limited binding. The analysis of models in flow and non‐flow conditions revealed that the model of a vesicle in flow might be substituted by model C in the absence of the substrate depletion. Together, this study was the first which provided the direct comparison of more simple and more complex models. The reaction mechanisms were studied in a wide range of conditions. [ABSTRACT FROM AUTHOR]

This review contains the results of the studies of the hemostasis system in airline passengers and crew members, as well as ground-based model experiments simulating the effect of specific flight factors. According to most researchers, flight factors shift the coagulation balance towards increasing the procoagulant potential. However, the occurrence of thrombotic conditions in passengers is associated with the individual presence of certain endogenous risk factors, such as age, constitution, diseases of the cardiovascular system and hereditary pathology of the hemostasis system, and some types of hormone therapy. Aircraft pilots whose flight time significantly exceeds that of passengers have described cases of thrombosis. No mention of cases of hemorrhagic conditions in civil aviation flight personnel has been found in the available literature. [ABSTRACT FROM AUTHOR]

Haemorrhage control during surgery and following traumatic injury remains a critical, life-saving challenge. Cellulose products are already employed in commercially available haemostatic dressings. This work explores sourcing cellulose from sugarcane trash pulp to produce micro- and nanosized fibres with hydroxyl, carboxylic acid, and trimethylamine functional groups, resulting in either positive or negative surface charges. This paper assesses the influence of these fibres on multiple blood clotting parameters in both dispersed solutions and dry gauze applications. In vitro blood clotting studies demonstrated the significant haemostatic potential of cellulose fibres derived from sugarcane waste to initiate clotting. Plasma absorbance assays showed that the 0.25 mg/mL cellulose microfibre dispersion had the highest clotting performance. It was observed that no single property of surface charge, functionality, or fibre morphology exclusively controlled the clotting initiation measured. Instead, a combination of these factors affected clot formation, with negatively charged cellulose microfibres comprising hydroxyl surface groups providing the most promising result, accelerating the coagulation cascade mechanism by 67% compared to the endogenous activity. This difference in clot initiation shows the potential for the non-wood agricultural waste source of cellulose in haemostatic wound healing applications, contributing to the broader understanding of cellulose-based materials’ versatility and their applications in biomedicine.

We recently reported the potential application of recombinant prothrombin activator ecarin (RAPClot™) in blood diagnostics. In a new study, we describe RAPClot™ as an additive to develop a novel blood collection prototype tube that produces the highest quality serum for accurate biochemical analyte determination. The drying process of the RAPClot™ tube generated minimal effect on the enzymatic activity of the prothrombin activator. According to the bioassays of thrombin activity and plasma clotting, γ-radiation (>25 kGy) resulted in a 30–40% loss of the enzymatic activity of the RAPClot™ tubes. However, a visual blood clotting assay revealed that the γ-radiation-sterilized RAPClot™ tubes showed a high capacity for clotting high-dose heparinized blood (8 U/mL) within 5 min. This was confirmed using Thrombelastography (TEG), indicating full clotting efficiency under anticoagulant conditions. The storage of the RAPClot™ tubes at room temperature (RT) for greater than 12 months resulted in the retention of efficient and effective clotting activity for heparinized blood in 342 s. Furthermore, the enzymatic activity of the RAPClot™ tubes sterilized with an electron-beam (EB) was significantly greater than that with γ-radiation. The EB-sterilized RAPClot™ tubes stored at RT for 251 days retained over 70% enzyme activity and clotted the heparinized blood in 340 s after 682 days. Preliminary clinical studies revealed in the two trials that 5 common analytes (K, Glu, lactate dehydrogenase (LD), Fe, and Phos) or 33 analytes determined in the second study in the γ-sterilized RAPClot™ tubes were similar to those in commercial tubes. In conclusion, the findings indicate that the novel RAPClot™ blood collection prototype tube has a significant advantage over current serum or lithium heparin plasma tubes for routine use in measuring biochemical analytes, confirming a promising application of RAPClot™ in clinical medicine.

Background: Acute myeloid leukaemia carries the risk of complications associated with dysfunctions in haemostasis system. The purpose of this study was to investigate the factors associated with the risk of bleeding in patients with newly diagnosed acute myeloid leukaemia (AML). Methods: This study involved the methods of immunoenzymatic analysis and classical coagulation studies. The number of biochemical parameters important for establishing coagulative dysfunction in acute myeloid leukaemia was determined, the main ones being the level of von Willebrand factor, the Ristocetin-cofactor activity of von Willebrand factor and factor VIII activity, prothrombin time, platelet count, and fibrinogen concentration. Results: According to the results of the present study, the reduced activity of von Willebrand factor in patients with AML was associated with severe bleeding. The authors observed an increase in the number of platelets count in patients with AML who experienced haemorrhages compared to patients with no bleeding signs. The study also established an increase in the concentration of fibrinogen in cancer patients, compared to the control sample. Symptoms and quantitative indicators for diagnosing the severity of haemorrhagic syndrome were grouped. The authors considered the advantages and disadvantages of many therapeutic preparations and focussed on specific markers of activated haemorrhage-predicting platelets. Conclusion: Further studies concern the search for effective markers and therapeutic approaches to minimize haemorrhagic syndrome. The results were statistically processed using the functions ANOVA, t test, CORREL, determination of the value of reliability, and mean square deviation. [ABSTRACT FROM AUTHOR]

