DEEP VENOUS THROMBOSIS (DVT)/ PULMONARY EMBOLUS (PE)/
VENOUS THROMBOEMBOLISM
Deep venous thrombosis (DVT) is a common occurrence. Either venous stasis, hypercoagulability, or damage of the venous intima must exist for a DVT to form. DVT may be idiopathic or secondary to an underlying disorder. Physical findings are inaccurate and insensitive in establishing a diagnosis. A pulmonary embolus is a common and potentially fatal complication of proximal venous thrombosis; however, since many distal DVTs propagate to the proximal veins it is a potential complication of any DVT. Impedance plethsmography and duplex ultrasonography (Doppler venous flow detection plus real-time B-mode imaging) are two commonly employed screening studies. Serial studies should be performed approximately one week apart in stable patients if the initial test was negative but the clinical suspicion of DVT is high. Impedance plethsmography is ineffective at detecting DVT which is limited to the calf vasculature. Spiral CT scanning with contrast or MRI may also be useful; however, venography is the gold standard diagnostic test for establishing the diagnosis. D-dimer testing is often employed. A negative D-dimer (ELISA) in a patient with a negative lower extremity radiographic study is convincing evidence against the presence of a DVT. Some of the newer latex agglutination D-dimer tests have sensitivity and negative predictive values approaching the ELISA tests.
Conditions associated with DVT include advanced age (>65 years-old), malignancies (especially adenocarcinomas), immobilization, surgery, pregnancy, estrogen therapy, obesity, trauma, sepsis, congestive heart failure, COPD, prior thrombotic events, and hypercoaguable states (anticardiolipin antibodies, lupus anticoagulant, factor V Leiden mutation, prothrombin G20210A mutation, antithrombin deficiency, protein C deficiency, protein S deficiency, and hyperhomocysteinemia). DVT prevention should be considered in any patient with any of these risk factors or who is hospitalized or bed ridden for a prolonged period of time. Preventative therapies, which are not 100% effective, include pneumatic compression stockings, lower extremity elevation, and pharmacologic measures. Unfractionated heparin given subcutaneously every 8 hours, low molecular weight heparins (enoxaparin, tinzaparin, and dalteparin) or the factor Xa inhibitor fondaparinux are effective pharmacologic prophylactic therapies. In patients with renal insufficiency stages 5 or 6 (GFR <30 mL/min), unfractionated heparin or fondparinux are prudent choices as low molecular weight heparins tend to accumulate in patients with significant renal impairment. If the patient suffers or has a history of heparin-induced thrombocytopenia, then fondaparinux is indicated. In any patient who has recurrent DVT despite adequate anticoagulation therapy (as determined by serial INR's of 2 to 3 with good compliance), placement of a Greenfield inferior vena cava filter should be considered. A Greenfield filter is also indicated in patients with DVT who have contraindications to anticoagulant therapy.
Clinicians often wrestle with determining which cases warrant a hypercoaguable work-up after a first DVT/PE. If there are obvious transient provoking factors preceding the thrombotic event (surgery, trauma, pregnancy, the postpartum period or oral contraceptive use) then a hypercoaguable work-up is not warranted unless there is a strong family history (> 1 first degree relative with a thrombotic event before the age of 50). In cases with no past history of thrombosis and no identifiable risk factors (first unprovoked venous thrombotic event) then the decision to work-up an underlying hypercoaguable state is left to the clinician. Antiphospholipid antibody syndrome (APS)and anticardiolipin antibodies should be considered in such patients because they confer a higher risk of recurrent thrombotic events and therefore warrant continued anticoagulation in the presence of persistent antibodies. Factor V Leiden and prothrombin G20210A mutations are also worthy of consideration. Since these mutations are common in a Caucasian population (rare in persons of African heritage), the results of testing should be interpreted with caution. If the patient is heterozygous for either mutation, then they should not be considered hypercoaguable as most patients with a single abnormality of either mutation never have a thrombotic event. However, if the patient is homozygous for either or compound heterozygous for both mutations, then they are considered hypercoaguable. Less common hereditary hypercoaguable states include protein C deficiency, protein S deficiency, and antithrombin III deficiency. If the patient does not possess an underlying hypercoaguable state, then sex, age, and the D-dimer value measured one month after therapy are the best variables to determine recurrent thrombosis. A higher risk of recurrence is seen in men, patients over 65 years of age, and those with an elevated post treatment D-dimer one month after therapy is discontinued.
