Understanding how JAK inhibitors may increase blood clot risk

Why do medications that are supposed to help patients with chronic inflammatory diseases sometimes lead to blood clots?

This is one of the questions that a team of researchers from Aarhus University has sought to answer in a study that has just been published in the journal Inflammopharmacology.

The study suggests that disturbances in the JAK-STAT signalling pathway, an important communication pathway in the body, may contribute to this side effect.

"In the study, we uncover the potential links between components of the JAK-STAK signalling pathway, blood markers in patients with blood clots, and the genetic factors that contribute to the risk of blood clots in patients. This helps improve our understanding of why we see an increased risk of blood clots when using JAK inhibitors," explains Stine Rabech Haysen, former medical student at the Department of Biomedicine at Aarhus University, who is the first author of the publication. 

The potential of the study

In the study, researchers used publicly available data from a number of published studies about patients with blood clots and compared them with a healthy control group.

They found no direct genetic explanation, but they did find a statistically significant enrichment of genes that are subject to regulatory control of the JAK-STAT signalling pathway among genes whose expression is altered in patients with blood clots.

"Although we cannot draw definitive conclusions about the mechanistic link between the use of JAK inhibitors and the risk of blood clots, our study demonstrates the potential of using data mining to identify and shed light on possible mechanisms of drug side effects," says one of the study's senior authors, associate professor at the Department of Biomedicine Per Qvist.

What does this mean for patients? 

Although JAK inhibitors rarely lead to blood clots, it's important to understand the mechanism behind them so that the risk can be reduced.

"For the average person, our study means that we're getting closer to understanding why some drugs can have dangerous side effects like blood clots. And going forward, our method could help identify and prevent serious side effects, potentially making drug treatment safer," explains the other senior author of the study, associate professor at the Department of Biomedicine Tue Wenzel Kragstrup.

The researchers will now test the method on other types of medication to see if it can be used to detect side effects more widely.