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The article "Acute subdural haemorrhage in a warfarin user following leech bite: Clinical note and review" published in the Current Journal of Neurology discusses a unique case of intracranial hemorrhage (ICH) in a patient taking warfarin after being bitten by leeches. The patient experienced symptoms after the leech bite, leading to a subdural hemorrhage and midline shift. Treatment involved prothrombin complex concentrate and vitamin K, with subsequent surgical intervention and anticoagulation resumption. The article highlights the potential risks associated with leech bites in patients on anticoagulation therapy and emphasizes the importance of early diagnosis and prompt treatment in such cases. [Extracted from the article]

Relevance. Diabetic retinopathy occupies one of the leading places in the frame of blindness and low vision. The very first changes in the retina in diabetic retinopathy are disorders of microcirculation and blood supply in the small vessels of the macula. There are few effective drugs that can restore perfusion in the small retina’s vessels. In this connection, it is relevant to search for anticoagulants that allow restoring blood supply in the macular area in diabetic retinopathy in the early stages.The purpose. To analyze the research of a domestic direct-action anticoagulant from animals, a drug of the heparin group Pyavit, both in ophthalmology for diabetic retinopathy and in other fields of medicine. The analysis of publications on eLibrary and PubMed resources for the last 30 years was done, by the keywords: direct-acting anticoagulants, diabetic retinopathy, hirudins, hemodynamics, optical coherence tomography (OCT), hemostasis. The data on the study and application of the drug from its development to its use in diabetic retinopathy, retinal vascular pathology, and pregnancy was analyzed. Researchers have studied the importance of the salivary gland secretion of a medical leech, which is a regulator of the hemostasis system. In 1992 I.P. Baskova patented a new drug Pyavit, which is officially approved for use in medical practice (registration number No. 000363/02). Dosage regimen: 300 mg three times a day for 20 days, and repeat the course through 1–2 months. In ophthalmology, researchers have proven the positive effect of the drug on the retina in diabetic retinopathy with an improvement in visual acuity, retinal thickness according to objective indicators of optical coherence tomography, fluorescence angiography, and hemostasis system.Conclusion. The analysis of scientists’ research allows us to expand knowledge about the positive effect of the drug Piavit on the path of diabetic retinopathy. Based on this review, the authors plan to further study the drug, which will assess the importance and significance of improving microcirculation in the macular area of the retina using the anticoagulant Pyavit to preserve visual functions.

Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Head injury is a potentially lethal and frequently occurring condition in the emergency department (ED). Reliable and fast diagnosis is important both for patients and flow in the ED. Circulating S100B is used to rule out the need for head computer tomography in low-risk patients with mild head injury. The flow of these patients through the ED would benefit from shorter turn-around time. Standard serum clotting tubes require 30-60 min clotting time, followed by an analysis time of 45 min. Here, we evaluated the performance of two alternative blood collection tubes; a rapid serum tube (RST) with a recommend clotting time of 5 min and a hirudin tube (HIR) for instant anticoagulation. S100B measurement was performed on paired blood samples from 221 subjects using a Roche Cobas 602 analyser. The performances of the alternative tubes were evaluated by method comparison to the standard serum clotting tube, repeatability and agreement of results obtained from alternative tubes compared with the standard clotting tube. Both alternative tubes had a minor positive bias (RST = 0.011 µg/L, HIR = 0.008 µg/L). The repeatability was 2% for RST and 10% for HIR, while being 4% for the standard clotting tube. In the agreement analysis, the positive and negative predictive values for RST were 62% and 100% while being 73% and 99% for HIR respectively. Our study suggests that RST is a feasible alternative to reduce laboratory turn-around time in S100b analysis.

