Elizabeth Andraska

Bio: Elizabeth Andraska is an academic researcher from University of Pittsburgh. The author has contributed to research in topics: Medicine & Revascularization. The author has an hindex of 8, co-authored 34 publications receiving 176 citations. Previous affiliations of Elizabeth Andraska include University of Michigan.

Pathophysiology of varicose veins

Abstract: Background Varicose veins, a common problem with effects on quality of life, account for a significant cost burden on the health care system. Despite their prevalence, the pathophysiologic mechanism of varicose veins remains incompletely understood. The fundamental issue is whether venous hypertension and valvular incompetence precede and influence the development of vein wall changes or whether the reverse is true. Methods We have reviewed the English-language literature to provide the most current understanding of the hemodynamic and cellular and molecular processes that underlie the development of varicose veins. Results Data at this time remain inconclusive, with compelling arguments to be made for both sides. It is clear that valvular incompetence and hemodynamic factors play a significant role, despite heterogeneity in study findings and lack of clear data for a specific pattern of valvular incompetence as an inciting factor. Numerous factors influence the development of varices on the cellular level, including hypoxia, dysregulated apoptosis, and alterations in the extracellular matrix. Conclusions Based on currently available evidence, varicose veins are a complex disease with multifactorial pathogenesis; it is as yet not possible to state conclusively what inciting factor is responsible for the development of varicose veins, and their development may result from imbalance of any number of several factors.

Endotoxaemia-augmented murine venous thrombosis is dependent on TLR-4 and ICAM-1, and potentiated by neutropenia

Abstract: Venous thromboembolism is a major cause of death during and immediately post-sepsis. Venous thrombosis (VT) is mediated by cell adhesion molecules and leukocytes, including neutrophil extracellular traps (NETs). Sepsis, or experimentally, endotoxaemia, shares similar characteristics and is modulated via toll like receptor 4 (TLR4). This study was undertaken to determine if endotoxaemia potentiates early stasis thrombogenesis, and secondarily to determine the role of VT TLR4, ICAM-1 and neutrophils (PMNs). Wild-type (WT), ICAM-1-/- and TLR4-/- mice underwent treatment with saline or LPS (10 mg/kg i. p.) alone, or followed by inferior vena cava (IVC) ligation to generate stasis VT. In vivo microscopy of leukocyte trafficking was performed in non-thrombosed mice, and tissue and plasma were harvested during early VT formation. Pre-thrombosis, circulating ICAM-1 was elevated and increased leukocyte adhesion and rolling occurred on the IVC of LPS-treated mice. Post-thrombosis, endotoxaemic mice formed larger, platelet-poor thrombi. Endotoxaemic TLR4-/- mice did not have an augmented thrombotic response and exhibited significantly decreased circulating ICAM-1 compared to endotoxaemic WT controls. Endotoxaemic ICAM-1-/- mice had significantly smaller thrombi compared to controls. Hypothesising that PMNs localised to the inflamed endothelium were promoting thrombosis, PMN depletion using anti-Ly6G antibody was performed. Paradoxically, VT formed without PMNs was amplified, potentially related to endotoxaemia induced elevation of PAI-1 and circulating FXIII, and decreased uPA. Endotoxaemia enhanced early VT occurs in a TLR-4 and ICAM-1 dependent fashion, and is potentiated by neutropenia. ICAM-1 and/or TLR-4 inhibition may be a unique strategy to prevent sepsis-associated VT.

Genome-wide association analysis of venous thromboembolism identifies new risk loci and genetic overlap with arterial vascular disease.

