Post-thrombotic syndrome

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Post-thrombotic syndrome (PTS, also called post-phlebitic syndrome and venous stress disorder) is the signs and symptoms that may occur as long-term complications of deep vein thrombosis (DVT).

Incidence[edit]

PTS can affect 23-60% of patients in the two years following DVT of the leg. Of those, 10% may go on to develop severe PTS, involving venous ulcers.[1]

Socioeconomic impact[edit]

PTS lowers patients' quality of life after DVT, specifically with regards to physical and psychological symptoms and limitations in daily activities.[2][3][4] Secondly, the treatment of PTS adds significantly to the cost of treating DVT. The annual health care cost of PTS in the United States has been estimated at $200 million, with costs over $3800 per patient in the first year alone, and increasing with disease severity.[1][5] PTS also causes lost work productivity: patients with severe PTS and venous ulcers lose up to 2 work days per year.[6]

Signs and symptoms[edit]

Signs and symptoms of PTS in the leg may include:[7]

  • pain (aching or cramping)
  • heaviness
  • itching or tingling
  • swelling (edema)
  • varicose veins
  • brownish or reddish skin discoloration
  • ulcer

These signs and symptoms may vary among patients and over time. With PTS, these symptoms typically are worse after walking or standing for long periods of time and improve with resting or elevating the leg.[7]

Diagnosis[edit]

When a physician finds a DVT in the clinical history of their patient, a post-thrombotic syndrome will be possible if the patient has suggestive symptoms. A Lower limbs venous ultrasonography must be performed to evaluate the situation: the degree of obstruction by clots, the location of these clots, the detection of deep and/or superficial venous insufficiency.[8][9] Since signs and symptoms of DVT and PTS may be quite similar, a diagnosis of PTS should be delayed for 3–6 months after DVT diagnosis so that an appropriate diagnosis can be made.[7]

Cause[edit]

Despite ongoing research, the cause of PTS is not entirely clear. Inflammation is thought to play a role [10][11] as well as damage to the venous valves from the thrombus itself. This valvular incompetence combined with persistent venous obstruction from thrombus increases the pressure in veins and capillaries. Venous hypertension induces a rupture of small superficial veins, subcutaneous hemorrhage[12] and an increase of tissue permeability. That is manifested by pain, swelling, discoloration, and even ulceration.[13]

Risk factors[edit]

The following factors increase the risk of developing PTS:[14][15][16][17][18][19][20]

  • age > 65
  • proximal DVT
  • a second DVT in same leg as first DVT (recurrent ipsilateral DVT)
  • persistent DVT symptoms 1 month after DVT diagnosis
  • obesity
  • poor quality of anticoagulation control (i.e. dose too low) during the first 3 months of treatment

Prevention[edit]

Prevention of PTS begins with prevention of initial and recurrent DVT. For hospitalized patients at high-risk of DVT, prevention methods may include early ambulation, use of compression stockings or electrostimulation devices, and/or anticoagulant medications.[21]

Increasingly, catheter-directed thrombolysis has been employed. This is a procedure in which interventional radiology will break up a clot using a variety of methods.

For patients who have already had a single DVT event, the best way to prevent a second DVT is appropriate anticoagulation therapy.[22]

A second prevention approach may be weight loss for those who are overweight or obese. Increased weight can put more stress and pressure on leg veins, and can predispose patients to developing PTS.[18]

Finally, some data suggest that the use of elastic compression stockings for up to 2 years post-DVT can be an effective method of PTS prevention,[23][24] while some data suggest otherwise.[25][26]

Treatment[edit]

Treatment options for PTS include proper leg elevation, compression therapy with elastic stockings, or electrostimulation devices, herbal remedies (such as horse chestnut, rutosides, pentoxifylline), and wound care for leg ulcers.[7][27] PTS in the legs is often exacerbated by blockage of draining veins in the pelvis or abdomen (iliac veins and IVC), and opening of these veins (by application of angioplasty and vascular stents by an experienced physician) can provide significant relief of swelling and healing of skin ulcers.

