Hemophilia Pseudotumors 101

Rare complication, but people with mild and moderate hemophilia may still be at risk
Author: Rebecca A. Clay

When Murali Pazhayannur slipped while getting into a rickshaw during a Calcutta monsoon, he had no inkling he’d still be dealing with repercussions three decades later. The fall didn’t hurt, and the high school senior was soon back on the cricket field and engaged in all his normal activities.

That changed a few days later. Pazhayannur, who has severe hemophilia A, began to feel weak and his hip started to hurt. Back in 1978, treatment was rudimentary in India—cryoprecipitate airlifted from Bombay, blood transfusions and physical therapy. Pazhayannur’s leg was paralyzed for several months.

During that time he developed a pseudotumor, a hemophilia complication that occurs when an injury causes blood to pool and the resulting hematoma—a swelling filled with blood—walls itself off and the mass starts to grow.

Nothing happened for several decades: Pazhayannur earned a PhD in immunology at the University of Bombay. He came to the US in 1989 to do postdoctoral research at the Medical College of Wisconsin, but he switched careers when he realized research would prove too demanding for his health. He was earning his master’s in computer science at the University of Chicago when he began to have problems: The blood clot on his hip had started growing.

“If I pressed hard, I could feel it,” says Pazhayannur, 50, a database administrator for a financial firm near Chicago. “When I looked at myself in the mirror, I could see myself leaning forward just slightly.”

Although the pseudotumor wasn’t painful, it was doing damage. It had invaded his hip bone. A computerized tomography (CT) scan revealed it was pushing against his internal organs and shifting their positions. And it was still growing. By the time the pseudotumor was removed in 2003, it was the size of a football.

“Physically, I don’t notice any difference except the lump is gone,” says Pazhayannur, who has since married and become a stepfather to two boys. “But just the thought that there’s no pseudotumor to worry about anymore, that’s definitely a life-changing event.”

One of the few individuals with bleeding disorders in the US to have firsthand experience with a pseudotumor, Pazhayannur drew on his own scientific background to co-author a medical journal article describing his groundbreaking operation. But despite pseudotumors’ rarity, it’s important for individuals and those who treat them to know about this potentially life-threatening complication.

Pseudotumors: A Rare Complication

Pseudotumors are extremely rare, occurring in just 1 or 2 percent of hemophilia cases worldwide. Cases are even rarer in the US, says Alice D. Ma, MD, an associate professor of medicine at the University of North Carolina (UNC) at Chapel Hill. Pseudotumors occur in individuals with access to some treatment, but not a lot, and not regularly, says Ma.

In developing nations where people with hemophilia have shorter life expectancies, she explains, people simply may not live long enough to develop pseudotumors. In developed countries, most people have enough access to care that they get treatment when they need it. But even in developed nations, certain individuals are still particularly vulnerable.

People with mild and moderate hemophilia, who often aren’t on regular factor therapy, are one group at risk. That’s because they may not seek treatment after a hematoma-producing injury, says Ma. “Then, 10, 15 or 30 years later, they’ll show up with a pseudotumor,” she says. Individuals with inhibitors are also at risk if they injure themselves and can’t get a bleed under control.

For a pseudotumor to develop, the original injury usually has to be fairly severe, says Ma. “Bumping your shin on a coffee table is probably not enough to do it,” she says. Possible causes include car accidents, sports injuries, falls—anything that leaves a large pool of blood under the skin.

Individuals may not realize they have a problem in the early stages, says Ma. “For people with mild to moderate hemophilia, bleeding isn’t necessarily a big part of their everyday life,” she explains. “When they get injured, they don’t say, ‘I’ve got to take clotting factor.’ They say, ‘Ow, that’s going to leave a bruise.’”

In some cases, that injury results in a hematoma that doesn’t go away and eventually forms a capsule around itself. Because it’s vascularized, meaning it has blood vessels and thus a blood supply, it keeps growing—just like a real tumor. In fact, Ma says, pseudotumors are sometimes mistaken for cancerous tumors. And the results can be terrible: While the pseudotumor itself is not usually painful, it can eventually invade adjacent bones, organs or other structures.

One of Ma’s patients, for instance, developed a pseudotumor 30 years after banging his face into a bedpost while jumping on his bed as a child. “They were going to treat him as if he had head and neck cancer,” says Ma, explaining that the mass was growing into his brain and sinuses. “It wasn’t a brain tumor at all; it was a pseudotumor.”

Another patient who had a pseudotumor at the site of a previous break in his leg also got a full work-up for cancer. By the following year, his pseudotumor had grown so much his thigh was bigger around than his waist. By the time he switched to UNC for treatment, the pseudotumor had grown into his femur. The only solution was surgical removal of the 90-pound pseudotumor and a hemipelvectomy—the amputation of half his pelvis and his leg.

