Hemophilia A undertreated in female patients, carriers: US study

Medical, pharmacy costs nearly 14 times lower for women with the disease

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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A cracked piggy bank with a Band-aid over it faces a prescription bottle.

Female hemophilia A  patients and carriers have more frequent bleeding than males, yet a much smaller proportion receive replacement therapy to prevent or stop them, a U.S. study finds.

The medical and pharmacy costs for women with hemophilia A or carriers were up to about 14 times lower than men, meaning they “may be undermanaged and undertreated,” the researchers wrote in “Real-world analysis of patients with haemophilia A and haemophilia A carriers in the United States: Demographics, clinical characteristics and costs,” which was published in Haemophilia.

Hemophilia A is a type of hemophilia that occurs when the body doesn’t make enough factor VIII (FVIII), a protein that helps the blood form clots, or produces a nonworking version of it.

Without FVIII, mild to severe spontaneous bleeds can occur in the joints and muscles, and cause long-term damage if not treated promptly. Bleeding can also occur after an injury or surgery.

The disease is caused by mutations in F8, the gene encoding FVIII, on the X chromosome. Since men have only one X chromosome they inherit from their mother, they’re more likely to develop hemophilia A, as that would automatically happen if their X chromosome contains a faulty F8 gene.

But women can also have hemophilia A, despite receiving two X chromosomes. This can happen when they inherit a faulty and a normal F8 gene copy, but the functional gene is in the X chromosome that becomes inactivated. It can also happen when they inherit two X chromosomes containing faulty copies of the F8 gene. Those who have only one faulty gene copy are said to be carriers.

Many women tend to be diagnosed only as carriers, even when their FVIII levels are less than half of what’s normal and they have symptoms like heavy menstrual bleeding and bleeding after giving birth.

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Treatment, cost comparisons between women and men

How many of these bleeding episodes are treated is unknown, leading researchers in the U.S. to review data from 2016 through 2019 on 1,731 male and female hemophilia A patients or carriers with commercial or Medicaid insurance. The data were retrieved from IBM MarketScan research databases.

Commercial insurance covered 1,007 people and 724 were covered by Medicaid. There were 1,259 male patients, 154 female patients, and 205 female carriers. Insurance claims as both patients and carriers were filed by 113 women.

The female patients were older than male patients by up to 19 years (commercial dataset) and 23 years (Medicaid dataset). Minor and spontaneous bleeding episodes were more common in female patients and carriers than in men. Up to one in four female patients or carriers had heavy menstrual bleeding.

Billed annualized bleeding rate, calculated as the number of bleeding episodes divided by the number of months in the reporting time window and multiplied by 12, also tended to be higher in women patients. In turn, insurance claims for major bleeding episodes, which were defined as those requiring inpatient or emergency care, were more common with men.

Most men received replacement therapy to supply the missing FVIII (75.8% in the commercial dataset, 76.3% in the Medicaid dataset). Replacement therapy included plasma-derived and recombinant, or man-made, standard or long-acting clotting factors.

A much smaller proportion of women received replacement therapy — up to 14.4% of women patients, 1.4% of female carriers, and 23.2% of those who had insurance claims as both patients and carriers.

While female patients or carriers had up to about three times as many all-cause inpatient visits, men stayed in the hospital for longer periods.

Total costs, which were calculated as the sum of medical and pharmacy costs, were lower for women than men, regardless of whether they had commercial or Medicaid insurance.

Costs totaled a mean of $40,388 for female patients, $15,647 for female carriers, and $28,320 for those with commercial insurance claims as both patients and carriers. For men, mean total costs rose to $214,083.

At least half the total costs incurred by women were driven by outpatient costs, whereas pharmacy costs accounted for nearly two-thirds (64.5%) of total costs in men. The Medicaid dataset was similar.

According to the researchers, “delayed diagnosis and inadequate treatment contribute to an increased burden of illness for [female patients with hemophilia A] and [hemophilia A carriers], and may result in long-term cost impacts on the healthcare system.”

More research, including analyzing bleeding rates, the presentation of symptoms, long-term complications and life quality would raise awareness and “define a diagnosis framework to provide more equitable and appropriate care” for women with bleeding disorders, they said.