Dual Inhibition of Factor XIIa and Factor XIa Produces a Synergistic Anticoagulant Effect.

ABSTRACT: Clinical practice shows that a critical unmet need in the field of thrombosis prevention is the availability of anticoagulant therapy without bleeding risk. Inhibitors against FXIa or FXIIa have been extensively studied because of their low bleeding risk. However, whether these compounds produce synergistic effects has not yet been explored. In this study, analyses of activated partial thromboplastin time in combination with the FXIa inhibitor PN2KPI and the FXIIa inhibitor Infestin4 at different proportions were performed using the SynergyFinder tool identifying synergistic anticoagulation effects. Both an FeCl 3 -induced carotid artery thrombosis mouse model and a transient occlusion of the middle cerebral artery mouse model showed that the combination of PN2KPI and Infestin4, which are 28.57% and 6.25% of the effective dose, respectively, significantly prevents coagulation, and furthermore, dual inhibition does not cause bleeding risk.

Anticoagulants versus Antiplatelet Treatment in the Medical Management of Carotid Floating Thrombus.

BACKGROUND: Carotid free-floating thrombus (CFT) is a rare cause of stroke describing an intraluminal thrombus that is loosely associated with the arterial wall and manifesting as a filling defect fully surrounded by flow on vascular imaging. Unfortunately, there is no clear consensus among experts on the ideal treatment for this pathology. METHODS: Retrospective analysis of acute ischemic stroke (AIS) and transient ischemic attack (TIA) patients diagnosed with CFT on computed tomography angiogram (CTA) between January 2015-March 2023. We aimed to compare two treatment regimens: anticoagulation (ACT) and antiplatelet (APT) in the treatment of CFT. APT regimens included the use of dual or single antiplatelets (DAPT or SAPT; aspirin, clopidogrel and ticagrelor) and ACT regimens included the use of direct oral anticoagulants, warfarin, heparin or low molecular weight heparin +/- ASA. Patients that underwent mechanical thrombectomy were excluded. RESULTS: During study time there were 8252 acute ischemic stroke hospitalizations, of which 135 (1.63 %) patients were diagnosed with CFT. Sixty-six patients were included in our analysis. Patients assigned to APT were older (60.41years ± 12.82;p < 0.01). Other demographic variables were similar between ACT and APT groups. Complete CFT resolution on repeat vascular imaging was numerically higher at 30 days (58.8 vs 31.6 %, respectively; p = 0.1) and at latest follow-up (70.8 vs 50 %; p = 0.1) on ACT vs APT, respectively without reaching statistical significance. Similarly, there was numerically higher rates of any ICH with ACT compared to APT but it did not achieve statistical significance (27.6 % vs 13.5 %; p = 0.5). There were similar rates of PH1/2 hemorrhagic transformation, independence at discharge and similar hospital length of stay between ACT and APT groups. Patients assigned to APT were more likely to be discharged on their assigned treatment compared to those assigned to ACT (86.5 vs 55.2 %; p < 0.001). The rate of 30-day recurrent stroke was comparable among ACT and APT at 30 days (3.4 vs 0 %; p = 0.1, respectively). Subgroup analysis comparing exclusive ACT vs Dual APT lead to similar results. CONCLUSION: Our study showed comparable efficacy and safety outcomes in CFT patients who were exclusively managed medically with ACT vs APT. Larger prospective studies are needed.

Carotid free-floating thrombus in patients with acute ischaemic stroke and active cancer.

In patients with ischaemic stroke, a carotid free-floating thrombus (CFFT) raises diagnostic and therapeutic challenges. We describe two women, each taking tamoxifen for invasive non-metastatic breast cancer, who developed large-vessel occlusion ischaemic strokes. The first had a CFFT 24 hours after receiving intravenous thrombolysis and mechanical thrombectomy; the thrombus completely resolved after 1 week of therapeutic anticoagulation. The second had a tandem occlusion with a CFFT at admission; her neurological deficits rapidly improved after intravenous thrombolysis without needing a mechanical thrombectomy. However, subsequently, under therapeutic anticoagulation, distal migration of the CFFT caused a recurrent large vessel occlusion ischaemic stroke, requiring mechanical thrombectomy. The CTFF in both cases appeared to relate to a cancer-related prothrombotic state. Both received long-term oral anticoagulation and their tamoxifen was switched to anastrozole. At 3 months, both were functionally independent without recurrent vascular events.

