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1.
J Vis Exp ; (206)2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38709073

ABSTRACT

Fibrinogenolytic agents that can dissolve fibrinogen directly have been widely used in anti-coagulation treatment. Generally, identifying new fibrinogenolytic agents requires the separation of each component first and then checking their fibrinogenolytic activities. Currently, polyacrylamide gel electrophoresis (PAGE) and chromatography are mostly used in the separating stage. Meanwhile, the fibrinogen plate assay and reaction products based PAGE are usually adopted to display their fibrinogenolytic activities. However, because of the spatiotemporal separation of those two stages, it is impossible to separate and display the active fibrinogenolytic agents with the same gel. To simplify the separating and displaying processes of fibrinogenolytic agent identification, we constructed a new fibrinogen-PAGE method to rapidly separate and display the fibrinogenolytic agents of peanut worms (Sipunculus nudus) in this study. This method includes fibrinogen-PAGE preparation, electrophoresis, renaturation, incubation, staining, and decolorization. The fibrinogenolytic activity and molecular weight of the protein can be detected simultaneously. According to this method, we successfully detected more than one active fibrinogenolytic agent of peanut wormhomogenate within 6 h. Moreover, this fibrinogen-PAGE method is time and cost-friendly. Furthermore, this method could be used to study the fibrinogenolytic agents of the other organisms.


Subject(s)
Electrophoresis, Polyacrylamide Gel , Fibrinogen , Fibrinogen/chemistry , Fibrinogen/metabolism , Animals , Electrophoresis, Polyacrylamide Gel/methods , Fibrinolytic Agents/chemistry , Fibrinolytic Agents/pharmacology , Fibrinolytic Agents/isolation & purification
2.
Am Heart J ; 272: 109-112, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38705637

ABSTRACT

Data comparing catheter-based thrombectomy (CBT) and catheter-directed thrombolysis (CDT) in acute pulmonary embolism are lacking. To address this, we performed a meta-analysis of prospective and retrospective studies of CBT and compared it to performance goal rates of mortality and major bleeding from a recently published network meta-analysis. When compared with performance goal for CDT based on historical studies, CBT was noninferior for all-cause mortality (6.0% vs 6.87%; P-valueNI < .001), non-inferior and superior for major bleeding (4.9% vs 11%; P-valueNI < .001 and P < .001 for superiority).


Subject(s)
Pulmonary Embolism , Thrombectomy , Thrombolytic Therapy , Humans , Pulmonary Embolism/therapy , Thrombectomy/methods , Thrombolytic Therapy/methods , Acute Disease , Treatment Outcome , Fibrinolytic Agents/administration & dosage , Fibrinolytic Agents/therapeutic use
3.
Trials ; 25(1): 324, 2024 May 16.
Article in English | MEDLINE | ID: mdl-38755709

ABSTRACT

BACKGROUND: The optimal antithrombotic strategy early after aortic valve replacement surgery with a biological valve remains controversial due to lack of high-quality evidence. Either oral anticoagulants or acetylsalicylic acid should be considered for the first 3 months. Hypo-attenuated leaflet thickening on cardiac computed tomography has been associated with latent bioprosthetic valve thrombosis and may be prevented with anticoagulation. We hypothesize that anticoagulation with apixaban is superior to single antiplatelet therapy with acetylsalicylic acid in reducing hypo-attenuated leaflet thickening of bioprosthetic aortic valve prostheses. METHODS: In this prospective, open-label, randomized trial, patients undergoing isolated aortic valve replacement surgery with rapid deployment bioprosthetic valves will be randomized. The treatment group will receive 5 mg of apixaban twice a day for the first 3 months and 100 mg of acetylsalicylic acid thereafter. The control group will be administered 100 mg of acetylsalicylic acid once a day, indefinitely. After the 3-month treatment period, a contrast-enhanced electrocardiogram-gated cardiac computed tomography will be performed to identify hypo-attenuated leaflet thickening of the bioprosthetic valve. The primary objective of the study is to assess the impact of apixaban on the prevention of hypo-attenuated leaflet thickening at 3 months. The secondary and exploratory endpoints will be clinical outcomes and safety profiles of the two strategies. DISCUSSION: Antithrombotic therapy after aortic valve replacement is used to prevent valve thrombosis and systemic thromboembolism. Latent bioprosthetic valve thrombosis is a precursor of clinically significant prosthetic valve dysfunction or thromboembolic events. The hallmark feature of latent bioprosthetic valve thrombosis is hypo-attenuated leaflet thickening on cardiac computed tomography. Subclinical leaflet thrombosis occurs frequently in bioprosthetic aortic valves, more commonly in transcatheter than in surgical valves. There is no evidence on the effect of direct oral anticoagulants on the incidence of hypo-attenuated leaflet thickening after surgical aortic valve replacement with rapid deployment bioprostheses. TRIAL REGISTRATION: ClinicalTrials.gov NCT06184113. Registered on December 28, 2023.


