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Neurology(R) Neuroimmunology &... Jul 2023Vaccine-induced immune thrombotic thrombocytopenia (VITT), a recently described entity characterized by thrombosis at unusual locations such as cerebral venous sinus and...
OBJECTIVES
Vaccine-induced immune thrombotic thrombocytopenia (VITT), a recently described entity characterized by thrombosis at unusual locations such as cerebral venous sinus and splanchnic vein, has been rarely described after adenoviral-encoded COVID-19 vaccines. In this study, we report the immunohistological correlates in 3 fatal cases of cerebral venous thrombosis related to VITT analyzed at an academic medical center.
METHODS
Detailed neuropathologic studies were performed in 3 cases of cerebral venous thrombosis related to VITT after adenoviral COVID-19 vaccination.
RESULTS
Autopsy revealed extensive cerebral vein thrombosis in all 3 cases. Polarized thrombi were observed with a high density of neutrophils in the core and a low density in the tail. Endothelial cells adjacent to the thrombus were largely destroyed. Markers of neutrophil extracellular trap and complement activation were present at the border and within the cerebral vein thrombi. SARS-CoV-2 spike protein was detected within the thrombus and in the adjacent vessel wall.
DISCUSSION
Data indicate that neutrophils and complement activation associated with antispike immunity triggered by the vaccine is probably involved in the disease process.
Topics: Humans; COVID-19 Vaccines; Endothelial Cells; COVID-19; SARS-CoV-2; Thrombocytopenia; Vaccines; Thrombosis; Venous Thrombosis
PubMed: 37236806
DOI: 10.1212/NXI.0000000000200127 -
CNS Neuroscience & Therapeutics Sep 2023Cerebral venous thrombosis (CVT) is a special cerebrovascular disease that accounts for around 0.5%-1.0% of all strokes and often occurs in younger adults. Intracranial...
BACKGROUND AND PURPOSE
Cerebral venous thrombosis (CVT) is a special cerebrovascular disease that accounts for around 0.5%-1.0% of all strokes and often occurs in younger adults. Intracranial hypertension is the most frequent symptom of acute CVT due to venous occlusion. This study aimed to ascertain the risk factors for intracranial hypertension after CVT and to investigate whether intracranial hypertension at diagnosis may affect patient outcomes.
METHODS
We performed a retrospective cohort analysis of all patients treated for acute/subacute CVT at our department between 2018 and 2021. Logistic regression analysis was performed to identify potential risk factors associated with intracranial hypertension after CVT and clinical outcomes at the 6-month follow-up.
RESULTS
A total of 293 acute/subacute CVT survivors were eligible for inclusion, with 245 patients (83.60%) experiencing concomitant intracranial hypertension at diagnosis. In the multivariable regression analysis, hereditary thrombophilia (OR 2.210, 95% CI 1.148-4.254, p = 0.018) and thrombosis location of superior sagittal sinus (SSS) and right lateral sinus (LS) (OR 4.115, 95% CI 1.880-9.010, p = 0.000) were independently associated with intracranial hypertension. 83.67% of patients with intracranial hypertension after CVT had favorable functional outcomes (mRS score, 0-2), whereas they more often had residual visual impairment (15.51% vs. 4.17%, p = 0.036) at follow-up. The risk factors for residual visual impairment were papilledema (OR 2.971, 95% CI 1.231-7.170, p = 0.015) and visual disturbances at diagnosis (OR 2.869, 95% CI 1.123-7.327, p = 0.028), thrombosis location (SSS and right LS [OR 10.811, 95% CI 4.208-27.773, p = 0.000]; SSS and left LS [OR 3.139, 95% CI 1.409-6.995, p = 0.005]), and CVT recurrence (OR 4.763, 95% CI 1.556-14.584, p = 0.006).
CONCLUSIONS
Intracranial hypertension is the most common clinical symptom of acute CVT. At follow-up, patients with intracranial hypertension after CVT were more prone to develop residual visual impairment.
Topics: Adult; Humans; Retrospective Studies; Venous Thrombosis; Risk Factors; Intracranial Thrombosis; Intracranial Hypertension; Sinus Thrombosis, Intracranial
PubMed: 36987606
DOI: 10.1111/cns.14194 -
Environmental Pollution (Barking, Essex... Aug 2023Air pollution is a major contributor to the global burden of disease and has been linked to several diseases and conditions, including cardiovascular disease. The...