Background & Objectives: The intricate process of wound healing involves replacing the cellular or tissue structure that has been destroyed. In recent years various wound dressings were launched but reported several limitations. The topical gel preparations are intended for certain skin wound conditions for local action. Chitosan-based hemostatic materials are the most effective in halting acute hemorrhage, and naturally occurring silk fibroin is widely utilized for tissue regeneration. So, this study was conducted to evaluate the potential of chitosan hydrogel(CHI-HYD) and chitosan silk fibroin hydrogel (CHI-SF-HYD) on blood clotting and wound healing. Methods: Hydrogel was prepared using various concentrations of silk fibroin with guar gum as a gelling agent. The optimized formulations were evaluated for visual appearance, Fourier transforms infrared spectroscopy (FT-IR), pH, spreadability, viscosity, antimicrobial activity, HR-TEM analysis, ex vivo skin permeation, skin irritation, stability studies, and in vivo studies by using adult male Wistar albino rats. Results: Based on the outcome of FT-IR, no chemical interaction between the components was noticed. The developed hydrogels exhibited a viscosity of 79.2 ± 4.2 Pa.s (CHI-HYD), 79.8 ± 3.8 Pa.s (CHI-SF-HYD), and pH of 5.87 ± 0.2 (CHI-HYD), 5.96 ± 0.1 (CHI-SF-HYD). The prepared hydrogels were sterile and non-irritant to the skin. The in vivo study outcomes show that the CHI-SF-HYD treated group has significantly shortened the span of tissue reformation than other groups. This demonstrated that the CHI-SF-HYD could consequently accelerate the regeneration of the damaged area. Interpretation & Conclusion: Overall, the positive outcomes revealed improved blood coagulation and re-epithelialization. This indicates that the CHI-SF-HYD could be used to develop novel wound-healing devices.

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.

Blood clotting involves the coupled processes of platelet aggregation and coagulation. Simulating clotting under flow in complex geometries is challenging due to multiple temporal and spatial scales and high computational cost. clotFoam is an open-source software developed in OpenFOAM that employs a continuum model of platelet advection, diffusion, and aggregation in a dynamic fluid environment and a simplified coagulation model with proteins that advect, diffuse, and react within the fluid and with wall-bound species through reactive boundary conditions. Our framework provides the foundation on which one can build more complex models and perform reliable simulations in almost any computational domain.

ABSTRAK Pendahuluan: Ekstraksi gigi adalah salah satu tindakan umum di bidang kedokteran gigi yang sering dilakukan oleh dokter gigi. Tindakan ekstraksi gigi dapat menyebabkan komplikasi salah satunya adalah pendarahan. Tanaman gambir (Uncaria gambier roxb.) merupakan tanaman asli Indonesia yang pemanfaatannya masih sangat terbatas dan memiliki potensi untuk mempercepat pembekuan darah. Tanaman gambir mengandung katekin yang merupakan golongan flavonoid yang dapat menjaga permeabilitas pembuluh darah. Penelitian menganalisis potensi katekin gambir sebagai agen mempercepat pembekuan darah pasca ekstraksi gigi. Metode: Jenis penelitian quasi eksperimen dengan jumlah sampel 16 orang. Sebelum diujikan dengan darah, katekin gambir dibuat dari daun gambir dan diekstrak menggunakan metode maserasi. Pengujian dilakukan dengan menggunakan darah manusia dengan golongan darah A, B, AB, dan O dengan masing-masing 5 perlakuan yaitu kontrol positif dengan asam traneksamat, kontrol negatif tanpa perlakukan, ekstrak katekin gambir dengan konsentrasi 25, 35, dan 45%. Hasil: Data yang telah didapatkan terdistribusi normal dan menunjukkan bahwa hasil uji one way ANOVA pemberian perlakuan ekstrak katekin daun gambir pada setiap golongan darah menunjukkan hasil signifikan (p=0,0005). Hasil uji post hoc menunjukkan terdapat perbedaan nilai signifikansi pada setiap kelompok perlakuan terhadap setiap golongan darah. Simpulan: Ekstrak katekin daun gambir dapat mempercepat proses pembekuan darah terutama dengan konsentrasi 45% sehingga berpotensi sebagai agen mempercepat pembekuan pasca ekstraksi gigi. Kata kunci: katekin gambir; ekstraksi gigi; pembekuan darah ABSTRACT Introduction: Tooth extraction is one of the common procedures in dentistry that dentists often perform. Tooth extraction can cause complications, one of which is bleeding. The gambier plant is a native Indonesian plant whose utilization is still rare and has the potential to accelerate blood clotting. Gambier plants contain catechins, a group of flavonoids that can maintain the permeability of blood vessels. This study aimed to analyze the potential of gambir catechins as agents to accelerate blood clotting after tooth extraction. Methods: This research was a quasi-experimental study with a sample of 16 people. Before being tested with blood, gambier catechins were made from gambier leaves and extracted using the maceration method. The test was carried out using human blood with blood types A, B, AB, and O with five treatments each, namely positive control with tranexamic acid, negative control without treatment, gambir catechin extract with a concentration of 25, 35, and 45%. Result: The data that has been obtained is normally distributed and shows that the results of the one-way test ANOVA treatment of gambir leaf catechin extract for each blood group showed results significant (p=0.0005). The results of the post hoc test showed that there were differences in the significance value for each treatment group for each blood group. Conclusion: Catechin extract from gambir leaves can accelerate the process of blood clotting, especially with a concentration of 45%. Hence, it has the potential as an agent to accelerate clotting after tooth extraction. Keywords: gambir catechin; tooth extraction; blood clotting