Subject(s)
Aortic Valve , Aspirin , Bioprosthesis , Factor Xa Inhibitors , Heart Valve Prosthesis Implantation , Heart Valve Prosthesis , Pyrazoles , Pyridones , Randomized Controlled Trials as Topic , Thrombosis , Humans , Aspirin/administration & dosage , Aspirin/therapeutic use , Aspirin/adverse effects , Pyridones/therapeutic use , Pyridones/administration & dosage , Pyridones/adverse effects , Prospective Studies , Heart Valve Prosthesis/adverse effects , Aortic Valve/surgery , Aortic Valve/diagnostic imaging , Thrombosis/prevention & control , Thrombosis/etiology , Pyrazoles/therapeutic use , Pyrazoles/administration & dosage , Pyrazoles/adverse effects , Factor Xa Inhibitors/administration & dosage , Factor Xa Inhibitors/adverse effects , Factor Xa Inhibitors/therapeutic use , Heart Valve Prosthesis Implantation/adverse effects , Heart Valve Prosthesis Implantation/instrumentation , Heart Valve Prosthesis Implantation/methods , Treatment Outcome , Platelet Aggregation Inhibitors/administration & dosage , Platelet Aggregation Inhibitors/therapeutic use , Platelet Aggregation Inhibitors/adverse effects , Female , Male , Middle Aged , Time Factors , Aged , Adult , Fibrinolytic Agents/administration & dosage , Fibrinolytic Agents/adverse effects
4.
Medicine (Baltimore) ; 103(20): e38228, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38758868

ABSTRACT

Hematuria is the most common symptom of bladder cancer (BCa). It is well-known that the frequency of hematuria increases with the use of antithrombotic drugs (ATDs). We designed our study with the hypothesis that patients using antithrombotic drugs who present with the complaint of hematuria and are subsequently diagnosed with BCa may receive an earlier diagnosis, leading to lower tumor grades and stages. Data of 441 consecutive patients who presented to our urology outpatient clinic with macroscopic hematuria between 2020 and 2023 were retrospectively evaluated. A total of 88 patients (21.4%) with a primary diagnosis of BCa were included in our study. Patients were divided into 2 groups: those using ATDs during the episode of macroscopic hematuria (group 1) and those not using ATDs (group 2). Univariate and multivariate binary logistic regression analysis was performed to identify risk factors that could predict tumor grade. The incidence of multiple tumors (>1) was significantly lower in patients using ATDs (P = .033). The number of patients with tumor size larger than 3 cm was significantly higher in the group not using ATDs (P = .005). The rates of pathological T1 stage in the group using ATDs were significantly lower than those in the nonuser group (P = .038). According to the results of the multivariate model, the effect of pathology stage and ATD use on predicting tumor grade was significant (P = .002 and P < .001, respectively). The probability of having a high-grade tumor in patients with pathology stage T1 was 5.32 times higher than in patients with pathology stage TA. The probability of having a high-grade tumor in patients not using ATDs was 7.73 times higher than in those using ATDs. The effect of pathology stage and ATD use on predicting tumor grade was found to be significant. The probability of having a high-grade tumor was higher in patients not using ATDs compared to those using ATDs. In light of these results, we can state that the use of ATDs is a positive predictive factor in the early diagnosis of BCa, bringing along the chance of early diagnosis and treatment.


Subject(s)
Early Detection of Cancer , Fibrinolytic Agents , Hematuria , Urinary Bladder Neoplasms , Humans , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/diagnosis , Male , Female , Retrospective Studies , Aged , Middle Aged , Early Detection of Cancer/methods , Hematuria/etiology , Fibrinolytic Agents/therapeutic use , Risk Factors , Neoplasm Staging , Neoplasm Grading
5.
Neurology ; 102(12): e209442, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38771998

