Biology
Identifying the drugs behind unintended bleeding disorders By Elizabeth Bennett
Image credit: Pexels
M
edications are a powerful and important tool at a physician’s disposal, but they can become problematic when the full extent of their behavior is unknown. Many drugs come with long lists of known side effects, yet unintended reactions to prescribed medications, called adverse drug reactions (ADRs), are a leading cause of death worldwide. Associated with numerous drug classes, uncontrollable bleeding is a particularly dangerous and common ADR presented by patients. Identifying the risk of drug-induced bleeding disorders associated with specific medications would represent a vital step toward reducing the hospitalizations and deaths associated with drug-induced bleeding disorders.1 Although antithrombotic drugs, or blood thinners, understandably confer the greatest risk of drug-induced bleeding, ADRs associated with the use of blood thinners tend to be predictable and manageable. Scientists know how these drugs interfere with coagulation, through targeting the vitamin K cycle, and understand how to counter their effects.
In contrast, other drugs such as anti-inflammatory medications, antibiotics, anti-depressants, and chemotherapeutic agents pose bleeding risks that are not predictable or controllable.1 Understanding how these medications interfere with coagulation and which of them could cause bleeding disorders would save lives, rendering many ADRs preventable and controllable. The Stafford Lab at the University of North Carolina at Chapel Hill hopes to achieve this goal. The Stafford Lab seeks to investigate “the structure and function study of enzymes in the vitamin K cycle and…vitamin K-dependent proteins involved in blood coagulation.” 2 The lab, located in UNC’s Biology Department, used its own cell-based assay, developed in 2013 by Dr. Jack Tie & Dr. Da-yun Jin, to screen the drugs—a testament to years of carefully researching the vitamin K cycle.3 In a recent study led by Xuejie Chen, a postdoctoral researcher in the Stafford Lab, the group “established a cell-based, high-throughput approach for screening drugs that have bleeding risks caused by off-target inhibition of vitamin K redox cycling,” a process involved in blood coagulation.1
Figure 1: Bleeding disorders can occur when the vitamin K cycle is disturbed. Image source: RicHard-59, CC BY-SA 4.0, via Wikimedia Commons.
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Dr. Xuejie Chen
