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.
The Hemostasis and Thrombosis Research Society (HTRS) Registry was used to monitor the postapproval use of recombinant factor VIIa. The objective of this manuscript is to provide key insights on the ...demographics of patients with acquired hemophilia in the HTRS Registry. Acquired hemophilia patient registration in HTRS captured age; sex; comorbidities and predisposing conditions; first bleeding location; laboratory parameters; exposure to blood products, factor, and bypassing agents; and initiation of immune suppression/tolerance therapy. Overall, 166 patients with acquired hemophilia were registered in HTRS (83 women, 73 men, median age 70 years); the majority were non-Hispanic whites (61.4%). The most common comorbidities were autoimmune disease (28.4%) and malignancy (14.5%). The most common first site of bleeding was subcutaneous (27.1%); this was more common in whites (29.1%) than blacks (12.5%) and in non-Hispanics (26.4%) than Hispanics (11.8%). Blood product exposure was reported for 33.1% of patients; the most commonly reported product was packed red blood cells (28%). Of the 57 patients with outcome data available for immune tolerance therapy, 26 patients (46%) reported successful treatment, 13 reported unsuccessful treatment (23%), and 18 (32%) were receiving active treatment at the time of registration. The HTRS Registry final analysis provides the only current comprehensive look at acquired hemophilia in the US population, including details on underlying autoimmune diseases and malignancies. Pertinent to recognition and diagnosis of the disease, subcutaneous bleeding as a presenting bleeding symptom was more common in white and non-Hispanic individuals.
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•GO/CaCO3/SiO2 nanocomposite shows anti bioflim property.•Carrageenan/Chitosan injectable hydrogel shows enhanced blood clotting.•The hydrogel is highly biocompatible and ...hemocompatible.•In vivo analysis shows enhanced hemostasis.
Every year, millions of civilian casualties are caused by excessive bleeding, often known as hemorrhage. Even if the initial bleeding is effectively controlled, wound sequelae such as infection remains a substantial cause for persistent morbidity. Numerous blood clotting materials have been found, tried, and used to stop the bleeding. Topical dressings such gauzes, as well as organic and bioinspired materials are used to stop bleeding. None of these substances, however, can accurately duplicate the intricate and dynamic characteristics of blood clotting and the body's natural ability for wound healing. In this research work we have synthesized GO/CaCO3/SiO2 nanocomposite and incorporated them in a polymeric hydrogel for blood clotting application. The nanocomposite is characterized with XRD, FTIR and TEM. The injectable hydrogel is characterized with FTIR and SEM. Colony count and growth curve analysis are done for the nanocomposite. The injectable hydrogel consisting of the GO/CaCO3/SiO2 nanocomposite enhances the blood clotting property. This hydrogels with graphene oxide nanocomposite will be an ideal choice for addressing the clear need for better blood clotting material.
Blood clot contraction, volume shrinkage of the clot, is driven by platelet contraction and accompanied by compaction of the erythrocytes and their gradual shape change from biconcave to polyhedral, ...with the resulting cells named polyhedrocytes.
Here, we examined the role of erythrocyte rigidity on clot contraction and erythrocyte shape transformation.
We used an optical tracking methodology that allowed us to quantify changes in contracting clot size over time.
Erythrocyte rigidity has been shown to be increased in sickle cell disease (SCD), and in our experiments erythrocytes from SCD patients were 4-fold stiffer than those from healthy subjects. On average, the final extent of clot contraction was reduced by 53% in the clots from the blood of patients with SCD compared to healthy individuals, and there was significantly less polyhedrocyte formation. To test if this reduction in clot contraction was due to the increase in erythrocyte rigidity, we used stiffening of erythrocytes via chemical cross-linking (glutaraldehyde), rigidifying Wright
antibodies (Wr
), and naturally more rigid llama ovalocytes. Results revealed that stiffening erythrocytes result in impaired clot contraction and fewer polyhedrocytes. These results demonstrate the role of erythrocyte rigidity in the contraction of blood clots and suggest that the impaired clot contraction/shrinkage in SCD is due to the reduced erythrocyte deformability, which may be an underappreciated mechanism that aggravates obstructiveness of erythrocyte-rich (micro)thrombi in SCD.
