ASH president highlights ‘potentially practice-changing’ venous thromboembolism research
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During a recent webinar, ASH President Roy L. Silverstein, MD, highlighted three “potentially practice-changing” abstracts on venous thromboembolism that will be presented at the upcoming meeting in Orlando, Fla.
“We all know that venous thrombosis is a very significant clinical problem, and a public health problem. Latest estimates [indicate there] are about 900,000 cases per year in the United States,” Silverstein, who is also chairman of the department of medicine at Medical College of Wisconsin (MCW), associate director of MCW Cancer Center and senior investigator for Versiti Blood Research Institute, said. “These are associated with very significant morbidity, and even mortality.”
‘New standard of care for children’
The first abstract Silverstein discussed included results from the phase 3 EINSTEIN-Jr study, a dose-exposure-response evaluation of rivaroxaban (Xarelto; Janssen, Bayer) in children with VTE.
“The EINSTEIN-Jr phase 3 study showed in a number of patients that the direct-acting oral anticoagulant, particularly rivaroxaban, is equivalent to low-molecular-weight heparin in this setting,” he said.
The current analysis assessed an “easy-to-administer” liquid formulation of the agent that was previously unavailable.
“[The researchers] documented and evaluated a dosing algorithm that is based on body weight because it is a little bit difficult to extrapolate what we do for adults in kids,” Silverstein said.
The study showed that bodyweight-adjusted dosing was safe and effective, resulting in peak drug levels comparable to those observed in adults who received standard rivaroxaban doses.
“This, I believe, will be the new standard of care for children,” Silverstein said. “It is not yet FDA approved, but we should expect that relatively quickly.”
Adding aspirin to direct oral anticoagulants: ‘Less is more’
The second abstract examined the effects of adding aspirin to direct oral anticoagulants in patients with nonvalvular atrial fibrillation or VTE.
“This refers to the fact that a large number of adults with nonvalvular atrial fibrillation or with acute or chronic venous thromboembolic disorders are now being treated with direct oral anticoagulants,” Silverstein said. “Many of these patients are also receiving aspirin for reasons that are not really indicated.”
The researchers found no changes in the rates of thrombosis, recurrent thrombosis or stroke among patients who received aspirin as well as a direct oral anticoagulant. However, aspirin was associated with an increase in “clinically relevant nonmajor bleeding events” that required attention, as well as an increase in ED visits and hospitalization, according to Silverstein.
“This is an example of what we call, ‘less is more,’” he said. “We will provide good evidence to our community practitioners that when starting a direct-acting oral anticoagulant for nonvalvular atrial fibrillation or venous thrombosis, a patient should not be on aspirin unless there is a clear indication for the aspirin, such as a recent stenting for coronary disease.”
Potential therapeutic target for catastrophic antiphospholipid syndrome
The third abstract that Silverstein reviewed on VTE examined factors associated with the catastrophic form of antiphospholipid syndrome. The abstract will be presented during the plenary session.
“This one is very exciting because it represents a very good example of how precision medicine and genomics brings power to our field to find disease pathophysiology and points out novel mechanisms for therapeutic interventions,” Silverstein said.
Although rare, catastrophic antiphospholipid syndrome results in severe life-threatening blood clots and is associated with high mortality rates, according to Silverstein.
atients,” he said.
For the study, researchers evaluated serum from patients with thrombotic antiphospholipid syndrome, catastrophic antiphospholipid syndrome and systemic lupus erythematosus. They found that serum from patients with catastrophic antiphospholipid syndrome was “very effective at activating complement” in vitro, Silverstein said.
“The activation of complement in these patients was associated with increased likelihood of having thrombosis,” he added.
A genomic sequencing analysis of complement regulatory genes revealed that approximately 60% of patients with catastrophic antiphospholipid syndrome harbored a rare germline mutation in the complement system vs. about 20% of patients with other autoimmune diseases or normal control, according to Silverstein.
“[This is] a very significant finding,” he said. “There are [complement-specific inhibitors] currently available ... and there are others that are in the pipeline. This points to the potential of using those drugs to treat catastrophic antiphospholipid syndrome and perhaps even patients with the more standard form of antiphospholipid syndrome who are refractory to standard therapy.”
Additional benign hematology sessions
ASH is the largest hematology conference worldwide, bringing together more than 25,000 hematology professionals. Thein H. Oo, MD, FRCPE, FACP, of the Section of Benign Hematology, Department of Pulmonary Medicine, at The University of Texas MD Anderson Cancer Center, told Healio that some of the most interesting opportunities that the conference offers for clinicians involved in benign hematology are special-interest sessions on systems-based hematology, which review best practices for implementing evidence-based programs and virtual hematology consults; combined basic science and education sessions on cancer-associated thrombosis; and scientific workshops that evaluate the interplay between coagulation and malignancy, among other topics.
For Oo, ASH also is an opportunity to work with his colleagues from the Venous thromboEmbolism Network U.S., also known as VENUS, on current research projects. He warned that a shortage of benign hematologists in the United States could threaten future research efforts.
“I have been training 14 hematology-oncology fellows in my program each year for the last 9 years,” he said. “Of more than 100 fellows, only one opted to make a career in the field of benign hematology. In the whole country, less than 2% of the trainees are making a career in the field of benign hematology. That will be very problematic in the next 5 years in terms of diagnosis, treatment and research.” – by Stephanie Viguers
References:
The following are scheduled for presentation at ASH Annual Meeting and Exposition; Dec. 7-10, 2019; Orlando, Fla:
Chaturvedi S, et al. Abstract 4.
Schaefer JK, et al. Abstract 787.
Young G, et al. Abstract 164.
Disclosures: Oo reports being a co-investigator on studies funded by Janssen; serving on the advisory board for Bristol-Myers Squibb; and receiving honoraria from the Medical Education Speakers Network. Healio could not confirm Silverstein’s relevant financial disclosures at the time of publication.