Unstable Carotid Artery Thrombus in a Patient With COVID-19 Infection.

We present a case of an unvaccinated, 43-year-old African American female patient with COVID-19 infection and clinical evidence of a left hemispheric stroke. A non-occlusive thrombus with a radiographic target lesion was identified on computed tomography angiography (CTA). A multi-disciplinary discussion regarding concern for embolization was provided due to its unstable nature, as well as evidence of recent stroke. Given her acute COVID-19 infection, symptomatology, and radiographic findings, it was concluded that the etiology of her stroke appeared most consistent with a hypercoagulable-related embolism rather than an atheroembolic event. The patient underwent left carotid artery thrombectomy with bovine patch angioplasty. Operative findings included: left carotid thrombus, minimal plaque after evacuation of the thrombus, and a small proximal internal carotid artery diameter. Given concern for stenosis with primary repair a bovine pericardial patch angioplasty was performed. We present a paradigm for extracranial carotid thrombectomy with therapeutic anticoagulation for COVID-related spontaneous arterial thrombosis.

The extent of awareness of southern Jordanian people to thedifference between venous thrombosis and arterial thrombosis / El grado de concienciación de los habitantes del sur de Jordania sobre la diferencia entre trombosis venosa y trombosis arterial

Objective: Venous thrombosis (VTE) and arterial thrombosis are two different diseases. Although they differ in causes, types, and treatment, they share many risk factors. Many people are not able to differentiate between them. So assessing the awareness of people toward these two diseases and determining the variables that affect their awareness was the aim of the study. Methods: This is a cross-sectional validated questionnaire which was conducted on social media. It targeted the southern Jordanian public above 18 years between October and December 2022. Results: A total of 630 people participated in the current study. Only 42.2% knew the cause of arterial thrombosis compared to 58.7% in case of venous thrombosis. More than half (63.2%) of the participants knew that there is a difference between venous and arterial thrombosis. DVT (36.8%) and PE (23%) were correctly identified as types of VTE, while only myocardial infarction was identified as a type of arterial thrombosis by 52.2% of respondents. About 69.5% and 80.2% of respondents think that venous and arterial thrombosis are fatal, respectively. Regarding the socio-demographic variables that affect the awareness of the public, old age, high educational level, working, and earning at least 500 JD per month were significantly associated with better awareness of the study population about venous and arterial thrombosis with a p-value of 0.0027, < 0.001, 0.0017, and < 0.001 respectively. Conclusion: The current study reveals that there is a lack of awareness about VTE and arterial thrombosis and the difference between them among the southern Jordanian public. VTE and arterial thrombosis are preventable diseases, so more attention should be given by increasing the educational campaign and the initiatives of public health about the difference between them in terms of signs and symptoms, risk factors, and complications.(AU)

Alta frecuencia de trombo endoluminal en pacientes con ictus isquémico tras la infección por coronavirus 2019 / High frequency of endoluminal thrombus in patients with ischaemic stroke following SARS-CoV-2 infection

