The current investigation focused on separating Cerastes cerastes venom to produce the first Kunitz-type peptide. Based on its anti-trypsin effect, Cerastokunin, a 7.75 kDa peptide, was purified until homogenity by three steps of chromatography. Cerastokunin was found to include 67 amino acid residues that were obtained by de novo sequencing using LC-MALDI-MSMS. Upon alignment with Kunitz-type peptides, there was a high degree of similarity. Cerastokunin\'s 3D structure had 12% α-helices and 21% β-strands with pI 8.48. Cerastokunin showed a potent anticoagulant effect by inhibiting the protease activity of thrombin and trypsin as well as blocking the intrinsic and extrinsic coagulation pathways. In both PT and aPPT, Cerastokunin increased the blood clotting time in a dose-dependent way. Using Lys48 and Gln192 for direct binding, Cerastokunin inhibited thrombin, Factor Xa and trypsin as shown by molecular docking. Cerastokunin exhibited a dose-response blockade of PARs-dependent pathway platelet once stimulated by thrombin. An increased concentration of Cerastokunin resulted in a larger decrease of tail thrombus in the mice-carrageenan model in an in vivo investigation when compared to the effects of antithrombotic medications. At all Cerastokunin doses up to 6 mg/kg, no in vivo toxicity was seen in challenged mice over the trial\'s duration.

BACKGROUND: Highlighting affordable alternative crops that are rich in bioactive phytoconstituents is essential for advancing nutrition and ensuring food security. Amaranthus blitum L. (AB) stands out as one such crop with a traditional history of being used to treat intestinal disorders, roundworm infections, and hemorrhage. This study aimed to evaluate the anthelmintic and hematologic activities across various extracts of AB and investigate the phytoconstituents responsible for these activities.
METHODS: In vitro anthelmintic activity against Trichinella spiralis was evaluated in terms of larval viability reduction. The anti-platelet activities were assessed based on the inhibitory effect against induced platelet aggregation. Further, effects on the extrinsic pathway, the intrinsic pathway, and the ultimate common stage of blood coagulation, were monitored through measuring blood coagulation parameters: prothrombin time (PT), activated partial thromboplastin time (aPTT), and thrombin time (TT), respectively. The structures of isolated compounds were elucidated by spectroscopic analysis.
RESULTS: Interestingly, a previously undescribed compound (19), N-(cis-p-coumaroyl)-ʟ-tryptophan, was isolated and identified along with 21 known compounds. Significant in vitro larvicidal activities were demonstrated by the investigated AB extracts at 1 mg/mL. Among tested compounds, compound 18 (rutin) displayed the highest larvicidal activity. Moreover, compounds 19 and 20 (N-(trans-p-coumaroyl)-ʟ-tryptophan) induced complete larval death within 48 h. The crude extract exhibited the minimal platelet aggregation of 43.42 ± 11.69%, compared with 76.22 ± 14.34% in the control plasma. Additionally, the crude extract and two compounds 19 and 20 significantly inhibited the extrinsic coagulation pathway.
CONCLUSIONS: These findings extend awareness about the nutritional value of AB as a food, with thrombosis-preventing capabilities and introducing a promising source for new anthelmintic and anticoagulant agents.