ABSTRACT

BACKGROUND AND OBJECTIVES: Few population-based studies have assessed associations between the use of antithrombotic (platelet antiaggregant or anticoagulant) drugs and location-specific risks of spontaneous intracerebral hemorrhage (s-ICH). In this study, we estimated associations between antithrombotic drug use and the risk of lobar vs nonlobar incident s-ICH. METHODS: Using Danish nationwide registries, we identified cases in the Southern Denmark Region of first-ever s-ICH in patients aged 50 years or older between 2009 and 2018. Each verified case was classified as lobar or nonlobar s-ICH and matched to controls in the general population by age, sex, and calendar year. Prior antithrombotic use was ascertained from a nationwide prescription registry. We calculated odds ratios (aORs) for associations between the use of clopidogrel, aspirin, direct oral anticoagulants (DOACs) or vitamin K antagonists (VKA), and lobar and nonlobar ICH in conditional logistic regression analyses that were adjusted for potential confounders. RESULTS: A total of 1,040 cases of lobar (47.9% men, mean age [SD] 75.2 [10.7] years) and 1,263 cases of nonlobar s-ICH (54.2% men, mean age 73.6 [11.4] years) were matched to 41,651 and 50,574 controls, respectively. A stronger association with lobar s-ICH was found for clopidogrel (cases: 7.6%, controls: 3.5%; aOR 3.46 [95% CI 2.45-4.89]) vs aspirin (cases: 22.9%, controls: 20.4%; aOR 2.14 [1.74-2.63; p = 0.019). Corresponding estimates for nonlobar s-ICH were not different between clopidogrel (cases: 5.4%, controls: 3.4%; aOR 2.44 [1.71-3.49]) and aspirin (cases: 20.7%, controls: 19.2%; aOR 1.77 [1.47-2.15]; p = 0.12). VKA use was associated with higher odds of both lobar (cases: 14.3%, controls: 6.1%; aOR 3.66 [2.78-4.80]) and nonlobar (cases: 15.4%, controls: 5.5%; aOR 4.62 [3.67-5.82]) s-ICH. The association of DOAC use with lobar s-ICH (cases: 3.5%, controls: 2.7%; aOR 1.66 [1.02-2.70]) was weaker than that of VKA use (p = 0.006). Corresponding estimates for nonlobar s-ICH were not different between DOACs (cases: 5.1%, controls: 2.4%; aOR 3.44 [2.33-5.08]) and VKAs (p = 0.20). DISCUSSION: Antithrombotics were associated with higher risks of s-ICH, but the strength of the associations varied by s-ICH location and drug, which may reflect differences in the cerebral microangiopathies associated with lobar vs nonlobar hemorrhages and the mechanisms of drug action.


Subject(s)
Cerebral Hemorrhage , Fibrinolytic Agents , Registries , Humans , Male , Female , Aged , Cerebral Hemorrhage/epidemiology , Cerebral Hemorrhage/chemically induced , Denmark/epidemiology , Middle Aged , Fibrinolytic Agents/adverse effects , Aged, 80 and over , Platelet Aggregation Inhibitors/adverse effects , Anticoagulants/adverse effects , Clopidogrel/adverse effects , Clopidogrel/therapeutic use , Aspirin/adverse effects , Incidence
6.
BMJ Case Rep ; 17(5)2024 May 24.
Article in English | MEDLINE | ID: mdl-38789271

ABSTRACT

Cancer-associated stroke is an evolving subgroup of embolic strokes of undetermined source. A man in his mid-20s with progressive follicular variant acinic cell carcinoma of the parotid was admitted because of new onset left-sided weakness. Neuroimaging confirmed a right middle cerebral artery infarction. After extensive diagnostics, stroke aetiology was deemed from cancer-induced hypercoagulability. Questions which arose regarding his management included (1) What was the best antithrombotic for secondary stroke prevention? (2) What was his risk for intracranial or tumorous bleeding once antithrombotics had been started? (3) How many days post-stroke could the antithrombotic be initiated? and (4) When could he be cleared for palliative chemotherapy and whole brain irradiation? The approach to address the abovementioned questions in the management of a rare cancer complicated by stroke is presented. Although treatments are guided by known pathomechanisms, additional studies are needed to further support current treatment strategies for this subgroup of patients.