Introducción El ictus isquémico puede ser una complicación grave en los pacientes con infección por SARS-CoV-2. Estudiar y caracterizar los diferentes subtipos etiológicos, las características clínicas y el pronóstico funcional podrá resultar útil en la selección de pacientes para un manejo y tratamiento óptimos. Métodos La recogida de variables se hizo de forma retrospectiva en pacientes consecutivos con infección por SARS-CoV-2 que desarrollaron un episodio de isquemia cerebral focal (entre el 1 de marzo del 2020 y el 19 de abril del 2020). Se llevó a cabo en un hospital universitario de tercer nivel en la Comunidad de Madrid (España). Resultados Durante el período de estudio 1.594 pacientes fueron diagnosticados de infección por SARS-CoV-2. Identificamos a 22 pacientes con ictus isquémico (1,38%); de estos, no cumplieron los criterios de inclusión 6. Un total de 16 pacientes con isquemia cerebral focal constituyeron la serie del estudio (15 con ictus isquémico y uno con accidente isquémico transitorio). En la valoración basal en el National Institutes of Health Stroke Scale la mediana fue de 9 (rango intercuartil: 16), la edad media ± desviación estándar fue de 73 ± 12,8 años; 12 pacientes fueron varones (75%). El tiempo desde los síntomas de COVID-19 hasta el ictus fue de 13 días. Se encontró oclusión de gran vaso en 12 pacientes (75%). El dímero-D estuvo elevado en el 87,5% y la proteína C reactiva en el 81,2% de los casos. La etiología más frecuente del ictus isquémico fue la aterotrombosis (9 pacientes, 56,3%) con un subtipo predominante que fue el trombo endoluminal sobre placa de ateroma (5 pacientes, 31,2%), 4 de ellos en la arteria carótida interna y uno de ellos en el arco aórtico. La mortalidad en nuestra serie fue del 44% (7 de 16 pacientes). Conclusiones En los pacientes con ictus y COVID-19 la etiología más frecuente fue la aterotrombótica, con una elevada frecuencia de trombo endoluminal sobre placa de ateroma... (AU)

Background Ischaemic stroke may be a major complication of SARS-CoV-2 infection. Studying and characterising the different aetiological subtypes, clinical characteristics, and functional outcomes may be valuable in guiding patient selection for optimal management and treatment. Methods Data were collected retrospectively on consecutive patients with SARS-CoV-2 infection who developed acute focal brain ischaemia (between 1 March and 19 April 2020) at a tertiary university hospital in Madrid (Spain). Results During the study period, 1594 patients were diagnosed with COVID-19. We found 22 patients with ischaemic stroke (1.38%), 6 of whom did not meet the inclusion criteria. The remaining 16 patients were included in the study (15 cases of ischaemic stroke and one case of transient ischaemic attack). Median baseline National Institutes of Health Stroke Scale score was 9 (interquartile range: 16), and mean (standard deviation) age was 73 years (12.8). Twelve patients (75%) were men. Mean time from COVID-19 symptom onset to stroke onset was 13 days. Large vessel occlusion was identified in 12 patients (75%). We detected elevated levels of D-dimer in 87.5% of patients and C-reactive protein in 81.2%. The main aetiology was atherothrombotic stroke (9 patients, 56.3%), with the predominant subtype being endoluminal thrombus (5 patients, 31.2%), involving the internal carotid artery in 4 cases and the aortic arch in one. The mortality rate in our series was 44% (7 of 16 patients). Conclusions In patients with COVID-19, the most frequent stroke aetiology was atherothrombosis, with a high proportion of endoluminal thrombus (31.2% of patients). Our clinical and laboratory data support COVID-19–associated coagulopathy as a relevant pathophysiological mechanism for ischaemic stroke in these patients. (AU)

Alta frecuencia de trombo endoluminal en pacientes con ictus isquémico tras la infección por coronavirus 2019 / High frequency of endoluminal thrombus in patients with ischaemic stroke following SARS-CoV-2 infection

Introducción El ictus isquémico puede ser una complicación grave en los pacientes con infección por SARS-CoV-2. Estudiar y caracterizar los diferentes subtipos etiológicos, las características clínicas y el pronóstico funcional podrá resultar útil en la selección de pacientes para un manejo y tratamiento óptimos. Métodos La recogida de variables se hizo de forma retrospectiva en pacientes consecutivos con infección por SARS-CoV-2 que desarrollaron un episodio de isquemia cerebral focal (entre el 1 de marzo del 2020 y el 19 de abril del 2020). Se llevó a cabo en un hospital universitario de tercer nivel en la Comunidad de Madrid (España). Resultados Durante el período de estudio 1.594 pacientes fueron diagnosticados de infección por SARS-CoV-2. Identificamos a 22 pacientes con ictus isquémico (1,38%); de estos, no cumplieron los criterios de inclusión 6. Un total de 16 pacientes con isquemia cerebral focal constituyeron la serie del estudio (15 con ictus isquémico y uno con accidente isquémico transitorio). En la valoración basal en el National Institutes of Health Stroke Scale la mediana fue de 9 (rango intercuartil: 16), la edad media ± desviación estándar fue de 73 ± 12,8 años; 12 pacientes fueron varones (75%). El tiempo desde los síntomas de COVID-19 hasta el ictus fue de 13 días. Se encontró oclusión de gran vaso en 12 pacientes (75%). El dímero-D estuvo elevado en el 87,5% y la proteína C reactiva en el 81,2% de los casos. La etiología más frecuente del ictus isquémico fue la aterotrombosis (9 pacientes, 56,3%) con un subtipo predominante que fue el trombo endoluminal sobre placa de ateroma (5 pacientes, 31,2%), 4 de ellos en la arteria carótida interna y uno de ellos en el arco aórtico. La mortalidad en nuestra serie fue del 44% (7 de 16 pacientes). Conclusiones En los pacientes con ictus y COVID-19 la etiología más frecuente fue la aterotrombótica, con una elevada frecuencia de trombo endoluminal sobre placa de ateroma... (AU)

