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Patient with post-thrombotic syndrome and legulcers

Post-thrombotic syndromeFrom Wikipedia, the free encyclopedia

Post-thrombotic syndrome (PTS), also calledpostphlebitic syndrome and venous stress disorder is amedical condition that may occur as a long-termcomplication of deep vein thrombosis (DVT).

Contents1 Incidence2 Socioeconomic impact3 Signs and symptoms4 Diagnosis5 Cause

5.1 Risk factors6 Prevention7 Treatment8 Upper-extremities9 Research directions10 References

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

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

Signs and symptoms

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

pain (aching or cramping)

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heavinessitching or tinglingswelling (edema)varicose veinsbrownish or reddish skin discolorationulcer

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

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

Cause

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

Risk factors

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

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

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

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Increasingly, catheter-directed thrombolysis has been employed. This is a procedure in which interventionalradiology 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 appropriateanticoagulation therapy.[22]

A second prevention approach may be weight loss for those who are overweight or obese. Increased weight canput 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 aneffective method of PTS prevention,[23][24] while some data suggest otherwise.[25][26]

TreatmentTreatment options for PTS include proper leg elevation, compression therapy with elastic stockings, orelectrostimulation devices, herbal remedies (such as horse chestnut, rutosides, pentoxifylline), and wound carefor 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 anexperienced physician) can provide significant relief of swelling and healing of skin ulcers.

Compression bandages are useful to treat edemas.[12]

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

Research directionsThe field of PTS still holds many unanswered questions that are important targets for more research. Thoseinclude

fully defining the pathophysiology of PTS, including the role of inflammation and residual thrombus aftercompletion of an appropriate duration of anticoagulant therapydeveloping a PTS risk prediction modelrole of thrombolysis ("clot-busting" drugs) in PTS preventiondefining 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 ofcompression therapy)whether PTS prevention methods are necessary for patients with asymptomatic or distal DVTadditional treatment options for PTS with demonstrated safety and efficacy (compression andpharmacologic therapies)

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References1. 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 (https://dx.doi.org/10.1007%2Fs11239-009-0309-3). PMID 19224134(https://www.ncbi.nlm.nih.gov/pubmed/19224134).

2. Kahn SR, Hirsch A, Shrier I. Effect of postthrombotic syndrome on health-related quality of life after deep venousthrombosis. 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 onquality 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 lifeduring 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-termcomplications 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 thrombosisof the lower extremities: an analysis of a defined patient population in Sweden. Ann Intern Med 1997;126:454-7.

7. Kahn SR (2009). "How I treat postthrombotic syndrome"(http://bloodjournal.hematologylibrary.org/content/114/21/4624.long). Blood 114 (21): 4624–31. doi:10.1182/blood-2009-07-199174 (https://dx.doi.org/10.1182%2Fblood-2009-07-199174). PMID 19741190(https://www.ncbi.nlm.nih.gov/pubmed/19741190).

8. Sato, D. T., Masuda, E. M. (July 1998). "The natural history of calf vein thrombosis: Lysis of thrombi and developmentof reflux" (http://www.jvascsurg.org/article/S0741-5214(98)70201-0/fulltext). Journal of Vascular Surgery 28 (1): 67–74.

9. Kahn SR, Partsch H, Vedantham S, Prandoni P, Kearon C. Definition of post-thrombotic syndrome of the leg for use inclinical 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-thromboticsyndrome. 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 indeep vein thrombosis and the development of post-thrombotic syndrome: a prospective study. J Thromb Haemost2009;7:582-7.

12. Pirard D., Bellens B., Vereecken P. The post-thrombotic syndrome - a condition to prevent. Dermatology Online Journal14 (3): 13

13. Vedantham S. Valvular dysfunction and venous obstruction in the post-thrombotic syndrome. Thromb Res 2009; 123Suppl 4: S62-5.

14. Tick LW, Kramer MH, Rosendaal FR, Faber WR, Doggen CJ. Risk factors for post-thrombotic syndrome in patients witha 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 deepvenous 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. 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. Kearon C, Kahn SR, Agnelli G, Goldhaber S, Raskob GE, Comerota AJ. Antithrombotic therapy for venousthromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th

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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.

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