Subject(s)
Carcinoma, Acinar Cell , Parotid Neoplasms , Humans , Male , Carcinoma, Acinar Cell/complications , Parotid Neoplasms/complications , Adult , Infarction, Middle Cerebral Artery/etiology , Infarction, Middle Cerebral Artery/diagnostic imaging , Fibrinolytic Agents/therapeutic use
7.
Phytochemistry ; 223: 114109, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38697239

ABSTRACT

A previously undescribed open-loop decarbonizing cembranolide, sarcocinerenolide A, and eight undescribed cembranolides, sarcocinerenolides B-I, characterized by poly-membered oxygen ring fragments were isolated from the soft coral Sarcophyton cinereum collected from the South China Sea. The structures and absolute configurations of these previously undescribed compounds were precisely determined by analysis of NMR data, DP4+ and ECD spectra. The bioactivities of the compounds were evaluated using zebrafish models and sarcocinerenolides C and H exhibited anti-thrombotic activity.


Subject(s)
Anthozoa , Diterpenes , Animals , Anthozoa/chemistry , Diterpenes/chemistry , Diterpenes/pharmacology , Diterpenes/isolation & purification , Molecular Structure , Zebrafish , Fibrinolytic Agents/pharmacology , Fibrinolytic Agents/chemistry , Fibrinolytic Agents/isolation & purification , China , Structure-Activity Relationship
8.
J Am Heart Assoc ; 13(10): e034716, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38726922

ABSTRACT

BACKGROUND: A rapid shift has occurred from vitamin K antagonists toward direct oral anticoagulants, which have a lower risk of intracerebral hemorrhage (ICH). However, effects on clinical outcomes after ICH are understudied. We aimed to describe the prevalence of antithrombotic drugs and to study the prognosis among prestroke functionally independent Swedish patients with ICH. METHODS AND RESULTS: We identified all patients diagnosed with nontraumatic ICH in 2017 to 2021 from the Swedish Stroke Register (n=13 155) and assessed death and functional outcome at 3 months after ICH in prestroke functionally independent patients (n=10 014). Functional outcome was estimated among 3-month survivors on the basis of self-reported activities of daily living scores. Risks of outcomes were estimated using Poisson regression. In 13 155 patients, 14.5% used direct oral anticoagulant, 10.1% vitamin K antagonists, and 21.6% antiplatelets at ICH onset. Among 10 014 pre-stroke activities of daily living-independent patients, oral anticoagulants and antiplatelets were associated with increased mortality risk (adjusted risk ratio, 1.27 [95% CI, 1.13-1.43]; P<0.001; and adjusted risk ratio, 1.23 [95% CI, 1.13-1.34]; P<0.001 respectively). Mortality risk did not statistically differ between antiplatelets and oral anticoagulants nor between direct oral anticoagulant and vitamin K antagonists. Among 5126 patients with nonmissing functional outcome (69.1% of survivors), antiplatelets (adjusted risk ratio, 1.06 [95% CI, 0.99-1.13]; P=0.100) and oral anticoagulants (adjusted risk ratio, 1.01 [95% CI, 0.92-1.12]; P=0.768) were not statistically significantly associated with functional dependence. CONCLUSIONS: There was no statistically significant difference in mortality risk between direct oral anticoagulant and vitamin K antagonists in prestroke functionally independent patients (unadjusted for oral anticoagulant class indication). Furthermore, mortality risk in antiplatelet and oral anticoagulant users might differ less than previously suggested.


Subject(s)
Anticoagulants , Cerebral Hemorrhage , Fibrinolytic Agents , Registries , Humans , Male , Female , Sweden/epidemiology , Aged , Retrospective Studies , Cerebral Hemorrhage/chemically induced , Cerebral Hemorrhage/mortality , Cerebral Hemorrhage/epidemiology , Fibrinolytic Agents/therapeutic use , Fibrinolytic Agents/adverse effects , Aged, 80 and over , Anticoagulants/adverse effects , Anticoagulants/therapeutic use , Middle Aged , Platelet Aggregation Inhibitors/therapeutic use , Platelet Aggregation Inhibitors/adverse effects , Treatment Outcome , Stroke/mortality , Stroke/epidemiology , Stroke/drug therapy , Vitamin K/antagonists & inhibitors , Administration, Oral , Activities of Daily Living , Risk Factors , Risk Assessment/methods
9.
Methodist Debakey Cardiovasc J ; 20(3): 36-48, 2024.
Article in English | MEDLINE | ID: mdl-38765215

ABSTRACT

Pulmonary embolism is a debilitating and potentially life-threatening disease characterized by high mortality and long-term adverse outcomes. Traditional treatment options are fraught with serious bleeding risks and incomplete thrombus removal, necessitating the development of innovative treatment strategies. While new interventional approaches offer promising potential for improved outcomes with fewer serious complications, their rapid development and need for more comparative clinical evidence makes it challenging for physicians to select the optimal treatment for each patient among the many options. This review summarizes the current published clinical data for both traditional treatments and more recent interventional approaches indicated for pulmonary embolism. While published studies thus far suggest that these newer interventional devices offer safe and effective options, more data is needed to understand their impact relative to the standard of care. The studies in progress that are anticipated to provide needed evidence are reviewed here since they will be critical for helping physicians make informed treatment choices and potentially driving necessary guideline changes.