Aim. To evaluate thrombus characteristics in patients with atrial fibrillation (AF) taking different direct oral anticoagulants (DOACs) using Thrombodynamics test.Materials and methods. Thrombodynamics test was performed in 100 patients with paroxysmal and permanent forms of AF taking different DOACs, dose choice was done in accordance with the instructions for drugs use. For analysis samples of fresh citrated platelet-free plasma were taken just before regular DOACs dose intake (trough concentration). Statistical data processing was carried out using R software packages.Results. All patients had no history of thrombosis or bleeding before inclusion in this study. All parameters of Thrombodynamics test taken at residual concentration of DOACs were in general within reference values, that is in the area of normal coagulation: spatial clot growth rate (V) – 26.56 (25.0; 29.2) μm/min, the time to the start of clot growth (Tlag) – 1.05 (0.85; 1.27) min, initial spatial clot growth rate (Vi) – 44.3±7.7 μm/min, stationary spatial clot growth rate (Vst) – 26.5 (24.9; 28.4) μm/min, clot size (CS) – 999.7 (912.9; 1084.7) μm, clot density (D) – 22883.1±3199.9 arb. units. D was appeared to be higher in women [22947.7 (21477.5; 22947.7) vs men [22124.8 (19722.8; 22124.8), p=0.035] and Tlag was significantly higher in patients with chronic heart failure [1.2 (1.0; 1.2) vs 1.0 (0.8; 1.0), p=0.008]. A correlation was found between level of creatinine and Tlag parameter, glomerular filtration rate (GFR) and clot density. With an increase in the level of creatinine in the blood and a decrease in GFR, respectively, there was an increase in Tlag parameter (p-value 0.038); with an increase in GFR, clot density decrease (p-value 0.005).Conclusion. All parameters of Thrombodynamics test on residual concentration of DOACs were within reference values that indicated optimal anticoagulant effect of all DOACs. The obtained data of normal coagulation at the residual concentration of the anticoagulant are consistent with the previously obtained data on the safety and effectiveness of DOACs using other methods. Further studies with clinical end points are needed to assess the clinical value of this method.

Post-extraction bleeding and alveolar bone resorption are the two frequently encountered complications after tooth extraction that result in poor healing and rehabilitation difficulties. The present study covalently bonded polyphosphate onto a collagen scaffold (P-CS) by crosslinking. The P-CS demonstrated improved hemostatic property in a healthy rat model and an anticoagulant-treated rat model. This improvement is attributed to the increase in hydrophilicity, increased thrombin generation, platelet activation and stimulation of the intrinsic coagulation pathway. In addition, the P-CS promoted the in-situ bone regeneration and alveolar ridge preservation in a rat alveolar bone defect model. The promotion is attributed to enhanced osteogenic differentiation of bone marrow stromal cells. Osteogenesis was improved by both polyphosphate and blood clots. Taken together, P-CS possesses favorable hemostasis and alveolar ridge preservation capability. It may be used as an effective treatment option for post-extraction bleeding and alveolar bone loss. Statement of significance: Collagen scaffold is commonly used for the treatment of post-extraction bleeding and alveolar bone loss after tooth extraction. However, its application is hampered by insufficient hemostatic and osteoinductive property. Crosslinking polyphosphate with collagen produces a modified collagen scaffold that possesses improved hemostatic performance and augmented bone regeneration potential.

The intricate process of wound healing involves replacing the cellular or tissue structure that has been destroyed. In recent years various wound dressings were launched but reported several limitations. The topical gel preparations are intended for certain skin wound conditions for local action. Chitosan-based hemostatic materials are the most effective in halting acute hemorrhage, and naturally occurring silk fibroin is widely utilized for tissue regeneration. So, this study was conducted to evaluate the potential of chitosan hydrogel(CHI-HYD) and chitosan silk fibroin hydrogel (CHI-SF-HYD) on blood clotting and wound healing. Hydrogel was prepared using various concentrations of silk fibroin with guar gum as a gelling agent. The optimized formulations were evaluated for visual appearance, Fourier transforms infrared spectroscopy (FT-IR), pH, spreadability, viscosity, antimicrobial activity, HR-TEM analysis, ex vivo skin permeation, skin irritation, stability studies, and in vivo studies by using adult male Wistar albino rats. Based on the outcome of FT-IR, no chemical interaction between the components was noticed. The developed hydrogels exhibited a viscosity of 79.2 ± 4.2 Pa.s (CHI-HYD), 79.8 ± 3.8 Pa.s (CHI-SF-HYD), and pH of 5.87 ± 0.2 (CHI-HYD), 5.96 ± 0.1 (CHI-SF-HYD). The prepared hydrogels were sterile and non-irritant to the skin. The in vivo study outcomes show that the CHI-SF-HYD treated group has significantly shortened the span of tissue reformation than other groups. This demonstrated that the CHI-SF-HYD could consequently accelerate the regeneration of the damaged area. Overall, the positive outcomes revealed improved blood coagulation and re-epithelialization. This indicates that the CHI-SF-HYD could be used to develop novel wound-healing devices. [ABSTRACT FROM AUTHOR]