Pulmonary emboli (PE) are a complication of a proximal vein DVT. PE are both underdiagnosed and overdiagnosed. Symptoms of PE include dyspnea, pleuritic pain, and hemoptysis. Associated symptoms may include fever, anxiety, and syncope. Common physical findings include tachycardia and tachypnea. EKG changes may include axis deviation, right atrial enlargement, and tachycardia. Arterial blood gas sampling may reveal hypoxia and an elevated alveolar-arterial oxygen gradient or may be entirely normal. CXR is nonspecific and many cases are misdiagnosed as pneumonia; however, chest radiography is essential to exclude other potential etiologies. In fact, PE should be considered as an etiology in all pleural effusions when an underlying etiology cannot be established after an adequate evaluation. Ventilation/perfusion scanning (V/Q scan) or CT scanning are often employed as the initial screening test. In cases of PE where there are symptoms of DVT, establishing the diagnosis of the DVT makes any further testing unnecessary and treatment may be initiated once the presence of a DVT is established. If the V/Q scan or CT are normal, then the presence of a PE but not a DVT has been eliminated in cases where there is a low to intermediate suspicion. If the probability of a PE is high, then further testing is warranted. If the V/Q scan is consistent with a high probability, then treatment may be initiated without further testing. Intermediate probability scans (all scans except normal and high probability scans) require further work up to establish the diagnosis before initiating therapy. Pulmonary angiography is the gold standard for establishing the diagnosis of a PE. Other methods of establishing the diagnosis include MRI, spiral CT scanning with contrast or establishing the presence of a DVT. Spiral CT scanning with contrast is limited in detecting PE of the subsegmental pulmonary arteries. For this reason, a positive spiral CT scan can be used to establish the diagnosis of PE but a negative scan can not confidently exclude the presence of PE of the subsegmental arteries. The advantage of spiral CT scanning is that it can detect other forms of pulmonary pathology when the diagnosis of PE is erroneous. Findings associated with more severe underlying disease include syncope, right ventricular hypertrophy/enlargement on EKG or ECHO, and positive cardiac markers (troponins and BNP).
Treatment for DVT and PE is with intravenous unfractionated heparin, subcutaneous low molecular weight heparins or the factor Xa inhibitor, fondaparinux . Therapy may be initiated while diagnostic studies are being performed in patients with clinical symptoms of PE. Concomitant coumadin or dabigatran therapy may be initiated. Heparin therapies should be continued for two to three days after the INR becomes therapeutic if coumadin is being used as chronic anticoagulation as the initial change in the INR reflects a decrease in anticoagulant factor II only and the patient may in fact be hypercoaguable. Adequate coumadin therapy (INR 2-3 with good compliance) should continue for three months and then be discontinued if the thrombotic event was provoked (an obvious transient cause is identified) and there are no remaining thrombotic risk factors and the repeat D-dimer levels normalize post treatment and then one month thereafter.
The role of thrombolytics is still being evaluated in the treatment of PE; however, catheter-directed instillation of these drugs may prove helpful in cases which are refractory to the above mentioned conventional therapies or severe underlying disease that is immediately life threatening. Thrombolytics have been used in clots of greater than one month’s duration so may be considered in cases of a chronic DVT. The most feared complication of thrombolytic therapy (bleeding) is lessened with local instillation when compared to systemic therapy. Thrombolytics have not routinely replaced conventional therapy as there is no significant improvement in long term outcomes in most cases and the cost is prohibitive.
As stated above, patients with DVT should be evaluated for the need for PE prophylaxis with the placement of a Greenfield filter. A filter should be placed for prophylaxis in any patient who has a contraindication to anticoagulant therapy or who suffers recurrent DVT despite anticoagulant therapy. Greenfield placement should also be considered in any patient who is considered high risk for pulmonary emboli such as cancer patients or victims of trauma. Patients who developed DVT associated with an identifiable transient risk factor (post surgery, postpartum, secondary to immobilization or lower extremity trauma) are at low risk for DVT recurrence. Whereas, patients with idiopathic DVT and an underlying hypercoaguable state are at risk for recurrence following discontinuation of anticoagulant therapy. Obesity also increase the risk of DVT recurrence. Patients who develop DVT secondary to an underlying malignancy are the highest risk for recurrence, and in fact may suffer a relapse even while on therapeutic anticoagulation therapy. The risk of recurrence is independent of the clinical presentation, DVT versus pulmonary embolism; however, there is a great mortality for patients with pulmonary embolism from recurrent disease.