Venous Thromboembolism - Management Follow Up

Monitoring

Deep Vein Thrombosis and Non-Massive Pulmonary Embolism  

Provoked venous thromboembolism with persistent risk factors and a second episode of unprovoked venous thromboembolism have the highest recurrence rates at 1 year and 5 years after stopping anticoagulation therapy. The rate of recurrent venous thromboembolism is approximately 10% during the first year and 30% after 5 years, and approximately 40% in 10 years in patients with unprovoked deep vein thrombosis. Other strong risk factors for recurrence include a pulmonary embolism, proximal deep vein thrombosis, or a previous venous thromboembolism. A high (>8%/year) risk for long-term recurrence is seen in patients with active cancer, antiphospholipid antibody syndrome, and ≥1 prior venous thromboembolism episodes without a transient factor. 

Five-year recurrence risk is as follows:

• Low risk (3%): Transient risk factors (eg surgery, Estrogen therapy)
• Intermediate risk (15%): Non-surgical transient risk factors (eg leg injury, significant medical illness, travel associated)
• High risk (30%): Unprovoked venous thromboembolism

Recurrences tend to develop in a similar site to the initial episode, with more proximal venous thromboembolism having higher recurrences rates. Risk factors for recurrent venous thromboembolism in patients with calf deep vein thrombosis include age >50 years old, male sex, multiple unilateral thromboses, bilateral deep vein thrombosis, unprovoked deep vein thrombosis, and cancer. The risk of proximal extension of deep vein thrombosis and/or pulmonary embolism in patients with distal deep vein thrombosis without anticoagulation is >10%.  

Patients with acute pulmonary embolism are recommended to follow up 3 to 6 months after an acute episode. These patients have a high frequency (20 to 50%) of symptomatic extension of thrombus and/or recurrent venous thromboembolism and therefore require long-term anticoagulant treatment.  

Extended anticoagulation treatment should be considered in the following patients with an index pulmonary embolism episode: Have no identifiable risk factor or with a minor transient risk factor; and those with a persistent risk factor other than antiphospholipid antibody syndrome.  

Patients receiving extended treatment should be followed up at least annually and checked for the presence of bleeding and recurrent venous thromboembolism, changes in hepatic or renal function, adherence to therapy, treatment preferences, and new drug interactions. Consider further evaluation for pulmonary embolism survivors who are asymptomatic and at increased risk for chronic thromboembolic pulmonary hypertension.  

If anticoagulation treatment failure occurs, check the patient's adherence to therapy, check for malabsorption or treatment suspension for a planned procedure, increase the anticoagulant dose or administration frequency or switch to an anticoagulant with a different mechanism of action, and address other causes of hypercoagulability.  

LMWH  

Treatment options for patients with recurrent venous thromboembolism unresponsive to vitamin K antagonist therapy or for those with breakthrough venous thromboembolism during vitamin K antagonist therapy. The dose may be increased if there is treatment failure to present the dose.  

For patients with pulmonary embolism and cancer, LMWH is preferred over vitamin K antagonists and should be used for the first 6 months of long-term anticoagulant therapy. After which, these patients should receive oral anticoagulant therapy indefinitely or until the cancer has resolved.  

Oral Anticoagulant

Treatment with oral anticoagulant is the preferred method of long-term management of most patients with pulmonary embolism. Adjusted doses of UFH or LMWH may be indicated for selected patients in whom oral anticoagulants are contraindicated or impractical. 

Venous Thromboembolism - Management_Follow Up

Duration of anticoagulation is dependent on the type of event and the coexistence of prolonged risk factors:

• Continue for ≥3 months: First event with provoked risk factors, in cancer patients with symptomatic catheter-related thrombosis, patients with unprovoked proximal deep vein thrombosis with low to moderate bleeding risk, or patients with symptomatic distal deep vein thrombosis (provoked or unprovoked)
• Continue for ≥6 months: First episode, idiopathic venous thromboembolism
• Continue for ≥12 months: Recurrent, idiopathic venous thromboembolism or continuing risk factor
• Continue for 6-12 weeks: Symptomatic isolated calf vein thrombosis
• Consider for indefinite anticoagulation: Second episode of unprovoked pulmonary embolism, unprovoked proximal deep vein thrombosis, chronic risk factor (provoked non-surgical and non-reversible risk factors), or patients with pulmonary embolism and cancer without high bleeding risk

For patients with provoked proximal deep vein thrombosis, non-vitamin K antagonist oral anticoagulants are preferred over vitamin K antagonist agents for the principal treatment phase. For patients with unprovoked proximal deep vein thrombosis, non-vitamin K antagonist oral anticoagulants are recommended over LMWH followed by vitamin K antagonist agents for the principal treatment phase; non-vitamin K antagonist oral anticoagulants are recommended over vitamin K antagonist agents for extended anticoagulation. 