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Porous materials, from macroscopic bulk materials (MBs) with (sub‐)millimeter‐scale pores to tiny particles (TPs) with (sub‐)nanometer‐scale pores, have attracted ever‐growing interest in various fields. However, the integration of multi‐scale pores in one composite is promising but challenging, owing to the considerable gap in the scale of the pores. Inspired by blood coagulation, a fibrin‐based dynamic bridging strategy is developed to fabricate a multiscale‐assembled hierarchical porous material (MHPM), in which fibrin formed as the sub‐framework for the weaving‐narrow of MBs and the enwinding‐load of TPs. The bio‐polymerization nature makes the fabrication rapid, facile, and universal for the customizable integration of seven kinds of TPs and four kinds of MBs. Besides, the integration is controllable with high load capacity of TPs and is stable against external shock forces. The unique multi‐level structure endows the MHPM with large and accessible surface area, and efficient mass transfer pathways, synergistically leading to high adsorption capacity and rapid kinetics in multiple adsorption models. This work suggests a strategy for the rational multi‐level design and fabrication of hierarchical porous architectures. [ABSTRACT FROM AUTHOR]

The aim of this study was to introduce novel dressing with different extracts of mangosteen for quick blood clotting and wound healing. Insufficient use of natural biomaterials for blood clotting and wound healing in the medical textile sector has been observed. In order to improve the situation, viscose woven fabrics treated with mangosteen leaf, peel and pericarp extract were examined. Fresh mangosteens were collected from local market and different pastes were prepared by using an electric blender. The pretreated viscose woven fabrics were dyed with these pastes using glycerin as mordant. After the sample preparation, an antibacterial test, odor test, blood clotting test, strength test, color fastness tests were done. The treated samples exhibited good antibacterial activity against gram negative bacteria and mild antibacterial activity against gram positive bacteria, especially the fabrics treated with mangosteen leaf and pericarp. Besides, the treated samples did not create annoying odors as like the untreated one. To justify healing properties, implementations of the samples were done on a rabbit. Leaf and pericarp treated fabrics exhibited good blood clotting in comparison with untreated fabric. All the treated samples exhibited average to good color fastness to wash and rubbing properties with sufficient tensile strength. Morphological changes of the treated and untreated fibers were examined by SEM and FTIR analysis and the results clearly showed the differences in the untreated and treated samples. The experiments were carried out in an environment friendly way which indicates the production and processing of these dressing materials can have an enormous contribution to sustainable operations and products for the development of medical textiles sector.

Abstract The number of deaths associated with cardiovascular diseases (CVD) increases every year, leading to an intense search for new compounds that may be employed as anticoagulants. One of the classes of bioprospected molecules comprises sulfated polysaccharides (SP) from seaweed, as heparin displays many adverse effects associated with its use. The present study aimed to characterize and evaluate the anticoagulant potential of SP extracted from the green algae Halimeda opuntia. Four PS-rich fractions, F23, F44, F60 and F75, were obtained by proteolytic digestion in papain followed by ethanol precipitation. The presence of SP was confirmed by agarose gel electrophoresis, revealing different populations in each fraction. The F44 fraction is noteworthy compared to the other fractions, presenting a 5% yield compared to the initial algae weight and anticoagulant activity revealed by the activated partial thromboplastin time (APTT) assay (intrinsic/common coagulation pathway). Surprisingly, F44 purification (SP peak P1F44) resulted in prothrombin time (PT) activity (extrinsic coagulation pathway) at a 160 µg/mL, in addition to enhanced APTT activity. The P1F44 anticoagulant activity mechanism was shown to be dependent on two coagulations factors, IIa and Xa, more potent via IIa. Future assessments will be performed to assess this fraction in the medical clinic.

The chitosan added to heparinized blood plasma in vitro at concentrations of 10–2, 10–1, 1, 5, and 10 mg/mL dose-dependent reduced fibrinolysis, the prothrombin time, platelet aggregation, and blood clotting and increased the activity of factor XIIIa. A decrease in fibrinolysis and plasmin activity and increased FXIIIa activity and platelet aggregation were also detected in vivo in a rat model with hypocoagulation caused by intravenous administration of high-molecular heparin (400 IU/kg of body mass), 30 minutes after injection of chitosan (10 mg/kg of body mass). At the same time, the fibrinogen concentration was restored to the normal levels. It was accompanied by an increase in the activity of the tissue plasminogen activator and an extension of the blood clotting time (APTT test). A conclusion on the multidirectional effect of chitosan on the hemostasis parameters under hypocoagulation was made, and the possible mechanisms of chitosan action were considered. [ABSTRACT FROM AUTHOR]

