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In healthy volunteers, a monoclonal antibody fragment that binds ticagrelor and its active metabolite led to reversal of the antiplatelet effects of ticagrelor, with very few toxic effects. The presence of low titers of antibody to the active agent had no detectable effect on efficacy.

Efanesoctocog alfa is a factor VIII fusion agent that permits weekly treatment to prevent bleeding. In this study, two thirds of treated patients had no bleeding episodes, and the annualized bleeding rate fell by 77%.

Haemophilia A and B are hereditary haemorrhagic disorders characterised by deficiency or dysfunction of coagulation protein factors VIII and IX, respectively. Recurrent joint and muscle bleeds lead to severe and progressive musculoskeletal damage. Existing treatment relies on replacement therapy with clotting factors, either at the time of bleeding (ie, on demand) or as part of a prophylactic schedule. The major complication of such therapy is the development of neutralising antibodies (ie, inhibitors), which is most frequent in haemophilia A. Treatment might improve considerably with the availability of new modified drugs, which might overcome existing prophylaxis limitations by reducing dosing frequency and thereby rendering therapy less distressing for the patient. Subcutaneous administration of some new therapies would also simplify prophylaxis in children with poor venous access. Gene therapy has the potential for a definitive cure, and important results have been obtained in haemophilia B. Despite improvements in haemophilia care, the availability of clotting factor concentrates for all affected individuals worldwide remains the biggest challenge.

Coagulation/Flocculation (C/F) process aims to efficiently eliminate turbidity, TSS, COD, BOD, toxic metals, phosphates, and UV254nm from wastewater. Both natural and synthetic coagulants, used alone or in conjunction with flocculants, play crucial roles in this treatment. This review summarizes recent trends in coagulants for wastewater treatment, highlighting a wide array of inorganic and organic coagulants that have demonstrated significant efficacy based on reviewed studies. Notably, Crab Shell Bio-Coagulant (CS) excels in turbidity remov5al, achieving a remarkable 98.91% removal rate, while oak leaves protein shows superior performance in TSS and COD removal. Synthetic inorganic coagulants like PALS, PSiFAC1.5:10:15, and PAPEFAC1.5-10-15 demonstrate outstanding turbidity removal rates, over 96%. POFC-2 coagulant stands out for efficiently removing TSS and COD from domestic wastewater, achieving up to 93% removal for TSS and 89% for COD. Moreover, the utilization of FeCl3 as an inorganic coagulant alongside chitosan as an organic flocculant shows promise in reducing turbidity, COD, and polyphenols in wastewater from vegetable oil refineries. PE-2, a novel organic coagulant, demonstrates exceptional efficacy in eliminating turbidity, TSS, COD, and BOD from sugar industry wastewater. Chitosan shows effectiveness in removing TOC and orthophosphates in brewery wastewater. Additionally, CTAB shows high efficiency in removing various toxic metal ions from wastewater. The hybrid coagulants: PAAP0.1,0.5 and PPAZF accomplish exceptional turbidity removal rates, approximately 98%.

REG1 is a novel anticoagulation system consisting of pegnivacogin, an RNA aptamer inhibitor of coagulation factor IXa, and anivamersen, a complementary sequence reversal oligonucleotide. We tested the hypothesis that near complete inhibition of factor IXa with pegnivacogin during percutaneous coronary intervention, followed by partial reversal with anivamersen, would reduce ischaemic events compared with bivalirudin, without increasing bleeding. We did a randomised, open-label, active-controlled, multicentre, superiority trial to compare REG1 with bivalirudin at 225 hospitals in North America and Europe. We planned to randomly allocate 13 200 patients undergoing percutaneous coronary intervention in a 1:1 ratio to either REG1 (pegnivacogin 1 mg/kg bolus [>99% factor IXa inhibition] followed by 80% reversal with anivamersen after percutaneous coronary intervention) or bivalirudin. Exclusion criteria included ST segment elevation myocardial infarction within 48 h. The primary efficacy endpoint was the composite of all-cause death, myocardial infarction, stroke, and unplanned target lesion revascularisation by day 3 after randomisation. The principal safety endpoint was major bleeding. Analysis was by intention to treat. This trial is registered at ClinicalTrials.gov, identifier NCT01848106. The trial was terminated early after enrolment of 3232 patients due to severe allergic reactions. 1616 patients were allocated REG1 and 1616 were assigned bivalirudin, of whom 1605 and 1601 patients, respectively, received the assigned treatment. Severe allergic reactions were reported in ten (1%) of 1605 patients receiving REG1 versus one (<1%) of 1601 patients treated with bivalirudin. The composite primary endpoint did not differ between groups, with 108 (7%) of 1616 patients assigned REG1 and 103 (6%) of 1616 allocated bivalirudin reporting a primary endpoint event (odds ratio [OR] 1·05, 95% CI 0·80–1·39; p=0·72). Major bleeding was similar between treatment groups (seven [<1%] of 1605 receiving REG1 vs two [<1%] of 1601 treated with bivalirudin; OR 3·49, 95% CI 0·73–16·82; p=0·10), but major or minor bleeding was increased with REG1 (104 [6%] vs 65 [4%]; 1·64, 1·19–2·25; p=0·002). The reversible factor IXa inhibitor REG1, as currently formulated, is associated with severe allergic reactions. Although statistical power was limited because of early termination, there was no evidence that REG1 reduced ischaemic events or bleeding compared with bivalirudin. Regado Biosciences Inc.