ObjectivesThe study sought to compare the clinical efficacy and safety of P2Y12 inhibitors in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous intervention (PPCI).BackgroundLimited data exist regarding the comparative efficacy and safety of P2Y12 inhibitors in STEMI patients undergoing PPCI.MethodsClinical trials enrolling STEMI patients were identified and relevant data was extracted. Major adverse cardiovascular events (MACE) were defined as the composite of all cause mortality, MI, and target vessel revascularization. Network meta-analysis was performed using Bayesian methods.ResultsA total of 37 studies with 88,402 STEMI patients and 5,077 MACE were analyzed. Outcomes at 1 month (22 studies and 60,783 patients) suggest that prasugrel was associated with: lower MACE than clopidogrel (standard dose odds ratio [OR]: 0.59, 95% confidence interval [CI]: 0.50 to 0.69; high-dose OR: 0.60, 95% CI: 0.51 to 0.71; upstream OR: 0.79, 95% CI: 0.66 to 0.94), and ticagrelor (standard dose OR: 0.69, 95% CI: 0.56 to 0.84; upstream OR: 0.72, 95% CI: 0.50 to 1.05); lower mortality and MI than clopidogrel and standard ticagrelor; lower stroke risk than standard clopidogrel and standard or upstream ticagrelor; and lower stent thrombosis than standard or upstream clopidogrel. At 1-year (10 studies, n = 40,333) prasugrel was associated with lower mortality and MACE than other P2Y12 inhibitors. MACE was particularly lower with prasugrel in studies where patients received bivalirudin, drug-eluting stents, and but not glycoprotein IIb/IIIa inhibitor.ConclusionsIn STEMI patients undergoing PPCI, prasugrel and ticagrelor are more efficacious than clopidogrel; in addition, prasugrel was superior to ticagrelor particularly in conjunction with bivalirudin and drug-eluting stents.

Objectives: Heparin-induced thrombocytopenia is a known complication of heparin exposure with potentially life-threatening sequelae. Direct thrombin inhibitors can be substituted for heparin in patients with heparin-induced thrombocytopenia that require anticoagulation. However, the use of direct thrombin inhibitors as a substitute for heparin has not been widely reported in the neuroendovascular literature., Materials and Methods: Here we report the first use of the direct thrombin inhibitor bivalirudin in a neuroendovascular procedure as a substitute for heparin in a patient with a ruptured pseudoaneurysm and heparin-induced thrombocytopenia, and review the literature on the use of bivalirudin and argatroban for such patients., Results: Bivalirudin was safely and effectively used in the case reported, with no thrombotic or hemorrhagic complications. Our literature review revealed a paucity of studies on the use of heparin alternatives, including bivalirudin, in neuroendovascular procedures in patients with heparin-induced thrombocytopenia., Conclusions: Heparin-induced thrombocytopenia is an important iatrogenic disease process in patients undergoing neuroendovascular procedures, and developing protocols to diagnose and manage heparin-induced thrombocytopenia is important for healthcare systems. While further research needs to be done to establish the full range of anticoagulation options to substitute for heparin, our case indicates bivalirudin as a potential candidate., Competing Interests: Declaration of competing interest None to disclose., (Copyright © 2023. Published by Elsevier Inc.)

Introduction: Polycystic Ovary Syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age. Complementary medicine with a comprehensive and holistic approach in treating the diseases has become more popular in many countries. Since ancient times, leech therapy has been used to treat many diseases in Iranian traditional medicine. The present study was conducted with aim to review Iranian traditional medicine about leech therapy in polycystic ovary syndrome. Methods: In this review study, the issues related to polycystic ovary syndrome and leech therapy were studied in Iranian traditional medicine sources such as Qanun, kholasat al-hekmeh, Exir-e-aazam and Mofarrah al-gholub. Then, searching was performed in databases of PubMed, Google Scholar, Scopus, SID, and Magiran using the keywords such as “leech”, “leech therapy”, “Hirudo medicinalis”, “Hirudins” with “polycystic ovary syndrome”, “uterus”, and “oligoamenorrhea”. The review papers and clinical trial studies were searched in Persian and English languages without any time limitation, and the related materials were extracted and categorized. Results: The symptoms of PCOS such as the enlargement and stiffness of the ovaries and oligoamenorrhea were reported in ITM references entitled as “Ehtebas tams”. Leech therapy is useful in treatment of these patients by reducing the ovarian swelling, causing menstruation, eliminating waste material, as well as antioxidant and anti-inflammatory effects. Conclusion: Leech therapy can be used as a complementary treatment in patients with polycystic ovarian syndrome.

