Anticoagulant therapies are crucial in the management of surgical complications as well as the prophylaxis of thrombosis. Many studies are being conducted on the Habu snake-venom anticoagulant, FIX-binding protein (FIX-Bp), for its greater potency and strong affinity to FIX clotting factor. On the other hand, the capacity to promptly reverse such acute anticoagulation is equally important. Combining a reversible anticoagulant with FIX-Bp may be advantageous in maintaining the balance between adequate anticoagulation and repealing when necessary. In this study, authors integrated FIX-Bp and RNA aptamer-based anticoagulants into a single target, FIX clotting factor, in order to achieve a robust anticoagulant effect. An in-silico and electrochemical approach were used to investigate the combination of FIX-Bp and RNA aptamers as a bivalent anticoagulant and to verify the competing or predominant binding sites of each anticoagulant. The in-silico analysis discovered that both the venom- and aptamer-anticoagulant had a strong affinity for the FIX protein at the Gla-domain and EGF-1 domain by holding 9 conventional hydrogen bonds with the binding energy of -34.859 kcal/mol. The electrochemical technique verified that both anticoagulants had different binding sites. The impedance load upon RNA aptamer binding to FIX protein was 14 %, whereas the addition of FIX-Bp caused a significant impedance rise of 37 %. This indicates that the addition of aptamers prior to FIX-Bp is a promising strategy for the conception of a hybrid anticoagulant.
1. The biological properties of venoms from juvenile and adult common tiger snakes (Notechis scutatus) were compared. 2. The lethality, procoagulant activity and enzymatic activities of the juvenile venom were not substantially different from those of the adult venom. 3. Electrophoretic studies, however, indicated some minor differences in the protein composition of the juvenile and adult venoms.
Hemostasis initiates a wound healing process and stops bleeding of blood within a damaged tissue, an important process in human and animal systems. However, this process needs to revert temporarily during surgery and analyze the clotting mechanism. In the past decade, heparin has been used widely as an anticoagulant in surgery to prevent unwanted blood clotting as it is not expensive, not difficult to control, lack of suitable replacement as well as less harmful to the human. However, heparin has several disadvantages, which include thrombocytopenia and non-specific plasma binding. Moreover, using heparin it may lead dysfunction and platelet aggregation. In this overview, potential clotting factors and anticoagulants are reviewed and special focus was given to get more insights.
It is now recognized that growth hormone (GH) deficiency in adults represents a distinct clinical syndrome that encompasses reduced psychological well-being as well as specific metabolic abnormalities. The latter features, which include hypertension, central obesity, insulin resistance, dyslipidaemia and coagulopathy, closely resemble those of metabolic insulin resistance syndrome. The increased cardiovascular morbidity and mortality demonstrated in these GH-deficient (GHD) adults reinforce the close association between the two syndromes. Replacement of GH in GHD adults has resulted in a marked reduction of central obesity and significant reduction in total cholesterol but little change in other risk factors, in particular insulin resistance and dyslipidaemia. The persistent insulin resistance and dyslipidaemia, together with the elevation of plasma insulin levels and lipoprotein (a) with GH replacement in these subjects are of concern. Long-term follow-up data are required to assess the impact of GH replacement on the cardiovascular morbidity and mortality of GHD adults. Further exploration of the appropriateness of the GH dosage regimens currently being employed is also indicated.
Artificial intelligence of things (AIoT) has become a potential tool for use in a wide range of fields, and its use is expanding in interdisciplinary sciences. On the other hand, in a clinical scenario, human blood-clotting disease (Royal disease) detection has been considered an urgent issue that has to be solved. This study uses AIoT with deep long short-term memory networks for biosensing application and analyzes the potent clinical target, human blood clotting factor IX, by its aptamer/antibody as the probe on the microscaled fingers and gaps of the interdigitated electrode. The earlier results by the current-volt measurements have shown the changes in the surface modification. The limit of detection (LOD) was noticed as 1 pM with the antibody as the probe, whereas the aptamer behaved better with the LOD at 100 fM. The time-series predictions from the AIoT application supported the obtained results with the laboratory analyses using both probes. This application clearly supports the results obtained from the interdigitated electrode sensor as aptamer to be the better option for analyzing the blood clotting defects. The current study supports a great implementation of AIoT in sensing application and can be followed for other clinical biomarkers.
Haemophilia is a blood clotting disorder known as 'Christmas disease' caused when the blood has defect with the clotting factor(s). Bleeding leads various issues, such as chronic pain, arthritis and a serious complication during the surgery. Identifying this disease is mandatory to take the necessary treatment and maintains the normal clotting. It has been proved that the level of factor IX (FIX) is lesser with haemophilia patient and the attempt here is focused to quantify FIX level by interdigitated electrode (IDE) sensor. Single-walled carbon nanotube (SWCNT) was utilized to modify IDE sensing surface. On this surface, dual probing was evaluated with aptamer and antibody to bring the possible advantages. The detection limit with antibody was found to be 1 pM, while aptamer shows 100 fM. Further, a fine-tuning was attempted with sandwich pattern of aptamer-FIX-antibody and antibody-FIX-aptamer and compared. Specific elevation of detection with 10 folds was noticed and displayed the detection at 100 f. in both sandwich patterns. In addition, FIX was detected in the diluted human serum by aptamer-FIX-antibody sandwich, it was found that FIX detected from the dilution factor 1:640. A novel demonstration is with higher discrimination against other clotting factors, XI and VII.
