If patients with G6PD deficiency are exposed to risk factors, such as certain medications, environmental factors, or foods, it can lead to hemolysis.
G6PD deficiency is one of the most common enzyme disorders in the world, explained Cyrine E. Haidar, PharmD, BCPS, BCOP, FASHP, during her presentation at the HOPA Annual Conference 2023. Patients with this inherited deficiency can experience hemolysis when exposed to certain triggers.
G6PD deficiency is also one of the oldest known and documented enzyme deficiencies in history, explained Haidar. In 510 BC, Pythagoras recognized it as a “broad bean problem,” which he also termed favism. Then, in 1956, genetic G6PD deficiency was observed to be the cause of primaquine-induced anemia.
Currently, G6PD deficiency affects 5% of the world’s population, with approximately 400 million people estimated to have the disorder.
“It's something that is common in specific parts of the world,” Haidar said during the presentation. “There's a higher prevalence in Southeast Asia, Sub Saharan Africa, the Mediterranean Peninsula, and there are areas of moderate prevalence, such as in the United States, depending on where the population [with this disorder] has migrated to.”
Additionally, Haidar noted that G6PD works in red blood cells by detoxifying the cells of oxygen free radicals. When patients do not have G6PD, the red blood cells die due to an accumulation of reactive oxygen species, leading to hemolysis if exposed to certain medications, environmental factors, or foods that can cause an accumulation of reactive oxygen species in the red blood cells.
“So there are 2 ways to diagnose G6PD deficiency. The most common one that we probably have all seen is a phenotypic assay, which is just quantifying the amount of G6PD in red blood cells,” Haidar said. “The second one is genotyping. So historically, G6PD enzyme activity testing has been what has always been used, and it's a relatively easy test to do. You get a blood sample, and the lab can quantify how much G6PD activity is in a gram of hemoglobin in that blood sample.”
However, Haidar explained that this test has advantages and disadvantages. For example, since the test is a seminal test, the results do not often become available quick enough for patients. Yet, a blood draw is relatively easy to do, and most clinical laboratories know how to run G6PD activity testing.
Another method that is gaining some traction is G6PD genotyping, since G6PD deficiency is a genetically linked disorder on the X chromosome and there's approximately 200 variants that are known to cause G6PD deficiency, according to Haidar. Because this is a disease that affects the population across different continents and different parts of the world, WHO has helped with specifying what are classifications of G6PD deficiency based on genotyping, as well as other parameters.
There are medications, environmental risk factors, and foods that patients with G6PD deficiency should not consume, according to Haidar. Specifically, fava beans are the only real food of concern and can be present in Egyptian falafels. However, Haidar noted that in Lebanon, her country of origin, falafels are not made with fava beans.
“Fava beans are something that we don't necessarily always eat in the United States, but they are a common ingredient in falafels,” Haidar said. “Egyptian falafels have fava beans, Lebanese falafels do not. So Egyptians want to kill you, and we don't.”
Additionally, there are certain chemicals that can be in patients’ environment that can be risk factors, such as naphthalene, which is found in mothballs, explained Haidar.
“Thankfully, we don't use mothballs anymore. However, there are a lot of case reports of kids who saw these white balls in the closets and drawers of their parents. And of course, they're little balls, and they're easy to ingest. So there's a lot of case reports of kids being admitted to the ER for hemolysis because they ingested mothballs,” Haidar said.
As for the medications to avoid in patients with G6PD deficiency, there has not yet been a universally adopted list due to mixed evidence, which has led to different conclusions and recommendations, according to Haidar. Further, peer reviewed evidence is currently scarce.
Additionally, Haidar noted that there may also be a lack of consensus due to issues around clarity on medications’ risk levels and other confounding factors, such as infections. However, both patients and prescribers can refer to G6PD.org as a reference point for medications that may be beneficial to avoid for those with G6PD deficiency.
“I've always been taught that if you want to know which medications should be avoided in patients who are G6PD deficient, go to primary literature or go to G6PD.org, and you'll find that information,” Haidar said. “G6PD.org has a lot of medications listed on it—upwards of 100 medications. But there's a lot of conflicting data.”
Haidar CE. What’s the Risk: Update on the Safe Use of Medicines in G6PD Deficiency. Presented at HOPA Annual Conference 2023 in Phoenix, AZ; March 30, 2023.