Showing papers by "Thomas W. Wakefield published in 2014"

Low-molecular-weight heparin modulates vein wall fibrotic response in a plasminogen activator inhibitor 1-dependent manner.

Abstract: Background Treatment with low-molecular-weight heparin (LMWH) favorably alters the vein wall response to deep venous thrombosis (DVT), although the mechanisms remain unclear. Previous studies have suggested that LMWH alters the levels of circulating plasminogen activator inhibitor 1 (PAI-1), a known mediator of fibrosis, and may improve endogenous fibrinolysis. We hypothesized that LMWH favorably alters the vein wall response by binding of PAI-1 and acceleration of fibrinolysis. Methods Wild-type and PAI-1 −/− mice underwent treatment with LMWH after induction of occlusive DVT. Vein wall and plasma were harvested and analyzed by enzyme-linked immunosorbent assay, zymography, real-time polymerase chain reaction, and immunohistochemistry. Results Wild-type mice treated with LMWH exhibited diminished vein wall fibrosis (0.6 ± 0.6 vs 1.4 ± 0.2; P P −/− mice treated with LMWH were not similarly protected from fibrosis, despite improved thrombus resolution. Treatment with LMWH was associated with decreased intrathrombus interleukin-1β (68.6 ± 31.0 vs 223.4 ± 28.9 ρg/mg total protein; P −/− mice exhibited significantly elevated intrathrombus (257.2 ± 51.5 vs 14.3 ± 3.8 ρg/mg total protein; n = 5) and vein wall interleukin-13 (187.2 ± 57.6 vs 9.9 ± 1.1 ρg/mg total protein; P P Conclusions LMWH did not accelerate venous thrombosis resolution but did protect against vein wall fibrosis in a PAI-1-dependent manner in an occlusive DVT model. Lack of PAI-1 correlated with accelerated venous thrombosis resolution but no protection from fibrosis. PAI-1 inhibition as a treatment strategy for DVT is likely to accelerate clearance of the thrombus but may come at the expense of increased vein wall fibrosis.

P-Selectin Inhibition Therapeutically Promotes Thrombus Resolution and Prevents Vein Wall Fibrosis Better than Enoxaparin and an Inhibitor to von Willebrand Factor.

Abstract: Deep vein thrombosis (VT) and pulmonary embolism, known collectively as venous thromboembolism, affect an estimated 900 000 people in the United States each year, resulting in ≈300 000 deaths. Most of those deaths occurred within 1 month of the initial diagnosis. Anticoagulation is the current standard treatment for the prevention of VT, VT recurrence, pulmonary embolism, and the progression of the thrombus. However, it does not lyse the thrombus or prevent the development of post-thrombotic syndrome. In addition, it carries with it significant bleeding risks, such as intracranial hemorrhage, which occurs in 1.15% patients per year with a case fatality rate (major bleeding) of 13%. Thus, new treatment options that limit bleeding risk, while decreasing thrombotic risk, should be investigated. Recently, it has been demonstrated that P-selectin and von Willebrand factor (vWF) can mediate events associated with VT. Both proteins are stored by platelets and endothelial cells (P-selectin is a component of the membrane and also the matrix of the α granule and the Weibel–Palade bodies), can be released from platelets and endothelial cells by prothrombotic and inflammatory factors generated on cell activation, and can be localized to the surface of the cells. The surface that expresses P-selectin and vWF can promote accumulation of plasma-derived, cell-associated procoagulant factors and cells (platelets and leukocytes) that will promote vein wall injury and thrombus formation. Previous studies have demonstrated that P-selectin and vWF

An Aspirin a Day to Keep the Clots Away Can Aspirin Prevent Recurrent Thrombosis in Extended Treatment for Venous Thromboembolism

Abstract: Patients presenting with deep vein thrombosis (DVT) in the absence of any identifiable risk factors are said to have an unprovoked or idiopathic DVT. Recurrent events are much more common in these patients (10% versus ≤ 3% at 1 year) compared with patients with a DVT provoked by a reversible risk factor, and such events represent a major healthcare problem.1 Three months of anticoagulation is sufficient to decrease the risk of recurrent thrombosis related to the initial DVT. However, once therapy is discontinued, the risk for recurrence rises dramatically. It has been suggested that 30% to 50% of patients experience a recurrence at 10 years.2,3 Factors associated with a higher likelihood of recurrence are male sex, elevated D dimer, incomplete resolution of DVT, body mass index ≥30, and post-thrombotic syndrome.4 In fact, a number of tools have been developed to determine the risk of recurrence after DVT. Article see p 1062 In the current management paradigm, patients with unprovoked DVT are evaluated for long-term anticoagulation after initial treatment with 3 to 6 months of anticoagulation. The risks of major bleeding during prolonged therapy are periodically weighed against the benefits of continuing anticoagulation in high-risk patients. Data supporting this approach come from 4 studies demonstrating a decrease in recurrent venous thromboembolism (VTE) by 90% with extended conventional dose vitamin K antagonists (VKA) therapy.5 Major bleeding occurs in 20 per 1000 patients, and as of yet no validated prediction tool exists to predict risk–benefit ratio of extended therapy.6 Factors associated with an increased risk of bleeding include advanced age >75 years, history of gastrointestinal bleeding, noncardioembolic stroke, renal or hepatic disease, concomitant antiplatelet usage, and poor control of anticoagulation.5 In the interest of diminishing the bleeding risk while conferring protection against recurrent venous thromboembolism …

Core content for training in venous and lymphatic medicine.

Abstract: The major venous societies in the United States share a common mission to improve the standards of medical practitioners, the educational goals for teaching and training programs in venous disease, and the quality of patient care related to the treatment of venous disorders. With these important goals in mind, a task force made up of experts from the specialties of dermatology, interventional radiology, phlebology, vascular medicine, and vascular surgery was formed to develop a consensus document describing the Core Content for venous and lymphatic medicine and to develop a core educational content outline for training. This outline describes the areas of knowledge considered essential for practice in the field, which encompasses the study, diagnosis, and treatment of patients with acute and chronic venous and lymphatic disorders. The American Venous Forum and the American College of Phlebology have endorsed the Core Content.