Dr. Kabrhel is Instructor of Surgery, Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA. Within the past 12 months, Dr. Kabrhel reports no commercial conflicts of interest.
The process that ends in a PE usually begins when a blood clot forms in one of the large veins of the legs. This is called a deep vein thrombosis, or DVT. If this blood clot becomes dislodged it can flow (the medical term is 'embolize') back from the leg, through the heart and become wedged in one of the blood vessels (pulmonary arteries) of the lungs. This is called a PE. While the vast majority of PEs are caused by blood clots, it is worth noting that in rare cases they are caused by tumors, air, fat or amniotic fluid.
PE is an important public health problem. It is estimated that there are between 500,000 and 600,000 cases of acute PE in the U.S. each year, leading to an estimated 50,000 to 200,000 deaths. This makes PE the third most common cause of cardiovascular death in the U.S., behind only heart attack and stroke.
PE [is] the third most common cause of cardiovascular death in the U.S., behind only heart attack and stroke.
This article will discuss factors that put people at risk for developing PE, the tests used for diagnosis and common treatments.
Because there are so many false positives, a positive D-dimer test cannot be used to diagnose PE. If a patient has a positive D-dimer level, they need further testing.
Unfortunately, no test is perfect. While most patients with PE have an elevated D-dimer, many patients without PE also have an elevated D-dimer. In other words, there are lots of "false positives." This is because D-dimers are formed as a normal part of the body's system of creating and breaking down clots. It's also because many other processes can lead to the formation of clots — which may or may not be in the bloodstream. Examples include pregnancy, cancer, autoimmune diseases like Lupus, surgery, trauma, and even advancing age. You may have noticed that many of these items are also on the list of risk factors for PE. This overlap makes knowing when to use D-dimer tests very challenging for physicians. Because there are so many false positives, a positive D-dimer test cannot be used to diagnose PE. If a patient has a positive D-dimer level, they need further testing.
Studies have shown that these PE-CT scans are safe and detect about 90% of all PE.Unfortunately again, no test is perfect and there are still false negatives and false positives associated with PE-CT. If a physician is not convinced by the results of a PE-CT (for example, if the patient's pretest probability of PE is high but the PE-CT does not show a PE), he/she may order additional tests.
Other imaging tests are available to diagnose PE, though they are used less commonly than PE-CT. Ventilation/perfusion scanning is a test performed by the hospital's nuclear medicine department. It involves breathing in one radioisotope, injecting another radioisotope and comparing how the two fill the lungs. Areas of lung that fill with isotope when breathed but not when injected through the bloodstream must have something blocking the blood flow — i.e., a clot. This test was very common before PE-CT was developed, but it is limited by the fact that many patients have non-diagnostic (i.e., not positive or negative) tests. Catheter Pulmonary Angiography has long been the gold standard test, as it shows very detailed images of the pulmonary arteries. However, it involves threading a catheter through a blood vessel in the groin up into the lungs, so it is invasive, technically difficult, and carries a risk of complications. Ultrasound can be used to identify blood clots in the leg veins, but this test is only helpful when positive because many patients with PE no longer have blood clots in the leg veins (the clots have traveled to the lungs).
For decades, the standard treatment for acute PE has been unfractionated heparin. Heparin is a naturally occurring blood thinner that is given through a continuous IV drip. More recently however, low-molecular-weight, or "fractionated" heparin has emerged as a safe and effective alternative to unfractionated heparin. Low-molecular-weight heparin can be given as a subcutaneous (just below the skin) injection once or twice a day, rather than a continuous drip. The level of anticoagulation with low-molecular-weight heparin is also more reliable, and recent studies suggest similar or lower rates of recurrent PE and major bleeding when patients are treated with low-molecular-weight heparin versus unfractionated IV heparin.
Some people react badly to heparin products but there are alternative anticoagulants. They include synthetic heparin analogues (e.g., fondaparinux) and direct thrombin inhibitors (e.g., hirudin, bivalirudin and argatroban).
Eventually, most patients with PE will be converted from heparin to a blood thinner that can be taken as a pill. The most commonly prescribed oral anticoagulant in the U.S. is warfarin. Warfarin takes several days to work, so it can't be used in the treatment of acute PE, but it is a very effective blood thinner overall. The level of anticoagulation can vary from person to person, and from day to day, so patients on warfarin require frequent monitoring of the "thinness" of their blood. Also, some patients with PE, such as those with cancer, do better on heparin than on warfarin, so long-term treatment with a low-molecular-weight heparin may be appropriate.
For those with very large PE resulting in unstable vital signs (blood pressure, heart rate), anticoagulation therapy may not be enough. These patients may need strong drugs that actively dissolve the blood clot (called thrombolytics). The most commonly used thrombolytic medicine is called tissue plasminogen activator (tPA). While tPA is a very potent medicine for dissolving PE, it carries a 2-5% risk of major bleeding, so it should be reserved for the most severe cases of PE.