Anticoagulation Is Important Element of Adjunctive Therapy in Thrombosis Management

Patients at risk of developing thrombosis should receive anticoagulants, in the form of Xa inhibitors and, if necessary, andexanet alfa (Andexxa) or prothrombin concentrates to control excessive bleeding, explained Alvin H. Schmaier, MD.

“When you give an anticoagulant in the current era, it's a balance between preventing clots, but not giving [too much] anticoagulation in that patients hemorrhage. That's the major complication,” said Schmaier. “To address that, we now have antidotes to the Xa inhibitors as well as direct thrombin inhibitors.”

In an interview with OncLive, Schmaier, a professor in the Department of Medicine and the Department of Pathology at Case Western Reserve University School of Medicine, discussed the primary and secondary management of cancer-related thrombosis.

OncLive: Could you provide an overview of the use of anticoagulant agents in patients with cancer?

Schmaier: To some extent, 2019 and 2020 have been the years of cancer-associated thrombosis. We now have a fair amount of evidence-based data to be able to give good information on how to prevent thrombosis, how to manage [patients with thrombosis], and how to provide secondary management after the [initial] treatment of thrombosis.

We have a new era of anticoagulants. It’s truly a step forward in this adjunctive management of patients with cancer.

What can be done to prevent thrombosis?

[Use] anticoagulant agents. We have good risk assessment markers we can use to assess which of our patients need to be put on prophylactic anticoagulation and how to manage them. There are good evidence-based data on how to manage patients’ thrombosis [while on] chemotherapy and how to stratify [patients], based on the nature of the cancer as well as its presence in an intraluminal surface, such as the gastrointestinal tract or genitourinary tract. Once a period of treatment for thrombosis is completed, we have good evidence-based data for long-term risk reduction for recurrence with anticoagulants.

Could you elaborate on management strategies for thrombosis?

We have these oral anticoagulants called Xa inhibitors. We will, depending on if it's prevention or secondary prevention, give prophylactic doses. For primary treatment, there are well-established treatment doses, which are given daily without injections or monitoring. The evidence shows that there is improved safety compared with previous anticoagulants with no compromise in efficacy. In some cases, there is improved efficacy. The Xa inhibitors have gone through phase III evidence-based trials to show safety and efficacy.

How do you approach secondary management of thrombosis?

[Oral anticoagulants can cause bleeding]. The goal of secondary management is to ensure patients don’t have excessive bleeding. The FDA approved andexanet alfa, which is an inactivated blood coagulation factor Xa that sops up the anti-Xa anticoagulant but does not participate in blood coagulation in and of itself. The approval [helped fill] an unmet need. It hasn't been studied in a prospective, randomized trial.

The other [class of] agents that is out there are prothrombin concentrates, which have not met the same criteria for FDA approval, including multinational clinical trials, as well as good metrics for efficacy as andexanet alfa. However, there is a prospective randomized clinical trial currently going forward comparing andexanet alfa with prothrombin concentrates, which are standard of care.

What is the take-home message regarding thrombosis management?

Thrombosis is an important adjunct. The data indicate that if you get thrombosis, especially within the first year of diagnosis, you have a 66% mortality rate. Thrombosis is a bad sign not only from the clot itself, but also because it indicates the underlying performance status of the patient. To ignore the management of the thrombosis really compromises the patient’s initial treatment.

This work is really less developed in hematologic malignancies. That area becomes more complex when you become thrombocytopenic. It's better developed through the risk stratification for solid tumors. However, we have to include lymphomas in the group of solid tumors because these patients are considered at high risk for thrombosis. Hence, these patients suffer the same consequences as patients with higher-risk solid tumors, such as lung, gastric and pancreatic cancers.