Venous Thromboembolism - Management Follow Up

Monitoring

DVT and Non-Massive Pulmonary Embolism

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

Cumulative VTE risk over 5 years is as follows:

• Low risk (<14%): Transient risk factors (eg surgery, Estrogen therapy)
• Intermediate risk (14-30%): Non-surgical transient risk factors (eg leg injury, significant medical illness, travel associated)
• High risk (?30%): Unprovoked VTE

Recurrences tend to develop in a similar site to the initial episode, with more proximal VTE having higher recurrences rates. Risk factors for recurrent VTE in patients with calf DVT include age >50 years old, male sex, multiple unilateral thromboses, bilateral DVT, unprovoked DVT, and cancer. 

Risk factors for proximal extension of distal DVT favoring anticoagulation include D-dimer ≥500 ng/mL, non-minor symptoms, unprovoked event, extensive thrombosis involving multiple veins, persistent or non-reversible risk factors (eg active cancer, prolonged immobility), prior DVT or pulmonary embolism, and inpatient status. The risk of proximal extension or pulmonary embolism in patients with distal DVT without anticoagulation is >10%.   

Factors favoring surveillance of distal DVT include D-dimer level <500 ng/mL, no or minor symptoms, absence of high-risk features of proximal extension, minor thrombosis in the muscular veins, high risk of or contraindications to bleeding and patient preference.

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 VTE 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 VTE, 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 VTE unresponsive to vitamin K antagonist therapy or for those with breakthrough VTE 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 DVT with low to moderate bleeding risk, or patients with symptomatic distal DVT (provoked or unprovoked)
• Continue for ≥6 months: First episode, idiopathic VTE
• Continue for ≥12 months: Recurrent, idiopathic VTE 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 DVT, 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 DVT, NOACs are preferred over vitamin K antagonist agents for the principal treatment phase. For patients with unprovoked proximal DVT, NOACs are recommended over LMWH followed by vitamin K antagonist agents for the principal treatment phase; NOACs are recommended over vitamin K antagonist agents for extended anticoagulation. 
 
A reduced dose of NOACs may be an option for extended anticoagulation. Reduced doses of Apixaban or Rivaroxaban may be options for patients with unprovoked proximal DVT requiring extended anticoagulation for >6 months but without high risk for recurrence.  

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

For patients with leg DVT or pulmonary embolism, NOACs 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 VTE. For VTE patients with cancer, LMWH is preferred over vitamin K antagonist agents and NOACs are alternative agents. 
 
For patients who need to continue on extended anticoagulant therapy, therapeutic or low-dose NOACs (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 VTE 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 VTE in patients with unprovoked proximal DVT or pulmonary embolism who refused continued anticoagulant therapy. Aspirin or Sulodexide may be considered for an extended VTE prophylaxis in patients who refuse or cannot tolerate oral anticoagulation.   

For patients who sustained a VTE 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, diabetes mellitus)
• 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 VTE. Regularly monitor therapeutic levels to ensure effective anticoagulation in patients weighing <50 kg or >120 kg. Monitor patient for recurrence, bleeding, adverse effects of medication and signs and symptoms of conditions that could alter the half-life of the anticoagulant used (eg kidney failure, weight loss or gain).
 
Monitoring without Anticoagulation Therapy  

Monitoring without anticoagulation therapy is recommended for patients with isolated distal leg DVT and no severe symptoms or risk factors for proximal extension, and those with high bleeding risk. Serial ultrasound imaging of both legs for 2 weeks is suggested.

Surveillance is recommended in patients with subsegmental pulmonary embolism and without proximal DVT and low risk of recurrence for VTE.