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Missed doses of prophylactic anticoagulation account for much of the deep vein thrombosis (DVT) that occurs in surgery and trauma patients, a study showed.

Among 202 such patients admitted to a level 1 trauma center, (Lovenox) and 16% developed DVT, Scott G. Louis, MD, of the Oregon Health and Science University in Portland, and colleagues found.

The rate of DVT was 24% in patients who missed at least one dose of the low molecular weight heparin compared with just 5% among those whose therapy was uninterrupted (P<0.01), the researchers reported in the April issue of JAMA Surgery.

Interruptions in dosing were the only independent risk factor aside from older age in the study.

"Missed doses are the only identified risk factor for DVT that can be ameliorated by physicians, and efforts to minimize interrupted enoxaparin prophylaxis in patients at risk for DVT should be optimized," Louis' group wrote.

A second study in the same journal issue blamed suboptimal prophylaxis for .

Clinical Implications

"Although it is generally agreed by clinicians that pharmacologic prophylaxis should begin as soon as possible based on the physician's assessment of a patient's bleeding risk, the decision to withhold a dose of enoxaparin is often undertaken without comprehensively assessing the consequences," Louis' group noted.

Common reasons for missed doses were pending procedures, absence of the patient from the room, and epidural catheter use, although documentation was poor and many patients had no reason documented, , of the University of California Davis Medical Center, pointed out in an accompanying editorial.

Despite millions invested in electronic medical records, computer order entry systems, and other attempts by hospital and physician practices to cut medical errors, individual patients still aren't getting the care their physicians intend, he said, calling the results disturbing.

"The persistence of missed medication doses should prompt continued review of mechanisms used to deliver care at the individual patient's bedside," Galante argued.

One area to tackle might be doses missed due to nursing errors or patient refusal, Louis' group suggested, recommending thorough education for both of those groups.

Physicians might also take a harder look at whether patients really need to stop prophylaxis for subsequent procedures, they noted.

"While we do not recommend continuing anticoagulation during high-risk operations such as intracranial or spinal procedures, the decision to withhold prophylaxis before multiple low-risk operations should not be taken lightly," they wrote.

Studies and some guidelines have supported not stopping anticoagulation, even with warfarin (Coumadin), for less serious surgeries ranging from dental procedures to cardiac device implantations.

Risks of Stopping Prophylaxis

In Louis' study of prospectively-collected data, the DVT rate did not differ between surgical and trauma patients or in patients getting a once- versus twice-daily regimen.

About half of patients who did not develop a DVT missed a dose, but that rate was significantly higher among those who did develop a DVT, at 88% (P<0.001).

While missing a single dose of enoxaparin wasn't significantly associated with higher risk of DVT, missing two doses was and the risk rose from there. The odds were:

• 8.49-fold higher with two to four missed doses
• 10.13 with five to eight missed doses
• 14.73 with 9 to 17 missed doses

Beyond 17 missed doses, the relationship ceased to exist, "likely because of the small sample size."

Notably, the association was despite no difference between those with and without an interruption in prophylactic anticoagulation in measured coagulation variables, including the mean platelet count, fibrinogen level, partial thromboplastin time, and international normalized ratio.

The first of the newer generation of anticoagulants -- rivaroxaban (Xarelto) -- was approved in July 2011, in time for some use to have started before the end of the 4-year study period in September 2012.

However, patients on any anticoagulant other than enoxaparin were excluded.

What Louis' group called a "rigorous standardized protocol" for thromboembolic detection included bilateral whole-leg duplex ultrasonography on a weekly basis for ICU and trauma patients and when an event was suspected for general surgery patients. Other tests were run as needed, but no pulmonary emboli were detected.

"Because of the significant findings of this study, missed doses of enoxaparin now represent a quality improvement measure at our hospital, and we have educated surgeons about the adverse consequences of missing doses," they noted. "These interventions have already resulted in a reduced percentage of doses withheld."

Hospital-Level Strategies Ineffective?

However, hospital strategies overall appear to be lacking, based on results from Elliott R. Haut, MD, of Johns Hopkins, and colleagues.

Their research letter documented that hospital-level prophylaxis performance on the measure used and reported by Centers for Medicare and Medicaid (CMS) was not associated with risk-adjusted venous thromboembolism (VTE) rate over 2 years (P=0.13).

That measure, the Surgical Care Improvement Project (SCIP) VTE-2, captures the percentage of a hospital's surgical patients who received any VTE prophylaxis within 24 hours of surgery.

It was fairly high across the board, with a median of 95%. But exclusion of outliers didn't change the results.

Hospitals with 100% VTE prophylaxis coverage averaged a nearly identical VTE rate of 4.18 per 1,000 surgical discharges as the 4.17 per 1,000 in the bottom quartile.

"This may reflect the current low, minimum standard for VTE prophylaxis because the SCIP VTE-2 gives credit for even the most basic, suboptimal prophylaxis," Haut's group wrote. "Perhaps a more rigorously applied benchmark to report adherence to optimal, risk-appropriate prophylaxis would have a greater chance of differentiating hospitals and improving outcomes."

From the American Heart Association:

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