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Low-molecular-weight heparin (LMWH) retained a prominent role in the prevention of venous thromboembolism (VTE) in a comprehensive new clinical guideline from the American Society of Hematology (ASH).

For inpatients who require VTE prophylaxis and do not have an increased bleeding risk, blood thinners are preferred over mechanical intervention, and LMWH is the preferred medication. LMWH received the nod over unfractionated heparin because of simpler administration and fewer complications. Mechanical prophylaxis is the preferred approach for patients with an increased bleeding risk.

In-hospital administration of LMWH is preferred over a direct oral anticoagulant administered during hospitalization or after discharge, according to one of the initial chapters of the guideline, .

"We also evaluated the best or optimal treatment when considering newer anticoagulants, the so-called direct oral anticoagulants, and had data comparing those to low-molecular-weight heparin," Mary Cushman, MD, of the University of Vermont in Burlington, said during a press briefing on the new guideline. "We found that low-molecular-weight heparin is preferred over direct oral anticoagulants."

"Something new in this guideline, as compared to previous ones, is an evaluation of post-discharge treatment," she continued. "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."

Cushman was one of six speakers who reviewed chapters of the guideline, addressing VTE prophylaxis for patients, diagnosis, optimal management of anticoagulation, heparin-induced thrombocytopenia, VTE in pregnancy, and treatment of pediatric patients with VTE. Four additional chapters are expected to be released in 2019: treatment of deep-vein thrombosis (DVT) and pulmonary embolism, VTE in patients with cancer, thrombophilia, and prophylaxis in surgical patients.

The guideline development process involved representatives of ASH and the McMaster University GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) Center in Hamilton, Ontario. During an introduction to the guideline chapters, Holger Schünemann, MD, PhD, of McMaster University, said the process involved more than 100 experts in the field of VTE, including patient representatives and advocates. Panels for each chapter used explicit criteria for developing recommendations and for rating the supporting evidence for each recommendation.

"Guidelines are only as good as the approach and methods that are used to develop them," said Schünemann. "These guidelines, we believe, meet the Institute of Medicine standards for trustworthiness... that guidelines should be developed by multidisciplinary panels, they should be based on trustworthy syntheses of the literature and the evidence (systematic reviews), they should appropriately manage conflicts of interest, and they should provide an explicit link between recommendations and evidence."

Chairs of the six panels with completed chapters touched on key sections from the dozens of recommendations included in the overall guideline.

Prophylaxis for Medical Patients

Beyond the points previously described, Cushman said the panel concluded that the use of combined modalities (such as compression devices plus a blood-thinning agent) is not warranted. Patients who travel long distances by air and do not have an increased risk of VTE do not need to wear compression socks or take blood thinners (including aspirin). Air travelers who have a substantial risk of VTE "may benefit" from the use of graduated compression socks or blood thinners.

Diagnosis of VTE

A rigorous review of existing evidence confirmed recommendations made in previous guidelines, said Wendy Lim, MD, also of McMaster University. In contrast to previous guideline-development efforts, mathematical modelling was performed to predict outcomes of various diagnostic pathways that had not been evaluated previously.

Clinicians should establish a patient's VTE risk category before ordering a test. D-dimer is the best initial test for patients with a low pretest probability of VTE, and a negative test rules out the need for additional testing. When possible, VQ scans should be used instead of CT scans to minimize radiation exposure.

Optimal Management of Anticoagulation

This chapter addresses the management of anticoagulation in patients with a history of VTE, said Daniel Witt, PharmD, of the University of Utah College of Pharmacy in Salt Lake City. Because of the complexity of anticoagulation therapy, management should be led by a specialized service center whenever possible, as opposed to primary care providers.

Patients who must stop warfarin during an invasive procedure do not require bridge therapy with a short-acting anticoagulant. Life-threatening bleeding during anticoagulant therapy requires "thoughtful use of anticoagulant-reversal therapies." Patients who survive major bleeding episodes should typically resume anticoagulation.

Heparin-Induced Thrombocytopenia (HIT)

Suspected HIT is the most common reason for a hematology consultation for hospitalized patients, said Adam Cuker, MD, of the University of Pennsylvania in Philadelphia and co-chair of the ASH VTE guideline coordination panel. He highlighted two recommendations: Use of the improves the accuracy of diagnosis and patient outcomes; and treatment options include conventional agents (such as argatroban, bivalirudin, and danaparoid) and newer/novel agents, such as fondaparinux and direct oral anticoagulants.

VTE in Pregnancy

VTE remains a leading cause of maternal morbidity and mortality in Western countries, said Shannon Bates, MDCM, of McMaster. Factors associated with VTE risk in pregnancy include inherited clotting disorders, older age, cesarean delivery, coexisting diseases (such as sickle cell and lupus), and obesity.

Key recommendations: A conservative, evidence-backed approach to VTE prophylaxis; LMWH is the best treatment for most episodes of superficial thrombosis; weight-adjusted dosing of LMWH is acceptable for both pulmonary embolism and DVT; and most patients with a low risk of complications can be treated as outpatients.

Pediatric VTE

VTE is uncommon in children, but poses a significant clinical challenge because thrombosis always occurs within the context of another serious condition that requires treatment, said Paul Monagle, MD, MBBS, of the University of Melbourne in Australia. The guideline addresses both symptomatic and incidental DVT.

Key observations and recommendations: Clots associated with central venous lines are the most common cause of clots in children. If a child is at the end of treatment, a nonworking central venous line probably should be removed. All renal vein thromboses, the most common type of spontaneous VTE in children, should be treated with anticoagulation. An overall low level of evidence mandates additional research to develop more evidence-based guidelines.

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