Prevention of venous thromboembolism in the cancer surgery patient
ABSTRACT
Cancer patients, especially those undergoing surgery for cancer, are at extremely high risk for developing venous thromboembolism (VTE), even with appropriate thromboprophylaxis. Anticoagulant prophylaxis in cancer surgery patients has reduced the incidence of VTE events by approximately one-half in placebo-controlled trials, and extended prophylaxis (for up to 1 month) has also significantly reduced out-of-hospital VTE events in clinical trials in this population. Clinical trials show no difference between low-molecular-weight heparin (LMWH) and unfractionated heparin in VTE prophylaxis efficacy or bleeding risk in this population, although the incidence of heparin-induced thrombocytopenia is lower with LMWH. The risk-benefit profile of low-dose anticoagulant prophylaxis appears to be favorable even in many cancer patients undergoing neurosurgery, for whom pharmacologic VTE prophylaxis has been controversial because of bleeding risks.
Dr. Jaffer: Dr. Amin, based on your study on thrombo-prophylaxis rates in US medical centers, will you comment on rates of prophylaxis for cancer surgery patients?
Dr. Amin: The overall study included approximately 200,000 medical patients and about 80,000 surgical patients enrolled over more than a 3-year period between 2002 and 2005.39,40 Our goal was to assess rates of prophylaxis and, when it was provided, whether it was appropriate (in terms of type, dosage, and duration) based on the ACCP guidelines. A subanalysis assessed medical cancer patients and surgical cancer patients separately. Medical cancer patients received thromboprophylaxis 56% of the time but received appropriate prophylaxis only 28% of the time. Among surgical cancer patients, appropriate prophylaxis was given only about 24% of the time for those undergoing gynecologic surgery and about 12% of the time for those undergoing neurosurgery. These percentages are consistent with data from other national registries, such as the IMPROVE registry, which documented prophylaxis rates on the order of 45% in medical patients with cancer.41 We also analyzed the data according to individual practitioners and found that medical oncologists use prophylaxis about 25% of the time, which is relatively consistent with other providers, such as internists and surgeons.
So there is a huge opportunity to improve rates of prophylaxis for this group of patients that national guidelines say are at high risk. Why is prophylaxis so underutilized in the cancer population? One factor may be a misperception about the risk of bleeding with anticoagulants. Yet several studies have shown that the rate of bleeding from prophylaxis is extremely low, whether LMWH or UFH is used, so more awareness of actual bleeding risk is needed. Another factor is the obvious focus among internists and oncologists on treating the patient, with perhaps a reduced consideration of prophylaxis and prevention. A third factor may be a concern about thrombocytopenia. However, in our study of prophylaxis rates in US medical centers, we excluded patients who had thrombocytopenia, yet rates of prophylaxis were still low. Nothing in the literature indicates that anticoagulants cannot be used in patients with platelet counts of 50,000 to 150,000 cells/µL or higher, so this suggests that we need to do more education.
Dr. Jaffer: Dr. Brotman, can you tell us more about how clinicians in practice should use prophylaxis in their neurosurgery patients, such as those undergoing craniotomy or spine surgery for cancer? What is the safest and most efficacious way to prevent DVT in these patients?
Dr. Brotman: First, it’s important to recognize that some sort of prophylaxis needs to be used. Neurosurgery patients are at an extremely high risk for thromboembolic events, and such events are often fatal in these patients. Having said that, the jury is still out on whether the prophylaxis in these patients should be compression devices or anticoagulation. This gives physicians some latitude in their decisions. They can decide not to use pharmacologic prophylaxis so long as they use pneumatic compression devices consistently, perhaps even starting during the operation and certainly throughout hospitalization when the patient is immobilized.
Certainly, the concerns about using full-dose anticoagulation in the immediate postoperative setting in neurosurgery patients are valid. Yet these patients are at very high risk for thromboembolic events, and if we take too cautious an approach to prophylaxis in the immediate perioperative setting, more patients are going to have thromboembolic events, at which point management decisions become much more difficult. The risk of intracranial bleeding with anticoagulation to treat a patient who develops a DVT at postoperative day 10 will certainly be higher than it would have been with lower-dose perioperative prophylactic anticoagulation. Plus, if you put in a filter at that point, the outcomes tend to be poor. Therefore, I believe there is some degree of risk that we should be willing to take with regard to perioperative bleeding, even in neurosurgery patients.
Dr. McKean: I’d like to make a point about combination prophylaxis. At many institutions, compression stockings and sequential compression devices are used preoperatively and intraoperatively, and then pharmacologic prophylaxis—for example, twice-daily UFH—is used postoperatively. There is concern that these patients are hypercoagulable, and most clinicians believe that mechanical prophylaxis alone, even with sequential compression devices plus compression stockings, is not aggressive enough in these high-risk patients.
Dr. Jaffer: Dr. Spyropoulos, what is the optimal duration of pharmacologic prophylaxis for cancer surgery patients?
Dr. Spyropoulos: First let’s consider in-hospital prophylaxis. The supportive data for in-hospital prophylaxis are strong, and the duration of therapy used in the major in-hospital prophylaxis trials was 7 to 10 days. With regard to extended prophylaxis, we have at least two moderately sized randomized controlled trials, ENOXACAN II23 and the substudy of FAME,24 that demonstrated that extending prophylaxis with LMWH at doses of 3,400 U once daily (5,000 IU of dalteparin; 40 mg of enoxaparin) reduces VTE risk at postoperative day 30. Also, recent data from the @RISTOS registry show that in cancer surgery patients, especially those having abdominal or pelvic procedures, the leading cause of 30-day mortality was VTE.8 This registry also shows that despite prophylaxis, the rate of symptomatic VTE can be as high as 2%, with the rate of fatal VTE approaching 1%. Thus, in cancer patients undergoing abdominal or pelvic surgery, physicians should strongly consider prophylaxis of up to 30 days’ duration.
Dr. Jaffer: One striking finding from the @RISTOS registry was that 40% of VTE events in these cancer surgery patients occurred after postoperative day 21. This really underscores the need to consider prophylaxis for at least 4 weeks in these patients in real-world practice.
Dr. Brotman: The other striking finding from that registry was that the in-hospital prophylaxis rate was quite high, about 80%, and the rate of extended prophylaxis approached 35%. These are rates that are rarely achieved in clinical practice. Yet despite these high levels of prophylaxis, patients in this registry still had a high incidence of morbidity and mortality from VTE. This suggests that we need to improve our out-of-hospital VTE prevention paradigms.
Dr. Jaffer: Dr. Deitelzweig, oncologists and internists are often unsure about whether their ambulatory cancer patients who are receiving chemotherapy should be on any form of prophylaxis. What is your opinion?
Dr. Deitelzweig: That question comes up regularly because these patients are encountered across many medical specialties. At this point, all of the large organizations, including ASCO and NCCN, are advocating that prophylaxis is not indicated for such patients.
