ITP associated with high risk of blood clots that block circulation
Analysis: US, Europe have greater rates of clotting events compared to Asia
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People with immune thrombocytopenia (ITP) are at high risk of developing blood clots that block circulation, according to an analysis that combined results of multiple studies.
The research team also found greater rates of clotting events, or thrombosis, in the U.S. and Europe compared to Asia.
Age, the presence of other underlying conditions, and the use of thrombopoietin receptor agonists (TPO-RAs) were all connected with a higher risk of thrombosis.
These findings highlight “the need for targeted screening and preventive strategies in high-risk populations,” researchers wrote.
The study, “Geographic and diagnostic variations in thrombosis risk among patients with immune thrombocytopenia: A systematic review and meta-analysis,” was published in the journal Thrombosis Research.
People with ITP may have a ‘paradoxical predisposition’ to forming clots
ITP is a bleeding disorder in which the immune system mistakenly attacks cell fragments called platelets that help blood form clots. Most often, this occurs with no clear cause and is called primary ITP, but it can also develop as a result of other conditions, such as infections or separate autoimmune disorders, which is known as secondary ITP. Low platelet counts in ITP, known as thrombocytopenia, are associated with risk for easy bruising and bleeding.
Treatment may include TPO-RAs, which aim to increase platelet production. This category of medications includes Alvaiz (eltrombopag), Doptelet (avatrombopag), Promacta (eltrombopag), and Nplate (romiplostim).
Despite ITP-related problems with bleeding, people with ITP may have a “paradoxical predisposition” to forming clots that lead to thrombosis, according to the researchers. This complication “profoundly affects treatment outcomes and prognosis, while also imposing significant psychological and financial burdens on patients,” they wrote.
Scientists don’t entirely understand the biological processes that put people with ITP at higher risk of thrombosis. Several studies have examined this relationship, but risk factors remain unclear. For example, the role of TPO-RAs in thrombosis development remains under debate.
“This study conducted a meta-analysis to evaluate the incidence and risk factors of thrombosis in ITP patients, with the goal of raising clinicians’ awareness of this serious complication, optimizing thromboprophylaxis [prevention] and therapeutic strategies, and ultimately enhancing patient quality of life,” the investigators wrote.
Findings highlight importance of proactive thrombosis screening
Their meta-analysis included 20 published studies. Together, these included 100,446 participants with ITP and 9,010 thrombotic events.
With statistical modeling to account for differences between studies, results showed a 6.03% incidence rate (new cases) of thrombosis. After further statistical adjustment to account for potential biases in publications, the estimated incidence rate increased to 10.43%.
“Clinically, these findings imply that the true thrombotic burden among ITP patients might be greater than previously appreciated, thereby highlighting the importance of proactive thrombosis screening,” the researchers wrote.
Across different geographical regions, incidence was higher in the U.S. (7.13%) and Europe (6.92%) than in Asia (4.5%).
Similarly, the researchers found significant differences in thrombosis rates depending on the diagnostic criteria the studies used to define ITP. Studies that used the 2011 American Society of Hematology criteria, which may include mild and early-stage cases, had an incidence rate of 8.18%. Studies that used the more stringent Chinese Medical Association 2020 guidelines had a lower rate (2.08%).
This suggests that “stricter [ITP] diagnostic criteria may lead to an underestimation of the true thrombotic risk in this population,” the team wrote.
Although men tended to have higher thrombosis rates than women, this difference didn’t reach statistical significance.
Future research should focus on high-quality, multicenter prospective cohort studies and the development of more accurate thrombotic risk prediction models to guide clinical decision-making.
Several factors related to patient characteristics, disease features, and treatment had significant correlations with the risk of thrombosis. Older participants had a 7.5 times higher risk than younger patients, and having secondary ITP was associated with a 29% higher risk of thrombosis.
“Patients with secondary ITP frequently have concomitant autoimmune diseases, such as systemic lupus erythematosus and antiphospholipid syndrome, or underlying infections,” the researchers wrote, adding that these “may further elevate the risk of thrombosis by triggering inflammatory responses.”
Having high blood pressure and testing positive for specific antibodies involved in clotting also raised the risk.
People who received treatment with TPO-RAs had an over threefold higher risk of developing thrombosis than those who didn’t.
“While low platelet counts rise the risk of bleeding and often require platelet-enhancing therapies, the concurrent thrombotic risk necessitates careful use of TPO-RAs and corticosteroids to avoid exacerbating clot formation,” the researchers wrote.
Individualized monitoring and treatment plans taking into consideration an individual’s risk factors could help prevent thrombosis and manage bleeding.
“Future research should focus on high-quality, multicenter prospective cohort studies and the development of more accurate thrombotic risk prediction models to guide clinical decision-making,” the team concluded.
