Thrombosis in the setting of obesity or inflammatory bowel disease

Abstract

Obesity and inflammatory bowel disease (IBD) are systemic inflammatory disorders that predispose to arterial and venous thrombosis through similar prothrombotic mechanisms. Obesity and IBD are chronic risk factors that lead to a persistently elevated risk of thrombosis, although the thrombotic risk with IBD appears to wax and wane with disease severity. Because of the lack of high-quality evidence to guide management decisions, approaches to the prevention and treatment of thrombosis in patients with obesity or IBD are based on extrapolation from general guidelines for antithrombotic therapy. Obesity alters the pharmacokinetics of some anticoagulant drugs, and IBD patients present the added management challenge of having a high risk of gastrointestinal bleeding while taking anticoagulants. An extended duration of anticoagulant therapy is often recommended for obese or IBD patients with unprovoked venous thromboembolism unless there is a high risk of bleeding, although more data and better biomarkers are needed to determine whether anticoagulation can be safely stopped in a subset of IBD patients during remission of active disease. Most patients with obesity or IBD require thromboprophylaxis in conjunction with hospitalization or surgery, with adjustment of anticoagulant dosing in patients with severe obesity.

Conflict of interest statement

Conflict-of-interest disclosure: The author has received research funding from and has consulted for Novo Nordisk.

© 2016 by The American Society of Hematology. All rights reserved.

Figures

Figure 1.

Influence of obesity and IBD on the relative risk of a first episode of VTE. (A) Meta-analysis of the influence of obesity (BMI >30 mg/m2) on VTE risk. Reproduced from Ageno et al. (B) Meta-analysis estimating the risk of VTE in patients with IBD. Reproduced from Nguyen et al. CI, confidence interval.

Figure 2.

Influence of clinical factors, including obesity and IBD, on the relative risk (RR) of recurrent VTE. Risk estimates are taken from the World Health Organization, Ageno et al, and Kearon and Akl. The lengths of the bars represent rough approximations of the variance in relative risk.

Figure 3.

Proposed mechanisms of thrombosis in obesity. Obesity causes a prothrombotic state driven by chronic inflammation, impaired fibrinolysis, and clinical factors such as immobility, obstructive sleep apnea, and heart failure. Adipokines and proinflammatory cytokines secreted by M1 macrophages within adipose tissue contribute to the upregulation of procoagulant factors such as tissue factor and plasminogen activator inhibitor-1 (PAI-1), leading to increased thrombin generation, enhanced platelet activation, and an increased risk of thrombosis.

Figure 4.

Proposed mechanisms of thrombosis in IBD. IBD predisposes to thrombosis by inducing episodes of acute and chronic intestinal inflammation, leading to a systemic prothrombotic state characterized by upregulation of tissue factor, an elevated platelet count, and impaired fibrinolysis as a result of decreased expression of tissue plasminogen activator (t-PA) and decreased expression of plasminogen activator inhibitor-1 (PAI-1). Clinical risk factors, such as dehydration, malnutrition, and placement of central venous catheters also contribute to thrombotic risk in patients with IBD.