Compression bandages are useful to treat edemas.[12]

Upper-extremities[edit]

Patients with upper-extremity DVT may develop upper-extremity PTS, but the incidence is lower than that for lower-extremity PTS (15-25%).[28][29] There are no established treatment or prevention methods, but patients with upper-extremity PTS may wear a compression sleeve for persistent symptoms.[22]

Research directions[edit]

The field of PTS still holds many unanswered questions that are important targets for more research. Those include

  • fully defining the pathophysiology of PTS, including the role of inflammation and residual thrombus after completion of an appropriate duration of anticoagulant therapy
  • developing a PTS risk prediction model
  • role of thrombolysis ("clot-busting" drugs) in PTS prevention
  • defining the true efficacy of elastic compression stockings for PTS prevention (and if effective, elucidating the minimum compression strength necessary and the optimal timing and duration of compression therapy)
  • whether PTS prevention methods are necessary for patients with asymptomatic or distal DVT
  • additional treatment options for PTS with demonstrated safety and efficacy (compression and pharmacologic therapies)[citation needed]

References[edit]

  1. ^ a b Ashrani AA, Heit JA. Incidence and cost burden of post-thrombotic syndrome. J Thromb Thrombolysis 2009; 28: 465-76.
  2. ^ Kahn SR, Hirsch A, Shrier I. Effect of postthrombotic syndrome on health-related quality of life after deep venous thrombosis. Arch Intern Med 2002;162:1144-8.
  3. ^ Kahn SR, M'Lan CE, Lamping DL, Kurz X, Berard A, Abenhaim L. The influence of venous thromboembolism on quality of life and severity of chronic venous disease. J Thromb Haemost 2004;2:2146-51.
  4. ^ Kahn SR, Shbaklo H, Lamping DL, Holcroft CA, Shrier I, Miron MJ, et al. Determinants of health-related quality of life during the 2 years following deep vein thrombosis. J Thromb Haemost. 2008;6:1105-12.
  5. ^ Caprini JA, Botteman MF, Stephens JM, Nadipelli V, Ewing MM, Brandt S, et al. Economic burden of long-term complications of deep vein thrombosis after total hip replacement surgery in the United States. Value Health 2003;6:59-74.
  6. ^ Bergqvist D, Jendteg S, Johansen L, Persson U, Odegaard K. Cost of long-term complications of deep venous thrombosis of the lower extremities: an analysis of a defined patient population in Sweden. Ann Intern Med 1997;126:454-7.
  7. ^ a b c d Kahn SR (2009). "How I treat postthrombotic syndrome". Blood 114 (21): 4624–31. doi:10.1182/blood-2009-07-199174. PMID 19741190. 
  8. ^ Sato, D. T., Masuda, E. M. (July 1998). Journal of Vascular 28 (1): 67–74 http://www.jvascsurg.org/article/S0741-5214(98)70201-0/fulltext |url= missing title (help). 
  9. ^ Kahn SR, Partsch H, Vedantham S, Prandoni P, Kearon C. Definition of post-thrombotic syndrome of the leg for use in clinical investigations: a recommendation for standardization. J Thromb Haemost 2009;7:879-83.
  10. ^ Shbaklo H, Holcroft CA, Kahn SR. Levels of inflammatory markers and the development of the post-thrombotic syndrome. Thromb Haemost 2009; 101:505-12.
  11. ^ Roumen-Klappe EM, Janssen MC, Van Rossum J, Holewijn S, Van Bokhoven MM, Kaasjager K, et al. Inflammation in deep vein thrombosis and the development of post-thrombotic syndrome: a prospective study. J Thromb Haemost 2009;7:582-7.
