PNH linked to thrombosis, kidney failure in Nordic study
1 in 5 newly diagnosed patients affected
About one in five patients newly diagnosed with paroxysmal nocturnal hemoglobinuria (PNH) in the Nordic countries has a history of blood clots obstructing blood vessels — known as thrombosis — or develops kidney failure, a study in Denmark, Finland, Norway, and Sweden found.
“The high number of thromboses and kidney failures underlines the need for knowledge about this rare disease,” the researchers wrote.
They detailed their findings in a study, “The incidence of paroxysmal nocturnal hemoglobinuria cell clones in the Nordic countries,” published as correspondence to the Annals of Hematology.
PNH is an acquired disease that occurs due to mutations in stem cells in the bone marrow. These stem cells normally give rise to red blood cells that carry oxygen throughout the body, white blood cells that defend the body against infection, and platelets that form clots to stop bleeding.
Genetic mutations in PNH cause blood cells to lack certain protective proteins on their surface, making them vulnerable to destruction by the immune system. This can lead to a range of PNH symptoms — including fatigue, shortness of breath, dark urine, and abdominal pain — that often occur in sudden bursts.
Unpacking 6 years of PNH data
Each year, up to three new cases are diagnosed per million people worldwide. However, there have been few studies on the incidence of PNH — that is, the number of new diagnoses — in the Nordic countries. This study looked at the incidence of PNH in a six-year period in Denmark, Finland, Norway, and Sweden.
Between early 2011 and the end of 2016, 126 people in those countries were diagnosed with PNH at a median age of 56, the researchers found. The mean incidence was 1.71 new cases per million people each year. It was highest in Denmark, at 2.77, and lowest in Finland, at 1.34 new cases per million people each year.
At diagnosis, the mean size of PNH clones — the proportion of blood cells carrying PNH-causing genetic mutations — was 23.9%. In most patients (38.9%), PNH clones comprised less than 1% of all blood cells. Another 33 (26.2%) patients had a PNH clone size between 1% and 10%; for 13 (10.3%) it was between 10% and 50%; and 30 (23.8%) had clone sizes between 50% and 100%.
In patients with a smaller PNH clone size (less than 10%), the main reasons for testing were unexplained low blood cell counts (cytopenias), or aplastic anemia, which occurs when the bone marrow fails to produce enough blood cells. In people with larger clone sizes (over 50%), testing was linked to hemolytic anemia, a type of anemia driven by the destruction of red blood cells.
Thrombosis was found in 23 patients, including 17 who had a history of thrombosis before being diagnosed with PNH, five who developed it after diagnosis, and one who had it both before and after receiving a PNH diagnosis.
At the time of diagnosis, 10 patients had kidney failure, which occurs when the kidneys no longer function properly. By the latest follow-up, 28 patients had signs of kidney failure.
“PNH is thought to be underdiagnosed and time to diagnosis is often delayed,” the researchers wrote. “Cross-country collaboration gives us the opportunity to gather larger patient populations and encourage further studies on PNH.”
They also suggested updating Nordic PNH guidelines, “including recommendations for testing subset of patients with a high likelihood of finding new cases, such as in patients presenting with thrombosis in unusual locations.”
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