The stress–strain characteristics of a clot during loading/unloading mechanical cycles are significant features to assess the underlying mechanisms of thrombectomy, especially when multiple thrombectomy attempts are required. We investigated a damage model to predict loading/unloading response of clots. To study the validity of the model, we tested theoretical models to reproduce the experimentally obtained mechanical characteristics of clots under various conditions. Three types of clot analogs with different red blood cell (RBC) compositions were prepared. Cylindrical clot analogs were formed for the tensile and compression tests. Loading/unloading tests at 80% of strain were conducted, where the material parameters were determined by fitting the results to a theoretical curve combining the damage model and the elasto-plastic constitutive model. Through the computation for theoretical curves, unique characteristics of clots were revealed such that the hysteresis loss rate did not change by varying RBC contents, except for the clot created with 0% RBC composition, under compressive loading. In addition, the plastic strain decreased as the RBC content decreased under tensile loading, whereas it increased as the RBC content decreased under compressive loading. A three-dimensional finite element method (FEM) was employed with the determined parameters. The FEM could accurately reproduce the experimental stress–strain curves for all types of clot analogs and for both loading types up to a strain of 80%. The results indicate that the theoretical model which incorporates and combines the damage model and the elasto-plastic constitutive model is applicable to predict the non-linear stress–strain behavior of clots under loading and unloading. [ABSTRACT FROM AUTHOR]

The hemostasis system is designed to maintain a balance between the processes of blood clotting, anticoagulation, as well as fibrinolysis, to ensure constant effective blood circulation in the body and rapid cessation of bleeding in the event of their occurrence. The procoagulant potential of the hemostasis system is based on molecular mechanisms that lead to the formation of fibrin in the bloodstream, which is the framework of the thrombus, and to the aggregation of platelets — the basis of the thrombus body. The anticoagulant potential of blood plasma is provided by mechanisms aimed at inhibiting blood coagulation processes. Thorough study and understanding of these mechanisms will open up numerous treatments for pathologies associated with both intravascular thrombosis and bleeding of various origins. The purpose of this review is to analyze ways to prevent intravascular thrombosis and stimulate extravascular thrombosis. The review describes and analyzes available and promising means of thrombosis prevention, in particular, direct and indirect anticoagulants and antiplatelets, as well as methods of effective stimulation of thrombosis, which is necessary in case of vascular damage. The result of this analysis is to determine the nodal points of the protein network of the hemostasis system, the action of which by specific molecular effectors will control the process of thrombosis.

Abstract Background Medical hemostatic biological materials are necessary for the development of the process of preventing and stopping damaged intravascular bleeding. In the process, some red blood cells and white blood cells are trapped in nets. The resulting plug is called a blood clot. This is often a good step in wound healing, but separation of blood clots from blood vessel walls can cause serious health problems. Main body The advance in the development of hemostatic biomaterials is necessary for biomedical application. Firstly, the historical background of artificial hemostasis has been included and the current research of hemostasis has been included in more detail. Secondly, the current research of hemostasis has been included on the oxidized cellulose-based hemostatic biomaterials such as starch based on composite cross-linking hemostatic networks, hemostatic materials on NHS-esters, hemostatic agent from local materials and biomaterials for hemostatic management. Thirdly, polysaccharide hemostatic materials, bio-inspired adhesive catechol-conjugated chitosan, mesoporous silica and bioactive glasses for improved hemostasis, minimally invasive hemostatic biomaterials and chitosan-base materials for hemostatic application have been included. Fourthly, the biological properties of natural hemostatic agent by plasma technology and the hemostatic agents based on gelatin-microbial transglutaminase mixes have been also included. Conclusion Current research on hemostasis includes hemostatic biomaterials such as cellulose-based hemostatic starch based on a complex cross-linked hemostatic network. It also includes polysaccharide hemostatic materials, biomimetic adhesive catechol-binding chitosan, mesoporous silica or physiologically active glass for hemostatic improvement, minimally invasive hemostatic chitosan-based materials, and gelatin-microbial transglutaminase-based hemostatic agents. Future studies should focus on modular combination of hemostatic imitation and reinforcement mechanisms of different materials and technologies to find the optimal system to promote and strengthen active platelet or platelet imitation aggregation in bleeding sites. The second optionally increases the production of thrombin and fiber formation at the site. Third, the formed fibrin biopolymer network has strengthened to reduce thrombosis and amplify hemostasis.

Summary: To slow down the coronavirus disease 2019 (COVID‐19) pandemic an unequalled vaccination campaign was initiated. Despite proven efficacy and safety, a rare but potentially fatal complication of adenoviral‐vector vaccines, called vaccine‐induced immune thrombotic thrombocytopenia (VITT), has emerged the pathogenesis of which seems to be related to the development of platelet‐activating anti‐platelet factor 4 (PF4) antibodies. While a few studies have evaluated the incidence of anti‐PF4 positivity in anti‐severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) vaccine recipients, to date no studies have assessed whether an antiplatelet immunological response develops and if this associates with platelet and blood clotting activation. We carried out a prospective study in healthy subjects who received the first dose of ChAdOx1 or Ad26.COV2.S or BNT162b2 vaccines to evaluate platelet‐specific and non‐specific immune response and in vivo platelet activation and blood clotting activation. Individuals receiving ChAdOx1 and, less so, Ad26.COV2.S developed with high frequency auto‐ or alloantiplatelet antibodies, increased circulating platelet‐derived microvesicles and soluble P‐selectin associated with mild blood clotting activation. Our study shows that an immunological reaction involving platelets is not uncommon in individuals receiving anti‐SARS‐CoV‐2 vaccination, especially after ChAdOx1 and Ad26.COV2.S, and that it associates with in vivo platelet and blood clotting activation. [ABSTRACT FROM AUTHOR]