Background Ischaemic stroke may be a major complication of SARS-CoV-2 infection. Studying and characterising the different aetiological subtypes, clinical characteristics, and functional outcomes may be valuable in guiding patient selection for optimal management and treatment. Methods Data were collected retrospectively on consecutive patients with SARS-CoV-2 infection who developed acute focal brain ischaemia (between 1 March and 19 April 2020) at a tertiary university hospital in Madrid (Spain). Results During the study period, 1594 patients were diagnosed with COVID-19. We found 22 patients with ischaemic stroke (1.38%), 6 of whom did not meet the inclusion criteria. The remaining 16 patients were included in the study (15 cases of ischaemic stroke and one case of transient ischaemic attack). Median baseline National Institutes of Health Stroke Scale score was 9 (interquartile range: 16), and mean (standard deviation) age was 73 years (12.8). Twelve patients (75%) were men. Mean time from COVID-19 symptom onset to stroke onset was 13 days. Large vessel occlusion was identified in 12 patients (75%). We detected elevated levels of D-dimer in 87.5% of patients and C-reactive protein in 81.2%. The main aetiology was atherothrombotic stroke (9 patients, 56.3%), with the predominant subtype being endoluminal thrombus (5 patients, 31.2%), involving the internal carotid artery in 4 cases and the aortic arch in one. The mortality rate in our series was 44% (7 of 16 patients). Conclusions In patients with COVID-19, the most frequent stroke aetiology was atherothrombosis, with a high proportion of endoluminal thrombus (31.2% of patients). Our clinical and laboratory data support COVID-19–associated coagulopathy as a relevant pathophysiological mechanism for ischaemic stroke in these patients. (AU)

Endovascular Thrombectomy for a Progressive Stroke Patient With a High-Burden Carotid Free-Floating Thrombus.

Carotid free-floating thrombus (FFT) is a rare cause of acute ischemic events. The optimal management of carotid FFT remains unclear. The optimal and individualized management of carotid FFT should be determined based on the underlying etiology, clinical manifestation, and imaging characteristics. we reported a case with endovascular thrombectomy for a progressive stroke patient with a high-burden carotid free-floating thrombus. ANN NEUROL 2024;95:362-364.

High Contrast Detection of Carotid Neothrombus with Strong Near-Infrared Absorption Selenium Nanosphere Enhanced Photoacoustic Imaging.

Background: Carotid artery thrombosis is the leading cause of stroke. Since there are no apparent symptoms in the early stages of carotid atherosclerosis onset, it causes a more significant clinical diagnosis. Photoacoustic (PA) imaging provides high contrast and good depth information, which has been used for the early detection and diagnosis of many diseases. Methods: We investigated thrombus formation by using 20% ferric chloride (FeCl3) in the carotid arteries of KM mice for the thrombosis model. The near-infrared selenium/polypyrrole (Se@PPy) nanomaterials are easy to synthesize and have excellent optical absorption in vivo, which can be used as PA contrast agents to obtain thrombosis information. Results: In vitro experiments showed that Se@PPy nanocomposites have fulfilling PA ability in the 700 nm to 900 nm wavelength range. In the carotid atherosclerosis model, maximum PA signal enhancement up to 3.44, 4.04, and 5.07 times was observed by injection of Se@PPy nanomaterials, which helped to diagnose the severity of carotid atherosclerosis. Conclusion: The superior PA signal of Se@PPy nanomaterials can identify the extent of atherosclerotic carotid lesions, demonstrating the feasibility of PA imaging technology in diagnosing carotid thrombosis lesion formation. This study demonstrates nanocomposites and PA techniques for imaging and diagnosing carotid thrombosis in vivo.

