Prevention of venous thromboembolism in the hospitalized medical patient
ABSTRACT
Hospitalized acutely ill medical patients are at high risk for venous thromboembolism (VTE), and clinical trials clearly demonstrate that pharmacologic prophylaxis of VTE for up to 14 days significantly reduces the incidence of VTE in this population. Guidelines recommend use of low-molecular-weight heparin (LMWH) or unfractionated heparin (5,000 U three times daily) for VTE prophylaxis in hospitalized medical patients with risk factors for VTE; in patients with contraindications to anticoagulants, mechanical prophylaxis is recommended. All hospitalized medical patients should be assessed for their risk of VTE at admission and daily thereafter, and those with reduced mobility and one or more other VTE risk factors are candidates for aggressive VTE prophylaxis. Based on results from the recently reported EXCLAIM trial, extended postdischarge prophylaxis with LMWH for 28 days should be considered for hospitalized medical patients with reduced mobility who are older than age 75 or have a cancer diagnosis or a history of VTE.
DISCUSSION: ADDITIONAL PERSPECTIVES FROM THE AUTHORS
Dr. Jaffer: Dr. Spyropoulos, are there any guidelines, other than those from the ACCP, that speak to VTE prophylaxis in hospitalized medical patients? If so, what are their take-home messages and how do they differ from the ACCP guidelines?
Dr. Spyropoulos: I was part of the group that developed the International Consensus Statement (ICS) published in International Angiology in 2006,11 which is more recent than the latest ACCP guidelines, which were published in 2004. The ICS drew on much of the same data that the ACCP did, but we did an updated review of clinical trials.
For VTE prophylaxis in hospitalized medical patients, the ICS recommendations are more specific with regard to the type, dose, and dosing frequency of anticoagulant agents. First, they specify doses for both LMWH agents in this patient setting: 40 mg once daily for enoxaparin, and 5,000 IU once daily for dalteparin.
The ICS document also states that if UFH is the choice for prophylaxis, a regimen of 5,000 U three times daily should be considered. In the past year alone, two analyses suggest that three-times-daily dosing of UFH in medical patients provides superior efficacy to twice-daily dosing, although perhaps at the expense of more bleeding episodes.12,16 It is important to remember that no large placebo-controlled trial supports the efficacy of a UFH regimen of 5,000 U twice daily in this population.
Finally, the ICS document states that fondaparinux 2.5 mg once daily is a viable option for prophylaxis in medical patients, based on the ARTEMIS trial,3 even though this represents an off-label use.
Dr. Jaffer: Real-world use of VTE prophylaxis is far from optimal, especially in medical patients, and this is partly a result of system-of-care issues. I’d like to conclude by asking each of my colleagues to offer your perspectives on how your own institutions have improved their systems of care to promote better use of VTE prophylaxis and what lessons might be shared with others. Dr. McKean, you work at Brigham and Women’s Hospital, which recently reported impressive results with an electronic alert system designed to increase clinicians’ consideration of VTE risk assessment and use of prophylaxis.24 Please tell us about that study and the alert system.
Dr. McKean: Despite many educational initiatives at Brigham and Women’s Hospital, there were still some patients at high risk for VTE who were not receiving appropriate prophylaxis. What Dr. Samuel Goldhaber and his colleagues wanted to determine was whether changing the system of care could result in a reduced incidence of VTE.24 They devised a computer software program linked to the patient database that used eight common risk factors to determine each hospitalized patient’s risk profile for VTE. Each risk factor was weighted according to a point scale, with major risk factors (cancer, prior VTE, or hypercoagulability) assigned 3 points, the intermediate risk factor of surgery assigned 2 points, and minor risk factors (advanced age, obesity, immobility, or use of hormone replacement therapy or oral contraceptives) assigned 1 point. For patients with a total risk score of 4 or greater, the computer screen generates a color-coded VTE risk alert that requires the physician to acknowledge the alert and choose one of three options: order prophylaxis as appropriate, review a 60-page document on the computer to learn more about prophylaxis, or do nothing.
The study found that hospitalized patients who were randomized to treatment under the computer alert system were significantly more likely to receive VTE prophylaxis and significantly less likely to develop VTE than were patients randomized to a control group. The alert system reduced the risk of DVT or PE at 90 days by 41% in patients considered to be at high risk. It was particularly interesting that the incidence of VTE was lower in the intervention group even when physicians chose not to use prophylaxis, which suggests that simply having this alert system in place improved outcomes, perhaps by raising awareness of the risk of VTE.24
Additional studies are needed to better understand physicians’ behavior and determine why they seem to have a disproportionate fear of the risk of bleeding relative to the risk of clotting, including fatal PE, because that is really the heart of the matter. When patients are not given prophylaxis, often it is because of fear of bleeding. It is not clear, however, why some of these patients did not receive mechanical devices as an alternative form of prophylaxis, but this seems to be the case worldwide, as shown recently by the multinational ENDORSE study.22 Meanwhile, as we await studies to better understand physician perceptions and behaviors regarding prophylaxis, we need to work hard to change the system of care.
Dr. Deitelzweig: Over the past couple of years, the Ochsner Clinic has grown from a one-hospital teaching organization to a seven-hospital system with a mix of closed and open medical staff. The challenge is how to take a process that worked well in the one center, where appropriate prophylaxis was used about 90% of the time, and transfer it to the other centers in the larger system. We have endorsed several types of performance tools, such as the change-acceleration processes used by General Electric. The aim is to share a vision of heightening awareness. To do that, we have worked to mobilize the key stakeholders, at least half of them, to build algorithms that they all will endorse. It is easier said than done, however, and we have found it essential to involve both physicians and non-physician colleagues from pharmacy and nursing who have political and organizational clout.
Dr. Brotman: At Johns Hopkins, I took a bit more draconian approach to this issue because I thought that hospitalists often knew that they should be using VTE prophylaxis but sometimes weren’t, and I am not convinced that clinicians always look at prompts. So we came up with a system that incorporates both billing and documentation simultaneously. We put a hard stop on users’ documentation so that they could not sign off on a note or bill for their care until they checked off the kind of VTE prophylaxis they were using. Since hospitalists ultimately care about billing for their work, this system has at least ensured that everybody has considered and documented VTE prophylaxis on a daily basis. There are other hard stops that can be implemented in computer order-entry systems as well, and we are considering ways to roll them out on a broader scale.
However, all of these systems can have problems because patient situations change from day to day. For instance, VTE prophylaxis is not necessarily indicated in a 38-year-old ambulatory patient who comes in with a sickle cell crisis, but you will need to reconsider if the patient ends up in acute chest syndrome in the intensive care unit. I do not yet have a good way to ensure that this is being done on a daily basis with all patients.
Dr. Amin: At the University of California, Irvine, we implemented an electronic alert system, but we locked users in so that they could not complete their admission orders until they answered questions about VTE prevention. This practice increased our VTE prophylaxis rates tremendously. Because we are a level I trauma center, we allow users to bypass the screens one time, but the next time they log in, even to get a simple lab result, they have to answer the questions about VTE prevention.
With any system you develop, you also have to continue with the education process, because clinicians sometimes get into bad habits or simply forget things.
Dr. Spyropolous: At Lovelace Medical Center, we didn’t have the sophistication of an electronic order-entry system, but we had an experienced clinical pharmacist (the director of inpatient pharmacy) who helped to develop and champion VTE prevention guidelines that have then been used throughout the system in close conjunction with our hospitalists’ rounds. This system has been used successfully for the past 7 years.
