BACKGROUND: ; Factor (F)V is pivotal in both procoagulant and anticoagulant mechanisms. The present report describes a novel F5 mutation in a FV-deficient patient (FV:C 6 IU/dL, FV:Ag 32 IU/dL), complicated with recurrent deep vein thrombosis. The patient demonstrated activated protein C resistance (APCR) with compound heterozygous mutations consisting of FV-Y1961C (FVKanazawa) and FV-1982_1983del. AIM;: To clarify thrombotic mechanisms associated with this FV abnormality.
RESULTS: Levels of FV-1982_1983del were below the detection sensitivity in our expression experiments using HEK293T cells, and analyses were targeted, therefore on the FV-Y1961C mutation. APTT-based clotting assays demonstrated that FV-Y1961C exhibited APCR, and that the reduced APC susceptibility in FVa-Y1961C resulted in a marked depression of APC-catalyzed inactivation with delayed cleavage at Arg506 and little cleavage at Arg306 with or without protein (P)S. The APC cofactor activity of FV-Y1961C in APC-catalyzed FVIIIa inactivation promoted by Arg336 cleavage in FVIII was impaired. The binding affinity of FVa-Y1961C to phospholipid membranes was reduced in reactions involving APC/PS-catalyzed inactivation and in prothrombinase activity. Furthermore, the addition of FVa-Y1961C to plasma failed to inhibit tissue factor (TF)-induced procoagulant function. These characteristics were similar to those of FV-W1920R (FVNara) and FV-A2086D (FVBesançon).
CONCLUSIONS: ; We identified a compound heterozygous. FV-Y1961C mutation in the C1 domain representing a novel FV mutation (FVKanazawa) resulting in not only APCR due to impaired FVa susceptibility and FV cofactor activity for APC function, but impaired inhibition of TF-induced procoagulant function. These defects in anticoagulant function associated with FV in FV-Y1961C contributed to a prothrombotic state.

The venoms of Australasian elapid snakes are known to possess coagulant activity, including some with strong procoagulant activity and others with anticoagulant activity, although the latter are less well known. This study investigates the anticoagulant activity of Australasian elapid snake venoms, and whether this activity is neutralised by commercial snake antivenom and varespladib (PLA2 inhibiting agent). Clotting assays were completed for 34 species of Australasian elapids. Antivenom neutralisation assays with tiger snake antivenom (TSAV) were performed on five species to determine if there was cross-neutralisation. Varespladib neutralisation assays were also completed for the same five species. All Pseudechis species venoms had anticoagulant activity, except P. porphyriacus, which was procoagulant. Pseudechis species venoms had similar anticoagulant potency ranging from the most potent P. colletti venom to the least potent P. butleri venom. The three Austrelaps (copperhead) species venoms were the next most potent anticoagulants. Six further snakes, Elapognathus coronatus, Acanthophis pyrrhus, A. antarcticus, Suta suta, Denisonia devisi and D. maculata, had weaker anticoagulant activity, except for D. maculata which had similar anticoagulant activity to Pseudechis species. Tiger Snake Antivenom (1200mU/mL) neutralised the anticoagulant effect of P. australis for concentrations up to 1 mg/mL. TSAV (1200mU/mL) also neutralised P. colletti, D. maculata, A. superbus and A. pyrrhus venoms at their EC50, demonstrating cross neutralisation. Varespladib neutralised the anticoagulant effect of P. australis venom at 5 μM and for venoms of P. colletti, D. maculata, A. superbus and A. pyrrhus. We found anticoagulant activity to be present in six genera of Australasian snakes at low concentrations, which can be completely neutralised by both antivenom and varespladib. Anticoagulant activity in Australian elapid venoms was associated with species possessing high PLA2 activity without procoagulant snake venom serine proteases.

Cor triatriatum is a rare congenital heart abnormality in which a membrane separates the left atrium (LA; sinister) or the right atrium (dexter) into two compartments. It is also a long-forgotten cause of atrial fibrillation (AF) and substantially higher rates of blood stagnation, particularly proximal to the additional septum in the LA. In this case report, we faced a CHA2DS2-VASc score of 1 in patients with non-valvular AF due to Cor triatriatum sinister (CTS). The decision to start anticoagulants in this particular case was controversial, so we reviewed the literature to assess and address it. We present our case and discuss the indication of anticoagulants in this unique clinical scenario, accompanied by a literature review. Facing this dilemma of starting anticoagulants in special cases of CTS and AF should be individualized and need more investigation. However, till this moment, based on similar reports, it seems to be rational to consider CTS Per se as an additional risk stratification marker beyond the CHA2DS2-VASc score start anticoagulant until the surgical resection. Considering CTS as the sole indication of anticoagulant in patients with normal sinus rhythm is a complex matter that needs further investigation.