The causes of an isolated prolonged activated partial thromboplastin time (APTT) with a normal prothrombin time (PT) are either a deficiency of clotting factors VIII, IX, XI or XII or the presence of an inhibitor. The inhibitor may be specific to an individual clotting factor or it may be a non-specific inhibitor like the lupus anticoagulant which has opposite therapeutic implications. We report a patient referred to our hospital for treatment that was previously diagnosed at another medical institution as an acquired factor IX inhibitor following an investigation for a prolonged APTT. On further testing this turned out to be a potent lupus anticoagulant which interfered with the phospholipid-dependent factor assays. The use of dilution studies, chromogenic assays and phospholipid neutralization can help differentiate these inhibitors. Great care must be taken in the interpretation of factor assays in the presence of lupus anticoagulant to avoid misdiagnosis and inappropriate treatment.
Disseminated Intravascular Coagulation (DIC) develops in patient with prostate cancer, which is manifested by systemic, intracranial, intracavitary or intracutaneous bleeding indicating uncompensated or excessive fibrinolysis (XFL). This case report is a description of a 61-year-old male with metastatic prostate cancer that progressed to manifest DIC. The condition is rare in clinical practice, and even rarer when is coupled with XFL. Treatment was mainly replenishing coagulation factors, platelets and controlling the disease progression with aggressive hormonal therapy. The patient progressed to coagulopathy further with fibrinolysis, hence leading to mortality. This case study discusses the pathophysiology of this complication and various methods to monitor the disease progression are discussed.
Photochemical treatment is one of the pathogen inactivation method to treat plasma, part of a proactive approach used for blood and blood component safety. Three photochemical treatments that have been used were methylene blue, riboflavin and psoralen treatment. This study was done on Fresh Frozen Plasma (FFP) to evaluate the treatment effects of psoralen, methylene blue and riboflavin on coagulation factors level. Methods: FFP was collected from apheresis plasma units and kept at 22oC to 24oC. A sum of 90 apheresis plasma units and segments were used, separated from each bag and a part used as controls, placed in a -30oC freezer for storage, thawed, and coagulation proteins function was evaluated before and after treatment, at immediate, 30 days and 270 days storage. Results: Significant differences in fibrinogen and coagulation factor levels between before and after treatment with methylene blue, psoralen and riboflavin. However, most of the mean values in treated plasma were within reference ranges. Methylene blue treated FFP showed the lowest changes in fibrinogen and other coagulation factors level whilst riboflavin treated FFP demonstrated the highest changes in coagulation proteins concentrations especially for fibrinogen, FV, FVIII, FIX and FXII. However, FXIII showed the best recovery for all three photochemical methods with reduction level of 3% to 8% compared to pre-treatment. Storage time comparison of immediate, 30 days and 270 days was inconclusive. Conclusion: The coagulation proteins in psoralen treated FFP and MB-FFP were adequately preserved, where MB-FFP showed better preservation than other two photochemical treatments.
Polyurethane (PU) with three different functional groups: carboxyl, hydroxyl and sulphonyl group on its molecular structure were synthesised in this work. The synthesised material suppresses blood clotting and exhibits anticoagulant characteristics due to the presence of the important anionic groups. The synthesised PU was blended with polyethersulphone (PES) and fabricated into flat-sheet membrane to study the physico-chemical and biocompatibility properties of the PES membrane for blood purification application. PES-PU flat-sheet membranes were fabricated via the dry-wet phase separation technique. Different loading of PU (0, 1, 2, 3, 4, and 5%) blended with PES was studied and compared. Based on the in-vitro biocompatibility analysis of the membrane, it can be suggested that the membrane incorporated with PU has better anticoagulant properties compared to the pristine PES membrane. PU incorporation prolonged the clotting time, decreased the formation of thrombin, decreased soluble complement component 3a (C3a) generation and suppressed platelet adhesion and aggregation. The anionic groups on the membrane surface might bind to coagulation factors (antithrombin) and the calcium ions, Ca2+ and thus improve anticoagulant ability. Based on both physico-chemical and in-vitro studied, 4% loading of PU is the optimum loading for incorporation with PES membrane. These results suggested that the blended PES-PU membranes with good haemocompatibility allowed practical application in the field of blood purification.
Nephrotic syndrome is often associated with a hypercoagulable state and thrombotic complications. Thrombosis may be due to a number of abnormalities in blood, including AT III deficiency, increased concentrations of fibrinogen, factors V and VIII, and platelet hyperaggregability. The therapeutic approach to thrombosis in nephrotic syndrome is the use of anticoagulants as a preventive measure or an attempt at thrombolysis with streptokinase, urokinase, or stanozolol.
Coagulation, fibrinolytic activity and platelet function were studied in 104 Asian women volunteers who received 150 mg of depot medroxyprogesterone acetate intramuscularly every three months for two years or more. The results were compared with those in matched controls. There was a paucity of change in coagulation factors. The fibrinogen levels were increased and prothrombin time was shortened. The fibrinolytic activity, as shown by the euglobulin clot lysis time, was significantly increased. This latter change contrasts with the many reports concerning Caucasian women and may reflect an increase in fibrinolytic potential in Asian women.