Post-thrombotic syndrome

Post-thrombotic syndrome
Synonym postphlebitic syndrome, venous stress disorder
Person with post-thrombotic syndrome and leg ulcers
Specialty Cardiology Edit this on Wikidata

Post-thrombotic syndrome (PTS), also called postphlebitic syndrome and venous stress disorder is a medical condition that may occur as a long-term complication of deep vein thrombosis (DVT).

Signs and symptoms

Signs and symptoms of PTS in the leg may include:[1]

  • 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.[1]

PTS lowers a person's quality of life after DVT, specifically with regards to physical and psychological symptoms and limitations in daily activities.[2][3][4]

Cause

Despite ongoing research, the cause of PTS is not entirely clear. Inflammation is thought to play a role [5][6] 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[7] and an increase of tissue permeability. That is manifested by pain, swelling, discoloration, and even ulceration.[8]

Risk factors

The following factors increase the risk of developing PTS:[9][10][11][12][13][14][15]

  • 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

Diagnosis

When physicians find a DVT in the clinical history of their patients, a postthrombotic syndrome is possible if the patients have suggestive symptoms. Ultrasonography for deep venous thrombosis must be performed to evaluate the situation: the degree of obstruction by clots, the location of these clots, and the detection of deep and/or superficial venous insufficiency.[16][17] 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 an appropriate diagnosis can be made.[1]

Prevention

Prevention of PTS begins with prevention of initial and recurrent DVT. For people hospitalized at high-risk of DVT, prevention methods may include early ambulation, use of compression stockings or electrostimulation devices, and/or anticoagulant medications.[18]

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 people who have already had a single DVT event, the best way to prevent a second DVT is appropriate anticoagulation therapy.[19]

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.[13]

Treatment

Treatment options for PTS include proper leg elevation, compression therapy with elastic stockings, or electrostimulation devices, pharmacotherapy (pentoxifylline), herbal remedies (such as horse chestnut, rutosides), and wound care for leg ulcers.[1][20]

The benefits of compression bandages is unclear. They may be useful to treat edemas.[7]

Upper extremities

Patients with upper-extremity DVT may develop upper-extremity PTS, but the incidence is lower than that for lower-extremity PTS (15-25%).[21][22] No treatment or prevention methods are established, but patients with upper-extremity PTS may wear a compression sleeve for persistent symptoms.[19]

Epidemiology

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.[23]

Socioeconomic impact

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.[23][24] PTS also causes lost work productivity: people with severe PTS and venous ulcers lose up to 2 work days per year.[25]

Research directions

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 thrombolytic ("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)