UNASSIGNED: Subclinical leaflet thrombosis (SLT) develops in 15% of patients undergoing trans-catheter aortic valve replacement (TAVR). TAVR is a procedure in which a faulty aortic valve is replaced with a mechanical one. An aortic valve replacement can be done with open-heart surgery; this is called surgical aortic valve replacement (SAVR). A significant problem is defining the best course of treatment for asymptomatic individuals with SLT post-TAVR, including the use of oral anticoagulation (OAC) in it.
UNASSIGNED: Systematic review.
UNASSIGNED: The most pertinent published research (original papers and reviews) in the scientific literature were searched for and critically assessed using the online, internationally indexed databases PubMed, Medline, and Cochrane Reviews. Keywords like \"Transcatheter valve replacement\" and \"Subclinical leaflet thrombosis\" were used to search the papers. Selected studies were critically assessed for inclusion based on predefined criteria.
UNASSIGNED: The review examined the prevalence and characteristics of SLT after TAVR. To note, the incidence of SLT is seen to be higher in TAVR compared SAVR. Dual antiplatelet therapy, which is utilized in antithrombotic regimens post-TAVR, can possibly hasten SLT progression which could result in the impaired mobility of leaflets and the worsening of pressure gradients.
UNASSIGNED: The use of dual antiplatelet drugs in routine antithrombotic therapy tends to accelerate initial subclinical leaflet thrombosis after TAVI, which results in a developing restriction of leaflet mobility and an increase in pressure differences.

OBJECTIVE: Anticoagulant therapy with vitamin K antagonists is recommended within 3 to 6 months after bioprosthetic valve replacement to prevent thromboembolic events. However, data regarding whether direct oral anticoagulants can be an alternative to warfarin in such patients are limited. The purpose of this study is to compare the efficacy and safety of edoxaban versus warfarin within 3 months after bioprosthetic valve replacement.
METHODS: The ENBALV trial is an investigator-initiated, phase 3, randomized, open-label, multicenter study. It involves patients aged 18 to 85 years undergoing bioprosthetic valve replacement at the aortic and/or mitral position. They are randomized 1:1 to receive either edoxaban or warfarin. Administration of edoxaban or warfarin is to be continued for 12 weeks after surgery. The primary outcome is the occurrence rate of stroke or systemic embolism at 12 weeks after surgery. The net clinical outcome is a composite of stroke, systemic embolism, or major bleeding, which is included in the secondary outcomes.
CONCLUSIONS: The ENBALV trial demonstrates the efficacy and safety of edoxaban compared with warfarin in patients early after bioprosthetic valve replacement, including patients with sinus rhythm, which will bring a significant benefit to patients in clinical practice.
BACKGROUND: Japan Registry of Clinical Trials (jRCT) 2051210209. 30 Mar 2022 https://jrct.niph.go.jp/latest-detail/jRCT2051210209 .

A 6-month-old intact female mixed-breed kitten presented with severe exophthalmos of the left eye. Periocular lesions, including subconjunctival haemorrhage, third eyelid protrusion, and left eyelid oedema, were detected in the absence of globe retropulsion. The left intraocular pressure was increased, and ocular ultrasonography revealed ipsilateral retrobulbar fluid. Coagulation panels were markedly prolonged and severe anaemia was detected. Ultrasound-guided retrobulbar centesis performed to decrease intraocular pressure yielded blood. Based on the history and clinical findings, anticoagulant rodenticide intoxication was suspected. Treatment included partial tarsorrhaphy and the administration of topical antibiotics, artificial tears, and vitamin K1. Fresh whole blood and fresh frozen plasma were transfused for supportive therapy. Coagulation parameters improved after 7 days of hospitalisation. The periocular lesions resolved within 14 days, despite persistent optic nerve damage and blindness. This case report raises the possibility that anticoagulant rodenticide toxicity may result in retrobulbar haemorrhage in the absence of other typical cavitary bleeding. Although uncommon, anticoagulant rodenticide toxicity should be considered in cats with retrobulbar haemorrhage.

