By Deb Burrows, BS, MA
Diagnostic considerations and complications of mild hemophilia were discussed at the 2023 Bleeding Disorders Conference during the session, Mild Hemophilia. Shannon Carpenter, MD, MS, Children's Mercy Hospital Kansas City, MO, and Craig Kessler, MD, Georgetown University Hospital, provided perspective and definitions.
Although the nomenclature indicates that it may not be concerning, Carpenter pointed out that Maybe It’s a Little Dangerous. “It is mild in name only,” she said.
To be diagnosed as having mild hemophilia, Carpenter said factor level is between 5-40 percent. “Prevalence varies between countries, and diagnosis is often delayed and complicated by bleeding,” Carpenter said. She noted that with inflammation or trauma, FVIII may be falsely elevated. “Some individuals may not have a lot of bleeding while others may, and it is more common among certain genotypes. Often one-stage assays (OSA) are higher than chromogenic assays, so the diagnosis is missed.”
Most individuals with mild hemophilia report a low number of joint bleeds, she said, though overt joint bleeding may not fully predict joint damage. “In a study of 85 men with mild hemophilia, MRI imaging showed 90 percent had joint disease with the ankle most affected.”
Carpenter also said, “We want to remember that women and girls with one X chromosome affected by hemophilia have variable factor levels. Those with less than 40 percent should be noted.”
The incidence of inhibitors is estimated to be 3-13 percent. “These usually occur later in life, probably due to less frequent exposure days,” she said. “There may also be a link to the amount of intensive treatment.”
Individuals with mild hemophilia experience a significant impact to of their quality of life (QOL). “The scores considering QOL physical aspects are very close to scores in the general population, but the mental/emotional scores are much lower,” Carpenter said. “It is wearing to deal with this disorder and it has a significant impact on mental health and people’s lives.”
Everyone thinks that mild hemophilia treatment should be the same as treating severe, Kessler said. In actuality, “it is very different and takes some strategizing to take care of a mild hemophilia patient. There are a large number of nuances and pharmacy issues.”
He said that individuals with mild hemophilia do not have spontaneous bleeding episodes, but they usually present with traumatic bleeds and are often not diagnosed until later in life. Abnormal bleeding after injuries, surgery, or tooth extractions are common.
“When you are looking at hemophilia A, the chromogenic assay will reflect better than OSA,” Kessler said. “I think you really need to have both assays available in your laboratory. If you only use the OSA for screening, some patients will seem to have normal FVIII levels. We are under-using the chromogenic assay in the U.S.”
Kessler spoke to the role of anti-fibrinolytics in mild hemophilia. “These are useful for mucocutaneous bleeds such as dental extractions, menorrhagia and epistaxis,” he said. “But they are contraindicated as initial therapies for hemophilia-related hematuria originating from the upper urinary tract because then can cause obstructive uropathy or anuria.”
Kessler pointed out that severe hemophilia patients who have undergone gene therapy are now mild hemophilia patients, as are individuals on certain prophylaxis regimens. “We have lots to learn about this disease,” he said.
