Whether a DVT is due to major transient risk factors (e.g., trauma, surgery), minor transient risk factors (prolonged hospitalization or medical illness), major persisting risk factors (e.g., cancer), or no identified risk factors (unprovoked) is a significant determinant of recurrence. The extent and location of the initial clot influence the risk of post-thrombotic syndrome, which is the major sequela of DVT. DVT seldom alters the overall prognosis of the patient; the presence or absence of an underlying malignancy, and the presence or absence of underlying medical comorbidity, such as liver disease or chronic kidney disease, remain the major prognostic determinants among DVT patients. People with cancer have reduced survival rates compared with people without cancer, and cancer patients who sustain DVT have a shorter life expectancy than cancer patients without venous thromboembolism (VTE), though this appears to be related to an association with more severe malignancy and VTE, rather than to the DVT itself. When a patient dies from DVT, it is usually from pulmonary embolus (PE) or from a major hemorrhage as a complication of the anticoagulation therapy.
In one systematic review, during the initial 3 months of anticoagulation, the rate of recurrent fatal VTE was 0.4% with a case-fatality rate of 11.3%. The rate of fatal major bleeding events was 0.2% with a case-fatality rate of 11.3%. After anticoagulation, the rate of fatal recurrent VTE was 0.3 per 100 patient-years with a case-fatality rate of 3.6%.[239]Carrier M, Le Gal G, Wells PS, et al. Systematic review: case-fatality rates of recurrent venous thromboembolism and major bleeding events among patients treated for venous thromboembolism. Ann Intern Med. 2010 May 4;152(9):578-89.
http://www.ncbi.nlm.nih.gov/pubmed/20439576?tool=bestpractice.com
In community cohort studies, the incidence of acute recurrent DVT within 60 days is as high as 25% to 30%. The reasons for this acute recurrence are not known, but subtherapeutic anticoagulant therapy or patient nonadherence to therapy may contribute.[240]Spencer FA, Emery C, Joffe SW, et al. Incidence rates, clinical profile, and outcomes of patients with venous thromboembolism: the Worcester VTE study. J Thromb Thrombolysis. 2009 Nov;28(4):401-9.
http://www.ncbi.nlm.nih.gov/pubmed/19629642?tool=bestpractice.com
[241]Heit JA, Mohr DN, Silverstein MD, et al. Predictors of recurrence after deep vein thrombosis and pulmonary embolism: a population-based cohort study. Arch Intern Med. 2000 Mar 27;160(6):761-8.
https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/485265
http://www.ncbi.nlm.nih.gov/pubmed/10737275?tool=bestpractice.com
In patients with acute DVT or PE enrolled in prospective cohort studies, only 5% of patients develop recurrent VTE during the initial 6 months of anticoagulation; however 30% of patients develop recurrent VTE between 6 months and 5 years after the initial event, if off anticoagulation.[242]Schulman S, Rhedin AS, Lindmarker P, et al. A comparison of six weeks with six months of oral anticoagulant therapy after a first episode of venous thromboembolism. Duration of Anticoagulation Trial Study Group. N Engl J Med. 1995 Jun 22;332(25):1661-5.
http://www.ncbi.nlm.nih.gov/pubmed/7760866?tool=bestpractice.com
[243]Schulman S, Granqvist S, Holmström M, et al. The duration of oral anticoagulant therapy after a second episode of venous thromboembolism. The Duration of Anticoagulation Trial Study Group. N Engl J Med. 1997 Feb 6;336(6):393-8.
http://www.ncbi.nlm.nih.gov/pubmed/9010144?tool=bestpractice.com
Compared with patients with no thrombophilic defects, the rate of recurrence during warfarin therapy is not increased in the presence of one or more defects.[244]Kearon C, Julian JA, Kovacs MJ, et al; ELATE Investigators. Influence of thrombophilia on risk of recurrent venous thromboembolism while on warfarin: results from a randomized trial. Blood. 2008 Dec 1;112(12):4432-6.
https://ashpublications.org/blood/article/112/12/4432/24454/Influence-of-thrombophilia-on-risk-of-recurrent
http://www.ncbi.nlm.nih.gov/pubmed/18791166?tool=bestpractice.com
The incidence of major life-threatening hemorrhage owing to anticoagulant treatment is low, with the precise risk varying by anticoagulant agent and patient characteristics.