Purpose: To describe the intraoperative use of bivalirudin during lower extremity revascularization in the setting of heparin-induced thrombocytopenia (HIT)., Case Summary: A 65 year-old man presented with left common iliac, external iliac, and femoral artery occlusion necessitating revascularization with left femoral endarterectomy and common and external iliac stent angioplasty. Three months before the femoral endarterectomy, the patient was hospitalized for a coronary artery bypass procedure. During this admission, the patient tested positive for the presence of heparin-PF4 antibody complexes. With the patient's recent history of HIT, bivalirudin was selected as the optimal agent for intraoperative anticoagulation. Bivalirudin was administered as a 50 mg bolus, followed by a continuous infusion initiated at 1.75 mg/kg/hr. Repeated bivalirudin boluses were necessary to maintain an activated clotting time (ACT) necessary for the revascularization procedures and recurrent subacute thrombi despite appropriate ACT values., Discussion: Bivalirudin has been utilized for cardiopulmonary bypass and carotid endarterectomy (CEA), but data for dosing in lower extremity revascularization are lacking. As the risk for thrombosis with HIT continues for months after diagnosis, it is important to elucidate optimal dosing of non-heparin anticoagulant options, such as the direct thrombin inhibitor, bivalirudin. The absence of validated dosing strategies for bivalirudin can result in prolonged operative times, increased risk of bleeding, and inadequate anticoagulation., Conclusion: Bivalirudin is an appropriate agent for intraoperative anticoagulation in lower extremity revascularization. However, further investigation into the optimal intraoperative bivalirudin dosing regimen is necessary., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: We aimed to evaluate thrombotic and hemorrhagic complications with heparin versus bivalirudin use in veno-venous extracorporeal membrane oxygenation (V-V ECMO)., Methods: We performed a retrospective cohort study of adult patients placed on V-V ECMO with intravenous anticoagulation with either heparin or bivalirudin. Time to thrombotic event and major bleed were analyzed in addition to related outcomes., Results: We identified 95 patients placed on V-V ECMO: 61 receiving heparin, 34 bivalirudin. The bivalirudin group had a higher rate of severe COVID-19, higher BMI, and longer ECMO duration. Despite this, bivalirudin was associated with reduced risk of thrombotic event (HR 0.14, 95% CI 0.06-0.32, p < .001) and increased average lifespan of the circuit membrane lung (16 vs. 10 days, p = 0.004). While there was no difference in major bleeding, the bivalirudin group required fewer transfusions of packed red blood cells and platelets per 100 ECMO days (means of 13 vs. 39, p = 0.004; 5 vs. 19, p = .014, respectively). Lastly, the bivalirudin group had improved survival to ECMO decannulation in univariate analysis (median OS 53 vs. 26 days, p = .015)., Conclusions: In this real-world analysis of bivalirudin versus heparin, bivalirudin is a viable option for V-V ECMO and associated with lower risk of thrombotic complications and fewer transfusion requirements., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The use of bivalirudin as the primary anticoagulant for children supported on extracorporeal membrane oxygenation (ECMO) is growing. Ideal management of bivalirudin dosing during therapeutic plasma exchange (TPE) on ECMO is unknown. We performed a single-center retrospective study of ECMO patients anticoagulated with bivalirudin who underwent TPE from January 2019 to December 2021. Therapeutic plasma exchange sessions were analyzed individually by bivalirudin dosing strategy (no change [NC] versus increased dose [dose change {DC} bivalirudin group]) and replacement fluid (all fresh-frozen plasma [FFP] versus all albumin or FFP and albumin [FFP/Albumin]). Primary outcomes included bleeding, coagulopathy, and circuit thrombosis within 24 hours of TPE. Secondary outcomes included change in bivalirudin dose and coagulation parameters following TPE. There were 60 unique TPE sessions. Bivalirudin dosing or replacement fluid strategies were not associated with bleeding, coagulopathy, or thrombosis post-TPE. All albumin or fresh frozen plasma and albumin combinations (FFP/Albumin) group had longer post-TPE thromboelastography (TEG) reaction time, clot time, and more acute angle. The FFP/Albumin group had increased post-TPE international normalization ratio (INR) and partial thrombin time (PTT). Therapeutic plasma exchange for children on ECMO and bivalirudin anticoagulation is feasible; however, optimal dosing during TPE requires further investigation. Replacement fluid with FFP/Albumin is associated with more coagulopathic laboratory parameters. Patients may benefit from all FFP fluid replacement strategy. Further investigation is needed to prove generalizability., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2023.)