BACKGROUND: There are no clinical trials with head-to-head comparison between the two most commonly used oral anticoagulants (apixaban and rivaroxaban) in patients with atrial fibrillation (AF). The comparative efficacy and safety between these drugs remain unclear, especially among older patients who are at the highest risk for stroke and bleeding.
OBJECTIVE: To compare the risk of major bleeding and thromboembolic events with apixaban versus rivaroxaban in older patients with AF.
METHODS: We conducted a population-based, retrospective cohort study of all adult patients (66 years or older) with AF in Ontario, Canada who were treated with apixaban or rivaroxaban between April 1, 2011 and March 31, 2020. The primary safety outcome was major bleeding and the primary efficacy outcome was thromboembolic events. Secondary outcomes included any bleeding. Rates and hazard ratios (HRs) were adjusted for baseline comorbidities with inverse probability of treatment weighting (IPTW).
RESULTS: This study included 42,617 patients with AF treated with apixaban and 30,725 patients treated with rivaroxaban. After IPTW using the propensity score, patients in the apixaban and rivaroxaban groups were well balanced for baseline values of demographics, comorbidities and medications; both groups had similar mean age of 77.4 years and 49.9% were female. At one year, the apixaban group had reduced risk for both major bleeding with an absolute risk reduction at one year of 1.1% (2.1% vs 3.2%; HR 0.65 [95% CI, 0.59-0.71]) and any bleeding (8.1% vs 10.9%; HR 0.73 [95% CI, 0.69-0.77]) with no difference in the risk for thromboembolic events (2.2% vs 2.2%; HR 1.02 [95% CI, 0.92-1.13]).
CONCLUSIONS: Among AF patients, 66 years or older, treatment with apixaban was associated with reduced risk for major bleeding with no difference in risk for thromboembolic events compared with rivaroxaban.

BACKGROUND: The most frequent location of thrombosis development in acute mesenteric venous thrombosis is the superior mesenteric vein. It is an uncommon but potentially fatal condition. Patients with underlying medical conditions that interfere with the Virchow Triad hypercoagulability, stasis, and endothelial injury are more likely to experience it.
METHODS: A 37-year-old female reported to our emergency department with a 5-day history of severe abdominal discomfort, vomiting, and constipation, as well as two episodes of bleeding per rectum. The patient had a clean medical history, no HTN, no diabetes, no chronic medication, no history of contraceptive pill use or non-steroid anti-inflammatory drug use, no history of chronic disease or operation. Patient was directly transferred to the intensive care unit for additional evaluation and preoperative stabilization.
CONCLUSIONS: A patient with acute mesenteric venous thrombosis and possible intestinal damage is the case we\'ve presented. Upon presentation patient was unstable, we assessed her condition and transferred to the intensive care unit for stabilization and pre-operative preparation. She didn\'t respond to conservative management and we had to operate, we highly emphasize how crucial it is for early intervention in these type of conditions. Acute mesenteric venous thrombosis is a complicated case due to its nonspecific symptoms, it requires a multidisciplinary team approach between internal medicine and surgical team to plan for the most appropriate treatment strategy suitable for each patient as all options are associated with significant risks. Multiple options are available for the management of mesenteric venous thrombosis. In patients with peritoneal signs to suggestive bowel infarction or perforation or those who failed to progress with conservative management, operative intervention may be necessary. Other options include anticoagulation therapy, local or systemic thrombolysis, interventional or surgical thrombectomy.
CONCLUSIONS: Acute mesenteric venous thrombosis is a complex situation that calls for a multidisciplinary team approach between the surgical and internal medicine departments to determine the best course of action for each patient, as there are major risks involved with each alternative. If peritonism is present, it is preferable to assess and resuscitate as soon as possible and to proceed with surgery.