UNASSIGNED: Mild traumatic brain injury (mTBI) is a frequent presentation in Emergency Department (ED). There are standardised guidelines, the Canadian CT Head Rule (CCHR), for CT scan in mTBI that rule out patients on either anticoagulant or anti-platelet therapy. All patients with these therapies undergo a CT scan irrespectively of other consideration.
UNASSIGNED: To determine whether standard guidelines could be applied to patients on anticoagulants or anti-platelet drugs.
UNASSIGNED: 1,015 patients with mTBI and Glasgow Coma Score (GCS) of 15 were prospectively recruited, 509 either on anticoagulant or anti-platelet therapy and 506 on neither. All patients on neither therapy underwent CT scan following guidelines. All patients with mTBI on either therapy underwent CT scan irrespective of the guidelines.
UNASSIGNED: Primary endpoint was the incidence of post-traumatic intracranial bleeding in patients either on anticoagulants or anti-platelet drugs and in patients who were not on these therapies. Bayesian statistical analysis with calculation of Confidence Intervals (CI) was then performed.
UNASSIGNED: Sixty scans were positive for bleeding: 59 patients fulfilled the criteria and 1 did not. Amongst patients with haemorrhage, 24 were on either therapy and only one did not meet the guidelines but in this patient the CT scan was performed before 2 h from the mTBI. Patients on either therapy did not have higher bleeding rates than patients on neither. There were higher bleeding rates in patients on anti-platelet therapy who met the guidelines vs. patients who did not. These rates overlapped with patients on neither therapy, meeting CCHR.
UNASSIGNED: The CCHR might be used for mTBI patients on either therapy. Anticoagulants and anti-platelet drugs should not be considered a risk factor for patients with mTBI and a GCS of 15. Multicentric studies are needed to confirm this result.

UNASSIGNED: Spontaneous coronary artery dissection (SCAD) is an important cause of acute coronary syndrome in young women. There is no consensus on optimal treatment, though a conservative approach including antiplatelet agents is commonly used. We hypothesized that most cases of SCAD would not demonstrate true lumen thrombus in the dissected artery, suggesting that anti-platelet agents might not have a role in the treatment of SCAD.
UNASSIGNED: We conducted a systematic review of the published literature through March 2022 to identify pathology images from individuals who died of SCAD. The images were independently reviewed by a pathologist to assess for the presence of thrombus and inflammatory cells.
UNASSIGNED: We identified 40 cases from 34 publications with available pathology images and found only one case of true lumen thrombus. Additionally, we found that 53% of cases involved eosinophilic inflammation.
UNASSIGNED: The role of antiplatelet agents in the treatment of SCAD should be re-evaluated. Further studies are needed to better understand the significance and treatment implications of eosinophilic inflammation.

Glycoprotein (GP) VI (GPVI) plays a major role in thrombosis but not haemostasis, making it a promising antithrombotic target. The primary role of GPVI on the surface of platelets is a signalling receptor for collagen, which is one of the most potent thrombotic sub-endothelial components that is exposed by atherosclerotic plaque rupture. Inhibition of GPVI has therefore been investigated as a strategy for treatment and prevention of atherothrombosis, such as during stroke and acute coronary syndromes. A range of specific GPVI inhibitors have been characterized, and two of these inhibitors, glenzocimab and revacept, have completed Phase II clinical trials in ischaemic stroke. In this review, we summarize mechanisms of GPVI activation and the latest progress of clinically tested GPVI inhibitors, including their mechanisms of action. By focusing on what is known about GPVI activation, we also discuss whether alternate strategies could be used to target GPVI.

Snake venoms are known to contain toxins capable of interfering with normal physiological processes of victims. Specificity of toxins from snake venoms give scope to identify new molecules with therapeutic action and/or help to understand different cellular mechanisms. Russell\'s viper venom (RVV) is a mixture of many bioactive molecules with enzymatic and non-enzymatic proteins. The present article describes Daboialipase (DLP), an enzymatic phospholipase A2 with molecular mass of 14.3 kDa isolated from RVV. DLP was obtained after cation exchange chromatography followed by size-exclusion high performance liquid chromatography (SE-HPLC). The isolated DLP presented strong inhibition of adenosine di-phosphate (ADP) and collagen induced platelet aggregation. It also showed anti-thrombin properties by significantly extending thrombin time in human blood samples. Trypan blue and resazurin cell viability assays confirmed time-dependent cytotoxic and cytostatic activities of DLP on MCF7 breast cancer cells, in vitro. DLP caused morphological changes and nuclear damage in MCF7 cells. However, DLP did not cause cytotoxic effects on non-cancer HaCaT cells. Peptide sequences of DLP obtained by O-HRLCMS analysis showed similarity with a previously reported PLA2 (Uniprot ID: PA2B_DABRR/PDB ID: 1VIP_A). An active Asp at 49th position, calcium ion binding site and anticoagulant activity sites were identified in 1 VIP_A. These findings are expected to contribute to designing new anti-platelet, anticoagulant and anti-cancer molecules.

