In patients with a high clinical suspicion of acute DVT, treatment with parenteral anticoagulants is recommended while awaiting the results of diagnostic tests. For those with documented DVT and PE, anticoagulation is the mainstay of treatment if no contraindications exist. The recently released 2016 ACCP guidelines suggest the use of direct oral anticoagulants (DOACs) such as dabigatran, rivaroxaban, apixaban, or edoxaban over vitamin K antagonist (VKA) in patients with DVT of the leg or PE and no cancer. For patients with DVT of the leg or PE and no cancer who are not treated with DOACs, the guidelines suggest the use of VKA therapy over low-molecular weight heparin (LMWH). Initial parenteral anticoagulation with unfractionated heparin or LMWH is given before dabigatran and edoxaban, is not given before rivaroxaban and apixaban, and is overlapped with VKA therapy. In patients with DVT of the leg or PE and cancer, LMWH is favored over VKA therapy and DOACs for the first 3 months. Routine use of compression stockings to prevent postthrombotic syndrome is not recommended in patients with acute DVT or PE who are treated with anticoagulants.
With regards to duration of therapy, at least 3 months of anticoagulation is recommended in patients with a proximal DVT of the leg or PE provoked by surgery or by a nonsurgical transient risk factor. After 3 months of treatment, patients with unprovoked DVT of the leg or PE should be evaluated for the risk-benefit ratio of extended therapy. Extended anticoagulant therapy is recommended in patients with a first VTE that is an unprovoked proximal DVT of the leg or PE and who have a low or moderate bleeding risk.
Administration of IV heparin is usually undertaken using the weight-based heparin dosing nomogram where patients receive a loading bolus dose of 80 units/kg followed by an 18 units/kg/h per hour infusion. The heparin dose is adjusted to maintain an activated partial thromboplastin time of 1.5 to 2.3 times control. IV heparin is favored in LMWH have greater bioavailability when given by SC injection, do not require strict laboratory monitoring, and have a lower risk of heparin-induced thrombocytopenia (HIT) compared with UFH. Enoxaparin, dalteparin, and tinzaparin are approved for use in the United States. Enoxaparin is typically given at 1 mg/kg SC twice daily or 1.5 mg/kg SC daily, while tinzaparin is given at 175 units/kg SC once daily. Monitoring antifactor Xa levels typically 4 hours after injection may be considered in patients who are morbidly obese, pregnant patients, and patients with renal insufficiency. Fondaparinux is given at a dose of 5 mg SC once daily for patients weighing less than 50 kg, 7.5 mg SC once daily for patients weighing 50 to 100 kg, and 10 mg SC once daily for patients weighing more than 100 kg. Caution should be observed in patients with renal impairment as both LMWH and fondaparinux are retained in these patients.
UFH is suggested for patients with renal impairment (creatinine clearance < 30 mL/min). Warfarin for the treatment of VTE is not ideal in ICU patients given the many drug and food interactions associated with its use and genetic variations in drug metabolism.
Complications of Anticoagulation
The major complications of anticoagulant therapy are hemorrhage and HIT. The frequency of major bleeding was reported at 1.9% and a fatal hemorrhage rate of 0.2% in a large meta-analysis involving over 15,000 patients treated with either UFH or LMWH. HIT is an immune-mediated adverse reaction to heparin that is associated with thrombocytopenia and can lead to venous and arterial thrombosis. Commonly, there is an otherwise unexplained fall in platelet count (absolute thrombocytopenia or > 50% decrease if the platelet nadir remains in the normal range) 5 to 10 days following exposure to heparin. In patients who develop HIT, the heparin should be immediately discontinued and direct thrombin inhibitors such as argatroban or lepirudin should be administered if anticoagulation continues to be required.
In patients receiving UFH or LMWH who develop clinically significant or devastating hemorrhage, protamine sulfate can be administered although the anticoagulant effect of LMWH is only partially reversed. Allergic reactions and bradycardia are side effects of protamine.
