Deep Vein Thrombosis (DVT)

Background

EarlyStages keyDeep vein thrombosis (DVT) refers to the formation of a blood clot in the deep veins of the body, typically in the calf. Patients with DVT may describe pain, swelling, and redness in the affected leg; however, up to half of those with this condition have no symptoms. While most DVT resolves spontaneously, two major complications may arise: pulmonary embolism and postphlebitic syndrome.

Pulmonary embolism (PE) occurs when a clot dislodges and becomes stuck in the pulmonary arterial vessels; it is often fatal. Postphlebitic syndrome, or chronic deep venous insufficiency, occurs due to damage of the venous valves and/or persistent obstruction by DVT. This may result in chronic leg swelling and skin ulcerations as venous blood flow back to the heart is impaired.

DVT is associated with a triad of risk factors which include stasis of blood flow, hypercoagulability, and vascular damage. Venous flow is slowed in conditions such as prolonged inactivity (long travel, post-surgery), heart failure, and increased blood viscosity. Various disorders, including inherited syndromes, cancer, and pregnancy can lead to systemic hypercoagulability of the blood. Vascular damage can be caused by external trauma or intravenous catheters.

Prevention against DVT is required in clinical situations where the risk of developing this condition is high, such as during periods of bed rest or following surgical procedures. Preventative measures include anticoagulation, compression stockings, physical compression of the legs, walking, and calf exercises.

Current data estimates that about 1 in 20 people develop a DVT during their lifetime, resulting in approximately 600,000 hospitalizations/year in the U.S However, DVT is an underdiagnosed disease and cases of PE are often diagnosed during autopsy.

Current Treatment

The main goals for the treatment of DVT are to prevent pulmonary embolism and postphlebitic syndrome. Medical treatment may be in the outpatient setting and consists of initial anticoagulation with drugs, which typically resolve the symptoms of DVT, and long-term (typically 3-12 months) anticoagulation with oral medication such as warfarin.

In patients with DVT or established PE who have contraindications to anticoagulation, an intravascular filter may be inserted to prevent emboli from reaching the pulmonary vessels. Certain patients may benefit from more invasive catheter-based procedures where the thrombus is either mechanically removed, lysed, and/or stenting of the obstruction is performed. Additionally, in patients with large PE in the chest, systemic treatment with agents that will dissolve the embolus (thrombolytics) or surgical removal may be warranted.

Focused Ultrasound Research

The use of focused ultrasound is being explored to break apart blood clots, either independently or in combination with bubbles and anti-clotting agents. Preclinical studies have shown that ultrasound energy can cause vibrations that either break apart the clot or make it more easily treated with thrombolytic therapy. While conventional anticoagulation treatment for DVT inhibits the propagation of the thrombus, it does not remove it, and there is a variable risk of significant bleeding. FUS can potentially provide a non-invasive method of clot lysis, which would allow for the reperfusion of the occluded vein. However, more research is needed to establish the safety and efficacy of FUS for thrombolysis.

Notable Papers

Xu S, Zong Y, Feng Y, Liu R, Liu X, Hu Y, Han S, Wan M. Dependence of pulsed focused ultrasound induced thrombolysis on duty cycle and cavitation bubble size distribution. Ultrason Sonochem. 2014 Jul 9. pii: S1350-4177(14)00227-2. doi: 10.1016/j.ultsonch.2014.06.024.

Hölscher T, Ahadi G, Fisher D, Zadicario E, Voie A. MR-guided focused ultrasound for acute stroke: a rabbit model. Stroke. 2013 Jun;44(6 Supp 1):S58-60.

Lapchak PA, Kikuchi K, Butte P, Hölscher T. Development of transcranial sonothrombolysis as an alternative stroke therapy: incremental scientific advances toward overcoming substantial barriers. Expert Rev Med Devices. 2013 Mar;10(2):201-13.

A. Burgess, Y. Huang, A. C. Waspe, M. Ganguly, D. E. Goertz, and K. Hynynen, “High-intensity focused ultrasound (HIFU) for dissolution of clots in a rabbit model of embolic stroke.,” PLoS ONE, vol. 7, no. 8, Aug. 2012.

N. Abi-Jaoudeh, W. F. Pritchard, H. Amalou, M. Linguraru, O. A. Chiesa, J. D. Adams, C. Gacchina, R. Wesley, S. Maruvada, B. McDowell, V. Frenkel, J. W. Karanian, and B. J. Wood, “Pulsed high-intensity-focused US and tissue plasminogen activator (TPA) versus TPA alone for thrombolysis of occluded bypass graft in swine.,” J. Vasc. Interv. Radiol. : JVIR, vol. 23, no. 7, pp. 953–961.e2, Jul. 2012.

C. Wright, K. Hynynen, and D. Goertz, “In vitro and in vivo high-intensity focused ultrasound thrombolysis.,” Investig. Radiol., vol. 47, no. 4, pp. 217–225, Apr. 2012.

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