Key Clinical Questions
Which patients with venous thromboembolism (VTE) can be treated as outpatients?
What is the treatment for acute VTE deep vein thrombosis and/or pulmonary embolism (PE)?
What is the role of thrombolytic therapy in the treatment of PE?
How are patients with acute VTE and bleeding managed?
How is the duration of treatment of VTE determined?
Should I perform a thrombophilic workup?
What is the risk of bleeding associated with long-term anticoagulant therapy?
Introduction
The foundation of treatment of venous thromboembolism (VTE) is anticoagulant therapy. The objectives of anticoagulant therapy are: (1) to prevent extension and potentially fatal embolization of the initial thrombus and (2) to prevent recurrent VTE.
Proximal deep vein thrombosis is defined as a deep vein thrombosis (DVT) that involves the popliteal and more proximal veins of the leg. Distal deep vein thrombosis is defined as a DVT that is confined to the calf veins (including the calf trifurcation).
Patients who are hemodynamically stable with a low bleeding risk and normal renal function, and who are likely to be compliant with anticoagulant therapy, can be safely treated as outpatients. Patients with DVT and severe intractable pain or phlegmasia cerulea dolens (blue, painful leg due to complete venous obstruction leading to impaired arterial flow) should be admitted to hospital for initiation of treatment. Patients with pulmonary embolism (PE) and severe symptoms or abnormal vital signs should be admitted to the hospital and those with signs of hemodynamic compromise (eg, low oxygen saturation, low systolic blood pressure, persistent tachycardia) should be considered for thrombolytic therapy (discussed later). Validated prognostic scores are available to help physicians select which patients with PE can be treated as outpatients.
A 40-year-old male underwent a craniotomy for glioblastoma multiforme (GBM) on hospital day #1. His preoperative platelet count was 244,000/mm3. Postoperatively, he received mechanical VTE prophylaxis and UFH 5,000 U subcutaneously twice a day. On postoperative day #11 he became acutely short of breath. CT-PA protocol imaging identified multiple bilateral PE and a common femoral DVT. What treatment should this patient receive? If this patient had thrombocytopenia (or a 50% drop in his platelet count), would you recommend a different treatment? |
A 58-year-old female with a past medical history of asthma was seen for shortness of breath on three occasions in the outpatient setting. Despite therapy for asthma, her symptoms progressed and on the day of admission she developed chest pain that radiated to her left shoulder. Routine admission testing revealed an abnormal ECG showing deeply inverted T waves in her anterior precordium without reciprocal changes in other leads and slightly abnormal liver function tests. Her vital signs were normal and stable. She had elevated troponin and brain naturetic hormone levels that did not increase on repeated testing. CT-PA protocol imaging revealed extensive pulmonary emboli, including a saddle embolus involving the right pulmonary artery, an enlarged right ventricle, and bilateral common femoral DVT. How should this patient with a significant clot burden and evidence of right heart strain be treated? Should she undergo testing to identify risk factors for VTE? |
Treatment of Acute Venous Thromboembolism
The first step in treating acute VTE is preventing further thrombus formation by starting an agent that rapidly inhibits thrombin. The agents approved for treatment of acute VTE in Europe and North America are low-molecular-weight heparin (LMWH), fondaparinux, and heparin (Table 260-1).
| Antihrombotic | Dose and Administration | Advantages | Disadvantages |
|---|---|---|---|
| LMWH | Weight-based subcutaneous injection daily or twice daily | Laboratory monitoring not required | Contraindicated in pts with CrCl < 30 ml/min |
| Allows for outpatient treatment | Protamine sulphate is only partially effective in reversing anticoagulant effect | ||
| Moderate risk of HIT | |||
| Fondaparinux | Weight-based subcutaneous injection daily | Laboratory monitoring not required | Contraindicated in pts with CrCl < 30 ml/min |
| Allows for outpatient treatment | No reversal agent available | ||
| Low risk of HIT | |||
| Heparin | 333 U/kg subcutaneous injection followed by 250 U/kg twice daily | Laboratory monitoring not required | Half-life too short to be given subcutaneously only once daily |
| Allows for outpatient treatment | |||
| 80 U/kg intravenous (IV) bolus followed by 18 U/kg/min (aPTT titrated to plasma heparin levels from 0.3 to 0.7 IU/mL anti-Xa activity) | Short half-life if bleeding occurs | Requires laboratory monitoring if given intravenously | |
| Can be reversed with protamine sulphate | Highest risk of HIT | ||
| Can be used in pts with renal failure |
|
Patients with VTE who have heparin-induced thrombocytopenia (HIT) or a past history of HIT should receive danaparoid, lepirudin, or argatroban instead of the agents listed in Table 260-1. The agents in Table 260-1 should be given for a minimum of five days and until the INR is greater than or equal to 2.0 on two consecutive measurements. A vitamin K antagonist (VKA) (eg, warfarin) with a target INR of 2.0 to 3.0 is typically started at the same time as the parenteral antithrombotic agent. Dosing algorithms for VKAs are available. Observational studies have shown that lower VKA maintenance doses are required in older patients, women, those with impaired nutrition, and vitamin K deficiency. Optimal VKA management requires a systematic approach to obtaining INR measurements, adjusting VKA dose, and communicating these instructions to patients. Anticoagulation clinics, and use of computer programs to schedule appointments, adjust VKA dose and maintain records, can facilitate this process.
A randomized trial of patients with DVT established the need for anticoagulant therapy beyond the first week by showing a much higher risk of recurrent VTE in patients who received low-dose heparin instead of warfarin after initial treatment with full-dose heparin for 10 days. The options for ongoing anticoagulant therapy include a VKA at a target INR 2.0–3.0, high-dose subcutaneous heparin, and LMWH (at 50–75% of acute treatment dose).
New antithrombotic agents (eg, dabigatran, rivaroxaban, apixaban) are in the advanced stages of development for treatment of VTE, but are not yet approved for this indication.
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