Subject(s)
Fibrinolytic Agents , Pulmonary Embolism , Thrombectomy , Thrombolytic Therapy , Humans , Clinical Decision-Making , Equipment Design , Fibrinolytic Agents/administration & dosage , Fibrinolytic Agents/adverse effects , Pulmonary Embolism/therapy , Pulmonary Embolism/diagnostic imaging , Pulmonary Embolism/mortality , Risk Factors , Thrombectomy/adverse effects , Thrombectomy/instrumentation , Thrombolytic Therapy/adverse effects , Treatment Outcome
10.
Curr Probl Cardiol ; 49(7): 102628, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38729276

ABSTRACT

Mechanical prosthetic valve thrombosis (MPVT) is a common complication of valvular implantations. This study compared the efficacy and safety of different treatments for MPVT. A systematic search of electronic databases identified studies evaluating surgical, anticoagulant, and thrombolytic therapies. Although several studies of different types have been conducted to evaluate the efficacy of these treatment strategies the lack of randomized controlled trials has resulted in the inability to make a definitive conclusion about the pros and cons of these treatments. Recent treatments, such as slow and ultraslow infusion of thrombolytics, showed comparable efficacy and lower complication rates than traditional methods. Inadequate anticoagulant use is a major risk factor for MPVT, highlighting the importance of prevention. Treatment selection should be individualized based on patient factors and available expertise. Overall, slow and ultraslow infusion of thrombolytics may be a promising treatment option for MPVT.


Subject(s)
Anticoagulants , Fibrinolytic Agents , Heart Valve Prosthesis , Thrombolytic Therapy , Thrombosis , Humans , Heart Valve Prosthesis/adverse effects , Thrombosis/etiology , Thrombosis/prevention & control , Thrombolytic Therapy/methods , Thrombolytic Therapy/adverse effects , Fibrinolytic Agents/therapeutic use , Anticoagulants/therapeutic use , Risk Factors , Heart Valve Prosthesis Implantation/adverse effects , Heart Valve Prosthesis Implantation/methods , Treatment Outcome
11.
BMC Ophthalmol ; 24(1): 218, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38773500

ABSTRACT

PURPOSE: Comparing between the visual outcomes and post operative complications of two surgical treatments for sub macular hemorrhage, pars plana vitrectomy with tissue plasminogen activator (tPA) injection procedure, and pneumatic displacement of submacular hemorrhage with intravitreal tPA injection. METHODS: A retrospective chart review of patients with sub macular hemorrhage (SMH) was performed. Data was collected from 150 patients with sub macular hemorrhage. Patients were followed up from the day of admission and up to a year post surgery. Evaluation included visual acuity, optical coherence tomography (OCT), fundus examination and rates of complications. RESULTS: Pars plana vitrectomy procedure has showed a better visual outcome in small SMH. Comparing complications between the two treatment modalities, no significant difference has been found in the study. CONCLUSIONS: Pars plana vitrectomy and tPA showed a clear advantage with a trend of better visual acuity as well as a significant predictor to better visual acuity for small and medium sub macular hemorrhage.


Subject(s)
Fibrinolytic Agents , Intravitreal Injections , Retinal Hemorrhage , Tissue Plasminogen Activator , Tomography, Optical Coherence , Visual Acuity , Vitrectomy , Humans , Tissue Plasminogen Activator/administration & dosage , Vitrectomy/methods , Retinal Hemorrhage/therapy , Retinal Hemorrhage/diagnosis , Retinal Hemorrhage/drug therapy , Retrospective Studies , Male , Female , Aged , Fibrinolytic Agents/administration & dosage , Middle Aged , Aged, 80 and over
12.
Platelets ; 35(1): 2353582, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38773939

