Eric Lowe, 31, needed knee replacement surgery 10 years ago. The small-business owner from Noblesville, Indiana, has severe hemophilia A. He was diagnosed with an inhibitor when he was 18 months old. Immune tolerance induction at age 12 caused the inhibitor to peak at more than 2,000, then level out at 50.
Lowe had recurrent knee bleeds in middle school and high school. When he was 16, he asked his hematologist at the Indiana Hemophilia & Thrombosis Center in Indianapolis about joint replacement surgery. Because he was still growing and surgery for inhibitor patients was uncommon, he was told to wait. Then, a pernicious right knee bleed during his sophomore year in college prompted Lowe to revisit the subject of surgery. This time his hematologist and surgeon were receptive. After looking at X-rays of Lowe’s left knee, the surgeon predicted it would need surgery, too. “He said it might be in my best interest to consider having them both done at the same time,” says Lowe. In May 2002, he had bilateral knee replacement surgery.
Although joint replacements are routinely performed on patients with hemophilia, inhibitors present a serious surgical challenge. Controlling bleeding is often problematic, requiring frequent monitoring and fine-tuning. Further, there is no standard protocol. Optimal outcomes depend on many factors. That’s why it’s vital that you work with your hemophilia treatment center (HTC) to see if you’re a good candidate for a joint replacement. (See “It’s About Time,” page 53.)
“The first thing I always ask is: Does the patient really need this surgery?” says Margaret Ragni, MD, MPH, director of the Hemophilia Center of Western Pennsylvania and professor of medicine at the University of Pittsburgh. “It’s difficult to provide hemostasis (arresting bleeding) and assure that it is maintained. The bypass agents we have are less predictable, and thus more difficult to control and monitor.”
When the immune system produces inhibitors, antibodies to infused factor products, patients are usually unable to use standard factor VIII (FVIII) products. (Because factor IX inhibitors are rare, this article is concerned only with inhibitors to FVIII.) Instead, they use bypass agents such as FEIBA, a plasma-derived product manufactured by Baxter, or NovoSeven®, an activated recombinant factor VII product manufactured by Novo Nordisk. Neither one is ideal for inhibitor patients facing surgery, especially since hemostasis is challenging, and the response to bypass agents is poorer than previously with FVIII products, says Ragni. “One of the problems with FEIBA is that once you’ve exceeded 20,000 units in 24 hours, there is a risk of thrombosis (blood clot formation).”
The type of inhibitor patients have and how it responds to bypass agents influence their eligibility for joint replacement surgery. The titer, or amount of inhibitor in the blood, is considered high if it exceeds 5 Bethesda units, the standard measure. A person with a high-responding inhibitor has an immune system that responds rapidly and strongly to infused factor product. In contrast, a person with a low titer and low-responding inhibitor is more easily managed.
“There are probably a lot of incidences where the patient is better advised not to have a joint replacement surgery,” says James V. Luck Jr., MD, director of orthopedics and rehabilitation at the Hemophilia Treatment Center at the Los Angeles Orthopaedic Hospital. Knee replacement surgery on a patient with a high titer inhibitor is high risk, he says. He stresses the importance of inhibitor patients meeting with their healthcare team to discuss surgery. “They need to do a risk-benefit ratio and decide if this is really appropriate.”
Young patients may be advised to wait until they’re older to have this type of surgery, as Lowe was told as a teen. “We have heard of cases of teenagers who have inhibitors having knee replacements and having a high failure rate,” Luck says. They tend to test the limits of the artificial components by playing sports that jar the joint. “That doesn’t work out well with knee replacement especially.”
While the surgery is challenging no matter a patient’s age, quality of life issues drive most to seek help. When the orthopedic surgeon looked at Pete Wells’ X-rays, he asked, “How did you walk in here?” The cartilage was virtually gone in Wells’ left hip joint, making it appear fused. The surgeon said that most patients in that condition were either in a wheelchair or used a walker.
