CAD, Other Hemolytic Anemias Increased in Denmark for Past 4 Decades, Study Finds

CAD, Other Hemolytic Anemias Increased in Denmark for Past 4 Decades, Study Finds
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The incidence and prevalence of most acquired hemolytic disorders, including cold agglutinin disease (CAD), have been rising in Denmark in the past decades, regardless of age and sex, a retrospective study including 36 years of data found.

Incidence is the proportion of new cases over a specified time period, while prevalence is the total number of cases in a population at a given point in time. The findings help further understand the contemporary distribution of these diseases, for which there is limited information available.

The study, “Increasing Incidence and Prevalence of Acquired Hemolytic Anemias in Denmark, 1980–2016,” was published in the journal Clinical Epidemiology.

Acquired hemolytic disorders are conditions that result in the destruction of red blood cells and are not inherited. In addition to CAD, these include autoimmune hemolytic anemia (AIHA), paroxysmal nocturnal hemoglobinuria (PNH), drug-induced hemolysis (DIHA), and acquired hemolysis not otherwise specified (AHNOS).

Despite being associated with a greater mortality, recent studies investigating the incidence and prevalence of these rare conditions are lacking. That is why researchers in Denmark set out to investigate the changes in prevalence and incidence in a Danish population.

The team reviewed medical records from the Danish National Patient Register and Civil Registration System databases, and identified 5,868 patients diagnosed with an acquired hemolysis disorder from 1980 to 2016.

These included 2,715 patients with AIHA, 112 with CAD, 116 with PNH, 397 with DIHA, 2,154 with AHNOS, and 374 with very rare hemolytic anemias classified as “other.”

Using those records, researchers calculated incidences for each disease in three time periods: 1980–1993, 1994–2007, and 2008–2016. Prevalence also was calculated at three points in time: The first day of January in 1980, 2000, and 2015.

Diseases were identified from databases based on their ICD codes, but CAD did not have a specific ICD code until 1994, so incidence and prevalence data for that disease could be assessed only after that date.

Results showed that the incidence increased over time for all hemolytic anemias, except for DIHA, “possibly mirroring the declining use of high-dose penicillin and methyldopa,” two medications known to induce hemolytic anemia in patients.

Notably, the incidence rate for AIHA, which also includes CAD, more than doubled from 1980–1993 (0.81 patients per 100,000 persons per year) to the 2008–2016 period (1.77 patients per 100,000 persons per year).

“The increasing incidence rate may be related to a more comprehensive diagnostic work-up, increased awareness, and a true increase of disease incidence and prevalence,” the researchers wrote.

But CAD showed one of the greatest increases in incidence, which rose from 0.03 in the 1994–2007 period to 0.18 in 2008–2016.

As for prevalence, AIHA, CAD, and drug-induced hemolysis were the most prevalent in patients older than 50, while PNH was the most prevalent in those 20–50.

The prevalence rate also increased for all hemolytic disorders, except for the drug-induced one. Again, CAD showed one of the greatest increases over time — from 0.02 in the year 2000 to 1.04 in 2015 — a 52-fold increase.

“With regards to the subtypes of hemolytic anemia AIHA, CAD, PNH, and acquired hemolysis NOS, and the residual group of other defined hemolysis, we found that the incidence rates and prevalence proportions markedly increased during the 36-year study period,” the researchers wrote.

The findings from a large, national cohort over an extended period provide a foundation for further epidemiological studies such as causes or risk factors that may contribute to the observed increases. The data also is useful for public healthcare planning.

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