Russell's viper being one of the most venomous snake species in Asia causes significant amount of snake bites and deaths due to neurotoxicity, coagulopathy, haemorrhage, cardiotoxicity, myotoxicity, hypotension, oedema, tissue damage and convulsion. Treatment with monoclonal antibodies, anti-snake venom is the only medically approved treatment available for snake envenomation and has many limitations and side effects such as anaphylactic shock, skin rashes, nausea to vomiting and fever, chills, hypotension, seizures, serum sickness, pruritus, urticaria, arthralgia, lymphadenopathy, encephalopathy etc. Recently, nanoscience and nanotechnology are playing an important role in medical field and has proven to be quite beneficial. In present study, chemically synthesized silver nanoparticles (40±3 nm) are used to inhibit Russell's viper venom activity. The silver nanoparticles and albumin conjugated with curcumin was prepared and characterized using spectroscopic techniques. Venom inhibitory potency of the prepared conjugate was analysed using acidimetry, protease assay and whole blood clotting test. The ultravioletvisible spectra showed enhancement in absorbance of venom with significant hyperchromic shift and thus confirmed modification of venom by silver nanoparticles. This also led to the enhanced interaction with bovine serum albumin-curcumin conjugates. Fluorescence data also showed strong interaction between the conjugates and venom. Interestingly the activity of Russell's viper venom was reduced to 75 %-96 %. The possible mechanism of action of bovine serum albumin-curcumin complex on venom treated with silver nanoparticles is explained at molecular level and biocompatibility of the same was also analysed. Blood agglutination by bovine serum albumin-curcumin complex showed its in vitro biocompatibility. [ABSTRACT FROM AUTHOR]

The development of multifunctional wound dressings has always been considered as a promising strategy to promote blood coagulation, inhibit bacterial infection, and accelerate wound healing. Herein, an antibacterial and hemostatic dressing (SA-PHMG) was developed based on sodium alginate (SA) nonwoven and polyhexamethylene guanidine hydrochloride (PHMG) through a completely green industrial route, including dipping, padding, and drying. According to studies, SA-PHMG dressings exhibited excellent liquid absorption capacity and water vapor permeability. Moreover, bactericidal assays have demonstrated that SA-PHMG dressings have ideal antibacterial activity against Escherichia coli , Staphylococcus aureus , Pseudomonas aeruginosa and mixed bacteria, maintaining potent antibacterial activity even after 10 cycles of antibacterial trials or 50 times of washing or soaping. The in vitro evaluation of the hemostatic effect indicated that the SA-PHMG could significantly promote blood clotting by activating platelets, and in vitro and in vivo hemolysis, cytotoxicity and skin irritation studies demonstrated the ideal biocompatibility of the dressings. In addition, better wound closure and tissue regeneration were recorded using SA-PHMG nonwoven as the dressing based on an infected full-thickness wound model. In conclusion, this antibacterial, hemostatic, biocompatible, and environmentally friendly SA-PHMG nonwoven exhibit the potential for infected wound healing. [ABSTRACT FROM AUTHOR]

Simple Summary: Humic acids are one of the main components of the natural organic matter in surface waters that give them brown color. These compounds are known to have positive effects on aquatic animals such as increased growth and stress resistance. At the same time, there is experimental evidence that humic acids, being natural xenobiotics, act as follows: they cause stress responses at the molecular level. Our aim was to study humic acid-related effects on fish by performing the proteomic analysis of the blood plasma from Japanese medaka exposed to humic acid in concentrations that can be found in natural waters. Results of the study showed that most of the plasma proteins in the exposed fish had a lower abundance compared to that of the intact fish; humic acid caused a reduction in circulating levels of complement components, coagulation factors, and their regulators. Humic acids (HA), one of the major components of dissolved organic matter, can interfere with different metabolic pathways in aquatic animals, causing various biological effects. This study aimed to provide a molecular basis for HA-related responses in fish by analyzing changes in the blood plasma proteome following short-term exposure to environmentally relevant HA concentrations using the Japanese medaka Oryzias latipes Hd-rR strain as a model organism. Proteomics data were obtained by high-performance liquid chromatography with tandem mass spectrometry analysis employing a label-free quantification approach. HA caused dysregulation of proteins involved in various biological processes, including protein folding, signaling, transport, metabolism, regulation, immune response, and coagulation. The majority of the differentially abundant proteins were down-regulated, including those involved in humoral immunity and coagulation. HA caused the decrease of the complement cascade and membrane attack complex proteins abundance, as well as proteins participating in activation and regulation of secondary hemostasis. The most pronounced suppression was observed at the highest tested HA concentration. [ABSTRACT FROM AUTHOR]

• A mechanisms-driven model of prothrombin activation by prothrombinase was designed. • Pathways of FII or Xa binding to FVa depended on the reactants' concentrations. • Large FVa concentration had inhibitory effect due to the membrane occupation by FVa. Prothrombinase complex, composed of coagulation factors Xa (FXa) and Va (FVa) is a major enzyme of the blood coagulation network that produces thrombin via activation of its inactive precursor prothrombin (FII) on the surface of phospholipid membranes. However, pathways and mechanisms of prothrombinase formation and substrate delivery are still discussed. Here we designed a novel mathematical model that considered different potential pathways of FXa or FII binding (from the membrane or from solution) and analyzed the kinetics of thrombin formation in the presence of a wide range of reactants concentrations. We observed the inhibitory effect of large FVa concentrations and this effect was phospholipid concentration-dependent. We predicted that efficient FII activation occurred via formation of the ternary complex, in which FVa, FXa and FII were in the membrane-bound state. Prothrombin delivery was mostly membrane-dependent, but delivery from solution was predominant under conditions of phospholipid deficiency or FXa/FVa excess. Likewise, FXa delivery from solution was predominant in the case of FVa excess, but high FII did not switch the FXa delivery to the solution-dependent one. Additionally, the FXa delivery pathway did not depend on the phospholipid concentration, being the membrane-dependent one even in case of the phospholipid deficiency. These results suggest a flexible mechanism of prothrombinase functioning which utilizes different complex formation and even inhibitory mechanisms depending on conditions. [ABSTRACT FROM AUTHOR]