ABSTRACT

Platelets are central to thrombosis. Research at the intersection of biological and physical sciences provides proof-of-concept for shear rate-dependent platelet slip at vascular stenosis and near device surfaces. Platelet slip extends the observed biological "slip-bonds" to the boundary of functional gliding without contact. As a result, there is diminished engagement of the coagulation cascade by platelets at these surfaces. Comprehending platelet slip would more precisely direct antithrombotic regimens for different shear environments, including for percutaneous coronary intervention (PCI). In this brief report we promote translation of the proof-of-concept for platelet slip into improved antithrombotic regimens by: (1) reviewing new supporting basic biological science and clinical research for platelet slip; (2) hypothesizing the principal variables that affect platelet slip; (3) applying the consequent construct model in support of-and in some cases to challenge-relevant contemporary guidelines and their foundations (including for urgent, higher-risk PCI); and (4) suggesting future research pathways (both basic and clinical). Should future research demonstrate, explain and control platelet slip, then a paradigm shift for choosing and recommending antithrombotic regimens based on predicted shear rate should follow. Improved clinical outcomes with decreased complications accompanying this paradigm shift for higher-risk PCI would also result in substantive cost savings.


Subject(s)
Blood Platelets , Humans , Blood Platelets/metabolism , Blood Platelets/drug effects , Fibrinolytic Agents/pharmacology , Fibrinolytic Agents/therapeutic use
13.
CNS Neurosci Ther ; 30(5): e14748, 2024 05.
Article in English | MEDLINE | ID: mdl-38727518

ABSTRACT

AIMS: To investigate the characteristics of dynamic cerebral autoregulation (dCA) after intravenous thrombolysis (IVT) and assess the relationship between dCA and prognosis. METHODS: Patients with unilateral acute ischemic stroke receiving IVT were prospectively enrolled; those who did not were selected as controls. All patients underwent dCA measurements, by quantifying the phase difference (PD) and gain, at 1-3 and 7-10 days after stroke onset. Simultaneously, two dCA-based nomogram models were established to verify the predictive value of dCA for patients with mild-to-moderate stroke. RESULTS: Finally, 202 patients who received IVT and 238 who did not were included. IVT was positively correlated with higher PD on days 1-3 and 7-10 after stroke onset. PD values in both sides at 1-3 days after stroke onset and in the affected side at 7-10 days after onset were independent predictors of unfavorable outcomes in patients who received IVT. Additionally, in patients with mild-to-moderate stroke who received IVT, the dCA-based nomogram models significantly improved the risk predictive ability for 3-month unfavorable outcomes. CONCLUSION: IVT has a positive effect on dCA in patients with acute stroke; furthermore, dCA may be useful to predict the prognosis of patients with IVT.


Subject(s)
Homeostasis , Ischemic Stroke , Thrombolytic Therapy , Humans , Male , Female , Aged , Middle Aged , Prognosis , Thrombolytic Therapy/methods , Homeostasis/physiology , Homeostasis/drug effects , Ischemic Stroke/drug therapy , Ischemic Stroke/physiopathology , Fibrinolytic Agents/administration & dosage , Fibrinolytic Agents/therapeutic use , Cerebrovascular Circulation/physiology , Cerebrovascular Circulation/drug effects , Prospective Studies , Tissue Plasminogen Activator/administration & dosage , Tissue Plasminogen Activator/therapeutic use , Administration, Intravenous , Predictive Value of Tests , Aged, 80 and over , Nomograms , Stroke/drug therapy , Stroke/physiopathology
14.
West J Emerg Med ; 25(3): 399-406, 2024 May.
Article in English | MEDLINE | ID: mdl-38801047

ABSTRACT

Background: Alteplase (tPA) is the initial treatment for acute ischemic stroke. Current tPA guidelines exclude patients who took direct oral anticoagulants (DOAC) within the prior 48 hours. In this propensity-matched retrospective study we compared acute ischemic stroke patients treated with tPA who had received DOACs within 48 hours of thrombolysis to those not previously treated with DOACs, regarding three outcomes: mortality; intracranial hemorrhage (ICH); and need for acute blood transfusions (as a marker of significant blood loss). Methods: Using the United States cohort of 54 healthcare organizations in the TriNetx database, we identified 8,582 stroke patients treated with tPA on DOACs within 48 hours of thrombolysis and 46,703 stroke patients treated with tPA not on DOACs since January 1, 2012. We performed propensity score matching on demographic information and seven prior clinical diagnostic groups, resulting in a total of 17,164 acute stroke patients evenly matched between groups. We recorded mortality rates, frequency of ICH, and need for blood transfusions for each group over the ensuing 7- and 30-day periods. Results: Patients treated with tPA on DOACs had reduced mortality (3.3% vs 7.3%; risk ratio [RR] 0.456; P < 0.001), fewer ICHs (6.8% vs 10.1%; RR 0.678; P < 0.001), and less risk of major bleeding as measured by frequency of blood transfusions (0.5% vs 1.5%; RR 0.317; p < 0.001) at 7 days post thrombolytic, than the tPA patients not on DOACS. Findings for 30 days post-thrombolytics were similar/statistically significant with lower mortality rate (7.2% vs 13.1%; RR 0.550; P < 0.001), fewer ICHs (7.6% vs 10.8%; RR 0.705; P < 0.001), and fewer blood transfusions (0.9% vs 2.0%; RR 0.448; P < 0.001). Conclusion: Acute ischemic stroke patients treated with tPA who received DOACs within 48 hours of thrombolysis had lower mortality rates, reduced incidence of ICH, and less blood loss than those not on DOACs. Our study suggests that prior use of DOACs should not be a contraindication to thrombolysis for ischemic stroke.


