venous%20thromboembolism%20-%20management
VENOUS THROMBOEMBOLISM - MANAGEMENT
Deep vein thrombosis is a frequent manifestation of venous thromboembolism in which there is a blood clot blocking a deep vein.
Clinical findings are important to the diagnosis of deep vein thrombosis but are poor predictors of the presence or severity of thrombosis.
Pulmonary embolism is the blockage of the blood vessels in the lungs usually due to blood clots from the veins, especially veins in the legs and pelvis.
Dyspnea, pleuritic chest pain, syncope and tachypnea occur in most cases of pulmonary embolism.
Massive pulmonary embolism has the prime symptom of dyspnea and systemic arterial hypotension that requires pressor support is the predominant sign.

Principles of Therapy

Deep Vein Thrombosis (DVT) and Non-Massive Pulmonary Embolism (PE)

Parental Anticoagulant Therapy

  • Heparin should be administered in patients with intermediate or high clinical probability of PE before imaging studies are performed and in low probability patients once PE is confirmed
  • If PE occurs postoperatively, Heparin therapy should not be started until 12-24 hours after major surgery and after consultation with surgeon
    • Treatment could be delayed even longer if there is any evidence of bleeding from the surgical site
  • Same initial and long-term treatment is recommended for asymptomatic DVT

Oral Anticoagulant Therapy

  • For patients with DVT or PE, long-term management of 3 months duration is recommended
    • For patients with unprovoked VTE, >3 months of anticoagulant therapy is suggested

Thrombolysis in Massive/Sub-massive Pulmonary Embolism

  • Studies have shown a more rapid improvement in radiographic and hemodynamic abnormalities in acute massive PE patients who received thrombolytic agents and anticoagulant agents over conventional anticoagulant agents alone
    • There were no clinically relevant outcomes for death rate or for the resolution of symptoms
  • May also be considered in younger patients with massive iliofemoral thrombosis (weigh risk versus benefit)

Massive Pulmonary Embolism

  • The use of thrombolytic therapy in PE should be individualized
    • Patients with hemodynamically unstable PE who are at low risk of bleeding are the most appropriate candidates
  • Thrombolytic therapy may also be considered in patients with the following:
    • Compromised oxygenation
    • Free-floating right ventricular thrombus or patent foramen ovale documented by echocardiography
    • Massive hemodynamically significant PE without systemic hypotension or profound hypoxemia

Sub-massive Pulmonary Embolism

  • The use of thrombolytics in patients with sub-massive PE [hemodynamically stable patients with echocardiographic evidence of right ventricular (RV) dysfunction] is controversial
    •  Further studies are needed to show a clinically relevant improvement in the benefit-risk ratio of thrombolytic treatment over traditional anticoagulant therapy in these patients

Pharmacotherapy

Non-massive Pulmonary Embolism (PE) and/or Deep Vein Thrombosis (DVT)

Parenteral Anticoagulant Therapy

Unfractionated Heparin (UFH) versus Low-Molecular-Weight Heparin (LMWH)
  • Both subcutaneous (SC) LMWH or intravenous (IV) UFH short course treatments are recommended for objectively confirmed non-massive PE
    • Either LMWH or UFH is appropriate for the initial treatment of PE

Unfractionated Heparin (UFH)

  • IV UFH treatment in PE is well-established
  • UFH should be considered:
    • As a 1st dose bolus
    • Massive/sub-massive PE
    • When rapid reversal of effect may be required
  • UFH is preferred over LMWH in patients with severe renal failure
  • Effects: IV UFH has been proven effective in the therapy of PE and DVT 
    • Studies have shown a reduced mortality rate when UFH has been used to treat VTE disease
    • Recurrence of VTE is unusual when UFH is infused at a rate that prolongs the activated partial thromboplastin time (aPTT) >1.5 times the control value and when adequate levels are reached within 24 hours
  • IV UFH typically requires hospitalization with frequent monitoring and dose adjustment
  • Most common complication is Heparin-induced thrombocytopenia

Low-Molecular-Weight Heparin (LMWH)

