Treatment of DVT: how long is enough and how do you predict recurrence

Abstract Currently available anticoagulants are effective in reducing the recurrence rate of venous thromboembolism (VTE). However, anticoagulant treatment is associated with an increased risk for bleeding complications. Thus, anticoagulation has to be discontinued when benefit of treatment no longer clearly outweigh its risks. The duration of anticoagulant treatment is currently framed based on the estimated individual risk for recurrent VTE. The incidence of recurrent VTE can be estimated through a two-step decision algorithm. Firstly, the features of the patient (gender), of the initial event (proximal or distal deep vein thrombosis or pulmonary embolism), and the associated conditions (cancer, surgery, etc) provide essential information on the risk for recurrence after anticoagulant treatment discontinuation. Secondly, at time of anticoagulant treatment discontinuation, d-dimer levels and residual thrombosis have been indicated as predictors of recurrent VTE. Current evidence suggests that the risk of recurrence after stopping therapy is largely determined by whether the acute episode of VTE has been effectively treated and by the patient’s intrinsic risk of having a new episode of VTE. All patients with acute VTE should receive oral anticoagulant treatment for three months. At the end of this treatment period, physicians should decide for withdrawal or indefinite anticoagulation. Based on intrinsic patient’s risk for recurrent VTE and for bleeding complications and on patient preference, selected patients could be allocated to indefinite treatment with VKA with scheduled periodic re-assessment of the benefit from extending anticoagulation. Alternative strategies for secondary prevention of VTE to be used after conventional anticoagulation are currently under evaluation. Cancer patients should receive low molecular-weight heparin over warfarin in the long-term treatment of VTE. These patients should be considered for extended anticoagulation at least until resolution of underlying disease. Abbreviated abstract The risk for recurrent venous thromboembolism can be estimated through a two-step algorithm. Firstly, the features of the patient (gender), of the initial event (proximal or distal deep vein thrombosis or pulmonary embolism), and the associated conditions (cancer, surgery, etc) are essential to estimate the risk for recurrence after anticoagulant treatment discontinuation. Secondly, a correlation has been shown between d-dimer levels and residual thrombosis at time of anticoagulant treatment discontinuation and the risk of recurrence. Currently available anticoagulants are effective in reducing the incidence of recurrent venous thromboembolism, but they are associated with an increased risk for bleeding complications. All patients with acute venous thromboembolism should receive oral anticoagulant treatment for three months. At the end of this treatment period physicians should decide for definitive withdrawal or indefinite anticoagulation with scheduled periodic re-assessment of the benefit from extending anticoagulation.     

Management of venous thromboembolism: a clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians

Venous thromboembolism is a common condition affecting 7.1 persons per 10,000 person-years among community residents. Incidence rates for venous thromboembolism are higher in men and African Americans and increase substantially with age. It is critical to treat deep venous thrombosis at an early stage to avoid development of further complications, such as pulmonary embolism or recurrent deep venous thrombosis. The target audience for this guideline is all clinicians caring for patients who have been given a diagnosis of deep venous thrombosis or pulmonary embolism. The target patient population is patients receiving a diagnosis of pulmonary embolism or lower-extremity deep venous thrombosis.     

Venous thromboembolism after severe injury in children

BACKGROUND: Deep vein thrombosis and pulmonary embolism are considered common complications after major trauma. Their incidence and the associated risk factors have rarely been identified in injured children. METHODS: Severely injured children (age <18 years; admitted in a pediatric intensive care unit or length of stay > or = 72 h) with a discharge diagnosis of venous thromboembolism (VTE; deep venous thrombosis and/or pulmonary embolism) were identified from the institutional trauma registry between January 1, 1999 and April 31, 2002. The study centers included a dedicated pediatric trauma center and an adult trauma center with pediatric patients. Risk factors for VTE were identified using multivariate analysis. RESULTS: VTE was found in 11 of the 3,291 admissions, for a rate of 3.3/1,000 admissions. Children with VTE were older and had higher Injury Severity Scores. Independent risk factors for VTE included thoracic injuries [odds ratio (OR): 6.9; 95% confidence interval (CI): 1.4-35.1] and spinal injuries (OR: 37.4; 95% CI: 3.5-396.7). The greatest risk of VTE was in children with central venous catheters (OR: 64.0; 95% CI: 16.8-243.9). CONCLUSION: Older children with high Injury Severity Scores, thoracic injuries, spinal injuries or venous catheters are at risk for VTE. Because VTE prophylaxis, screening and treatment are associated with complications and costs, it is essential to identify subgroups of pediatric patients in whom these strategies might be studied.     