Subject(s)
Anticoagulants , Fibrinolytic Agents , Propensity Score , Thrombolytic Therapy , Tissue Plasminogen Activator , Humans , Retrospective Studies , Female , Male , Aged , Thrombolytic Therapy/adverse effects , Tissue Plasminogen Activator/therapeutic use , Fibrinolytic Agents/therapeutic use , Fibrinolytic Agents/adverse effects , Anticoagulants/therapeutic use , Anticoagulants/adverse effects , United States/epidemiology , Administration, Oral , Ischemic Stroke/mortality , Ischemic Stroke/drug therapy , Middle Aged , Intracranial Hemorrhages/chemically induced , Intracranial Hemorrhages/mortality , Stroke/mortality , Stroke/drug therapy , Aged, 80 and over , Blood Transfusion/statistics & numerical data
17.
Vet Med Sci ; 10(4): e1448, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38818763

ABSTRACT

BACKGROUND: Recombinant intracameral tissue plasminogen activator (rTPA) administration can aid clearance of fibrin from the anterior chamber. MATERIALS AND METHODS: In this retrospective multicentre case series, the effect of intracameral rTPA administration to treat fibrin in the anterior chamber resulting from trauma or inflammatory ocular disease was evaluated. Clinical data from 30 treatments in 29 horses were obtained from medical records from 2003 to 2022. Association between time from onset of clinical signs and time for rTPA treatment to effect was studied with regression analysis. RESULTS: Twenty-seven horses (93.1%) had no previous history of ophthalmic disease; one had an iridic cyst, and another had equine recurrent uveitis. The majority of cases were related to trauma (79.3%). Median time from the onset of clinical signs to treatment was 12 h (IQR = 4-48 h). rTPA (72% 20 µg; 24% 25 µg; 3.3% 40 µg) was administered once in all but one eye, which was treated twice. Resolution of fibrin was seen in 96.9% (29/30) of treatments. Fibrin accumulation recurred in one case but resolved 14 days after the second treatment. Complications were seen in four treatments (13.3%): moderate pain for 24 h, intracameral debris and mild intracameral haemorrhage in a horse that received 40 µg of tissue plasminogen activator. Recurrence of fibrin accumulation was absent in 96.7% of cases. Median time to effect was 20 min (IQR = 10-45 min). Time for rTPA treatment to effect was not associated with time from fibrin formation (R2 = 0.09; p = 0.11). CONCLUSION: Intracameral rTPA treatment can be considered at 20-25 µg in 0.1 mL solution to aid resolution of fibrin accumulation.


Subject(s)
Anterior Chamber , Fibrin , Horse Diseases , Tissue Plasminogen Activator , Animals , Horses , Tissue Plasminogen Activator/administration & dosage , Horse Diseases/drug therapy , Retrospective Studies , Female , Male , Anterior Chamber/drug effects , Fibrinolytic Agents/pharmacology , Fibrinolytic Agents/administration & dosage , Recombinant Proteins/administration & dosage , Recombinant Proteins/therapeutic use , Eye Diseases/veterinary , Eye Diseases/drug therapy
18.
Int J Biol Macromol ; 270(Pt 1): 132278, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38750856

