Thromboembolism Treatment & Management

Anticoagulant and thrombolytic therapy options are available. Anticoagulant therapy prevents further clot deposition. It allows the natural fibrinolytic mechanisms to lyse the existing clot.^[16]

Anticoagulant therapy

Heparin is the first line of therapy. It is administered by bolus dosing, followed by a continuous infusion. Adequacy of therapy is determined by an activated partial thromboplastin time (aPTT) of 1.5-2 times baseline. Progression or recurrence of thromboembolism is 15 times more likely when a therapeutic aPTT is not achieved within the first 48 hours.

The results of a Cochrane Database of Systematic Reviews study found that the use of heparin in patients with cancer but with no therapeutic or prophylactic indication for it was related to a significant reduction in death at 24 months but not at 12 months. A statistically and clinically important reduction in venous thromboembolism was also noted. It had no effect on bleeding or quality of life. Future studies are needed to investigate the survival benefit of different types of anticoagulants in patients with different types and stages of cancer.^[17]

Another similar study from the Cochrane Database of Systematic Reviews compared the use of oral anticoagulants with either placebo or no intervention in patients with cancer who had no therapeutic or prophylactic indication for anticoagulation. The results found no significant reduction in mortality at 6 months, 1 year, 2 years, or at 5 years; however, the oral anticoagulant Warfarin was found to increase both major and minor bleeding.^[18]

One study evaluated data from 7 randomized trials that included 2925 men or women with a first venous thromboembolism who did not have cancer and who had received different durations of anticoagulant treatment. The results indicated a similar risk of recurrent venous thromboembolism, whether anticoagulation therapy was stopped after 3 months or whether longer treatment was received; proximal deep vein thrombosis and pulmonary embolism showed a higher risk of recurrence whenever treatment was stopped.^[19]

A weight-based nomogram has been used to determine adequate dosing, using heparin at 80 mg/kg for the bolus and 18 mg/kg/h for the infusion. A short course of heparin is followed by a longer course of oral anticoagulant, warfarin sodium. It should be started only after effective anticoagulation has been achieved, as there can be an increase in coagulability and thrombogenesis during the first few days of oral anticoagulant administration. The goal is to achieve an international normalized ratio (INR) of 2.0-3.0. The optimum duration of treatment still is controversial. A minimum of 3 months of oral therapy has been suggested following a first episode of DVT or PE.

Several studies have shown that low molecular weight heparin (LMWH), which is a fractionated heparin, is as effective as unfractionated heparin in treating deep venous thrombosis. Minimal requirements for outpatient therapy with LMWH regimens include stable PE or DVT, low risk for bleeding, absence of severe renal insufficiency, availability of systems of administration and monitoring of LMWH and warfarin, and surveillance and treatment of recurrent thromboembolic disease.

A Cochrane Database of Systemic Reviews study found that LMWH compared with oral anticoagulants (eg, vitamin K antagonist [VKA] or ximelagatran) reduces venous thromboembolic events but not death in patients with cancer.^[20]

Thrombolytic therapy

Thrombolytic therapy dissolves recent clots promptly by activating a plasma proenzyme, plasminogen, to its active form, plasmin. Plasmin degrades fibrin to soluble peptides. Thrombolytic therapy speeds pulmonary tissue reperfusion and rapidly reverses the right heart failure. It improves pulmonary capillary blood flow and more rapidly improves hemodynamic parameters. The Food and Drug Administration (FDA) has approved 3 thrombolytic regimens for PE. Streptokinase, urokinase, and recombinant tissue-type plasminogen activator (rt-PA) have been approved for thrombolytic use in PE. In head-to-head studies between rt-PA and heparin by Goldhaber and colleagues, there was a higher incidence of recurrent PE and death in the group receiving heparin. Patients in both groups had bleeding complications requiring transfusion therapy.^[21]

The indication for thrombolytic treatment, as advanced by the American College of Chest Physicians in their fourth consensus conference on antithrombotic therapy, is acute massive pulmonary embolism with hemodynamic instability in patients who do not seem prone to bleeding.^[22] Absolute contraindications to thrombolysis include gastrointestinal bleeding within the last 6 months, active or recent internal bleeding, a history of hemorrhagic stroke, intracranial or intraspinal disease, recent cranial surgery or head trauma, and pregnancy. Relative contraindications include major surgery or trauma within the last 2 weeks, biopsy within 10 days, other invasive procedures in a location inaccessible to external compression, uncontrolled coagulation defects such as thrombocytopenia, and nonhemorrhagic stroke.

Rivaroxaban (investigational in the United States) was compared with enoxaparin for acute deep vein thrombosis. Efficacy showed noninferiority to enoxaparin for short-term use. When used as continued treatment compared with placebo, rivaroxaban had superior efficacy (P < 0.001). A study comparing rivaroxaban to warfarin for long-term efficacy is warranted.^[23]

The vena caval filter is designed to trap potentially lethal emboli while maintaining vena caval patency. It is indicated in cases where there is a contraindication to anticoagulation, when there has been a complication of anticoagulation, in the event of failure of anticoagulation, and in the case of pulmonary embolectomy.

Catheter pulmonary embolectomy is performed by inserting a cup-tipped steerable catheter into the central venous system, accessing through the jugular vein or through the right common femoral vein. When the cup reaches the thrombus, suction is applied and the thrombus is extracted.

Surgical interventions for venous thromboembolic disorders include thrombectomy and venous interruption.

• Thrombectomy for venous embolism is performed less frequently given the incidence of rethrombosis, unless heparin infusion is added to the therapeutic regimen.
• Pulmonary embolectomy remains a therapeutic option, but with an extremely high mortality rate. It is reserved for cases of massive PE in which an absolute contraindication to thrombolysis is present or when all other treatment modalities have failed. It is only effective when the clot is in the large central vessels.
• Ligation of venous tributaries is an option that is rarely practiced today. Its use has been limited by a high mortality rate and the need for continuous anticoagulation. It essentially has been replaced by the percutaneous insertion of the intracaval filter.

• When pulmonary embolism is suspected, consultation with a pulmonologist may be useful to aid in the diagnosis or to guide therapy. When the intravascular filling defect is so severe that it causes cardiac dysfunction or hypotension, the patient can be best served by transfer to an intensive care setting.
• Consultation with an intensive care specialist or pulmonologist would be helpful in decision-making regarding thrombolysis and in following effectiveness of treatment.
• If cancer or a hematologic disorder is one of the contributing risk factors, consultation with a hematologist or oncologist may be appropriate.

No special dietary requirements or restrictions exist. Diet should be as tolerated. However, patients on oral warfarin therapy must avoid vitamin supplements that contain vitamin K and limit foods that are high in vitamin K (eg, broccoli, cabbage, red and green lettuce, onion, peppers, spinach, oils, mayonnaise, black and green leaf teas). The patient's diet should remain steady with no drastic changes in content to facilitate accurate regular monitoring of INR levels.

Activity should be limited until anticoagulation is achieved and the patient is on oral anticoagulant medication. Patients on oral warfarin therapy should avoid activities that could cause trauma.