Pseudotumor Diagnosis and Treatment

The potential for misdiagnosis underscores the importance of seeking care at hemophilia treatment centers, where clinicians are aware of pseudotumors, says Leonard A. Valentino, MD, director of the Rush Hemophilia and Thrombophilia Center at Rush University Medical Center in Chicago.

“If untreated, patients can die from pseudotumors,” says Valentino, who has seen half a dozen cases over the past 16 years. “Making the wrong management decision with these things can be fatal.”

Diagnosing a pseudotumor differs from diagnosing a cancerous tumor, something most oncologists have more experience with. “You wouldn’t want to biopsy a pseudotumor, because that can cause a significant amount of bleeding and be very dangerous,” says Valentino.

Instead, diagnosing a pseudotumor usually involves taking a history, conducting a physical exam and performing an imaging study, such as a CT scan or magnetic resonance imaging (MRI). The radiologist can usually distinguish a pseudotumor from a cancerous one, says Valentino. That’s because in contrast to the solid mass of a cancerous tumor, a pseudotumor is filled with blood.

What happens next depends on where the pseudotumor is, how fast it’s growing and what effect it’s having. “What usually happens is nothing,” says Valentino. Physicians generally prefer to observe the pseudotumor and leave it alone if it’s not causing any problems, he says.

If action is required, one option is to “embolize” the pseudotumor by cutting off its blood supply. In these cases, Ma explains, an interventional radiologist squirts dye into the blood vessels to identify which vessels are feeding the pseudotumor. Then, a clotting substance is used to fill those vessels and choke off the pseudotumor’s blood supply.

In other cases—when there’s significant pain, damage to bones or other body parts, or persistent anemia because of bleeding into the pseudotumor—surgery becomes necessary.

Surgical removal is different from removing an actual tumor, says Valentino. Unlike a malignant tumor, a pseudotumor is usually removed en bloc, meaning the surgeon removes it all in one piece. “Most times when tumors are taken out, they’ll try to carve them up because they’re so big,” Valentino explains. That’s not a good idea with pseudotumors, since it can cause dangerous bleeding. “The pseudotumor’s capsule has all these blood vessels,” he explains. Cutting through them can lead to uncontrollable bleeding.

Surgery is typically quite complex, Valentino adds. For Pazhayannur’s operation, for example, Valentino and his colleagues sought advice from an orthopedic surgeon in South America, reviewed a video demonstrating his surgical approach and invited an expert from Israel to help with the procedure. “In the cases we’ve been involved with, it’s been a very difficult decision to go ahead and do the surgery,” says Valentino.

A Difficult Surgery

Stephen Weisser, 49, a Lutheran chaplain at St. Paul’s Retirement Community near Philadelphia, is one patient who had to make that difficult decision. “Doing something as dramatic as surgery was a last resort,” says Weisser, who has hemophilia A with a high-titer inhibitor.

Weisser’s trouble began around 1975, when he was a freshman in high school. An injury caused bleeding in his calf so severe that circulation to his foot nearly stopped. “I was really close to losing my foot,” remembers Weisser. Although the bleed eventually stopped, a pseudotumor began forming.

In the 1990s, the pseudotumor began to grow until it reached the size of a golf ball. It stayed stable for another decade, then started growing again. Weisser and his doctor began monitoring the pseudotumor more closely, even measuring its growth. “Eventually it grew to the size of a baseball and was quite visible,” he says.

As the pseudotumor grew, it became more sensitive, so Weisser used a bandage to keep pressure on it and support it. Although his pants still fit over the bulge, says Weisser, it was hard to wear shorts. “Cosmetically, it was ugly,” he says. “If I was wearing shorts, people would look at it and wonder what it was.”

Eventually, the pseudotumor broke through the skin. “You could actually see the top of the tumor capsule,” says Weisser. That development prompted surgery in 2005. Weisser’s surgeon couldn’t remove all of the pseudotumor because it had become integrated with the calf muscle. And the clotting factor used to stop the bleeding at the wound site led to a stroke during the recovery period that affected Weisser’s vision and balance.

“It took a good six months before I got close to my baseline again,” says Weisser, who was unable to return to work for a few months. He is now able to drive again, as well as enjoy his hobby of flying single-engine planes. “I’ve more or less recovered completely from the stroke, but it was the kind of thing that could easily have taken my life.”

Now Weisser is concerned the pseudotumor will return, and he worries about the impact all this has had on his wife, Leslie, and 18-year-old son, Sam. “It’s hard to put a gauge on how much these kinds of things affect a family,” he says. “Everyone has to cope with the fragility of life, and having hemophilia, an inhibitor and a pseudotumor makes my life a little more fragile.”