People with severe hemophilia might envy their peers with mild hemophilia. No prophylaxis to deal with, relatively minor bleeds and few, if any, symptoms.
But life for patients with mild hemophilia can be fraught with problems. Their first indication of a problem is often a hemorrhage after an elective surgery, simple dental procedure or giving birth. Suddenly they have to deal with a bleeding disorder and getting needed medical care.
Tammy Davenport, 36, of Shepherd, Texas, has known she has mild hemophilia since she was 5 years old. Her father, who had severe hemophilia A, had her and her sister tested. But sharing that knowledge proved exasperating. When she went into labor with her son in 1994, she told the hospital staff, “I have mild hemophilia A; you need to be aware.” Their response was, “Oh, that’s impossible. Women can’t have hemophilia.” The baby was tested immediately and had severe hemophilia A. Even though he was premature and had underdeveloped lungs, requiring a breathing tube, he had no bleeding issues at birth.
His mother, on the other hand, did have complications. “I had not received any factor,” says Davenport, regional care coordinator with Matrix Health in Houston. “I was having issues, mainly from the epidural. I had a huge hematoma on my spine that caused a lot of problems for months.”
Davenport’s story is typical for many people with mild hemophilia: symptoms that don’t surface until major surgery or trauma; treatments that are infrequent; and medical personnel who disregard their concerns.
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Onset of Symptoms
Symptoms can be so few and far between that patients with mild hemophilia often don’t recognize a joint or muscle bleed. They may tolerate nosebleeds and bruising. Some may go through childhood without a joint or muscle bleed. Women may attribute menorrhagia (heavy, prolonged menstrual bleeding) to “the way things are for women in our family.”
There is often a delayed diagnosis. “Because it does take an injury or an invasive procedure, such as surgery or dental extraction, a lot of these patients get diagnosed much later in life,” says Sue Geraghty, RN, MBA, Mountain States Regional Hemophilia and Thrombosis Center in Aurora, Colorado. “One of the classic ways mild patients without a family history get diagnosed is in their teen years, when they have their wisdom teeth pulled.”
Dustin Johnson, 14, fits that profile perfectly. A defensive end and linebacker for two local football teams, he was nicknamed “Sack’em D” for his tackling prowess. He played hockey and was starting rugby. “He’s always been a rough-and-tumble kid,” says his mother, Shelly Haight, 33, a confidential paralegal for San Diego County. “He is an amazing athlete.”
But no amount of stamina or strength could help Johnson after his wisdom teeth were removed in March 2010. He bled intermittently for five days, while his mother shuttled him back and forth between the oral surgeon’s office and the emergency room. Haight shared her hunch that her son might have hemophilia—her father’s twin brother had died of complications from a head bleed in his early 50s. “I told the ER staff, ‘Look, I have a feeling he has a bleeding disorder. I think he may be factor IX (FIX) deficient,’” Haight says. “‘Can you please just run the tests?’” But the doctor refused, saying the tests were too expensive and time consuming.
Finally, an ear, nose and throat doctor admitted the teen to the hospital and ran some tests for hemophilia. “It turned out he does have mild hemophilia. His factor IX level was 5 percent,” says Haight. “As soon as they gave him the factor through his IV, he clotted immediately.” Johnson was in the hospital for three weeks. He then recovered at home for 11 days before returning to school.
The range for mild hemophilia is wide, between 5% and 50% of normal factor VIII (FVIII) or IX, and so are the bleeds. “Patients on the lower end of the spectrum bleed more frequently than those on the higher end,” Geraghty says. “However, once a bleed starts, the symptoms are very similar to those in patients with more severe hemophilia.” The difference, she says, is in the timing. A patient with severe hemophilia who sprains his ankle bleeds right away; one with mild hemophilia can take several hours or even days before the bleed becomes full-blown.