The article explores Widespread use of anticoagulant rodenticides (ARs) creates an ongoing global conservation concern for raptors. ARs have the potential to negatively affect birds primarily by secondary exposure (via scavenging or depredating primary consumers of ARs), which may cause toxicosis following the consumption of a poisoned prey. Exposure to ARs has been documented in numerous raptor species sampled from a wide range of regions, including North America.

In [Fogelson and Keener, Phys. Rev. E, 81 (2010), 051922], we introduced a kinetic model of fibrin polymerization during blood clotting that captured salient experimental observations about how the gel branching structure depends on the conditions under which the polymerization occurs. Our analysis there used a moment-based approach that is valid only before the finite time blow-up that indicates formation of a gel. Here, we extend our analyses of the model to include both pregel and postgel dynamics using the PDE-based framework we introduced in [Fogelson and Keener, SIAM J. Appl. Math., 75 (2015), pp. 1346-1368]. We also extend the model to include spatial heterogeneity and spatial transport processes. Studies of the behavior of the model reveal different spatial-temporal dynamics as the time scales of the key processes of branch formation, monomer introduction, and diffusion are varied. [ABSTRACT FROM AUTHOR]

Blood clotting is measured by using a pressure sensor in a blood circuit, but the sensor doesn’t respond quick enough because the blood clotting can only be detected by an increase of the pressure caused by the clotting itself. This research is to evaluate predictive maintenance on MATLAB, based on our report at SEIA’2019 Conference for imaging data from a new sensing method for blood clotting (photoacoustic imaging with LED light). When the luminance of the imaging data (0-255 levels) was randomly analysed from photoacoustic imaging in a grid pattern, an increase or decrease of the luminance was seen at certain levels before and after the clotting. These important changes suggest that it may lead to a reduction in the amount of data handled during predictive maintenance of blood coagulation status.

The unique antiwetting properties of superhydrophobic (SH) surfaces prevent the adhesion of water and bodily fluids, including blood, urine, and saliva. While typical manufacturable approaches to create SH surfaces rely on chemical and structural modifications, such approaches are expensive, require postprocessing, and are often not biocompatible. By contrast, it is demonstrated that purely structural SH features are easily formed using high throughput roll-to-roll (R2R) manufacturing by shrinking a prestressed thermoplastic with a thin, stiff layer of silver and calcium. These features are subsequently embossed into any commercially available and Food and Drug Administration (FDA)-approved plastic. The R2R SH surfaces have contact angles >150° and contact angle hysteresis 4200× reduction of blood residue area compared to the nonstructured controls of the same material. In addition, blood clotting is reduced >5× using whole blood directly from the patient. Furthermore, these surfaces can be easily configured into 3D shapes, as demonstrated with SH tubes. With the simple scale-up production and the eliminated need for anticoagulants to prevent clotting, the proposed conformable SH surfaces can be impactful for a wide range of medical tools, including catheters and microfluidic channels.

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.

Background: The platelet-driven contraction or retraction of blood clots has been utilized to obtain blood serum for laboratory studies, but now, in vitro clot contraction assays are used in research laboratories and clinics to assess platelet functionality. The static final extent of clot contraction measured using a clot size or expelled serum volume can be supplemented substantially with a dynamic analysis., Objectives: To provide a step-by-step protocol for a relatively simple and affordable new automated methodology to follow the kinetics of blood clot contraction, which allows for simultaneous measurements of various samples at a time and requires only a fluorescence plate reader., Methods: The kinetics of clot contraction in whole blood was assessed by continuously detecting the fluorescence intensity of fluorescein isothiocyanate-albumin added to a blood sample before clotting and expelled into the serum during clot shrinkage., Results: The clots are formed and fluorescence is measured in the wells of a black multiwell plate using a standard plate fluorescent reader. The specificity of this technique for clot contraction has been demonstrated by the strong inhibitory effects of blebbistatin, latrunculin A, and abciximab. To validate the new technique, increased fluorescence intensity in the contracting clots was measured in parallel with a visual decrease in clot size performed with the same blood samples., Conclusion: The resulting clot contraction dynamics based on the expulsion of fluorescein isothiocyanate-albumin can be quantified using a number of kinetic parameters as well as a phase kinetics analysis. The advantages and drawbacks of the new technique are discussed., Competing Interests: Declaration of competing interests There are no competing interests to disclose., (Copyright © 2024 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

