The Long-Term Complications of VTE

Once VTE develops, the risk of recurrence is high

In addition to the acute risk of pulmonary embolism (PE), a potentially life-threatening event, venous thrombosis also poses risks of intermediate- and long-term complications that include recurrent deep vein thrombosis (DVT), post-thrombotic syndrome, and chronic thromboembolic pulmonary hypertension, following PE.

The risk of recurrent DVT

The optimal treatment for patients at high risk of DVT is preventive therapy.³ The risk of recurrent DVT varies depending on the duration of the initial treatment. While clinical guidelines recommend 4-6 weeks of prophylactic treatment for DVT following orthopaedic surgery, treatment is often stopped on discharge despite the presence of silent DVT in up to 20% of patients.³¹⁵⁵ Increasing the duration of treatment in accordance with current guidelines can substantially decrease this risk.

For those who develop DVT, the recommended treatment duration is longer. For example, for DVT triggered by a transient factor, a 3-month course is recommended.¹²⁴ The recurrence rate has been reported as low as 3% when proximal DVT is treated with the standard 3-month course of effective anticoagulation.¹⁹⁷ Extending treatment beyond 3 months may further reduce the recurrence risk, to approximately 1% per patient-year.²¹¹ However, any increased benefit must be weighed against an increased risk of bleeding complications.¹⁷⁰ Shorter durations of therapy have been associated with a higher risk of recurrence. In one study of patients receiving 4 to 6 weeks of treatment for DVT (triggered by a transient risk factor), the recurrence rate was approximately 7% per patient-year.²¹²

Candidates for long-term oral anticoagulation include those at high risk for recurrence of venous thromboembolism (VTE). Patients at high risk include those with a previous history of recurrent VTE, malignancy or haematologic abnormality that predisposes to thrombus formation. Homozygous Factor V Leiden (FVL) or heterozygous FVL and the prothrombin G20210A mutation are examples of the types of haematologic abnormalities that confer a heightened risk of VTE recurrence.²⁸⁸

Measurement of specific proteins involved in coagulation can help guide clinical decision-making, although this type of laboratory assessment is rarely done in clinical practice. For example, a high level of coagulation Factor VIII signals an increased risk for recurrent VTE.²¹⁸ And an increased concentration of D-dimer, indicative of thrombus dissolution in the bloodstream, is associated with a 2.5-fold increased risk for VTE recurrence.¹⁸⁵

Elevated P-selectin levels are also associated with recurrent thrombosis within the first year after VTE.²⁷⁸ P-selectin is a biomarker that has procoagulant properties and reflects a prothrombotic state. This cell adhesion molecule is found on the surface of endothelial cells and on activated platelets. P-selectin also acts as an important mediator of the coagulation process.¹⁹⁵ High plasma levels of soluble P-selectin (sP-selectin) are modulated by variations of the P-selectin gene and are predictive biomarkers for recurrence of VTE in patients with a first episode of unprovoked VTE. However, the clinical applicability of P-selectin needs further investigation.²⁴⁸

The risk of post-thrombotic syndrome

Between 20% and 50% of those who develop DVT eventually develop a condition known as post-thrombotic syndrome (PTS).⁷⁴ The exact cause of PTS is not well understood, but it may involve damage to venous valves, ultimately leading to increased venous pressure.⁷⁵ The main symptom is chronic pain. Signs of PTS include swelling, discolouration of the affected leg, and, in severe cases, skin ulceration. In addition to pain, patients with PTS may experience a sensation of heaviness, as well as cramps, itching, and tingling.⁷⁴

PTS is not reliably prevented by prompt antithrombotic therapy following the diagnosis of DVT. This is another reason why preventive therapy is the optimal approach for high-risk patients.⁷⁶

The risk of chronic thromboembolic pulmonary hypertension

Pulmonary hypertension — chronically elevated blood pressure in the pulmonary circulation — occurs as a late complication in between 3% and 4% of patients who survive pulmonary embolism.⁷⁷

Symptoms include progressive shortness of breath and exercise intolerance. Later in the course of the disorder, chest pain with exertion and syncope may occur. Without intervention, the five-year survival rate once the mean pulmonary artery pressure reaches 40 mm Hg is about 30%.⁷⁸