A reduced dose of direct oral anticoagulants may be an option for extended anticoagulation. Reduced doses of Apixaban or Rivaroxaban may be options for patients with unprovoked proximal deep vein thrombosis requiring extended anticoagulation for >6 months but without high risk for recurrence.  

Dabigatran is effective for extended anticoagulation therapy for venous thromboembolism in patients with a high risk of recurrence.

For patients with leg deep vein thrombosis or pulmonary embolism, non-vitamin K antagonist oral anticoagulants are preferred over vitamin K antagonist agents for the first 3 months of long-term anticoagulant therapy. Vitamin K antagonist agents are preferred over LMWH for patients with venous thromboembolism. For venous thromboembolism patients with cancer, LMWH is preferred over vitamin K antagonist agents and non-vitamin K antagonist oral anticoagulants are alternative agents. 

For patients who need to continue on extended anticoagulant therapy, therapeutic or low-dose non-vitamin K antagonist oral anticoagulants (eg Apixaban or Rivaroxaban) can be given after the first 6 months and are preferred over Warfarin if without contraindications.  

Warfarin  

An INR range of 2.0-3.0 is recommended for patients with venous thromboembolism who will continue vitamin K antagonist therapy as extended anticoagulation after having completed the primary treatment.  

Aspirin  

Aspirin may be considered for the prevention of recurrent venous thromboembolism in patients with unprovoked proximal deep vein thrombosis or pulmonary embolism who refused continued anticoagulant therapy. Aspirin or Sulodexide may be considered for an extended venous thromboembolism prophylaxis in patients who refuse or cannot tolerate oral anticoagulation.  

For patients who sustained a venous thromboembolism while taking Aspirin for primary cardiovascular disease prevention or for stable coronary artery disease, it is advised to suspend Aspirin while taking anticoagulant therapy.  

International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) Bleeding Risk  

IMPROVE is used to assess a confined patient’s risk for bleeding prior to initiation of therapy. A score of ≥7 signifies increased bleeding risk.

Risk Factors for Major Bleeding During Anticoagulation

Patients without risk factors have an absolute risk of major bleeding of 0.8% per year, 1 risk factor is 1.6% per year, and ≥2 risk factors are ≥6.5% per year.

The risk factors for major bleeding during anticoagulation are as follows:

• Age >75 years
• History of previous bleeding 
• Previous non-cardioembolic stroke
• Chronic hepatic and renal disease
• Concomitant antiplatelet or nonsteroidal anti-inflammatory (NSAID) therapy
• Poor anticoagulant control
• Suboptimal monitoring of therapy
• Comorbid illness, eg cancer, hypertension, thrombocytopenia, anemia
• Frequent falls, alcohol abuse
• Recent surgery

Monitoring during Anticoagulation Therapy  

INR should be checked at least weekly during the first several weeks of Warfarin therapy. If stable, monitor every 2 weeks then every 4 weeks. The target INR is 2.5 for most patients and 3.0 for patients with recurrent venous thromboembolism. Regularly monitor therapeutic levels to ensure effective anticoagulation in patients weighing <50 kg or >120 kg. 

Monitoring without Anticoagulation Therapy  

Monitoring without anticoagulation therapy is recommended for patients with isolated distal leg deep vein thrombosis and no severe symptoms or risk factors of extension (eg inpatient status, history of venous thromboembolism, active cancer, persistent provoking factor, thrombosis near proximal veins, involvement of multiple veins, and positive D-Dimer), and those with subsegmental pulmonary embolism without proximal leg deep vein thrombosis.  

The risk of proximal extension of deep vein thrombosis and/or pulmonary embolism in patients with distal deep vein thrombosis without anticoagulation is >10%. Serial ultrasound imaging of both legs for 2 weeks is suggested for patients with isolated distal leg deep vein thrombosis without severe symptoms or risk factors of extension. Surveillance is recommended in patients with subsegmental pulmonary embolism and without proximal deep vein thrombosis and low risk of recurrence for venous thromboembolism.