ABSTRACT

Leeches secrete various biologically active substances which have important medical and pharmaceutical values in antithrombotic treatments. Here, we provide a high quality genome of two Asian medicinal leeches Hirudo nipponia and Hirudo tianjinensis, based on which, we identified 22 antithrombotic gene families, including fourteen coagulation inhibitors, four platelet aggregation inhibitors, three fibrinolysis enhancers, and one tissue penetration enhancer. The total numbers of antithrombotic genes were similar between H. nipponia (N = 86) and H. tianjinensis (N = 83). Molecular evolution analysis showed that no significant differences were detected between the two species in any of the three selection indices (dN, dS, and dN/dS), nor in the number of sites under positive/purifying selection. RNA-Seq based gene expression analysis showed that the overall expression patterns of the antithrombotic gene families were not significantly deviated between the two species. Our results indicated that there were rather close similarities between the two leeches on genomic characteristics, especially for the molecular evolution and expression of antithrombotic genes. Our study provides the most comprehensive collection of antithrombotic biomacromolecules from the two Asian medicinal leeches to date. These results will greatly facilitate the research and application of leech derivatives for medical and pharmaceutical purposes of thrombosis.


Subject(s)
Fibrinolytic Agents , Genomics , Leeches , Animals , Leeches/genetics , Genomics/methods , Fibrinolytic Agents/pharmacology , Phylogeny , Evolution, Molecular , Genome
19.
BMC Neurol ; 24(1): 183, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38822243

ABSTRACT

BACKGROUND: Serum uric acid (UA) and the neutrophil-to-lymphocyte ratio (NLR) have been reported to be associated with outcomes in acute ischemic stroke (AIS). However, whether UA is related to the prognosis of AIS patients undergoing intravenous thrombolysis (IVT) remains inconclusive. We sought to explore the combined effect of UA and NLR on the prognosis of AIS treated with IVT. METHODS: A total of 555 AIS patients receiving IVT treatment were enrolled. Patients were categorized into four groups according to the levels of UA and NLR: LNNU (low NLR and normal UA), LNHU (low NLR and high UA), HNNU (high NLR and normal UA), and HNHU (high NLR and high UA). Multivariable logistic regression analysis was used to evaluate the value of serum UA level and NLR in predicting prognosis. The primary outcomes were major disability (modified Rankin scale (mRS) score 3-5) and death within 3 months. RESULTS: After multivariate adjustment, a high NLR (≥ 3.94) increased the risk of 3-month death or major disability (OR, 2.23; 95% CI, 1.42 to 3.55, p < 0.001). However, there was no statistically significant association between a high UA level (≥ 313.00 µmol/L) and clinical outcome. HNHU was associated with a 5.09-fold increase in the risk of death (OR, 5.09; 95% CI, 1.31-19.83; P value = 0.019) and a 1.98-fold increase in the risk of major disability (OR, 1.98; 95% CI 1.07-3.68; P value = 0.030) in comparison to LNNU. CONCLUSIONS: High serum UA levels combined with high NLR were independently associated with 3-month death and major disability in AIS patients after IVT.


Subject(s)
Ischemic Stroke , Lymphocytes , Neutrophils , Thrombolytic Therapy , Uric Acid , Humans , Uric Acid/blood , Female , Male , Ischemic Stroke/blood , Ischemic Stroke/drug therapy , Ischemic Stroke/diagnosis , Ischemic Stroke/mortality , Aged , Middle Aged , Thrombolytic Therapy/methods , Prognosis , Retrospective Studies , Aged, 80 and over , Administration, Intravenous , Fibrinolytic Agents/administration & dosage , Fibrinolytic Agents/therapeutic use
20.
Molecules ; 29(10)2024 May 15.
Article in English | MEDLINE | ID: mdl-38792186

ABSTRACT

Thrombotic disease has been listed as the third most fatal vascular disease in the world. After decades of development, clinical thrombolytic drugs still cannot avoid the occurrence of adverse reactions such as bleeding. A number of studies have shown that the application of various nano-functional materials in thrombus-targeted drug delivery, combined with external stimuli, such as magnetic, near-infrared light, ultrasound, etc., enrich the drugs in the thrombus site and use the properties of nano-functional materials for collaborative thrombolysis, which can effectively reduce adverse reactions such as bleeding and improve thrombolysis efficiency. In this paper, the research progress of organic nanomaterials, inorganic nanomaterials, and biomimetic nanomaterials for drug delivery is briefly reviewed.


Subject(s)
Drug Delivery Systems , Fibrinolytic Agents , Thrombosis , Humans , Fibrinolytic Agents/chemistry , Fibrinolytic Agents/therapeutic use , Fibrinolytic Agents/administration & dosage , Thrombosis/drug therapy , Nanostructures/chemistry , Nanostructures/therapeutic use , Thrombolytic Therapy/methods , Animals
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