Nanoassemblies of Self-Immolative Boronate-Bridged Retinoic Acid Dimeric Prodrug as a Clot-Targeted Self-Deliverable Antithrombotic Nanomedicine.

All trans-retinoic acid (atRA) has potent anti-inflammatory and antiplatelet activity, but its clinical translation as an antithrombotic drug has been hampered by its low therapeutic efficacy. Here, we describe a facile and elegant strategy that converts atRA into systemically injectable antithrombotic nanoparticles. The strategy involves the dimerization of two atRA molecules using a self-immolative boronate linker that is cleaved specifically by hydrogen peroxide (H2O2) to release anti-inflammatory hydroxybenzyl alcohol (HBA), followed by dimerization-induced self-assembly to generate colloidally stable nanoparticles. The boronated atRA dimeric prodrug (BRDP) could form injectable nanoparticles in the presence of fucoidan that serves as an emulsifier and a targeting ligand to P-selectin overexpressed on the damaged endothelium. In response to H2O2, fucoidan-decorated BRDP (f-BRDP) nanoassemblies dissociate to release both atRA and HBA, while scavenging H2O2. In a mouse model of ferric chloride (FeCl3)-induced carotid arterial thrombosis, f-BRDP nanoassemblies target the thrombosed vessel and significantly inhibit thrombus formation. The results demonstrate that dimerization of atRA molecules via a boronate linker enables the formation of stable nanoassemblies with several benefits: high drug loading, drug self-delivery, on-demand multiple antithrombotic actions, and simple fabrication of nanoparticles. Overall, this strategy provides a promising expedient and practical route for the development of translational self-deliverable antithrombotic nanomedicine.

Intravenously administered APAC, a dual AntiPlatelet AntiCoagulant, targets arterial injury site to inhibit platelet thrombus formation and tissue factor activity in mice.

INTRODUCTION: Arterial thrombosis is the main underlying mechanism of acute atherothrombosis. Combined antiplatelet and anticoagulant regimens prevent thrombosis but increase bleeding rates. Mast cell-derived heparin proteoglycans have local antithrombotic properties, and their semisynthetic dual AntiPlatelet and AntiCoagulant (APAC) mimetic may provide a new efficacious and safe tool for arterial thrombosis. We investigated the in vivo impact of intravenous APAC (0.3-0.5 mg/kg; doses chosen according to pharmacokinetic studies) in two mouse models of arterial thrombosis and the in vitro actions in mouse platelets and plasma. MATERIALS AND METHODS: Platelet function and coagulation were studied with light transmission aggregometry and clotting times. Carotid arterial thrombosis was induced either by photochemical injury or surgically exposing vascular collagen after infusion of APAC, UFH or vehicle. Time to occlusion, targeting of APAC to the vascular injury site and platelet deposition on these sites were assessed by intra-vital imaging. Tissue factor activity (TF) of the carotid artery and in plasma was captured. RESULTS: APAC inhibited platelet responsiveness to agonist stimulation (collagen and ADP) and prolonged APTT and thrombin time. After photochemical carotid injury, APAC-treatment prolonged times to occlusion in comparison with UFH or vehicle, and decreased TF both in carotid lysates and plasma. Upon binding from circulation to vascular collagen-exposing injury sites, APAC reduced the in situ platelet deposition. CONCLUSIONS: Intravenous APAC targets arterial injury sites to exert local dual antiplatelet and anticoagulant actions and attenuates thrombosis upon carotid injuries in mice. Systemic APAC provides local efficacy, highlighting APAC as a novel antithrombotic to reduce cardiovascular complications.

CTSS Modulates Stress-Related Carotid Artery Thrombosis in a Mouse FeCl3 Model.