The “Carrier” Conundrum
A woman with mild hemophilia is urged to undergo prenatal testing during pregnancy. If she is carrying a son, the medical team can prepare a treatment plan for her and a delivery plan for the baby, who may have hemophilia.
Although women with mild hemophilia are often called “symptomatic carriers,” that label sometimes does not sit well with them. “I find that term very offensive,” says Davenport. “If I was a man with my factor level (23%), I would be treated more aggressively.”
Providers agree that the terminology is imperfect. “At our center, we call women with borderline low levels symptomatic carriers,” Geraghty says. “But a symptomatic carrier, for all intents and purposes, is a woman with mild hemophilia.”
“If there’s a family history, then we do the cord-blood testing on those infants, just like we would on a known severe patient,” says Geraghty. When there is no prior history, a partial thromboplastin time test (PTT) can be ordered, a preliminary measure of the time it takes blood to clot. “For a patient who was presenting with bleeding, the PTT would be part of a bleeding evaluation,” says Christine Kempton, MD, MSc, assistant professor, Aflac Cancer Center and Blood Disorders Service of Children’s Healthcare of Atlanta, and Department of Hematology/Oncology, Emory University in Atlanta. “A normal PTT doesn’t exclude mild FVIII deficiency, as different PTTs reagents may be insensitive to very mild FVIII deficiencies.” The normal range can vary by lab, she says. According to the Merck Manual, a typical PTT is 28–34 seconds. In Kempton’s lab, the upper limit is 39 seconds. When Johnson was in the ER, his PTT was 53.
Factor assays are more diagnostic. “The FVIII activity assay will give you their FVIII level and tell you whether that’s low or not,” Kempton says. If the level is low and there is a family history of mild hemophilia, the diagnosis is confirmed.
However, for a new diagnosis, the doctor may want to differentiate the low factor level from other causes. For instance, patients with von Willebrand disease type 2N also have low FVIII levels, as do those with combined FV/FVIII deficiency. (See sidebar, “Combined FV/FVIII Deficiency” in “FV Deficiency.”) Low FIX levels, on the other hand, can be caused by vitamin K deficiencies.
DDAVP (desmopressin acetate), a synthetic version of the natural antidiuretic hormone vasopressin, is often the product of choice for patients with mild hemophilia A. DDAVP is not recommended for patients with mild hemophilia B. It produces a rapid, three-fold increase in circulating FVIII and von Willebrand factor (VWF). Plus, it comes in a handy nasal spray called Stimate.® DDAVP is used pre- and post-operatively, for joint and muscle bleeds, and for mucous membrane bleeds in the nose and mouth.
But DDAVP/Stimate has drawbacks. “Usually mild hemophilia patients whose levels are greater than 5% but below 10% are not good candidates for DDAVP/Stimate,” Geraghty says. “However, some patients in this range will respond to Stimate/DDAVP, and their physician will recommend it following a challenge.” The Stimate challenge involves exposing the patient to a sample dose to see how the body’s VWF level changes later in the day and determine if the patient is a candidate for it. In rare circumstances and in young children, DDAVP causes the body to retain fluid, resulting in hyponatremia, an abnormally low concentration of sodium in the blood. Further, its effectiveness decreases after a few doses.
Infusions of factor product are sometimes needed for patients with mild hemophilia A or B. “For big surgeries, including hysterectomies or any other abdominal surgery, heart surgery, brain or spinal cord surgery or joint replacements, most times I would want to have 7- to 10-day factor coverage,” Kempton says.
Postpartum treatment may be necessary following childbirth. “In anybody who has baseline low levels, I would have them treat for 3–4 days after a vaginal delivery and 4–5 days after a cesarean delivery with a DDAVP product or a factor concentrate.”
Once clots are formed, antifibrinolytics, such as tranexamic acid and aminocaproic acid, can prevent them from breaking down. They are used before dental procedures and to treat nose, mouth and intestinal bleeds. They are effective in patients with mild hemophilia A or B, but with an added caution. “Care should be taken not to take an antifibrinolytic at the same time as the factor IX infusion,” says Geraghty.