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Article references

3 - 1. Geerts WH, Bergqvist D, Pineo GF, et al. Prevention of venous thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008;133(6)(suppl):381S-453S.
155 - AAOS [American Academy of Orthopedic Surgeons]. Clinical guideline on prevention of pulmonary embolism in patients undergoing total hip or knee arthroplasty. Adopted by the American Academy of Orthopedic Surgeons Board of Directors; 2007.
124 - 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(6)(suppl):454S-545S.
197 - Galanaud JP, Quenet S, Rivron-Guillot K, et al.; RIETE Investigators. Comparison of the clinical history of symptomatic isolated distal deep-vein thrombosis vs. proximal deep vein thrombosis in 11 086 patients. J Thromb Haemost. 2009;7(12):2028-2034.
211 - Kearon C, Gent M, Hirsh J, et al. A comparison of three months of anticoagulation with extended anticoagulation for a first episode of idiopathic venous thromboembolism. N Engl J Med. 1999;340(12):901-907.
170 - Campbell IA, Bentley DP, Prescott RJ, Routledge PA, Shetty HG, Williamson IJ. Anticoagulation for three versus six months in patients with deep vein thrombosis or pulmonary embolism, or both: randomised trial. BMJ. 2007;334(7595):674.
212 - Kearon C, Ginsberg JS, Anderson DR, et al; SOFAST Investigators. Comparison of 1 month with 3 months of anticoagulation for a first episode of venous thromboembolism associated with a transient risk factor. J Thromb Haemost. 2004;2(5):743-749.
288 - Zhu T, Martinez I, Emmerich J. Venous thromboembolism: risk factors for recurrence. Arterioscler Thromb Vasc Biol. 2009;29(3):298–310.
218 - Kyrle PA, Eichinger S. The risk of recurrent venous thromboembolism: the Austrian Study on Recurrent Venous Thromboembolism. Wien Klin Wochenschr. 2003;115(13-14):471-474.
185 - Eichinger S, Minar E, Bialonczyk C, et al. D-dimer levels and risk of recurrent venous thromboembolism. JAMA. 2003;290(8):1071-1074.
278 - Vormittag R, Panzer S, Ay C, Quehenberger P, Koder S, Pabinger I. Soluble P-selectin and thrombosis risk of patients with a persistent lupus anticoagulant in a prospective cohort study [abstract 0878]. Haematologica. 2007;92(suppl 2):327.
195 - Furie B, Furie BC. Mechanisms of thrombus formation. N Engl J Med. 2008;359(9):938-949.
248 - Pabinger I, Ay C. Biomarkers and venous thromboembolism. Arterioscler Thromb Vasc Biol. 2009;29(3):332-336.
74 - Kahn SR. The post-thrombotic syndrome: the forgotten morbidity of deep venous thrombosis. J Thromb Thrombolysis. 2006;21(1):41-48.
75 - Haenen JH, Janssen MC, van Langen H, et al. The postthrombotic syndrome in relation to venous hemodynamics, as measured by means of duplex scanning and strain-gauge plethysmography. J Vasc Surg. 1999;29(6):1071-1076.
76 - Prandoni P, Lensing AW, Cogo A, et al. The long-term clinical course of acute deep venous thrombosis. Ann Intern Med. 1996;125(1):1-7.
77 - Pengo V, Lensing AW, Prins MH, et al. Incidence of chronic thromboembolic pulmonary hypertension after pulmonary embolism. N Engl J Med. 2004;350(22):2257-2264.
78 - Fedullo PF, Auger WR, Kerr KM, Rubin LJ. Chronic thromboembolic pulmonary hypertension. N Engl J Med. 2001;345(20):1465-1472.

Hypertension: Persistently high arterial blood pressure. Hypertension may have no known cause (essential or idiopathic hypertension) or be associated with other primary diseases (secondary hypertension). This condition is considered a risk factor for the development of heart disease, peripheral vascular disease, stroke, and kidney disease.
Post-thrombotic syndrome: A syndrome that can follow a vascular thrombosis. Clinical signs and symptoms of this syndrome include chronic pain, swelling, oedema, discolouration, and in severe cases, venous ulceration. It is likely that valvular incompetence is associated with the clinical manifestations of post-thrombotic syndrome.
Prothrombin: Factor II, also called prothrombin, is converted into thrombin as part of the coagulation cascade.
Venous thromboembolism: A condition in which a blood clot (thrombus) forms in a vein, which in some cases then breaks free and enters the circulation as an embolus, finally lodging in and completely obstructing a blood vessel, e.g., in lungs causing a PE. The term encompasses both DVT and PE.
Procoagulant: A substance that promotes the coagulation of blood.