BACKGROUND: Exposure to chronic psychological stress is a risk factor for metabolic cardiovascular disease. Given the important role of lysosomal CTSS (cathepsin S) in human pathobiology, we examined the role of CTSS in stress-related thrombosis, focusing on inflammation, oxidative stress, and apoptosis. METHODS: Six-week-old wild-type mice (CTSS+/+) and CTSS-deficient mice (CTSS-/-) randomly assigned to nonstress and 2-week immobilization stress groups underwent iron chloride3 (FeCl3)-induced carotid thrombosis surgery for morphological and biochemical studies. RESULTS: On day 14 poststress/surgery, stress had increased the lengths and weights of thrombi in the CTSS+/+ mice, plus harmful changes in the levels of PAI-1 (plasminogen activation inhibitor-1), ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 13 motifs), and vWF (von Willebrand factor) and arterial tissue CTSS expression. Compared to the nonstressed CTSS+/+ mice, the stressed CTSS-/- mice had decreased levels of PAI-1, vWF, TNF (tumor necrosis factor)-α, interleukin-1ß, toll-like receptor-4, cleaved-caspase 3, cytochrome c, p16INK4A, gp91phox, p22phox, ICAM-1 (intercellular adhesion molecule-1), MCP-1 (monocyte chemoattractant protein-1), MyD88 (myeloid differentiation primary response 88), and MMP (matrix metalloproteinase)-2/-9 and increased levels of ADAMTS13, SOD (superoxide dismutase)-1/-2, eNOS (endothelial NO synthase), p-Akt (phospho-protein kinase B), Bcl-2 (B-cell lymphoma-2), p-GSK3α/ß (phospho-glycogen synthase kinases alpha and beta), and p-Erk1/2 (phospho-extracellular signal-regulated kinase 1 and 2) mRNAs and/or proteins. CTSS deletion also reduced the arterial thrombus area and endothelial loss. A pharmacological inhibition of CTSS exerted a vasculoprotective action. In vitro, CTSS silencing and overexpression, respectively, reduced and increased the stressed serum and oxidative stress-induced apoptosis of human umbilical vein endothelial cells, and they altered apoptosis-related proteins. CONCLUSIONS: CTSS inhibition appeared to improve the stress-related thrombosis in mice that underwent FeCl3-induction surgery, possibly by reducing vascular inflammation, oxidative stress, and apoptosis. CTSS could thus become a candidate therapeutic target for chronic psychological stress-related thrombotic events in metabolic cardiovascular disease.

An elderly case with late carotid stent thrombosis: possible role of antiphospholipid antibodies.

The case study speculates that the antiphospholipid antibodies acquired during the follow-up period of carotid artery stenting may cause late stent thrombosis that is resistant to direct oral anticoagulants. A 73-year-old man was hospitalized with complaints of weakness in the right lower extremity. The patient had undergone carotid artery stenting for symptomatic stenosis of the left internal carotid artery 6 years prior and had received antiplatelet therapy with clopidogrel 75 mg/day. As the patient had developed atrial fibrillation without stent stenosis at the age of 70 years, anticoagulation therapy with rivaroxaban15 mg/day was initiated while discontinuing clopidogrel. On admission, diffusion weighted imaging (DWI) revealed acute brain infarcts in the territory of the left middle cerebral artery. Contrast-enhanced computed tomography and cerebral angiography exposed severe stenosis in the left carotid artery accompanied by a filling defect caused by a floating thrombus. Laboratory examination revealed the presence of three types of antiphospholipid antibodies, with marked prolongation of activated partial thromboplastin time (APTT). Replacement of rivaroxaban with warfarin eliminated the thrombus without recurrent stroke. In conclusion, late stent thrombosis may be associated with antiphospholipid antibodies acquired during the follow-up period of carotid artery stenting.

Activated Coagulation FXII: A Unique Target for In Vivo Molecular Imaging.