We describe here the purification and cloning of a codon-optimized form of the snake prothrombin activator ecarin from the saw scaled viper (Echis carinatus) expressed in mammalian cells. Expression of recombinant ecarin (rEcarin) was carried out in human embryonic kidney cells (HEK) cells under conditions for the development and performance of a novel and scalable recombinant snake ecarin to industry standards. Clotting performance of the rEcarin was established in recalcified citrated whole blood, plasma, and fresh whole blood and found to be comparable to native ecarin (N-Ecarin). Furthermore, hemolysis was observed with N-Ecarin at relatively high doses in both recalcified citrated and fresh whole blood, while clotting was not observed with rEcarin, providing an important advantage for the recombinant form. In addition, rEcarin effectively clotted both recalcified citrated whole blood and fresh whole blood containing different anticoagulants including heparin, warfarin, dabigatran, Fondaparinux, rivaroxaban and apixaban, forming firm clots in the blood collection tubes. These results demonstrate that rEcarin efficiently clots normal blood as well as blood spiked with high concentrations of anticoagulants and has great potential as an additive to blood collection tubes to produce high quality serum for analyte analysis in diagnostic medicine.

Effective therapies are urgently needed to stabilize patients with marginally compressible junctional hemorrhage long enough to get them to the hospital alive. Herein, we report injectable and rapidly expandable cryogels consisting of polyacrylamide and thrombin (AT cryogels) created by cryo-polymerization for the efficient management of lethal junctional hemorrhage in swine. The produced cryogels have small pore sizes and highly interconnected porous architecture with robust mechanical strength. The cryogels exhibit rapid shape memory properties and prove to be resilient against fatigue. These cryogels also show high water/blood absorption capacity, fast blood clotting effect, and enhanced adhesion of red blood cells and platelets in vitro . Further, in vivo, hemostatic efficacy tests in a lethal swine junctional hemorrhage model suggest that treatment with AT cryogels, especially AT-2 cryogels, achieves the least blood loss and the highest survival rate (100 %) compared to currently employed products such as XStat® and combat gauze. The high hemostatic performance of the cryogels may be attributed to highly interconnected porous architecture with small pore size and the use of thrombin as a pro-coagulant agent. Collectively, injectable and rapidly expandable thrombin-decorated polyacrylamide-based cryogels show significant promise as hemostatic material, offering effective management of marginally compressible junctional hemorrhages in prehospital settings., Competing Interests: The authors declare no conflict of interest., (© 2024 The Authors.)

Background: In sepsis, fibrinolysis resistance correlates with worse outcomes. Practically, rotational thromboelastometry (ROTEM) is used to report residual clot amplitude relative to maximum amplitude at specified times after clot formation clot lysis indices (CLIs). However, healthy individuals can exhibit similar CLIs, thus making it challenging to solely diagnose the low fibrinolytic state. Furthermore, CLI does not include the kinetics of clot formation, which can affect overall fibrinolysis. Therefore, a more nuanced analysis, such as time to attain maximal clot amplitude after reaching maximal clot formation velocity (t-AUCi), is needed to better identify fibrinolysis resistance in sepsis., Objectives: To evaluate the correlation between the degree of fibrinolytic activation and t-AUCi in healthy or septic individuals., Methods: Whole blood (n = 60) from septic or healthy donors was analyzed using tissue factor-activated (EXTEM) and nonactivated (NATEM) ROTEM assays. Lysis was initiated with tissue-type plasminogen activator, and CLI and t-AUCi were calculated. Standard coagulation tests and plasma fibrinolysis markers (D-dimer, plasmin-α2-antiplasmin complex, plasminogen activator inhibitor type 1, and plasminogen) were also measured., Results: t-AUCi values decreased with increasing fibrinolytic activity and correlated positively with CLI for different degrees of clot lysis both in EXTEM and NATEM. t-AUCi cutoff value of 1962.0 seconds in EXTEM predicted low fibrinolytic activity with 81.8% sensitivity and 83.7% specificity. In addition, t-AUCi is not influenced by clot retraction., Conclusion: Whole-blood point-of-care ROTEM analyses with t-AUCi offers a more rapid and parametric evaluation of fibrinolytic potential compared with CLI, which can be used for a more rapid and accurate diagnosis of fibrinolysis resistance in sepsis., Competing Interests: Declaration of competing interests There are no competing interests to disclose., (Copyright © 2023 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

Wheatgrass is widely used in the alternative medicine, however, there is a lack of clinical evidence to support its efficacy. Although based on its chemical composition, data from animal experiments and clinical trials, the use of juice and extracts of Triticum shoots seems to be safe, clinical reports point out its potential interaction with oral anticoagulants. The aim of our study was to assess the interaction of wheatgrass with warfarin in rats and to assess its flavonoid content. Three groups of animals were treated orally with wheatgrass, warfarin, or the combination of wheatgrass and warfarin for five days. Clotting assays were performed using platelet-poor plasma. Prothrombin time was determined by optical and mechanical coagulometers. Flavonoid content of wheatgrass was measured by HPLC. The effect of wheatgrass on prothrombin time was not confirmed. Co-administration of wheatgrass and warfarin did not result in diminished anticoagulant activity. Low amount of flavonoids was detected in wheatgrass juice, the total flavonoid content was 0.467 mg/100 g lyophilized juice powder. The previously reported rutin, quercetin and apigenin was not detected by us. Our results do not confirm the probability of interaction of wheatgrass with oral anticoagulants. However, the low flavonoid content of wheatgrass does not support its use as an antioxidant. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]