HAE tied to a high risk of VTE in young, middle-aged patients: Study

Women, older patients with lower education most likely affected

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by Andrea Lobo |

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The risk of venous thromboembolism (VTE), which occurs when a blood clot forms in a vein and obstructs blood flow, is 2.5 times higher in people with hereditary angioedema (HAE) than in their relatives without it, a study of Swedish families shows.

The risk for VTE was higher in young and middle-aged HAE patients, and, compared with patients without VTE, those with VTE were more likely to be women, older, and have a lower educational level.

“The present study is the first family-based study to show that HAE is associated with a high risk of VTE … within the approximate range of thrombophilias,” the researchers wrote in “Increased risk of venous thromboembolism in young and middle-aged individuals with hereditary angioedema: a family study,” which was published in Blood. Thrombophilias are blood disorders that make the blood more likely to clot and are associated with a higher risk of VTE.

The deeper layers of the skin or the mucous membranes that line the respiratory or gastrointestinal tract are affected by the sudden swelling attacks featured in HAE. The disease is mainly caused by mutations in the SERPING1 gene that results in a deficiency or dysfunction of the C1-inhibitor (C1-INH) protein, which is involved in regulating the signaling molecule bradykinin.

When bradykinin is produced in excess, it causes blood vessels to widen and become more permeable, letting fluid leak into nearby tissues, causing swelling.

People with HAE have a higher risk of VTE, indicating C1-INH deficiency might lead to a systemic activation of blood coagulation, studies suggest.

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Assessing VTE risk in HAE patients

Here, researchers conducted a family study where they linked people with a confirmed diagnosis of HAE to their family members to determine the familial risk of VTE in HAE. For that, they intersected data from the Swedish National Patient Register and the Swedish Multi-Generation Register, gathered from 1964 to 2018.

A total of 2,006 participants, including 365 HAE patients and 1,641 relatives from 276 families, were included. Most were women (58.4 %) while the non-HAE relatives were mainly men (52.7%). The mean age at HAE onset was 40.

Among all the participants, 103 had at least one VTE episode. From these, 35 had HAE (9.6% among all HAE patients) and 68 were non-HAE family members (4.1% among all non-HAE participants). This indicated the risk for VTE was 2.5 times higher in HAE patients than their non-HAE relatives.

HAE patients who had VTE were more likely to be women, older, and have a lower level of education than those who didn’t have a VTE.

The patients were significantly younger than their non-HAE relatives (mean age, 51 vs. 63) at the time of the first VTE. Moreover, the risk of having a VTE event was 3.6 times higher in patients younger than 70, and 8.3 times higher in those born after 1964. The odds were lower in HAE patients born in 1964 or earlier, but still 1.8 times higher than in the non-HAE relatives.

More than half (57%) of HAE patients had thrombosis in the deep veins in their legs, while 23% had a pulmonary embolism, which happens when a blood clot breaks loose and travels to the lungs. These occurred in similar proportions in non-HAE relatives. More than half the participants who had a VTE had recurrent episodes.

“This study reports a significant association between HAE and VTE among young and middle-aged individuals in Swedish families,” the researchers wrote. “The effect size of the association is similar to several thrombophilias.”

“We suggest that HAE may be classified a new rare thrombophilia caused by congenital C1-INH deficiency,” they wrote.