WASHINGTON–Venous thromboembolism, which includes deep venous thrombosis and pulmonary embolism, is the most common preventable cause of hospital death, according to the VA.

The American Society of Hematology recently released new guidelines for venous thromboembolism. Those recommendations could change treatment of hospitalized and recently discharged patients at the VA.1

“Sixty thousand to 100,000 Americans die of venous thromboembolism every year,” said Adam C. Cuker, MD, MS, of the University of Pennsylvania and the chair of ASH’s VTE guidelines panel in a webcast. “There is an underappreciation for this disease.”

The new guidelines cover a broad range of topics from diagnosis to management as well as special situations such as pregnancy and pediatrics, but the most significant changes concern prophylaxis for medical patients, particularly in the use of anticoagulants.

The VA National Center for Patient Safety notes a number of common challenges involved in achieving safe anticoagulation therapy, especially for hospitalized patients. While acknowledging that “anticoagulant use [is] among the most difficult of all therapies to manage,” the agency has not developed its own guidelines for VTE or anticoagulant use.

“VA considers the best available scientific evidence when establishing clinical practice guidelines. VA/DoD Clinical Practice Guidelines are developed under the auspices of the VA/DoD Evidence Based Practice Working Group. Recent guidance will be considered if the EBPWG develops a clinical practice guideline for venous thromboembolism. No specific timeline is available at this time,” VA spokesperson Ndidi Mojay told U.S. Medicine.

The VA generally follows the American College of Chest Physician guidelines released in 2012.

Since those guidelines were published, “we now have four new drugs that are available on the market for people to prescribe, and we don’t have any guideline information on how to use those,” noted Daniel M. Witt, PharmD, University of Ohio and chair of the ASH Anticoagulation Therapy Panel. “We were able to dig in and make some recommendations on how to use those in patients with venous thromboembolism.”

The four new drugs are the direct oral anticoagulants apixaban, betrixaban, dabigatran, edoxaban and rivaroxaban.

Newer Anticoagulants?

The ASH guidelines prefer in-hospital administration of low-molecular weight heparin or fondaparinux over the newer anticoagulants, unfractionated heparin or mechanical prophylaxis for acutely ill hospitalized patients with acceptable bleeding risk. Mechanical prophylaxis is recommended for patients who have a high risk of bleeding.

The ASH panel only suggested—as opposed to recommended—use of pharmacological prophylaxis for acutely ill patients because the evidence provides low or very low certainty of benefit, and multiple studies have found no mortality benefit; it recommended prophylaxis for critically ill patients, however.

The ACCP guidelines recommended against the use of any prophylaxis in acutely ill hospitalized medical patients at low risk of thrombosis, as determined by the Padua Prediction Score and in patients with increased bleeding risk.

The ASH committee’s preference for LMWH came down to its once-a-day administration and lower risk of complications compared to unfractionated heparin. The ACCP guidelines placed LMWH, low dose unfractionated heparin and fondaparinux on equal footing.

While the direct oral anticoagulants have simplified dosing and are easy for patients to manage on their own at discharge, those advantages were not sufficient to overcome evidence favoring LMWH.

“The ASH panel addressed use of DOACs for inpatient and postdischarge prophylaxis in medical patients using data not available to other guideline groups and recommended against the use of DOACs over other treatments in the hospital,” according to the authors.

The new guidelines also do not recommend use of DOACs or any other agent for prophylaxis following discharge.

“Something new in this guideline, as compared to previous ones, is an evaluation of post-discharge treatment,” said Mary Cushman, MD, of the University of Vermont in Burlington at a press briefing. “We know that a good proportion of patients who develop VTE as a consequence of hospitalization develop this after discharge. We reviewed the literature on this and whether it made sense to continue anticoagulation after discharge, and we did not find sufficient evidence to recommend doing that or to recommend one drug over another for that purpose.”

While the ACCP guidelines recommended mechanical prophylaxis with graduated compression stockings or intermittent pneumatic compression for patients at risk of bleeding, the ASH guidelines recommended these methods of prophylaxis in patients who are not receiving pharmacological prophylaxis, regardless of bleeding risk.

Notably, the ASH panel found no advantage to combining mechanical and pharmacological prophylaxis.

The ASH guidelines concurred with ACCP recommendations against prophylaxis in chronically immobilized outpatients and nursing home residents. While neither organization advised prophylaxis during long distance travel for low-risk individuals, ASH did recommend LWMH or graduated compression stockings plus aspirin for those at higher risk. The ACCP guidelines recommended graduated compression stockings, calf muscle exercise, sitting in an aisle seat and getting up to walk frequently but did not support the use of anticoagulants or aspirin.

The ASH guidelines recommended D-dimer testing as the initial test for patients at low risk of VTE. No further testing is needed in the event of a negative result. For patients at high risk, the panel recommended a ventilation-perfusion scan over a computed tomography scan, as it has lower radiation risk. Ultrasonography can be used for DVT diagnosis in the extremities.

VA research presented at the CHEST 2018 meeting in December supported the need for both more D-dimer testing and reduced use of CT scans in the VA. Very few VA hospitals used D-dimer testing plus a clinical decision rule, a Top 5 Choosing Wisely recommendation in pulmonary medicine, to assess the need for CT pulmonary angiography in suspected pulmonary embolisms, according to Nancy Hsu, MD, of the VA Greater Los Angeles Healthcare System.3

Up to one-third of CTPA scans could be avoided with broader use of prescan assessments, she said. While the 14-fold increase in CTPAs over the last decade had not decreased mortality from pulmonary embolism, it had exposed more patients to unnecessary radiation, contrast exposure and treatment-related bleeding.

1. Schünemann HJ, Cushman M, Burnett AE, Kahn SR, Beyer-Westendorf J, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: prophylaxis for hospitalized and nonhospitalized medical patients. Blood Adv. 2018 Nov 27;2(22):3198-3225.

2. Kahn Sr, Lim W, Dunn AS, Cushman M, Dentali F, et al. Prevention of VTE in Nonsurgical Patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. February 2012;141(2):e1955-e2265.

3. Hsu N and Soo Hoo G. Underutilization of Clinical Decision Rules and D-Dimer in Suspected Pulmonary Embolism. Chest. October 2018;154(4)Suppl: 1039A.