Air pollution is a major contributor to the global burden of disease and has been linked to several diseases and conditions, including cardiovascular disease. The biological mechanisms are related to inflammation and increased coagulability, factors that play an important role in the pathogenesis of venous thromboembolism (VTE, i.e., deep vein thrombosis or pulmonary embolism). This study investigates if long-term exposure to air pollution is associated with increased VTE incidence. The study followed 29 408 participants from the Malmö Diet and Cancer (MDC) cohort, which consists of adults aged 44-74 recruited in Malmö, Sweden between 1991 and 1996. For each participant, annual mean residential exposures to particulate matter <2.5 μg (PM) and <10 μg (PM), nitrogen oxides (NO) and black carbon (BC) from 1990 up to 2016 were calculated. Associations with VTE were analysed using Cox proportional hazard models for air pollution in the year of the VTE event (lag0) and the mean of the prior 1-10 years (lag1-10). Annual air pollution exposures for the full follow-up period had the following means: 10.8 μg/m for PM, 15.8 μg/m for PM, 27.7 μg/m for NO, and 0.96 μg/m for BC. The mean follow-up period was 19.5 years, with 1418 incident VTE events recorded during this period. Exposure to lag1-10 PM was associated with an increased risk of VTE (HR 1.17 (95%CI 1.01-1.37)) per interquartile range (IQR) of 1.2 μg/m increase in PM exposure. No significant associations were found between other pollutants or lag0 PM and incident VTE. When VTE was divided into specific diagnoses, associations with lag1-10 PM exposure were similarly positive for deep vein thrombosis but not for pulmonary embolism. Results persisted in sensitivity analyses and in multi-pollutant models. Long-term exposure to moderate concentrations of ambient PM was associated with increased risks of VTE in the general population in Sweden.
Topics: Adult; Humans; Sweden; Venous Thromboembolism; Air Pollutants; Environmental Exposure; Air Pollution; Particulate Matter; Environmental Pollutants; Pulmonary Embolism; Venous Thrombosis
PubMed: 37209899
DOI: 10.1016/j.envpol.2023.121841 -
CNS Neuroscience & Therapeutics Oct 2023Cerebral venous thrombosis, a rare stroke, is characterized by neurological dysfunction caused by bleeding and/or infarction resulting from venous sinus thrombosis, the... (Review)
Review
BACKGROUND
Cerebral venous thrombosis, a rare stroke, is characterized by neurological dysfunction caused by bleeding and/or infarction resulting from venous sinus thrombosis, the so-called venous stroke. Current guidelines recommend anticoagulants as first-line therapy in the treatment of venous stroke. With complicated causes of cerebral venous thrombosis, treatment is difficult, especially when combined with autoimmune diseases, blood diseases, and even COVID-19.
AIMS
This review summarizes the pathophysiological mechanisms, epidemiology, diagnosis, treatment, and clinical prognosis of cerebral venous thrombosis combined with autoimmune diseases, blood diseases, or infectious diseases such as COVID-19.
CONCLUSION
A systematic understanding of particular risk factors that should not be neglected when unconventional cerebral venous thrombosis occurs and for a scientific understanding of pathophysiological mechanisms, clinical diagnosis, and treatment, thus contributing to knowledge on special types of venous stroke.
Topics: Humans; COVID-19; Anticoagulants; Stroke; Intracranial Thrombosis; Venous Thrombosis; Autoimmune Diseases; Sinus Thrombosis, Intracranial
PubMed: 37365966
DOI: 10.1111/cns.14321 -
Blood Advances Aug 2023Patients with cancer have an increased risk of developing venous thromboembolism (VTE), and this combination is reported to result in poorer survival compared with...
Patients with cancer have an increased risk of developing venous thromboembolism (VTE), and this combination is reported to result in poorer survival compared with cancer alone. This study aimed to investigate the impact of VTE on the survival of patients with cancer in a general population. The Scandinavian Thrombosis and Cancer (STAC) cohort, a population-based cohort including 144 952 participants without previous VTE or cancer, was used. During follow-up, cancer and VTE incidences were registered. "Cancer-related VTE" was defined as VTE diagnosed in patients with overt or occult cancer. The survival of participants without cancer and/or VTE ("disease-free") was compared with the survival of participants with cancer and cancer-related VTE. Cox regression models with cancer and VTE as time-varying exposures were performed to calculate hazard ratios for death. Subanalyses were performed across cancer types and stages and VTE type (deep vein thrombosis or pulmonary embolism). During follow-up (mean, 11.7 years), 14 621 participants developed cancer, and 2444 developed VTE, of which 1241 were cancer-related. The mortality rates (per 100 person years) for disease-free participants, VTE only, cancer only, and cancer-related VTE were 0.63, 5.0, 9.2, and 45.3, respectively. Compared with patients with cancer only, the risk of death for patients with cancer-related VTE was increased 3.4-fold. Within all cancer types, the occurrence of VTE increased the mortality risk 2.8- to 14.7-fold. In a general population, patients with cancer with VTE had a 3.4-fold higher mortality risk than patients with cancer without VTE, independent of cancer type.