Background: Myocardial infarction (MI) as a consequence of atherosclerosis-associated acute thrombosis is a leading cause of death and disability globally. Antiplatelet and anticoagulant drugs are standard therapies in preventing and treating MI. However, all clinically used drugs are associated with bleeding complications, which ultimately limits their use in patients with a high risk of bleeding. We have developed a new recombinant drug, targ-HSA-TAP, that combines targeting and specific inhibition of activated platelets as well as anticoagulation. This drug is designed and tested for a prolonged circulating half-life, enabling unique thromboprophylaxis without bleeding complications. Methods: Targ-HSA-TAP combines a single-chain antibody (scFv) that targets activated glycoprotein IIb/IIIa on activated platelets, human serum albumin (HSA) for prolonged circulation, and tick anticoagulant peptide (TAP) for coagulation FX inhibition. A non-binding scFv is employed as a non-targeting control (non-targ-HSA-TAP). Its efficacy was investigated in vivo using murine models of acute thrombosis and cardiac ischemia-reperfusion (I/R) injury. Results: Our experiments confirmed the targeting specificity of targ-HSA-TAP to activated platelets and demonstrated effective prevention of platelet aggregation and thrombus formation, as well as FXa inhibition in vitro. Thromboprophylactic administration of targ-HSA-TAP subcutaneously in mice prevented occlusion of the carotid artery after ferric chloride injury as compared to non-targ-HSA-TAP and PBS-control treated mice. By comparing the therapeutic outcomes between targ-TAP and targ-HSA-TAP, we demonstrate the significant improvements brought by the HSA fusion in extending the drug\'s half-life and enhancing its therapeutic window for up to 16 h post-administration. Importantly, tail bleeding time was not prolonged with targ-HSA-TAP in contrast to the clinically used anticoagulant enoxaparin. Furthermore, in a murine model of cardiac I/R injury, mice administered targ-HSA-TAP 10 h before injury demonstrated preserved cardiac function, with significantly higher ejection fraction and fractional shortening, as compared to the non-targ-HSA-TAP and PBS control groups. Advanced strain analysis revealed reduced myocardial deformation and histology confirmed a reduced infarct size in targ-HSA-TAP treated mice compared to control groups. Conclusion: The inclusion of HSA represents a significant advancement in the design of targeted therapeutic agents for thromboprophylaxis. Our activated platelet-targeted targ-HSA-TAP is a highly effective antithrombotic drug with both anticoagulant and antiplatelet effects while retaining normal hemostasis. The long half-life of targ-HSA-TAP provides the unique opportunity to use this antithrombotic drug for more effective, long-lasting and safer anti-thrombotic prophylaxis. In cases where MI occurs, this prophylactic strategy reduces thrombus burden and effectively reduces cardiac I/R injury.

Disseminated intravascular coagulation (DIC) is a pathologic state that follows systemic injury and other diseases. Often a complication of sepsis or trauma, DIC causes coagulopathy associated with paradoxical thrombosis and hemorrhage. DIC upregulates the thrombotic pathways while simultaneously downregulating the fibrinolytic pathways that cause excessive fibrin deposition, microcirculatory thrombosis, multiorgan dysfunction, and consumptive coagulopathy with excessive bleeding. Given these opposing disease phenotypes, DIC management is challenging and includes treating the underlying disease and managing the coagulopathy. Currently, no therapies are approved for DIC. We have developed clot-targeted therapeutics that inhibit clot polymerization and activate clot fibrinolysis to manage DIC. We hypothesize that delivering both an anticoagulant and a fibrinolytic agent directly to clots will inhibit active clot polymerization while also breaking up pre-existing clots; therefore, reversing consumptive coagulopathy and restoring hemostatic balance. To test this hypothesis, we single- and dual-loaded fibrin-specific nanogels (FSNs) with antithrombinIII (ATIII) and/or tissue plasminogen activator (tPA) and evaluated their clot preventing and clot lysing abilities in vitro and in a rodent model of DIC. In vivo, single-loaded ATIII-FSNs decreased fibrin deposits in DIC organs and reduced blood loss when DIC rodents were injured. We also observed that the addition of tPA in dual-loaded ATIII-tPA-FSNs intensified the antithrombotic and fibrinolytic mechanisms, which proved advantageous for clot lysis and restoring platelet counts. However, the addition of tPA may have hindered wound healing capabilities when an injury was introduced. Our data supports the benefits of delivering both anticoagulants and fibrinolytic agents directly to clots to reduce the fibrin load and restore hemostatic balance in DIC.