The guidelines recommend the use of systemically administered thrombolytic agents (alteplase, streptokinase, and alteplase) in patients with acute PE associated with hypotension (systolic BP < 90 mm Hg) who do not have a high bleeding risk. Thrombolysis may also be considered in selected patients with acute PE not associated with hypotension and with low bleeding risk whose initial clinical presentation or clinical course suggests a high risk of developing hypotension. In the Pulmonary Embolism Thrombolysis (PEITHO) trial published in 2014, the administration of tenecteplase plus heparin was associated a significant reduction in all-cause mortality or hemodynamic decompensation within 7 days, when compared to placebo plus heparin in patients with intermediate-risk PE (acute PE associated with RV dysfunction on echocardiography and myocardial injury as evidenced by a positive troponin I or T test). However, thrombolytic treatment with tenecteplase was associated with a 2% incidence of hemorrhagic stroke. Short-term infusion times (eg, 2-hour infusion of 100 mg of alteplase) through a peripheral vein are suggested over prolonged infusion times and over a pulmonary artery catheter, respectively. Urokinase and streptokinase are given as a loading dose (streptokinase 250,000 units over 30 minutes) followed by continuous infusion of 100,000 units/hour for 24 hours; urokinase 4400 units/kg over 10 minutes followed by a continuous infusion of 4400 units/kg/h for 12 to 24 hours. Heparin infusion is typically continued after thrombolytic therapy. Contraindications to thrombolysis include surgery in the past 10 days, recent puncture or invasion of noncompressible vessels, recent intracerebral hemorrhage or stroke, uncontrolled hypertension, recent trauma, pregnancy, hemorrhagic retinopathy, other sites of potential bleeding, and infective endocarditis. Thrombolytic therapy should be tailored to the complicated ICU patient and risks and benefits heavily weighed prior to administration.
Inferior Vena Cava Filter
The guidelines recommend the use of an IVC filter in patients with acute PE and contraindications to anticoagulation. No randomized clinical trial (RCT) has evaluated IVC filters as sole therapy in patients with DVT. IVC filters may increase the risk of recurrent DVT and do not reduce the risk of PE or alter mortality. If an IVC filter is indicated in a patient with acute DVT or PE because anticoagulant therapy is temporarily contraindicated (eg, active bleeding), a retrievable filter may be inserted and subsequently removed when it is safe to start anticoagulant therapy. Patients who have an IVC filter inserted should receive a conventional course of anticoagulation (eg, parenteral and long-term anticoagulation) if the contraindication to anticoagulation resolves and should be treated for the same length of time similar to patients who had not had an IVC filter placed. For upper extremity DVT, some institutions can place superior vena cava filters although these are associated with high complication rates than IVC filters; thus, their use should be confined to exceptional circumstances in specialized centers. The risk of recurrent pulmonary emboli after IVC filter placement is 2% to 3%. Complications of IVC filter placement include venous thrombosis at the site of filter insertion, procedural complications, filter malposition and migration, caval occlusion, and sepsis due to device infection. Permanent IVC filters may also predispose to postthrombotic syndrome.
Surgical pulmonary embolectomy is recommended only in patients with acute PE who have contraindications to thrombolysis, have failed thrombolysis or catheter-assisted embolectomy, or shock that is likely to cause death before thrombolysis can take effect (eg, within hours), provided surgical expertise and resources are available. Mortality from emergency pulmonary embolectomy can be as high as 30% and should be performed only in highly specialized centers.
Other modalities that have investigated include interventional catheterization techniques for massive such as mechanical fragmentation of thrombus with a standard pulmonary artery catheter, clot pulverization with a rotating basket catheter, percutaneous rheolytic thrombectomy, or pigtail rotational catheter embolectomy. Pharmacologic thrombolysis and mechanical interventions are usually combined unless bleeding risk is high.