In recent years, the proliferation of Harmful Cyanobacterial Blooms (CyanoHABs) has increased with water eutrophication and climate change, impairing human health and the environment in relation to water supply. In drinking water treatment plants (DWTPs), the bio-coagulation based on natural coagulants has been studied as an eco-friendly alternative technology to conventional coagulants for both turbidity and CyanoHABs removal. Plant-based coagulants have demonstrated their coagulation efficiency in turbidity removal, as reported in several papers but its ability in cyanobacterial removal is still limited. This paper mainly reviewed the application of plant-based coagulants in DWTPs, with focus on turbidity removal, including cyanobacterial cells. The future potential uses of these green coagulants to reduce noxious effects of cyanobacterial proliferation are presented. Green coagulants advantages and limitations in DWTPs are reviewed and discussed summarizing more than 10 years of knowledge.

Purpose of Review The use of conventional chemical coagulant in treatment of wastewater is gaining great attention. Drawbacks related to the prolonged effects on human health and environment due to the generation of by-product non-biodegradable sludge are becoming the latest topics. Transition from chemical to natural coagulant can be a good strategy to reduce the aforementioned drawbacks. Therefore, this review aims to provide critical discussions on the use of natural coagulant along with the comparative evaluation over the chemical coagulant. Recent Findings Treatment performances by chemical and natural coagulant have been reviewed on various types of wastewater with different success rates. Based on this review, a transition from the use of chemical to natural coagulant is highly suggested as the performance of the natural coagulant is comparable to that of the chemical coagulant and in some cases even better. The comparative advantages and disadvantages also convinced that the natural coagulant stands a great chance to be used as an alternative over the chemical coagulant. Summary Though the current utilization of natural coagulant is encouraging, three main aspects were overlooked by researchers: active coagulant agent, extraction, and optimization due to different wastewater characteristics. Furthermore, delving into these aspects could clarify the uncertainties on the natural coagulant. Hence, it makes this transition a prospect of green technology with sustainable application towards wastewater treatment.

Exposure of phosphatidylserine (PS) on the outer leaflet of the cell membrane is thought to play a critical role in tissue factor (TF) decryption. Recent molecular dynamics simulation studies suggested that the TF ectodomain may directly interact with PS. To investigate the potential role of TF direct interaction with the cell surface phospholipids on basal TF activity and the enhanced TF activity following the decryption, one or all of the putative PS-interactive residues in the TF ectodomain were mutated and tested for their coagulant activity in cell systems. Out of the 9 selected TF mutants, five of them -TFS160A, TFS161A, TFS162A, TFK165A, and TFD180A- exhibited a similar TF coagulant activity to that of the wild-type TF. The specific activity of three mutants, TFK159A, TFS163A, and TFK166A, was reduced substantially. Mutation of the glycine residue at the position 164 markedly abrogated the TF coagulant activity, resulting in ~90% inhibition. Mutation of all nine lipid binding residues together did not further decrease the activity of TF compared to TFG164A. A similar fold increase in TF activity was observed in wild-type TF and all TF mutants following the treatment of THP-1 cells with either calcium ionomycin or HgCl2, two agents that are commonly used to decrypt TF. Overall, our data show that a few select TF residues that are implicated in interacting with PS contribute to the TF coagulant activity at the cell surface. However, our data also indicate that TF regions outside of the putative lipid binding region may also contribute to PS-dependent decryption of TF.

A procoagulant snake venom serine protease was isolated from the venom of the nose-horned viper (Vipera ammodytes ammodytes). This 34 kDa glycoprotein, termed VaaSP-VX, possesses five kDa N-linked carbohydrates. Amino acid sequencing showed VaaSP-VX to be a chymotrypsin-like serine protease. Structurally, it is highly homologous to VaaSP-6 from the same venom and to nikobin from the venom of Vipera nikolskii, neither of which have known functions. VaaSP-VX does not affect platelets. The specific proteolysis of blood coagulation factors X and V by VaaSP-VX suggests that its blood-coagulation-inducing effect is due to its ability to activate these two blood coagulation factors, which following activation, combine to form the prothrombinase complex. VaaSP-VX may thus represent the first example of a serine protease with such a dual activity, which makes it a highly suitable candidate to replace diluted Russell’s viper venom in lupus anticoagulant testing, thus achieving greater reliability of the analysis. As a blood-coagulation-promoting substance that is resistant to serpin inhibition, VaaSP-VX is also interesting from the therapeutic point of view for treating patients suffering from hemophilia.