Venous%20thromboembolism%20-%20management Management

During Anticoagulation Therapy

• International normalized ratio (INR) should be checked at least weekly during the 1st several weeks of Warfarin therapy
• If stable, monitor every 2 weeks then every 4 weeks
• 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

Without Anticoagulation Therapy

• Recommended for patients with isolated distal leg DVT and no severe symptoms or risk factors of extension (eg inpatient status, history of VTE, active cancer, persistent provoking factor, thrombosis near proximal veins, involvement of multiple veins, and positive D-Dimer), and those with subsegmental PE without proximal leg DVT
• Risk of proximal extension of DVT and/or PE in patients with distal DVT without anticoagulation is >10%
• Serial ultrasound imaging of both legs for 2 weeks is suggested for patients with isolated distal leg DVT without severe symptoms or risk factors of extension
• Surveillance is recommended in patients with subsegmental PE and without proximal DVT and low risk of recurrence for VTE

• Provoked VTE with persistent risk factors and second episode of unprovoked VTE have the highest recurrence rates at 1 year and 5 years after stopping anticoagulation therapy 
  • Other strong risk factors for recurrence include a PE, 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 
• 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 of proximal extension of DVT and/or PE in patients with distal DVT without anticoagulation is >10%
• Patients with acute PE are recommended to follow up 3-6 months after acute episode
  • Have a high frequency (20-50%) 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 PE episode:  
  • Have no identifiable risk factor or with a minor transient risk factor 
  • With a persistent risk factor other than antiphospholipid antibody syndrome
• Patients receiving extended treatment should be followed up at least annually and checked for 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 PE survivors who are asymptomatic and at increased risk for chronic thromboembolic pulmonary hypertension
• If anticoagulation treatment failure occurs, check patient's adherence to therapy, check for malabsorption or treatment suspension for a planned procedure, increase anticoagulant dose or administration frequency or switch to an anticoagulant with a different mechanism of action, and address other causes of hypercoagulability

Low-Molecular-Weight Heparin (LMWH)

• Treatment option for patients with recurrent VTE unresponsive to vitamin K antagonists (VKA) therapy or for those with breakthrough VTE during VKA therapy 
  • Dose may be increased if there is treatment failure to present dose
• For patients with PE and cancer, LMWH is preferred over VKAs and should be used for the 1st 6 months of long-term anticoagulant therapy
  • After which, these patients should receive oral anticoagulant therapy indefinitely or until cancer has resolved

Oral Anticoagulant

• Treatment with oral anticoagulant is the preferred method of long-term management of most patients with PE 
  • Adjusted doses of UFH or LMWH may be indicated for selected patients in whom oral anticoagulants are contraindicated or impractical
• Duration of anticoagulation is dependent on the type of event and the coexistence of prolonged risk factors:
  • Continue x ≥3 months: 1st event with transient 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
  • Continue x ≥6 months: 1st episode, idiopathic VTE 
  • Continue x ≥12 months: Recurrent, idiopathic VTE or continuing risk factor
  • Continue x 6-12 weeks: Symptomatic isolated calf vein thrombosis
  • Consider for indefinite anticoagulation: 2nd episode of unprovoked PE, chronic risk factor, or patients with PE and cancer without high bleeding risk
• For patients with provoked proximal DVT, NOACs are preferred over VKA agents for the principal treatment phase
• For patients with unprovoked proximal DVT, NOACs are recommended over LMWH followed by VKA agents for the principal treatment phase
  • NOACs are recommended over VKA agents for extended anticoagulation
• Reduced dose of DOACs may be an option for extended anticoagulation
  • Reduced dose 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 high risk of recurrence
• For patients with leg DVT or PE, non-vitamin K oral anticoagulants (NOACs) are preferred over VKA agents for the 1st 3 months of long-term anticoagulant therapy
  • VKA agents are preferred over LMWH for patients with VTE
  • For VTE patients with cancer, LMWH is preferred over VKA 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 1st 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 VKA therapy as extended anticoagulation after having completed the primary treatment

Aspirin

• May be considered for the prevention of recurrent VTE in patients with unprovoked proximal DVT or PE 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

• Used to assess a confined patient’s risk for bleeding prior to initiation of therapy
• Score of ≥7 signifies increased bleeding risk

Risk Factors for Major Bleeding During Anticoagulation

• Age >75 years old
• History of previous bleeding
• Previous noncardioembolic stroke
• Chronic hepatic and renal disease
• Concomitant antiplatelet therapy
• Poor anticoagulant control
• Suboptimal monitoring of therapy
• Comorbid illness, eg cancer, hypertension, thrombocytopenia, anemia 
• Frequent falls, alcohol abuse

O₂ Supplementation

• May be necessary in patients with hypoxemia
• Hypoxemia can usually be reversed with nasal O₂ so that mechanical ventilation is rarely necessary

Mechanical Ventilation

• May be needed temporarily in patients who appear toxic and hypoxic
• Care should be taken to limit its hemodynamic adverse effects
  • Positive intrathoracic pressures induced by mechanical ventilation may reduce venous return and worsen RV failure
• Low tidal volumes of approximately 6 mL/kg body weight are recommended

Hemodynamic Support

Fluid Loading

• Fluids may be administered initially and cautiously, but other vasoactive therapy should promptly follow
• The usefulness of fluid challenge is controversial and should not exceed 500 mL over 15-30 minutes
  • May be harmful when systemic hypotension is present

Adrenergic Agonists

• Should be considered for patients with low cardiac index and normal blood pressure or with impending hypotension
• In high-risk PE patients, Dobutamine and/or Norepinephrine should be considered 

Dobutamine

• Considered 1st-line agent to treat right-sided heart failure and cardiogenic shock
• Action: Affects vasodilatation of both systemic and pulmonary vascular beds, increases myocardial contractility while decreasing right-sided filling pressures

Dopamine

• Has also been used for hemodynamic support in PE patients
• Use may be limited by the development of tachycardia

Epinephrine

• May be effective when shock complicates acute PE
• Action: Vasoconstrictor effect similar to Norepinephrine, inotropic effect more due to potent β1 stimulation rather than β2 effect, accounting for improved pulmonary vascular resistance

Norepinephrine

• May be appropriate in acute massive PE when there is profound hypertension, eg cardiogenic shock
• Action: Stimulates both α-adrenergic (inducing vasoconstriction) and β1-adrenergic receptors (augmenting cardiac contractility) resulting in improved systemic blood pressure, cardiac output, pulmonary vascular resistance and right ventricular pressure
• Combination with other vasoactive agents (eg Dobutamine) needs further evaluation

Nitric Oxide Inhalation

• May be indicated in patients with pulmonary hypertension and a patent foramen ovale
• Effects: May improve the hemodynamic status and gas exchange in patients with PE