  • LMWH should be used whenever possible for the initial inpatient treatment of DVT rather than UFH
    • LMWH is superior to UFH for the initial treatment of DVT in terms of reducing mortality and the risk for major bleeding during the initial therapy
  • LMWH is now preferred over UFH in patients with acute non-massive PE 
    • Also preferred over vitamin K antagonists (VKA)
  • A number of studies have shown that LMWH has equal efficacy to UFH in patients with non-massive PE
  • Patients with symptomatic PE should initially be treated in the hospital because of decreased cardiorespiratory reserve, complications and for monitoring of international normalized ratio (INR) to guide Warfarin therapy
  • The use of LMWH is safe, effective, may shorten hospital stay and improve the quality of life for patients
    • Outpatient management of DVT should be extended to include stable patients with stable PE who have been carefully screened for risk factors for hemorrhage
  • Lab monitoring is not required except for a regular platelet count before treatment initiation and on the 5th day, then every 2-3 days if LMWH treatment is continued

Fondaparinux

  • Also a preferred initial treatment for DVT and PE
  • Heparin assay (anti-factor Xa) has been used to monitor effects of Fondaparinux
  • Warfarin is initiated usually within 72 hours of therapy
  • Obtain a platelet count prior to the start of therapy

Duration of Therapy

  • Treatment with UFH, LMWH, or Fondaparinux should be continued for at least 5-7 days after the initiation of Warfarin and until therapeutic INR is stable and ≥2.0 (range: 2.0-3.0) for 2 consecutive days

Oral Anticoagulant Therapy

Warfarin

  • Warfarin is used to reduce the risk of VTE recurrence and complications
  • Should only be started once VTE has been reliably confirmed
    • Start on day 1 of Heparin therapy
  • Bolus dose is not effective, therefore it requires at least 5 days to achieve its full effects
    • Thus, it is recommended that Warfarin therapy overlap with Heparin at least 4-5 days until therapeutic INR is stable and >2.0 (range: 2.0-3.0)
    • Warfarin high loading dose (>10 mg) is not recommended as it has no clinical use and it predisposes patients to hemorrhage at start of therapy

Non-Vitamin K Oral Anticoagulants (NOACs)

  • Eg Apixaban, Dabigatran, Edoxaban, Rivaroxaban
  • Recommended anticoagulant agents for patients with leg DVT or PE during the 1st 3 months of therapy
  • Apixaban and Rivaroxaban are given according to the single-drug approach (monotherapy) while Dabigatran and Edoxaban should be given after initial treatment with Heparin (dual therapy)

Apixaban

  • Prior Heparin treatment is not necessary, though short courses of Heparin should be given when there is treatment delay 

Dabigatran etexilate

  • Approved for the management of DVT and PE in patients who have been treated with parenteral anticoagulant for 5-10 days, and to reduce risk of recurrent DVT and PE in patients who have been previously treated

Edoxaban

  • May be used for treatment of DVT and PE in patients who have been treated with parenteral anticoagulant for 5-10 days
  • Also used for the prophylaxis of stroke and systemic embolism in patients with non-valvular atrial fibrillation
  • Should only be used in patients with high creatinine clearance (>95 mL/minute)

Rivaroxaban

  • Initial treatment for both PE and DVT without additional anticoagulation
  • A direct factor X inhibitor that is non-inferior to Warfarin in the management of acute VTE 

Massive or Sub-massive Pulmonary Embolism

Thrombolytic Agents

Alteplase (rt-PA)

  • Has comparable thrombolytic capacity to Streptokinase and Urokinase but can be administered for a shorter duration (2 hours)
  • Preferred thrombolytic agent because of its shorter administration time

Streptokinase or Urokinase

  • These 2 agents have similar thrombolytic effects in PE and have been shown to resolve PE comparatively at 24 hours and 3x that as seen with Heparin alone
  • 12 hours of Urokinase have equivalent thrombolytic efficacy to 24 hours of Streptokinase

Non-Pharmacological Therapy

Deep Vein Thrombosis (DVT)

Bed Rest and Leg Elevation

  • Affected extremity should be elevated above the level of the heart until edema and tenderness subside

Early Ambulation

  • Preferred over bed rest when feasible in patients with acute DVT

Exercise

  • Encourage patients confined to a chair or bed to perform regular leg exercise

Mechanical Measures

Graduated Elastic Compression Stockings (GECS)

  • Provide continuous stimulation of blood flow and prevent dilation of venous system in the legs
  • GECS combined with early ambulation does not increase PE and provides faster resolution of pain and swelling
  • Recommended to start at 1 month of diagnosis of proximal DVT until a minimum of 2 years to prevent post-thrombotic syndrome
    • Use graduated compression knee-high custom-fitted stockings with at least 30-40 mmHg on the affected leg
  • Should be used with caution in patients with postthrombotic syndrome
  • Contraindicated in patients with peripheral artery disease
  • Although some studies show the ineffectiveness of GECS for prophylaxis and they also cause lower extremity skin damage 

 

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