Getting Anticoagulation Right: New VTE Guidelines From ASH

Pam Harrison

November 29, 2018

New guidelines for the prevention and treatment of venous thromboembolism (VTE) in adults and in children are now available from the American Society of Hematology (ASH) and highlights were recently presented during a webinar.

Dr Mary Cushman

The full guidelines document will contain 10 clinical guideline chapters — six of which were presented during the webinar and are outlined in a summary document — starting with prophylaxis of VTE in largely hospitalized patients but extending to long-term care residents and at-risk individuals who have to fly for more than 4 hours.

"Prevention is tricky because anticoagulants which are commonly used — even in low doses — have serious bleeding risks so an initial risk assessment for both thrombosis and bleeding is needed whenever we are considering options for VTE prevention," Mary Cushman, MD, University of Vermont in Burlington told webinar participants.

For patients who require VTE prophylaxis but who have an increased bleeding risk, panel members recommended that mechanical interventions (eg, pneumatic compression devices, graduated compression stockings) be favored over blood thinners.

On the other hand, if a patient's bleeding risk is acceptable, "we recommend anticoagulants rather than mechanical prophylaxis," Cushman noted.

Panel members also recommended physicians choose low molecular weight heparin (LMWH) over unfractionated heparin because of ease of administration.

LMWH should also be used for prophylaxis rather than any of the direct oral anticoagulants (DOAs).

Treating physicians should give consideration to post-discharge re-evaluation of patient risk for VTE because a good proportion of patients who develop a blood clot as a consequence of their hospital stay develop VTE after discharge.

Panel members also felt that people who are at increased risk for thrombosis might benefit from graduated compression stockings or LMWH if they have to fly for over 4 hours in any aircraft.

"The ability to identify patients who are at low likelihood of having VTE can minimize the need for diagnostic testing," Wendy Lim, MD, McMaster University, Hamilton, Ontario, continued.

To do this, physicians need to rely on a clinical decision rule to establish a pre-test probability for the presence of VTE, she noted.

"Those with a low pretest probability have a low prevalence of VTE, while those with a high pretest probability have a high prevalence of VTE," Lim explained.

A D-dimer test is the best first step to check for the presence of VTE in patients with a low pre-test probability; if results are negative, no further testing is required.

On the other hand, patients who have a positive D-dimer will require additional testing, Lim observed.

And in those patients who require diagnostic imaging of the lungs to detect for the presence of a pulmonary embolism (PE), the ASH guidance recommends performing a VQ scan rather than a CT pulmonary angiogram to minimize radiation exposure, unless patients have pre-existing lung disease. For that latter group, a CT scan is needed.

Optimal Management

Daniel Witt, PharmD, University of Utah School of Pharmacy in Salt Lake City, and fellow panel members focused mainly on which anticoagulant is best for which patient and how to optimally use it.

"There is an inevitable trade-off between the benefit of anticoagulant therapy that reduces the coagulability of the blood and prevents further VTE and bleeding risk that [anticoagulation] could potentially make more severe, so navigating that delicate balance is what this chapter [on optimal management] is all about," Witt explained.

Highlights presented from the “Optimal Management of Anticoagulation Therapy” chapter were kept to a minimum, but panel members did make one recommendation for patients to receive care from specialized anticoagulant management service centers if prescribed warfarin so as to improve outcomes.

"It used to be that healthcare providers would use injectable anticoagulants during the period of time patients came off warfarin to prepare them for invasive procedures," Witt said.

However, panel members found that the risks associated with this so-called "bridge" therapy far outweighed any benefits. They therefore recommend that most patients forego the use of LMWH during the bridging period.

Instead, warfarin should simply be interrupted before the procedure takes place and then resumed after it is over.

Panel members also noted that the "default position" should be to consider resuming anticoagulant therapy in patients who have survived a major bleed because patients remain at risk of recurrent VTE if anticoagulant therapy is not reinstated.

Heparin is a highly effective anticoagulant strategy. However, paradoxically, heparin-induced thrombocytopenia (HIT) is a prothrombotic response to heparin and can be limb or life-threatening, as pointed out by Adam Cuker, MD, Perelman School of Medicine, Philadelphia, Pennsylvania.

Though relatively uncommon, suspicion for HIT is actually far too common, and this suspicion can lead to overdiagnosis, poor management decisions, and adverse outcomes for patients, Cuker noted.

Thus, one of the key recommendations made by HIT panel members is for physicians to use a clinical scoring system called the 4Ts score rather than a gestalt approach to improve the accuracy of diagnosis.

"We also provided recommendations for the use of not only conventional treatment options such as argatroban, bivalirudin, and danaparoid but also new agents such as fondaparinux and the DOAs," Cuker observed.

VTE in Pregnancy and Pediatrics

As for prevention and treatment of VTE in pregnancy, Shannon Bates, MDCM, McMaster University, Hamilton, Ontario, reminded webinar participants that pregnancy is associated with a 5- to 10-fold increase in the risk of VTE and blood clots are, in fact, a leading cause of morbidity and maternal mortality even in Western countries.

Thus, for pregnant women with inherited clotting disorders or with clinical risk factors for VTE, panel members recommended physicians use VTE prophylaxis to prevent either the first VTE episode or recurrent VTE in women with a history of deep vein thrombosis (DVT) or PE.

"In the majority of cases, LMWH is likely to be the best approach for managing superficial thrombosis," Bates observed. LMWH is actually the only anticoagulant recommended for use in pregnancy.

It is also acceptable to use weight-based dosing instead of regular blood tests when treating either DVT or PE in pregnant women.

The majority of women with newly diagnosed VTE at low risk of complications may also be treated as outpatients provided the right support is in place, Bates added.

For the management of VTE in children, Paul Monagle, MD, University of Melbourne, Australia, emphasized that treating VTE in pediatric patients is very different from treating VTE in adults, primarily because VTE in children is always a disease of hospitalized children who have a major underlying illness.

"There is nothing more devastating than having a child who is cured of their cancer or who has done well with surgery than to have long-term effects from a complicating thrombosis," Monagle said.

Indeed, central venous line-associated clots are the most common precipitating factor for thrombosis in children, he noted.

Thus, pediatric panel members made a number of recommendations around not just how to treat central-line clots but whether or not the line itself should be removed and if so, how that line should be managed.

The most common VTE that occurs in children is renal vein thrombosis, as Monagle pointed out.

Having looked at the long-term outcomes of renal function in children who previously developed a renal vein thrombosis, "we now recommend that all children with renal vein thrombosis receive anticoagulant therapy," he emphasized.

The guideline documents are available on the ASH website.

Cushman reports she has served as either a consultant or an advisory board participant for Merck and Daiichi Sankyo and has received travel reimbursement from diaDexus. Lim reports she has served on an advisory board for Sanofi and has presented CME presentations on behalf of Leo Pharma. Cuker reports he has served on an advisory board for CSL Behring and as a consultant to Bracco Diagnostics and Genzyme. Monagle declares he holds a number of patents and has received research funding from Bayer. Witt and Bates have disclosed no relevant financial relationships.

ASH Webinar. Presented online November 27, 2018. Summary

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