Essentials Clot contraction influences the rate of fibrinolysis in vitro. Internal fibrinolysis is enhanced ∼2-fold in contracted vs. uncontracted blood clots. External fibrinolysis is ∼4-fold slower ...in contracted vs. uncontracted blood clots. Contraction can modulate lytic resistance and potentially the clinical outcome of thrombosis. SUMMARY: Background Fibrinolysis involves dissolution of polymeric fibrin networks that is required to restore blood flow through vessels obstructed by thrombi. The efficiency of lysis depends in part on the susceptibility of fibrin to enzymatic digestion, which is governed by the structure and spatial organization of fibrin fibers. How platelet-driven clot contraction affects the efficacy of fibrinolysis has received relatively little study. Objective Here, we examined the effects of clot contraction on the rate of internal fibrinolysis emanating from within the clot to simulate (patho)physiological conditions and external fibrinolysis initiated from the clot exterior to simulate therapeutic thrombolysis. Methods Clot contraction was prevented by inhibiting platelet myosin IIa activity, actin polymerization or platelet-fibrin(ogen) binding. Internal fibrinolysis was measured by optical tracking of clot size. External fibrinolysis was determined by the release of radioactive fibrin degradation products. Results and Conclusions Clot contraction enhanced the rate of internal fibrinolysis ∼2-fold. In contrast, external fibrinolysis was ~4-fold slower in contracted clots. This dichotomy in the susceptibility of contracted and uncontracted clots to internal vs. external lysis suggests that the rate of lysis is dependent upon the interplay between accessibility of fibrin fibers to fibrinolytic agents, including clot permeability, and the spatial proximity of the fibrin fibers that modulate the effects of the fibrinolytic enzymes. Understanding how compaction of blood clots influences clot lysis might have important implications for prevention and treatment of thrombotic disorders.
The 20-minute whole blood clotting test Monteiro, Wuelton Marcelo; Eddleston, Michael; Lamb, Thomas ...
PLoS neglected tropical diseases,
08/2021, Letnik:
15, Številka:
8
Journal Article
Recenzirano
Background The 20-minute whole blood clotting test (20WBCT) has been used to detect coagulopathy following snakebite for almost 50 years. A systematic review and meta-analysis of the 20WBCT was ...conducted to evaluate the accuracy of the 20WBCT to detect coagulopathy, indicative of systemic envenoming. Methods and findings Databases were searched from inception up to 09/12/2020 to identify studies that compared the 20WBCT and INR/fibrinogen on five or more subjects. Data was extracted from full-text articles by two reviewers using a predetermined form. Authors of 29 studies that lacked sufficient details in the manuscript were contacted and included if data meeting the inclusion criteria were provided. Included studies were evaluated for bias using a tailored QUADAS-2 checklist. The study protocol was prospectively registered on PROSPERO database (CRD42020168953). The searches identified 3,599 studies, 15 met the inclusion criteria and 12 were included in the meta-analysis. Data was reported from 6 countries and included a total of 2,270 patients. The aggregate weighted sensitivity of the 20WBCT at detecting INR >1.4 was 0.84 (CI 0.61 to 0.94), the specificity was 0.91 (0.76 to 0.97) and the SROC AUC was 0.94 (CI 0.91 to 0.96). The aggregate weighted sensitivity of the 20WBCT at detecting fibrinogen <100 mg/dL was 0.72 (CI 0.58 to 0.83), the specificity was 0.94 (CI 0.88 to 0.98) and the SROC AUC was 0.93 (0.91 to 0.95). Both analyses that used INR and fibrinogen as the reference test displayed considerable heterogeneity. Conclusions In the absence of laboratory clotting assays, the 20WBCT remains a highly specific and fairly sensitive bedside test at detecting coagulopathy following snakebite. However, clinicians should be aware of the importance of operator training, standardized equipment and the lower sensitivity of the 20WBCT at detecting mild coagulopathy and resolution of coagulopathy following antivenom.
We have developed an AI-aided multiple time stepping (AI-MTS) algorithm and multiscale modeling framework (AI-MSM) and implemented them on the AiMOS supercomputer. AI-MSM is the first of its kind to ...integrate multi-physics, including intra-platelet, inter-platelet, and fluid-platelet interactions, into one system. It has simulated a record-setting multiscale blood clotting model of 102 million particles, of which 70 flowing and 180 aggregating platelets, under dissipative particle dynamics to coarse-grained molecular dynamics. By adaptively adjusting timestep sizes to match the characteristic time scales of the underlying dynamics, AI-MTS optimally balances speeds and accuracies of the simulations.
There is emerging evidence for enhanced blood coagulation in coronavirus 2019 (COVID-19) patients, with thromboembolic complications contributing to morbidity and mortality. The mechanisms underlying ...this prothrombotic state remain enigmatic. Further data to guide anticoagulation strategies are urgently required.
We used viscoelastic rotational thromboelastometry (ROTEM) in a single-center cohort of 40 critically ill COVID-19 patients.
Clear signs of a hypercoagulable state due to severe hypofibrinolysis were found. Maximum lysis, especially following stimulation of the extrinsic coagulation system, was inversely associated with an enhanced risk of thromboembolic complications. Combining values for maximum lysis with D-dimer concentrations revealed high sensitivity and specificity of thromboembolic risk prediction.
The study identifies a reduction in fibrinolysis as an important mechanism in COVID-19-associated coagulopathy. The combination of ROTEM and D-dimer concentrations may prove valuable in identifying patients requiring higher intensity anticoagulation.
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