Vancomycin is one of the most empirically used antibiotics in severely ill patients in hospitalized settings. Vancomycin-induced thrombocytopenia (VITP) is a rare and potentially life-threatening complication that requires immediate recognition. Platelet destruction is largely immune-mediated and results in a precipitous drop in the platelet count over a short period of time. Most cases of VITP are drug-dependent, as discontinuation of the offending agent frequently results in a timely return to baseline to pre-exposure platelet levels. Here, we present a case of severe vancomycin-induced thrombocytopenia in a 35-year-old female with a history of multiple comorbidities who presented with pneumonia. She was undergoing treatment with vancomycin and piperacillin-tazobactam and developed thrombocytopenia within 24 hours of hospitalization. The patient was on a loading dose of 1250 mg intravenous vancomycin every 24 hours and piperacillin-tazobactam 3.375 g intravenously every six hours for presumed community-acquired pneumonia. Her other medications included ondansetron, bupropion, sertraline, tamsulosin, pantoprazole, ergocalciferol, and insulin glargine. Additionally, the patient was placed on a prophylactic dose of enoxaparin while in-patient. The patient\'s thrombocytopenia resolved with discontinuation of vancomycin. Clinicians should be well-informed about which medications can trigger thrombocytopenia whenever starting a medication in such cases.

BACKGROUND: We report the case of a postmenopausal female with a hemorrhagic Bartholin\'s cyst who has been using an antiplatelet medication.
METHODS: A postmenopausal woman, 84 years of age, had a medical history of hypertension, diabetes mellitus, coronary artery disease (three-vessel disease), chronic kidney disease (stage 3), and dementia. The patient has been taking clopidogrel, an antiplatelet medication, for several years. She presented at our outpatient clinic complaining of painful swelling over her left vulva for several days. A Bartholin\'s cyst over the left vulva was suspected, and the patient underwent marsupialization under local anesthesia, which was well-tolerated. During the incision procedure, bright-red blood with some blood clots was discharged, and a hemorrhagic Bartholin\'s cyst was observed. There was no recurrence of the hemorrhagic Bartholin\'s cyst during the 6-mo subsequent follow-up period.
CONCLUSIONS: Hemorrhagic Bartholin\'s cysts rarely occur. We report the case of a postmenopausal female with a hemorrhagic Bartholin\'s cyst who had been on antiplatelets and was successfully treated with marsupialization. No recurrence was noted during the 6-mo follow-up period. Older females taking antiplatelets should be cautious of bleeding when presenting with a Bartholin\'s cyst.

Transcatheter aortic valve implantation (TAVI) is an effective and established treatment for symptomatic aortic stenosis. However, there is a lack of consensus concerning the need for peri- and post-procedural anti-thrombotic medication. Contemporary guidelines recommend that anti-thrombotic therapy is balanced against a patient\'s bleeding risk following TAVI, but do not fully consider the evolving evidence base. The purpose of the Delphi panel recommendations presented here is to provide a consensus elicited from a panel of experts who regularly prescribe anti-thrombotic therapy post-TAVI. The goal was to address evidence gaps across four key topics: anti-thrombotic therapy (anti-platelet and/or anti-coagulant) in TAVI patients in sinus rhythm; anti-thrombotic therapy in TAVI patients with AF; direct oral anti-coagulants versus vitamin K antagonists; and the need for UK/Ireland specific guidance. This consensus statement aims to inform clinical decision-making by providing a concise, evidence-based summary of best practice for prescribing anti-thrombotic therapies following TAVI and highlights areas where further research is needed.

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