BACKGROUND: Current clinical imaging of thromboembolic diseases often relies on indirect detection of thrombi, which may delay diagnosis and ultimately the institution of beneficial, potentially lifesaving treatment. Therefore, the development of targeting tools that facilitate the rapid, specific, and direct imaging of thrombi using molecular imaging is highly sought after. One potential molecular target is FXIIa (factor XIIa), which initiates the intrinsic coagulation pathway but also activates the kallikrein-kinin system, thereby initiating coagulation and inflammatory/immune responses. As FXII (factor XII) is dispensable for normal hemostasis, its activated form (FXIIa) represents an ideal molecular target for diagnostic and therapeutic approaches, the latter combining diagnosis/identification of thrombi and effective antithrombotic therapy. METHODS: We conjugated an FXIIa-specific antibody, 3F7, to a near-infrared (NIR) fluorophore and demonstrated binding to FeCl3-induced carotid thrombosis with 3-dimensional fluorescence emission computed tomography/computed tomography and 2-dimensional fluorescence imaging. We further demonstrated ex vivo imaging of thromboplastin-induced pulmonary embolism and detection of FXIIa in human thrombi produced in vitro. RESULTS: We demonstrated imaging of carotid thrombosis by fluorescence emission computed tomography/computed tomography and measured a significant fold increase in signal between healthy and control vessels from mice injected with 3F7-NIR compared with mice injected with nontargeted probe (P=0.002) ex vivo. In a model of pulmonary embolism, we measured increased NIR signal in lungs from mice injected with 3F7-NIR compared with mice injected with nontargeted probe (P=0.0008) and healthy lungs from mice injected with 3F7-NIR (P=0.021). CONCLUSIONS: Overall, we demonstrate that FXIIa targeting is highly suitable for the specific detection of venous and arterial thrombi. This approach will allow direct, specific, and early imaging of thrombosis in preclinical imaging modalities and may facilitate monitoring of antithrombotic treatment in vivo.

QiShen YiQi and its components attenuate acute thromboembolic stroke and carotid thrombosis by inhibition of CD62P/PSGL-1-mediated platelet-leukocyte aggregate formation.

BACKGROUND: QiShen YiQi (QSYQ) dropping pill, a component-based Chinese medicine consisting of benefiting Qi (YQ) and activating blood (HX) components, has been reported to exert a beneficial effect on cerebral ischemia-induced stroke. However, its efficacy and pharmacological mechanism on acute thromboembolic stroke is not clear. PURPOSE: This study is to explore the preventative effect and pharmacological mechanism of QSYQ and its YQ/HX components on the formation of platelet-leukocyte aggregation (PLA) in acute thromboembolic stroke. STUDY DESIGN AND METHODS: In vivo thromboembolic stroke model and FeCl3-induced carotid arterial occlusion models were used. Immunohistochemistry, Western blot, RT-qPCR, and flow cytometry experiments were performed to reveal the pharmacological mechanisms of QSYQ and its YQ/HX components. RESULTS: In thromboembolic stroke rats, QSYQ significantly attenuated infarct area, improved neurological recovery, reduced PLA formation, and inhibited P-selection (CD62P)/ P-selectin glycoprotein ligand-1 (PSGL-1) expressions. The YQ component preferentially down-regulated PSGL-1 expression in leukocyte, while the HX component preferentially down-regulated CD62P expression in platelet. In carotid arterial thrombosis mice, QSYQ and its YQ/HX components inhibited thrombus formation, prolonged vessel occlusion time, reduced circulating leukocytes and P-selectin expression. PLA formation and platelet/leukocyte adhesion to endothelial cell were also inhibited by QSYQ and its YQ/HX components in vitro. CONCLUSION: QSYQ and YQ/HX components attenuated thromboembolic stroke and carotid thrombosis by decreasing PLA formation via inhibiting CD62P/PSGL-1 expressions. This study shed a new light on the prevention of thromboembolic stroke.

Carotid endarterectomy with saphenous vein patch angioplasty: a single-center experience.

