Lipedema and Lymphedema as Independent Risk Factors for Venous Thromboembolism

Description of Background: Lymphedema is an inflammatory vascular disorder manifesting as lymphatic dysfunction and is associated with difficulties in ambulation which may portend a higher risk of venous thromboembolism (VTE). Lipedema is an inflammatory disorder of limb adipocytes often mistaken for lymphedema. Obesity is also an inflammatory condition that increases VTE risk. Since patients with lymphedema or lipedema (LL) often have increased BMI, we considered the effect of LL on VTE in obese patients.

Methods: The Nationwide Inpatient Sample from 2016-2019 was queried for patients with a discharge diagnosis of Obesity using International Classification of Disease, 10th revision, Clinical Modification coding. Male gender and patients with age < 18 years were excluded. We used t-tests and chi-square tests to compare baseline characteristics. Patient sample was matched using nearest neighbor matching. Uni- and multivariate logistic regression identified predictors of VTE. Clot formation kinetics in plasma of patients with lymphedema and lipedema were evaluated by video-microscopy.

Results: 188,003 (0.8%) patients with LL were selected. LL patients were more likely to be obese than those without LL (48% and 17%, respectively). LL was one of the strongest independent predictors of VTE (OR 1.69; 95% CI 1.61-1.72; p< 0.01) compared with obesity alone (OR 1.27; 95% CI 1.24-1.27, P< 0.01). In obese patients, LL increased the odds of VTE (OR 1.4; 95% CI 1.36-1.45; p< 0.01). In a propensity matched analysis, Lipedema and Lymphedema were independent predictors of VTE in obese patients (OR 1.2; 95% CI 1.03-1.41; p=0.02) and (OR 1.4; 95% CI 1.26 – 1.49; p< 0.01) respectively. Fibrin clot formation kinetics for matched healthy subjects (n=21) were 28307U ± 1212 vs. 32949 U ± 1199 (p=0.02) for lymphedema (n=25) vs. 31274U ± 11086 (p=0.24) for lipedema (n=29).

Conclusion: Patients with LL have risk of VTE that is distinct from obesity. In addition, obese patients with lymphedema and lipedema have a higher risk of VTE events. These results are also confirmed by evaluation of thrombosis ex vivo that is driven more by a lymphedema phenotype.

Learning Objective: Weight loss strategies in LL should be prioritized, mechanism of thrombosis, and strategies to abrogate the VTE risk in LL require attention.