Risk factors for venous thromboembolism

Venous thromboembolism is a common and potentially lethal disease. Patients who have pulmonary embolism are at especially high risk for death. Death owing to pulmonary embolism is independent of other comorbid conditions (e.g., cancer, chronic heart disease, or lung disease). Sudden death is often the first clinical manifestation. Only a reduction in the incidence of venous thromboembolism can reduce sudden death owing to pulmonary embolism and venous stasis syndrome owing to deep vein thrombosis. The incidence of venous thromboembolism has been relatively constant since about 1980. Improvement in the incidence of venous thromboembolism will require better recognition of persons at risk, improved estimates of the magnitude of risk, the avoidance of risk exposure when possible, more widespread use of safe and effective prophylaxis when risk is unavoidable, and targeting of prophylaxis to those persons who will benefit most. Recognition of venous thromboembolism as a multifactorial disease with genetic and genetic-environmental interaction has provided significant insights into its epidemiology and offers the possibility of improved identification of persons at risk for incident and recurrent venous thromboembolism.     

Venous thromboembolism epidemiology: implications for prevention and management

Venous thromboembolism is a major health problem, with an incidence that exceeds 1 per 1000. Over 200,000 new cases occur in the United States annually. Of these, 30% of patients die within 30 days; one-fifth suffer sudden death due to pulmonary embolism. Despite improved prophylaxis, the incidence of venous thromboembolism has not changed significantly since 1980. Independent risk factors for venous thromboembolism include increasing age, male gender, surgery, trauma, hospital or nursing home confinement, malignancy, neurologic disease with extremity paresis, central venous catheter/ transvenous pacemaker, prior superficial vein thrombosis, and varicose veins; among women, the risk factors include pregnancy, oral contraceptives, and hormone replacement therapy. About 30% of surviving patients develop recurrent venous thromboembolism within 10 years. Independent predictors for recurrence include increasing age, obesity, malignant neoplasm, and extremity paresis. About 28% of patients develop venous stasis syndrome within 20 years. To reduce venous thromboembolism incidence, improve survival, and prevent recurrence and complications, patients with these characteristics should receive appropriate prophylaxis.     

Thrombophilic risk of individuals with rare compound factor V Leiden and prothrombin G20210A polymorphisms: an international case series of 100 individuals

The risk of thrombosis in individuals with rare compound thrombophilias, homozygous factor V Leiden (FVL) plus heterozygous prothrombin G20210A (PTM), homozygous PTM plus heterozygous FVL, and homozygous FVL plus homozygous PTM, is unknown. We identified, worldwide, individuals with these compound thrombophilias, predominantly through mailing members of the International Society on Thrombosis and Haemostasis. Physicians were sent a clinical questionnaire. Confirmatory copies of the genetic results were obtained. One hundred individuals were enrolled; 58% were female. Seventy‐one individuals had a venous thrombosis (includes superficial and deep vein thrombosis, and pulmonary embolism), 4 had an arterial thrombosis and 6 had both. Nineteen individuals had never had a thrombotic event. Thrombosis‐free survival curves demonstrated that 50% of individuals had experienced a thrombotic event by 35 yrs of age, while 50% had a first venous thromboembolic event (VTE; includes all venous thrombosis except superficial thrombosis) by 41 yrs of age; 38.2% of first VTEs were unprovoked. 37% of patients had at least one VTE recurrence. Seventy percent of first pregnancies carried to term and not treated with anticoagulation were thrombosis‐free. In conclusion, patients with these rare compound thrombophilias are not exceedingly thrombogenic, even though they have a substantial risk for VTE.     