Abstract: Venous thromboembolism is a significant cause of mortality1, yet its genetic determinants are incompletely defined. We performed a discovery genome-wide association study in the Million Veteran Program and UK Biobank, with testing of approximately 13 million DNA sequence variants for association with venous thromboembolism (26,066 cases and 624,053 controls) and meta-analyzed both studies, followed by independent replication with up to 17,672 venous thromboembolism cases and 167,295 controls. We identified 22 previously unknown loci, bringing the total number of venous thromboembolism-associated loci to 33, and subsequently fine-mapped these associations. We developed a genome-wide polygenic risk score for venous thromboembolism that identifies 5% of the population at an equivalent incident venous thromboembolism risk to carriers of the established factor V Leiden p.R506Q and prothrombin G20210A mutations. Our data provide mechanistic insights into the genetic epidemiology of venous thromboembolism and suggest a greater overlap among venous and arterial cardiovascular disease than previously thought. Genome-wide analysis of venous thromboembolism identifies 22 new risk loci and facilitates construction of a polygenic risk score. Comparison to arterial vascular disease highlights shared pathophysiology and potential therapeutic strategies.

Lemierre syndrome

Abstract: Lemierre syndrome is an acute systemic suppurative infection originating from internal jugular vein septic thrombophlebitis most commonly as sequel to oropharyngeal infection, with Fusobaeterium necrophorum as its most common pathogen. It is prone to misdiagnosis or under-diagnosis due to its lack of specific clinical manifestations, arising from multi-organ involvement. Diagnosis can be established based on positive findings of internal jugular vein septic thrombophlebitis from history collection,physical examination or imaging studies, in combination with evidence of hematogenous infection or metastatic abscesses. Early, sufficient and prolonged course of antimicrobial therapy covering anaerobic bacteria is recommended. Key words: Lemierre syndrome; Fusobacterium necrophorum; Diagnosis

Fibrinolysis and Inflammation in Venous Thrombus Resolution.

Abstract: Clinical observations and accumulating laboratory evidence support a complex interplay between coagulation, inflammation, innate immunity and fibrinolysis in venous thromboembolism (VTE). VTE, which includes deep vein thrombosis (DVT) and pulmonary embolism (PE), and the subsequent complications of post-thrombotic syndrome (PTS), are significant causes of morbidity and mortality in patients. Clinical risk factors for VTE include cancer, major trauma, surgery, sepsis, inflammatory bowel disease, paralysis, prolonged periods of immobility, and aging. Abnormalities in venous blood flow or stasis initiates the activation of endothelial cells, and in concert with platelets, neutrophils and monocytes, propagates VTE in an intact vein. In addition, inflammatory cells play crucial roles in thrombus recanalization and restoration of blood flow via fibrinolysis and vascular remodeling. Faster resolution of the thrombus is key for improved disease prognosis. While in the clinical setting, anticoagulation therapy is successful in preventing propagation of venous thrombi, current therapies are not designed to inhibit inflammation, which can lead to the development of PTS. Animal models of DVT have provided many insights into the molecular and cellular mechanisms involved in the formation, propagation, and resolution of venous thrombi as well as the roles of key components of the fibrinolytic system in these processes. Here, we review the recent advances in our understanding of fibrinolysis and inflammation in the resolution of VTE.

Thrombo-Inflammation in Cardiovascular Disease: An Expert Consensus Document from the Third Maastricht Consensus Conference on Thrombosis.

Abstract: Thrombo-inflammation describes the complex interplay between blood coagulation and inflammation that plays a critical role in cardiovascular diseases. The third Maastricht Consensus Conference on Thrombosis assembled basic, translational, and clinical scientists to discuss the origin and potential consequences of thrombo-inflammation in the etiology, diagnostics, and management of patients with cardiovascular disease, including myocardial infarction, stroke, and peripheral artery disease. This article presents a state-of-the-art reflection of expert opinions and consensus recommendations regarding the following topics: (1) challenges of the endothelial cell barrier; (2) circulating cells and thrombo-inflammation, focused on platelets, neutrophils, and neutrophil extracellular traps; (3) procoagulant mechanisms; (4) arterial vascular changes in atherogenesis; attenuating atherosclerosis and ischemia/reperfusion injury; (5) management of patients with arterial vascular disease; and (6) pathogenesis of venous thrombosis and late consequences of venous thromboembolism.