Topics: Humans; Venous Thromboembolism; Risk Factors; Venous Thrombosis; Neoplasms; Pulmonary Embolism
PubMed: 37013958
DOI: 10.1182/bloodadvances.2022009577 -
Neuro-oncology Aug 2023Patients with diffuse glioma are at high risk of developing venous thromboembolism (VTE) over the course of the disease, with up to 30% incidence in patients with...
Patients with diffuse glioma are at high risk of developing venous thromboembolism (VTE) over the course of the disease, with up to 30% incidence in patients with glioblastoma (GBM) and a lower but nonnegligible risk in lower-grade gliomas. Recent and ongoing efforts to identify clinical and laboratory biomarkers of patients at increased risk offer promise, but to date, there is no proven role for prophylaxis outside of the perioperative period. Emerging data suggest a higher risk of VTE in patients with isocitrate dehydrogenase (IDH) wild-type glioma and the potential mechanistic role of IDH mutation in the suppression of production of the procoagulants tissue factor and podoplanin. According to published guidelines, therapeutic anticoagulation with low molecular weight heparin (LMWH) or alternatively, direct oral anticoagulants (DOACs) in patients without increased risk of gastrointestinal or genitourinary bleeding is recommended for VTE treatment. Due to the elevated risk of intracranial hemorrhage (ICH) in GBM, anticoagulation treatment remains challenging and at times fraught. There are conflicting data on the risk of ICH with LMWH in patients with glioma; small retrospective studies suggest DOACs may convey lower ICH risk than LMWH. Investigational anticoagulants that prevent thrombosis without impairing hemostasis, such as factor XI inhibitors, may carry a better therapeutic index and are expected to enter clinical trials for cancer-associated thrombosis.
Topics: Humans; Heparin, Low-Molecular-Weight; Venous Thromboembolism; Retrospective Studies; Anticoagulants; Neoplasms; Glioma; Glioblastoma; Biology
PubMed: 37100086
DOI: 10.1093/neuonc/noad059 -
Medicine Oct 2023Major orthopedic surgery, including hip and knee replacement and lower extremity trauma fractures surgery, is associated with a high risk of venous thromboembolism... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Major orthopedic surgery, including hip and knee replacement and lower extremity trauma fractures surgery, is associated with a high risk of venous thromboembolism (VTE), especially proximal deep vein thrombosis (DVT), and pulmonary embolism (PE), and is linked with high morbidity and mortality rates. Chemical anticoagulation is routinely used to prevent VTE, with previous meta-analyses reporting on the efficacy and safety of aspirin and other anticoagulants, however, opinions are divided. In the past 2 years, several large randomized controlled trials have been published, therefore, we reanalyzed aspirin efficacy and safety when compared with other anticoagulants in preventing VTE in major orthopedic surgery.
METHODS
Using PubMed, The Cochrane Library, Embase, and Web of Science databases, we conducted a RCT search in August 2023. The main outcomes included VTE, proximal DVT or PE. Additional outcomes included bleeding events, wound complications, wound infections, blood transfusions, and death events.
RESULTS
In total, 17 eligible articles, involving 29,522 patients (15,253 aspirin vs 14,269 other anticoagulant cases), were included. Primary outcomes showed that VTE incidence was more high in the aspirin group when compared with other anticoagulants (risk ratio [RR] = 1.45, 95% confidence interval [CI] = 1.18-1.77, P = .0004) and proximal in the aspirin group the DVT and/or PE incidence was significantly higher in the aspirin group when compared with other anticoagulants (RR = 1.19, 95% CI = 1.02-1.39, P = .03). No significant secondary outcome differences were identified in the aspirin group when compared with other anticoagulants (bleeding events [RR] = 0.83, 95% CI = 0.63-1.10, P = .20); wound complications (RR = 0.45, 95% CI = 0.20-1.04, P = .06); wound infection (RR = 1.08, 95% CI = 0.85-1.38, P = .53); blood transfusion events (RR = 1.00, 95% CI = 0.84-1.19, P = 1.00) and death events (RR = 1.11, 95% CI = 0.78-1.57, P = .55).
CONCLUSIONS
Our updated meta-analysis showed that aspirin was inferior to when compared with other anticoagulants in VTE-related orthopedic major surgery, including proximal DVT and/or PE, and was more likely to form VTE. No differences between groups were identified for bleeding, wound complications, wound infections, transfusion, or death events.
Topics: Humans; Aspirin; Venous Thromboembolism; Randomized Controlled Trials as Topic; Venous Thrombosis; Anticoagulants; Hemorrhage; Pulmonary Embolism; Orthopedic Procedures; Wound Infection; Heparin, Low-Molecular-Weight
PubMed: 37861503
DOI: 10.1097/MD.0000000000035602