ObjectiveThis meta-analysis was performed to assess the efficacy and safety of bivalirudin compared with unfractionated heparin or enoxaparin plus glycoprotein (GP) IIb/IIIa inhibitors in patients undergoing percutaneous coronary intervention (PCI).BackgroundPharmacotherapy for patients undergoing PCI includes bivalirudin, heparin, and GP IIb/IIIa inhibitors. We sought to compare ischemic and bleeding outcomes with bivalirudin versus heparin plus GP IIb/IIIa inhibitors in patients undergoing PCI.MethodsA literature search was conducted to identify fully published randomized trials that compared bivalirudin with heparin plus GP IIb/IIIa inhibitors in patients undergoing PCI.ResultsA total of 19,772 patients in 5 clinical trials were included in the analysis (9785 patients received bivalirudin and 9987 patients received heparin plus GP IIb/IIIa inhibitors during PCI). Anticoagulation with bivalirudin, as compared with heparin plus glycoprotein IIb/IIIa inhibitors, results in no difference in major adverse cardiovascular events (odds ratio [OR] 1.07, 95% confidence interval [CI] 0.96 to 1.19), death (OR 0.93, 95% CI 0.72 to 1.21), or urgent revascularization (OR 1.06, 95% CI 0.86 to 1.30). There is a trend towards a higher risk of myocardial infarction (OR 1.12, 95% CI 0.99 to 1.28) but a significantly lower risk of TIMI major bleeding with bivalirudin (OR 0.55, 95% CI 0.44 to 0.69).ConclusionIn patients who undergo PCI, anticoagulation with bivalirudin as compared with unfractionated heparin or enoxaparin plus GP IIb/IIIa inhibitors results in similar ischemic adverse events but a reduction in major bleeding.

Heparin-induced thrombocytopenia (HIT) is a common complication of heparin therapy. There are three types of HIT. In the majority of patients, thrombocytopenia is modest and resolves without sequelae (HIT I). In a smaller number of patients, the thrombocytopenia is severe (HIT II), and in still others, the thrombocytopenia is also associated with thrombosis (HITT). Administration of heparin to this latter group of patients causes platelet aggregation, thromboembolism, and thrombocytopenia. It is advisable that heparin not be administered in any form to patients with documented or suspected HIT II or HITT. This situation, of course, poses a problem for those patients requiring cardiopulmonary bypass (CPB) surgery. In this report, we summarize our experience with Lepirudin (Hoechst, Frankfurt Ammain, Germany), which is a recombinant hirudin (r-hirudin), as an alternative to heparin for systemic anticoagulation, as well as the use of the ecarine clotting time (ECT) for monitoring anticoagulation status during CPB.

Abstract Purpose: To investigate whether hirudin exerts its antithrombin action to decrease the ratio of Human Microvascular Endothelial Cells (HMVECs) apoptosis. Methods: Human microvascular endothelial cells (HMVECs) cultured in the third and fifth generations were used. HMVECs were divided into normal group, thrombin group (T group), natrual hirudin group (H group), thrombin + natrual hirudin group (T + H group), AG490 group, thrombin + AG490 group (T + AG490 group), natrual hirudin + AG490 group (H + AG490 group), thrombin + natural hirudin + AG490 (T + H + AG490 group).Apart from the normal group, the other groups were exposed to the relevant drugs for 24 hours.HMVEC apoptosis was assessed by flow cytometric and double Immunofluorescence of phosphorylation of JAK (P-JAK2) and TUNEL assay. Results: Compared with the normal group, in thrombin group the HMVECs apoptosis rate were significantly increased (P