References

  1. 1 2 3 4 Kahn SR (2009). "How I treat postthrombotic syndrome". Blood. 114 (21): 4624–31. doi:10.1182/blood-2009-07-199174. PMID 19741190.
  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 (2004). "The influence of venous thromboembolism on quality of life and severity of chronic venous disease". J Thromb Haemost. 2: 2146–51. doi:10.1111/j.1538-7836.2004.00957.x.
  4. ↑ Kahn SR, Shbaklo H, Lamping DL, Holcroft CA, Shrier I, Miron MJ, et al. (2008). "Determinants of health-related quality of life during the 2 years following deep vein thrombosis". J Thromb Haemost. 6: 1105–12. doi:10.1111/j.1538-7836.2008.03002.x.
  5. ↑ Shbaklo H, Holcroft CA, Kahn SR (2009). "Levels of inflammatory markers and the development of the post-thrombotic syndrome". Thromb Haemost. 101: 505–12.
  6. ↑ Roumen-Klappe EM, Janssen MC, Van Rossum J, Holewijn S, Van Bokhoven MM, Kaasjager K, et al. (2009). "Inflammation in deep vein thrombosis and the development of post-thrombotic syndrome: a prospective study". J Thromb Haemost. 7: 582–7. doi:10.1111/j.1538-7836.2009.03286.x.
  7. 1 2 Pirard D.; Bellens B.; Vereecken P. "The post-thrombotic syndrome - a condition to prevent". Dermatology Online Journal. 14 (3): 13.
  8. ↑ Vedantham S (2009). "Valvular dysfunction and venous obstruction in the post-thrombotic syndrome". Thromb Res. 123 (Suppl 4): S62–5. doi:10.1016/s0049-3848(09)70146-x.
  9. ↑ Tick LW, Kramer MH, Rosendaal FR, Faber WR, Doggen CJ (2008). "Risk factors for post-thrombotic syndrome in patients with a first deep venous thrombosis". J Thromb Haemost. 6: 2075–81. doi:10.1111/j.1538-7836.2008.03180.x.
  10. ↑ Prandoni P, Lensing AW, Cogo A, Cuppini S, Villalta S, Carta M, et al. (1996). "The long-term clinical course of acute deep venous thrombosis". Ann Intern Med. 125: 1–7. doi:10.7326/0003-4819-125-1-199607010-00001.
  11. ↑ Shbaklo H, Kahn SR (2008). "Long-term prognosis after deep venous thrombosis". Curr Opin Hematol. 15: 494–8. doi:10.1097/moh.0b013e32830abde2.
  12. ↑ Kahn SR, Kearon C, Julian JA, Mackinnon B, Kovacs MJ, Wells P, et al. (2005). "Predictors of the post-thrombotic syndrome during long-term treatment of proximal deep vein thrombosis". J Thromb Haemost. 3: 718–23. doi:10.1111/j.1538-7836.2005.01216.x.
  13. 1 2 Ageno W, Piantanida E, Dentali F, Steidl L, Mera V, Squizzato A, et al. (2003). "Body mass index is associated with the development of the post-thrombotic syndrome". Thromb Haemost. 89: 305–9.
  14. ↑ Van Dongen CJ, Prandoni P, Frulla M, Marchiori A, Prins MH, Hutten BA (2005). "Relation between quality of anticoagulant treatment and the development of the postthrombotic syndrome". J Thromb Haemost. 3: 939–42. doi:10.1111/j.1538-7836.2005.01333.x.
  15. ↑ Kahn SR, Ginsberg JS (2004). "Relationship between deep venous thrombosis and the postthrombotic syndrome". Arch Intern Med. 164: 17–26. doi:10.1001/archinte.164.1.17.
  16. ↑ Sato, D. T., Masuda, E. M. (July 1998). "The natural history of calf vein thrombosis: Lysis of thrombi and development of reflux". Journal of Vascular Surgery. 28 (1): 67–74. doi:10.1016/s0741-5214(98)70201-0.
  17. ↑ Kahn SR, Partsch H, Vedantham S, Prandoni P, Kearon C (2009). "Definition of post-thrombotic syndrome of the leg for use in clinical investigations: a recommendation for standardization". J Thromb Haemost. 7: 879–83. doi:10.1111/j.1538-7836.2009.03294.x.
  18. ↑ Geerts WH, Bergqvist D, Pineo GF, Heit JA, Samama CM, Lassen MR, et al. (2008). "Prevention of venous thromboembolism: American College of Chest Physicians evidence-based clinical practice guidelines". Chest (8th ed.). 133: 381S–453S. doi:10.1378/chest.08-0656. PMID 18574271.
  19. 1 2 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.
  20. ↑ Vazquez SR, Freeman A, VanWoerkom RC, Rondina MT (2009). "Contemporary issues in the prevention and management of postthrombotic syndrome". Ann Pharmacother. 43: 1824–35. doi:10.1345/aph.1m185. PMC 3245967.
  21. ↑ Elman EE, Kahn SR (2006). "The post-thrombotic syndrome after upper extremity deep venous thrombosis in adults: a systematic review". Thromb Res. 117: 609–14. doi:10.1016/j.thromres.2005.05.029.
  22. ↑ Prandoni P, Bernardi E, Marchiori A, et al. (2004). "The long-term clinical course of acute deep vein thrombosis of the arm: prospective cohort study". BMJ. 329: 484–5. doi:10.1136/bmj.38167.684444.3a. PMC 515197. PMID 15256419.
  23. 1 2 Ashrani AA, Heit JA (2009). "Incidence and cost burden of post-thrombotic syndrome". J. Thromb. Thrombolysis. 28 (4): 465–76. doi:10.1007/s11239-009-0309-3. PMC 4761436. PMID 19224134.
  24. ↑ Caprini JA, Botteman MF, Stephens JM, Nadipelli V, Ewing MM, Brandt S, et al. (2003). "Economic burden of long-term complications of deep vein thrombosis after total hip replacement surgery in the United States". Value Health. 6: 59–74. doi:10.1046/j.1524-4733.2003.00204.x.
  25. ↑ Bergqvist D, Jendteg S, Johansen L, Persson U, Odegaard K (1997). "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. 126: 454–7. doi:10.7326/0003-4819-126-6-199703150-00006.
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