New onset of venous thromboembolism among hospitalized patients at Brigham and Women's Hospital is caused more often by prophylaxis failure than by withholding treatment

CONTEXT: Guidelines to prevent venous thromboembolism (VTE) have been widely distributed and generally have been assumed to be effective. Therefore, among hospitalized patients, the development of VTE is thought to occur in the context of omitted prophylaxis. OBJECTIVES: To describe hospitalized patients who develop VTE and to determine whether they received antecedent prophylaxis. DESIGN: Case series. SETTING: Brigham and Women's Hospital. PATIENTS: Three hundred eighty-four patients who developed in-hospital deep venous thrombosis or pulmonary embolism or who developed VTE within 30 days of prior hospital discharge. Main outcome measures: The relationship of developing new-onset VTE to the use or omission of antecedent in-hospital prophylaxis. RESULTS: Of the 384 identified patients, 272 had deep venous thrombosis alone, 62 had pulmonary embolism alone, and 50 had deep venous thrombosis and pulmonary embolism. Most were medical service patients; fewer than one fourth were general or orthopedic surgery patients. Overall, 52% had received antecedent VTE prophylaxis. Thirteen deaths (3.4%) were ascribed to pulmonary embolism, and prophylaxis was omitted in only 1 of those 13 patients. CONCLUSIONS: Most deaths from pulmonary embolism among patients hospitalized for other conditions occurred in the setting of failed prophylaxis rather than omitted prophylaxis. High-risk patients, especially medical service patients, warrant intensive VTE prophylaxis and close follow-up to ensure successful outcomes.     

Prevalence of venous thromboembolism in neurosurgical patients

This study was conducted to clarify the prevalence of venous thromboembolism (VTE) in neurosurgical patients. Prospective study for venous thromboembolism screening after neurosurgery was conducted. Thirty-seven patients were screened by ultrasonography for deep vein thrombosis in the lower extremities at an average of 12 days postoperatively. All patients received standard thromboprophylaxis using graded compression stocking with/without intermittent pneumatic compression following the VTE prevention guidelines. Definitive diagnosis of venous thromboembolism was made by contrast-enhanced whole-body computed tomography. Prevalence of deep vein thrombosis of the lower legs was 13.5% (5/37). Incidence of pulmonary embolism was 60% (3/5) in patients having deep vein thrombosis. All patients having venous thromboembolism were asymptomatic. In high-risk patients, VTE prevalence after neurosurgery was high even under mechanical prophylaxis. Additional pharmacological prophylaxis should be considered for patients with high risk of VTE.     

Pathogenesis,Diagnosis, and Treatment of Venous Thromboembolism in Older Adults

Older adults have a significantly greater risk of venous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism, than younger adults. The cause of this greater risk is thought to be multifactorial, including age‐related changes in hemostatic factors and greater comorbid conditions and hospitalizations, but is not completely understood. Moreover, VTE remains underrecognized in older adults and may present atypically. Thus, a low index of clinical suspicion is essential when evaluating older adults with possible VTE. Despite this underrecognition in older adults, the diagnostic approach remains similar for all age groups and includes estimation of pretest probability, measurement of the D‐dimer, and imaging. Antithrombotic agents are the mainstay of VTE treatment and, when used appropriately, substantially reduce VTE recurrence and complications. The approval of novel oral anticoagulants (NOACs), including dabigatran, rivaroxaban, apixaban, and edoxaban, provide clinicians with new therapeutic options. In some individuals, NOACs may offer advantages over warfarin, including fewer drug interactions, more‐predictable anticoagulation, and lower risk of bleeding. Nevertheless, anticoagulation of VTE in older adults should always be performed cautiously, because age is a risk factor for bleeding complications. Identifying modifiable bleeding risk factors and balancing the risks of VTE recurrence with hemorrhage are important considerations when using anticoagulants in older adults.