Chronic kidney disease (CKD) is a common public health concern. The global burden of CKD is increasing due to the high morbidity and mortality associated with it, indicating the shortcomings of therapeutic drugs at present. Renal fibrosis is the common pathology of CKD, which is characterized by glomerulosclerosis, renal tubular atrophy, and renal interstitial fibrosis. Natural hirudin is an active ingredient extracted from Hirudo medicinalis , which has been found to be the strongest natural specific inhibitor of thrombin. Evidence based on pharmacological data has shown that hirudin has important protective effects in CKD against diabetic nephrology, nephrotic syndrome, and renal interstitial fibrosis. The mechanisms of hirudin in treating CKD are mainly related to inhibiting the inflammatory response, preventing apoptosis of intrinsic renal cells, and inhibiting the interactions between thrombin and protease-activated receptors. In this review, we summarize the function and beneficial properties of hirudin for the treatment of CKD, and its underlying mechanisms.

Diabetic nephropathy (DN) is a major microvascular complication of diabetes and a common cause of chronic kidney disease. There is currently a lack of effective treatments for DN, and the prognosis for patients remains poor. Hirudin, one of the primary active components derived from leeches, demonstrates anti-coagulant, anti-fibrotic, anti-thrombotic, and anti-inflammatory properties, exhibiting significant protective effects on the kidneys. In recent years, there has been a surge of interest in studying the potential benefits of hirudin, especially in its role in the management of DN. This article delves into the mechanisms by which hirudin contributes to the treatment of DN and its clinical efficacy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Tian, Yi, Yang, Chen, Zhu, Liu and Li.)

The use of medicinal leeches in clinical therapy has been employed for a long time, as it was originally recognized for exerting antithrombin effects. These effects were due to the ability of the leech to continuously suck blood while attached to human skin. According to Chinese Pharmacopoei , leeches used in traditional Chinese medicine mainly consist of Whitmania pigra Whitman, Hirudo nipponia Whitman, and Whitmania acranulata , but the latter two species are relatively scarce. The main constituents of leeches are protein and peptide macromolecules. They can be categorized into two categories based on their pharmacological effects. One group consists of active ingredients that directly target the coagulation system, such as hirudin, heparin, and histamine, which are widely known. The other group comprises protease inhibitor components like Decorsin and Hementin. Among these, hirudin secreted by the salivary glands of the leech is the most potent thrombin inhibitor and served as the sole remedy for preventing blood clotting until the discovery of heparin. Additionally, leeches play a significant role in various traditional Chinese medicine formulations. In recent decades, medicinal leeches have been applied in fields including anti-inflammatory treatment, cardiovascular disease management, antitumor treatment, and many other medical conditions. In this review, we present a comprehensive overview of the historical journey and medicinal applications of leeches in various medical conditions, emphasizing their pharmaceutical significance within traditional Chinese medicine. This review offers valuable insights for exploring additional therapeutic opportunities involving the use of leeches in various diseases and elucidating their underlying mechanisms for future research.

Protease-activated receptor (PAR)-1 is a cellular receptor for thrombin that is activated after proteolytic cleavage. The contribution of PAR-1 to inflammatory cell-mediated renal injury was assessed in murine crescentic glomerulonephritis (GN). A pivotal role for thrombin in this model was demonstrated by the capacity of hirudin, a selective thrombin antagonist, to attenuate renal injury. Compared with control treatment, hirudin significantly reduced glomerular crescent formation, T cell and macrophage infiltration, fibrin deposition, and elevated serum creatinine, which are prominent features of GN. PAR-1-deficient (PAR-1(-/-)) mice, which have normal coagulation, also showed significant protection from crescentic GN compared with wild-type mice. The reductions in crescent formation, inflammatory cell infiltration, and serum creatinine were similar in PAR-1(-/-) and hirudin-treated mice, but hirudin afforded significantly greater protection from fibrin deposition. Treatment of wild-type mice with a selective PAR-1-activating peptide (TRAP) augmented histological and functional indices of GN, but TRAP treatment did not alter the severity of GN in PAR(-/-) mice. These results indicate that activation of PAR-1 by thrombin or TRAP amplifies crescentic GN. Thus, in addition to its procoagulant role, thrombin has proinflammatory, PAR-1-dependent effects that augment inflammatory renal injury.