During Monday’s State-of-the-Art Session titled “What Happens After Acute VTE?”, Arina ten Cate-Hoek, M.D., Ph.D. presented research regarding prevention and management of the post-thrombotic syndrome (PTS):
- PTS is an underappreciated complication that can occur in 20-50% of venous thromboembolism (VTE) patients.
- Traditional measures directed at reduction of edema and improvement in calf muscle action, such as compression, may be useful but may not target the underlying pathology of PTS.
- Other strategies include statins, low molecular weight heparins (LMWH), direct oral anticoagulants (DOACs), and catheter-directed thrombolysis. These may have a role in a more complex, patient-specific approach to preventing PTS.
- Management of PTS should be like “piecing the puzzle”: choosing the right treatment (compression, pharmacotherapy, lifestyle interventions, surgical interventions), using predictive rules to estimate baseline risk, and evaluating other patient outcomes such as quality of life and cost.
PTS is a chronic complication of VTE, occurring in 20-50% of patients. The clinical presentation is characterized by edema, skin changes such as redness and hyperpigmentation, and impaired skin perfusion with venous ulcerations in more serious cases.
PTS is an underestimated global problem, becoming increasingly appreciated over the last 10 years. Barriers for progress in the diagnosis and treatment of PTS have included a lack of gold standard for diagnosis, lack of prediction models to accurately identify risk, and a lack of effective interventions.
Historically, treatment options have been directed at reducing edema and improving calf muscle action including complex lymphedema therapy (CLT), exercise therapy, veno-wave therapy, elastic compression stockings (ECS), and veno-active drugs. However, these approaches may not appropriately target the pathophysiology of PTS, which involves an inflammatory mechanism dependent on leukocyte action as the thrombus resolves. In the case of inadequate thrombus resolution, there is continued obstruction and more extensive venous wall damage, resulting in venous wall remodeling and finally fibrosis. This is often accompanied by trabeculation.
External compression is a standard in PTS care. It reduces venous diameter and improves venous flow velocity, resulting in a reduction of edema and better efficiency of the calf muscle pump. Data support a benefit of external compression, but questions remain regarding the appropriate duration of external compression to optimally prevent PTS.
When looking at other factors involved in PTS, ten Cate-Hoek and colleagues observed that patients with PTS make denser clots with thinner fibers that are harder to lyse. Additionally, these types of clots are associated with a higher probability of recurrent DVT. Therefore, PTS patients may benefit from thrombolytic therapy. The use of statins might also be of interest, as they stimulate fibrinolysis and reduce coagulation and inflammation.
In PTS, the process of fibrinolysis itself can be impaired, creating conditions of sustained thrombin generation. This is an important therapeutic target for the prevention of PTS. Studies have shown a negative effect of sub-therapeutic INR levels on the incidence of PTS in patients treated with vitamin K antagonists. LMWHs were found to be associated with significantly better outcomes for both thrombus resolution and PTS. Very little data exist for DOACs, however one post-hoc analysis did not report better outcomes for patients with PTS.
The last strategy is catheter-directed thrombolysis. More rapid removal of the thrombus may prevent reflux, venous obstruction, and PTS. The longer the thrombus is adjacent to the vessel wall, the higher the risk of venous wall damage. Impaired fibrinolysis may result in trabeculation, which together with a scarred and stiff venous wall result in venous hypertension and consequent onset of PTS. Faster removal of the thrombus through thrombolysis may therefore prevent PTS.
With a multitude of potential strategies, management of PTS should be like “piecing the puzzle”: choosing the right treatment, using predictive rules to estimate baseline risk, and evaluating other patient outcomes such as quality of life and cost of therapeutic interventions. PTS therapy needs to evolve into a more nuanced, individualized approach.