BACKGROUND: When performing a conventional CEA it is recommended the use of patch angioplasty (PA), since previous meta-analyses have shown PA to be superior to primary closure (PRC) in terms of stroke and restenosis rates. Different materials patches can be employed although none of them has been proved to be superior. Although autologous veins are potentially more resistant to immediate thrombosis as well as infection, cons may be represented by patch rupture and late dilatation. Aim of this study is to evaluate immediate and long-term results of CEA with saphenous vein patch angioplasty (SVPA) in a single-center experience. METHODS: A retrospective study was performed analyzing all patients undergoing CEA with SVPA at our institution from January 2012 to March 2020. CEA was performed in symptomatic patients with 50-99% carotid stenosis degree or asymptomatic patients with 70-99% stenosis degree. Exclusion criteria were critical limb ischemia, varicose disease, unavailability of saphenous veins, vein diameter <3.5 mm. All CEAs were performed under general anesthesia with routine shunting. Primary endpoints were perioperative stroke, death, carotid thrombosis and hematoma requiring surgery rates. Secondary endpoints included the rate of recurrent stenosis >70%, patch aneurysm/rupture/infection at follow-up. RESULTS: Overall, 488 interventions were performed on 461 patients. Most patients were male (77.8%) with a mean age of 71.2±8.3 years. Thirty-day mortality and stroke rates were 0.4% and 1.2% respectively. Carotid thrombosis occurred in five patients (1%). Five patients (1%) developed a surgical site hematoma requiring surgical drainage. At a mean follow-up of 34.4±25.8 months 12 restenoses (2.5%) were detected. Five-year freedom from restenosis rate was 96.7%. Restenosis at follow-up was more frequent in patients who had contralateral carotid stenosis (P=0.019). Two patients (0.4%) developed carotid patch aneurysmal degeneration at a mean follow-up of 78.7 months. No infection nor patch disruption were detected. CONCLUSIONS: CEA with SVPA resulted safe and effective in terms of early and late results. The perioperative complications rates we recorded were quite similar to those reported by other larger reviews and meta-analyses.

Exclusively Posterior Circulation Stroke Caused by Internal Carotid Artery Thrombosis.

A fetal posterior cerebral artery (FPCA) is an anatomic variant in which the posterior cerebral artery (PCA) is an embryological derivative of the internal carotid artery (ICA). Patients with FPCA may experience posterior circulation stroke (PCS) after a thrombotic event in the ICA system, while exclusively PCS caused by thrombosis of the ICA has rarely been reported. We report a patient with FPCA and summarize 3 types of exclusively PCS caused by FPCA due to thrombotic events in the ICA system. Type A: the thrombus involves the opening of the FPCA and obstructs the blood flow of the entire ICA. The contralateral ICA compensates the ipsilateral middle cerebral artery (MCA) and anterior cerebral artery (ACA) through the anterior communicating artery (ACOM). Type B: the thrombus involves the opening of the FPCA but does not block the blood flow of the entire ICA, which still perfuses the ipsilateral ACA and MCA. Type C: the thrombus only involves the FPCA and not the ipsilateral ICA. Patients with types A and B may obtain a good prognosis through endovascular treatment (EVT), while the benefits of this procedure in type C patients are unclear.

Petrous Carotid Artery Thrombosis in an Immunocompromised Patient Presenting With Mastoiditis, A Case Report.

OBJECTIVES: The neurotologic literature commonly describes venous sinus thrombosis as a complication of mastoiditis. However, thrombosis of the internal carotid artery in the setting of mastoiditis is rarely described. We aim to document a case of carotid artery thrombosis in a patient presenting with mastoiditis. METHODS: We describe this case and review relevant literature. RESULTS: A renal transplant patient was transferred to our hospital with a left middle cerebral artery (MCA) infarct due to acute mastoiditis. Examination demonstrated middle ear effusion and radiologic workup confirmed mastoid infection adjacent to the site of arterial thrombosis. During cortical mastoidectomy and facial recess approach to the middle ear, the petrous carotid bone was found to be dehiscent with pneumatization of the petrous apex. Thrombosis was found to resolve following surgery, IV antibiotics and anticoagulation. Clinically, his focal neurological deficits improved. Proximity of the infectious process to an exposed petrous carotid artery supports the hypothesis that this patient's thrombus was a product of infectious spread and extra-luminal compression. CONCLUSION: To our knowledge, this is the first report of MCA infarction due to petrous ICA arterial thrombus in the setting of mastoid infection. The patient's immunocompromised state may have predisposed and contributed to the adverse outcome. We advocate for aggressive management of acute mastoiditis in the immunocompromised to prevent or manage complications (such as venous thrombophlebitis as well as ICA thrombus) as these patients don't show typical signs of infection and inflammation.