  12. ^ a b Pirard D., Bellens B., Vereecken P. The post-thrombotic syndrome - a condition to prevent. Dermatology Online Journal 14 (3): 13
  13. ^ Vedantham S. Valvular dysfunction and venous obstruction in the post-thrombotic syndrome. Thromb Res 2009; 123 Suppl 4: S62-5.
  14. ^ Tick LW, Kramer MH, Rosendaal FR, Faber WR, Doggen CJ. Risk factors for post-thrombotic syndrome in patients with a first deep venous thrombosis. J Thromb Haemost. 2008;6:2075-81.
  15. ^ Prandoni P, Lensing AWA, Cogo A, Cuppini S, Villalta S, Carta M, et al. The long-term clinical course of acute deep venous thrombosis. Ann Intern Med 1996;125:1-7.
  16. ^ Shbaklo H, Kahn SR. Long-term prognosis after deep venous thrombosis. Curr Opin Hematol 2008;15:494-8.
  17. ^ Kahn SR, Kearon C, Julian JA, Mackinnon B, Kovacs MJ, Wells P, et al. Predictors of the post-thrombotic syndrome during long-term treatment of proximal deep vein thrombosis. J Thromb Haemost 2005;3:718-23.
  18. ^ a b Ageno W, Piantanida E, Dentali F, Steidl L, Mera V, Squizzato A, et al. Body mass index is associated with the development of the post-thrombotic syndrome. Thromb Haemost 2003;89:305-9.
  19. ^ van Dongen CJ, Prandoni P, Frulla M, Marchiori A, Prins MH, Hutten BA. Relation between quality of anticoagulant treatment and the development of the postthrombotic syndrome. J Thromb Haemost 2005;3:939-42.
  20. ^ Kahn SR, Ginsberg JS. Relationship between deep venous thrombosis and the postthrombotic syndrome. Arch Intern Med 2004;164:17-26.
  21. ^ Geerts WH, Bergqvist D, Pineo GF, Heit JA, Samama CM, Lassen MR, et al. Prevention of venous thromboembolism: American College of Chest Physicians evidence-based clinical practice guidelines (8th edition). Chest 2008;133:381S-453S.
  22. ^ a b Kearon C, Kahn SR, Agnelli G, Goldhaber S, Raskob GE, Comerota AJ. Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008;133:454S-545S.
  23. ^ Brandjes DP, Buller HR, Heijboer H, Huisman MV, de Rijk M, Jagt H, et al. Randomised trial of effect of compression stockings in patients with symptomatic proximal-vein thrombosis. Lancet 1997;349:759-62.
  24. ^ Prandoni P, Lensing AW, Prins MH, Frulla M, Marchiori A, Bernardi E, et al. Below-knee elastic compression stockings to prevent the post-thrombotic syndrome: a randomized, controlled trial. Ann Intern Med 2004;141:249-56.
  25. ^ Ginsberg JS, Hirsh J, Julian J, Vander LaandeVries M, Magier D, MacKinnon B, et al. Prevention and treatment of postphlebitic syndrome: results of a 3-part study. Arch Intern Med 2001;161:2105-9.
  26. ^ Aschwanden M, Jeanneret C, Koller MT, Thalhammer C, Bucher HC, Jaeger KA. Effect of prolonged treatment with compression stockings to prevent post-thrombotic sequelae: a randomized controlled trial. J Vasc Surg 2008;47:1015-21.
  27. ^ Vazquez SR, Freeman A, VanWoerkom RC, Rondina MT. Contemporary issues in the prevention and management of postthrombotic syndrome. Ann Pharmacother 2009; 43:1824-35.
  28. ^ Elman EE, Kahn SR. The post-thrombotic syndrome after upper extremity deep venous thrombosis in adults: a systematic review. Thromb Res 2006;117:609-14.
  29. ^ Prandoni P, Bernardi E, Marchiori A, et al. The long-term clinical course of acute deep vein thrombosis of the arm: prospective cohort study. BMJ 2004; 329:484-5.