Recurrence
Consensus guidelines recommend 3 months of oral anticoagulant therapy, unless contraindicated by bleeding, in all patients with VTE, with reassessment for possible extended therapy after the initial 3 months of treatment.[245]Louzada ML, Majeed H, Wells PS. Efficacy of low-molecular-weight heparin versus vitamin K antagonists for long term treatment of cancer-associated venous thromboembolism in adults: a systematic review of randomized controlled trials. Thromb Res. 2009 Apr;123(6):837-44.
http://www.ncbi.nlm.nih.gov/pubmed/18977517?tool=bestpractice.com
Patients with DVT occurring in the setting of a major or minor transient provocation will usually stop anticoagulants after completion of at least 3 months of therapy. Consideration should be given to indefinite treatment among patients who have idiopathic or unprovoked DVT.[246]Kearon C. Extended anticoagulation for unprovoked venous thromboembolism: a majority of patients should be treated. J Thromb Thrombolysis. 2011 Apr;31(3):295-300.
http://www.ncbi.nlm.nih.gov/pubmed/21331558?tool=bestpractice.com
Patients with cancer continue anticoagulants, as long as they are tolerated, while the cancer is active, and if the risk of bleeding remains low to moderate without any recent major bleeding episodes.[18]Stevens SM, Woller SC, Kreuziger LB, et al. Antithrombotic therapy for VTE disease: second update of the CHEST guideline and expert panel report. Chest. 2021 Dec;160(6):e545-608.
https://journal.chestnet.org/article/S0012-3692(21)01506-3/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/34352278?tool=bestpractice.com
Regular reassessment is necessary in patients with cancer as the risks of VTE and bleeding regularly change given modifications in pharmacotherapeutic, surgical, and radiation therapies.[19]National Institute for Health and Care Excellence (UK). Venous thromboembolic diseases: diagnosis, management and thrombophilia testing. Aug 2023 [internet publication].
https://www.nice.org.uk/guidance/ng158
[42]Key NS, Khorana AA, Kuderer NM, et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: ASCO guideline update. J Clin Oncol. 2023 Jun 1;41(16):3063-71.
https://ascopubs.org/doi/10.1200/JCO.23.00294
http://www.ncbi.nlm.nih.gov/pubmed/37075273?tool=bestpractice.com
Many studies have attempted to identify subgroups of patients with unprovoked VTE who do not need to be treated indefinitely with oral anticoagulation. There is strong evidence that the risk of recurrent VTE is higher in the following patients: male sex; those with a diagnosis of a proximal DVT (versus isolated calf DVT); those with ultrasound evidence of residual clot; those who have an elevated D-dimer 1 month after stopping a 3- to 6-month course of oral anticoagulation; and those who had an unprovoked DVT.[18]Stevens SM, Woller SC, Kreuziger LB, et al. Antithrombotic therapy for VTE disease: second update of the CHEST guideline and expert panel report. Chest. 2021 Dec;160(6):e545-608.
https://journal.chestnet.org/article/S0012-3692(21)01506-3/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/34352278?tool=bestpractice.com
[41]Mazzolai L, Ageno W, Alatri A, et al. Second consensus document on diagnosis and management of acute deep vein thrombosis: updated document elaborated by the ESC Working Group on aorta and peripheral vascular diseases and the ESC Working Group on pulmonary circulation and right ventricular function. Eur J Prev Cardiol. 2022 May 27;29(8):1248-63.
https://academic.oup.com/eurjpc/article/29/8/1248/6319853
http://www.ncbi.nlm.nih.gov/pubmed/34254133?tool=bestpractice.com
Several risk assessment models have been developed for this purpose, including the DASH score, the Vienna Prediction Model, and the "Men Continue and HER-DOO2" model.[191]Kyrle PA, Eichinger S. Clinical scores to predict recurrence risk of venous thromboembolism. Thromb Haemost. 2012 Dec;108(6):1061-4.
http://www.ncbi.nlm.nih.gov/pubmed/22872143?tool=bestpractice.com
The latter model identifies a subset of women with low risk for recurrent VTE after an initial unprovoked event, and a prospective validation study of this model was published.[192]Rodger MA, Le Gal G, Anderson DR; REVERSE II Study Investigators. Validating the HERDOO2 rule to guide treatment duration for women with unprovoked venous thrombosis: multinational prospective cohort management study. BMJ. 2017 Mar 17;356:j1065.
https://www.bmj.com/content/356/bmj.j1065.long
http://www.ncbi.nlm.nih.gov/pubmed/28314711?tool=bestpractice.com