ACR/ARHP Annual Meeting 2012: What Rheumatologists Need to Know about the New Oral Anticoagulants

WASHINGTON, D.C.—A number of new oral anticoagulants now available in the United States will eventually be used to treat autoimmune and rheumatologic diseases associated with hypercoagulability complications, such as antiphospholipid antibody syndrome or catastrophic antiphospholipid syndrome, and rheumatologists will need to begin to understand their appropriate use and potential complications, according to Craig M. Kessler, MD, professor of medicine and pathology and director of the coagulation laboratory in the department of pathology and laboratory medicine at Georgetown University’s Lombardi Comprehensive Cancer Center in Washington, D.C.

To help rheumatologists become familiar with the new anticoagulants and how to determine their appropriate use in clinical situations, Dr. Kessler presented information on a new paradigm for coagulation, as well as advantages and disadvantages of the new anticoagulants, during a session titled, “New Anticoagulants: What a Hematologist Thinks a Rheumatologist Needs to Know!” at the 2012 ACR/ARHP Annual Meeting, held November 9–14. [Editor’s Note: This session was recorded and is available via ACR Session Select at www.rheumatology.org.]

Dr. Kessler shared his experience as an expert in disorders of anticoagulation to highlight what he thinks is essential for rheumatologists to know. To illustrate the indications and risks of anticoagulation, he presented a number of case studies that show how autoimmune diseases can be treated by modulating the B cell that is involved with producing antibodies—a strategy, he said, that underlies the treatment of many rheumatologic and hematological diseases, due to similar pathological etiologies.

New Paradigm of Coagulation

Dr. Kessler laid the foundation for understanding the role for the new oral anticoagulants by describing a new paradigm of coagulation that helps explain how rheumatological diseases trigger coagulation. In the older paradigm, described as a coagulation cascade, the thought was that tissue damage to the extrinsic circulating tissue factor and clotting factor VIIA complex activates the intrinsic pathway factor IX to initiate generation of thrombin for fibrinogen cleavage and fibrin formation.

According to Dr. Kessler, in the new paradigm, described as normal hemostasis, tissue-factor bearing cells are the mainstay of coagulation in which the process of FVIIa-tissue factor complex formation occurs on the surface of tissue factor laden cells, such as monocytes and macrophages. “These cells are critical to the symptomatology and progression of autoimmune diseases and links inflammation with coagulation,” he said, adding that new treatment strategies can be developed based on this new understanding of how rheumatological diseases trigger coagulation.

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Table 1

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Table 2

New Anticoagulants: Pros and Cons

Dr. Kessler described the pharmacology of the new oral anticoagulants along with warfarin, including the different mechanisms of action (see Table 1) and clinical application (see Table 2).

A number of advantages and disadvantages should be weighed when considering use of one of these new anticoagulants over warfarin, he said. The advantages include lower rates of stroke and mortality, along with lower rates of intracerebral hemorrhage (although the rates of gastrointestingal bleeding are higher) compared to warfarin. One of the main advantages, he said, is that these anticoagulants are more convenient to use because they don’t require the type of regular monitoring that warfarin requires.

However, the lack of monitoring could also affect adherence adversely, he said. Other disadvantages of the new anticoagulants include the short half-life, which may not benefit patients with limited adherence, as well as the inability to titrate doses and the high cost of these drugs. One main disadvantage, he said, is that these new anticoagulants have no antidote. To address this, he cited a study by Kaatz et al. that provides some information and suggestions on reversal of three of the new anticoagulants, apixaban, dabigatran, and rivaroxaban.¹ For example, oral activated charcoal can be used to reverse all three of these anticoagulants, whereas fresh frozen plasma will not be effective for any of these.

Mary Beth Nierengarten is a freelance medical journalist based in St. Paul, Minn.

Reference

1. Kaatz S, Kouides PA, Garcia DA, et al. Guidance on the emergent reversal of oral thrombin and factor Xa inhibitors. Am J Hematol. 2012;87(Suppl 1):S141-S145.