Some patients maintain peace of mind by storing factor product at home. “We keep a stock of factor IX in the refrigerator,” Haight says. “We have the kit so we can administer it through an IV if necessary.” Besides his stepfather, Johnson’s uncle has also learned to infuse him. That way, while the extended family is vacationing at a remote cabin, someone has the skills to treat a bleed. “Others should know how to start an IV, because it could be a matter of saving my son’s life,” says Haight. (See what Johnson’s stepfather is doing to raise awareness about mild hemophilia.)
Patients with mild hemophilia can develop inhibitors, antibodies to infused factor product. “One of the bigger risk factors is having intensive exposure to FVIII—5 days or more—because of significant injury or surgery,” says Kempton. “Patients with mild hemophilia can receive immune tolerance induction to treat it. But a lot of times, the inhibitor actually goes away on its own.” Inhibitors in mild hemophilia B patients are rare.
Fluctuating Factor Levels
Because factor levels can spike, knowing your baseline level is critical prior to a procedure or surgery. “Although I’m normally 23%, before my hysterectomy, my factor levels twice came back at 80%,” says Davenport. She attributes the rise to stress.
Factor fluctuations can also occur as a result of exercise, infection and hormones. “Hormonal changes from birth control pills and during pregnancy can affect FVIII levels in women,” says Kempton. Davenport recalls, “When I was pregnant with my daughter, my factor levels were about 90%.” Anticipating a precipitous drop in her FVIII level after childbirth, Davenport’s hematologist ordered factor concentrate. “That birth was very uneventful,” she says.
A woman’s menstrual cycle can also affect factor levels. “There are times during the month when I bruise easy and my gums bleed when I brush my teeth. Then a week later, everything’s fine,” Davenport says. She asked her HTC nurse about it. “That makes perfect sense,” the nurse said. “Your factor levels are tied to your hormones.”
The diagnosis of mild hemophilia can cause lifestyle changes. “Even for a child with mild hemophilia, we do not typically recommend the hard contact sports—ice hockey, football, lacrosse or wrestling,” says Geraghty. “We follow the guidelines in NHF’s Playing It Safe sports brochure.”
Those restrictions hit Johnson hard. “He’s no longer allowed to play football. He can’t play hockey. He can’t play soccer. He can’t start rugby,” says his mother. A stint as a goalie for a water polo team didn’t cut it. Still, Johnson enjoys swimming laps and lifting weights. His skateboard is a diversion, but with new precautions. “Before it was ‘Aw, I don’t need my helmet. I’ll be safe.’ Now it’s ‘If I don’t wear my helmet, I could die.’” says Haight. (NHF does not recommend skateboarding as a safe activity for people with hemophilia because the risk of trauma is high.)
Johnson wears a medical identification “dog tag” around his neck. His friends know he has mild hemophilia. “If he’s skateboarding and he falls and doesn’t know he hit his head, his friends need to know,” Haight says.
Patients with mild hemophilia are encouraged to visit their hemophilia treatment center (HTC) annually. “Because they’re not bleeding frequently, it’s important for them to come in and get updates on new products and for us to assess whether they missed something that should have been treated since their last visit,” Geraghty says.
The HTC staff can also help develop a treatment plan for a scheduled procedure. A patient should not rely on the surgeon or hospital to know what to do. “Your HTC needs to be your advocate,” Kempton stresses. “Call your HTC and say, ‘I’m having surgery with this surgeon. Help me with my treatment plan.’”
When Johnson was hit in the head with a soccer ball at school, having a hematologist made all the difference. “The hematologist called ahead. We didn’t even wait five minutes in the ER. We got the CT scans and everything we needed,” says Haight.
“As treaters, our goal is to make sure that mild patients understand they have a disorder and what the process for treatment is if they have a problem,” Geraghty says.