EGPA, kidney damage raise risk of blood clots in AAV patients: Study

Risk factors also include old age, AAV affecting lung and neurological function

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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People with the rarest type of ANCA-associated vasculitis (AAV), called eosinophilic granulomatosis with polyangiitis (EGPA), and AAV patients with reduced kidney function are more likely to experience thrombosis (blood clots that disrupt blood flow), according to a single-center study in China.

Results also indicated AAV patients with higher levels of a blood clot-related protein and those with lung or neurological involvement are at higher risk of thrombosis, as are those who are elderly.

The study, “Renal damage and old age: risk factors for thrombosis in patients with ANCA-associated vasculitis,” was published in Thrombosis Journal.

AAV is a group of autoimmune conditions marked by inflammation of small blood vessels.

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Previous research shows higher risk of blood clots in AAV patients

Prior studies have shown people diagnosed with AAV are at higher risk of thrombosis, which can cause serious and even life-threatening health problems, than the general population. The research also suggested risk factors for thrombosis in AAV patients include poor kidney function and older age.

Previous studies were mainly done in people of European descent, however, and AAV tends to vary in its presentation across different racial and ethnic groups. As such, it’s unclear if the prior results are applicable to other ethnic populations.

To learn more, a team of scientists in China retrospectively reviewed data from all 1,203 AAV patients who were hospitalized at the Peking Union Medical College Hospital from 2013 to 2022.

The mean age of the patients was 55 years, and more than one-third (36%) were older than 65. In terms of AAV types, half of the patients had microscopic polyangiitis, 29.7% had granulomatosis with polyangiitis, and 15.8% had EGPA.

Results first showed “thrombosis was not rare in Chinese patients with AAV,” the team wrote, being reported in more than one in 10 patients (11.3%).

Statistical models indicated the strongest independent risk factor of thrombosis was having EGPA, which was associated with a threefold higher risk.

Very high levels of creatinine, a marker of kidney damage, in the blood, and elevated blood levels of a blood clot-related protein called D-dimer were each significantly linked to a nearly threefold higher risk of thrombosis.

“The cut-off point of D-dimer (> 2 mg/L) might serve as an alerting biomarker to indicate disease activity, thrombosis, and adverse outcomes of AAV patients,” the researchers wrote.

Also, patients whose AAV affected their lungs or nervous system were about twice as likely to experience thrombosis as those without such involvement. Age was also an independent risk factor, with patients older than 65 about 65% more likely to experience thrombosis than younger patients.

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Kidney damage, old age emerging ‘critical risk factors’ for thrombosis

“[Kidney] damage and old age emerged as critical risk factors for thrombosis,” the researchers wrote, noting these results are generally in line with earlier studies in other ethnic groups.

Based on all identified risk factors, the scientists constructed a mathematical tool to predict thrombotic events in AAV patients. The team showed this tool could successfully discriminate between patients who experienced thrombosis or not with an accuracy of 76.9%.

In addition to looking for thrombosis risk factors, the researchers also assessed the cause-and-effect relationship between AAV and thrombosis using a method called Mendelian randomization, or MR, which uses genetic information to assess the causal nature of the link between a risk factor and an outcome based on observational data.

Simplistically, MR analysis is based on the idea that if a disease like AAV causes a complication such as thrombosis, then genetic mutations predisposing people toward AAV should also predispose them to thrombosis.

The MR analysis revealed a small but statistically significant association specifically between EGPA and thrombosis, including especially serious forms of thrombosis, like deep vein thrombosis and pulmonary embolism. No such associations were observed for each of the other two types of AAV.

These findings suggest EGPA in particular may set the stage for dangerous clots, which is consistent with findings of a previous nationwide study in Korea.

Still, the MR analysis was based on genetic association data from European populations, which the team said is a limitation in this analysis as genetic risk factors for AAV may vary by ethnicity.

Studies assessing genetic variants linked to AAV in Asian populations are “needed to confirm the conclusion,” the researchers wrote.