Risk of thrombosis ongoing for PNH patients, even with treatment

Blood-clotting events reported in 39% of study's 41 patients over time

Marisa Wexler MS avatar

by Marisa Wexler MS |

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Thrombosis — the serious and potentially life-threatening blood clots that can block blood flow — is a common occurrence in paroxysmal nocturnal hemoglobinuria (PNH) and can affect patients using more recent disease treatments, a study of PNH patients in Greece reported.

“Ongoing treatment with complement inhibitors has considerably reduced the risk of thrombosis, although it has not eliminate[d] it totally,” the researchers wrote.

The study, “Thromboembolic events in patients with paroxysmal nocturnal hemoglobinuria (PNH): Real world data of a Greek nationwide multicenter retrospective study,” was published in the journal Frontiers in Oncology.

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Thrombosis, a serious complication of PNH, historically has been the leading cause of death among patients. Recently developed PNH treatments help to markedly reduce its risk, while “anticoagulants alone are insufficient to prevent” a new thrombotic event, the researchers wrote.

Such events “necessitate initiation” of anticoagulant, or anticlotting, treatment, the team noted.

Scientists reviewed data covering 41 people with PNH who were treated at 14 centers across the country between 2002 and 2022.

“The cases reported represent a significant number of cases diagnosed and treated in Greece,” the researchers wrote.

Most patients were diagnosed with classical PNH only (56.1%), while 7.3% had subclinical PNH — meaning they showed signs of the disease, but didn’t have overt symptoms — and the remaining 36.6% had PNH co-occurring with another bone marrow disorder, most commonly aplastic anemia or myelodysplastic syndrome.

About half of the patients were male (53.7%), with a median age of 33 at the time of diagnosis.

About two-thirds (26 out of 41) of the patients were treated at some point with Soliris (eculizumab), the first therapy to be approved for PNH. Six patients were treated with Ultomiris (ravulizumab-cwvz), the second-generation therapy, while the remaining 13 did not receive any PNH-specific treatment. No one was given prophylactic (preventive) anti-clotting treatment.

Over the years of follow-up, thrombotic events were documented in a total of 16 patients. Most of these were clotting problems affecting blood vessels in the abdomen, especially those around the liver. Some patients had blood clots in multiple blood vessels or experienced several thrombotic events over the course of the study.

Five patients with thrombotic events had PNH co-occurring with another bone marrow disorder, while the other 11 had classical PNH alone.

“In the present study, 39% (16/41) of PNH patients experienced thrombosis during the course of their disease,” the researchers wrote, noting that this frequency is “comparable to that reported in the medical literature” for thrombotic events in PNH.

In seven patients, thrombotic events occurred at the time of PNH diagnosis. Another seven experienced blood-clotting problems after being diagnosed. The other two had experienced thrombosis many years before being formally diagnosed with PNH.

Thrombosis reported in 3 of 26 patients using Soliris

Thrombosis occurred in three of the 26 patients who were on Soliris and three of the 13 patients not using any PNH-specific therapies. Anti-coagulation therapies were given to all patients to treat a blood-clotting event.

Researchers noted that all three Soliris-treated patients who had thrombosis also had other co-occurring disorders, and they speculated that delays in administering treatment might have contributed to these events in some cases. Nevertheless, they noted that they cannot make definitive conclusions about the causes of thrombosis in these patients, highlighting the need for further research to understand risk factors for clotting problems in PNH patients on treatment.

Over the course of follow-up, eight patients in the study died, including three who had experienced thrombosis. However, none of the deaths were directly related to thrombosis. The most common causes of death were infections, namely, sepsis and COVID-19.

“None of the 16 patients who had PNH-induced thrombosis died as a result of the [thrombotic events],” the researchers wrote.

Eight of this study’s 31 scientists are advisory board members of Alexion Pharmaceutics, part of AstraZeneca, the company that markets Soliris and Ultomiris. The company was not involved in the study, whose support mainly came from a university research account.