Wells, 69, a municipal court judge from Pendleton, Oregon, has moderate hemophilia A and an inhibitor. By June 2011 he had to grab the railings to pull himself up stairs. He couldn’t lift his leg high enough to get on his bicycle. “I was reporting pain as a level 8 on a 1 to 10 scale,” he says. Wells was in desperate need of hip replacement surgery.
Wells’ inhibitor surfaced in 2008 when he was given FVIII during treatments to dissolve kidney stones. It peaked at 90 Bethesda units. Before his hip replacement surgery in August 2011, it had fallen to less than 5. “It was essentially in a dormant state,” Wells says.
“The nurse coordinator generally is the point person for bringing all of the disciplines together around a surgical procedure,” says Sue Geraghty, RN, MBA, University of Colorado Denver Hemophilia and Thrombosis Center (UCHTC) in Aurora. Those disciplines include surgery, hematology, physical therapy, anesthesiology, and pain management. A key role is interacting with patients and families.
Patients’ current pain control methods need to be notated, even if they’re self-medicating with alcohol or experimental drugs. “We’re not there to be judge and jury,” Geraghty says. “The only way we can help manage pain postoperatively is if we know what they’re taking preoperatively.”
Realistic expectations of pain are critical for patients with inhibitors undergoing joint replacement surgery, Geraghty says. “We have to make sure that the patients understand that they’re going to have pain related to the actual surgical procedure.” HTC nurses run through pain-control options beforehand. “The main thing we need to emphasize with patients preoperatively is they need to not play the hero and avoid taking pain medication,” says Geraghty. Adequate pain relief postoperatively is also discussed. “It’s okay to ask the nurse to call the pain management doctors to come if something’s not working.”
Nurses also help patients plan for the post-op period. “Having a total joint replacement is a process. It doesn’t end when you’re discharged from the hospital,” Geraghty says. The HTC nurse stresses to friends and family members that they need to be involved and available, especially for driving the patient to physical therapy sessions. Geraghty calls this “caregiver buy-in.” In addition, the patient may require a visiting nurse or physical therapist, as well as some light housekeeping.
Further, activities may have to be permanently modified following surgery. Marathon training, for instance, is probably out of the question. “But they can walk around the mall in comfort or take their granddaughter for a walk in the park,” says Geraghty. “All of these things are gone over, and the patient understands them before he enters into surgery.”
Controlling bleeding is a critical concern for inhibitor patients undergoing a joint replacement surgery. Typically a member of the HTC team, such as your nurse or hematologist, will review your current titer and ask you which product you use, how you treat bleeds and in what doses. Then your hematologist can create an infusion plan to manage your hemostasis throughout surgery.
The plan is not rigid, though. “In our experience with orthopedic surgery, we have found that in inhibitor patients using rFVIIa, a higher dose seems to provide better hemostasis initially,” says Ragni. “Later, the dose can be tapered.” But there’s no protocol for when to taper or by how much. When problems arise, sometimes trial and error is the only solution. “If someone has bleeding problems, it’s difficult to tell if the cause is the product, the dosing, the inhibitor or all of these,” Ragni says. Complications are also common. “It may be difficult to maintain good hemostasis.”
These days “prehab,” pre-op physical therapy, is scheduled one to two months before surgery. It helps accomplish two things, says Sharon Funk, PT, at the UCHTC. “We strengthen the patient ahead of time, and let him know how much work it might be.” Lowe was fairly forewarned. “I was told it was going to be a very long recovery,” he says. “They wanted to be sure I was dedicated to the cause and that I had the right resources to do it.”
Both Wells and Lowe did some prehab before their surgeries; Wells did it on his own, and Lowe worked with a physical therapist. “Getting that hip strengthened before surgery was extremely helpful in my recovery,” Wells says. But the “no pain, no gain” philosophy doesn’t necessarily apply. “I can’t say that it was super aggressive,” Lowe says. “We did what we could without causing my knee to re-bleed.”
Inhibitor patients share some similarities with their noninhibitor peers. Most have advanced arthritis, pain and impaired mobility. The difference is their age. “In many cases, their joint disease started at a far younger age than most of our other patients,” Funk says. For Lowe, the damage began in childhood, when he experienced two or three bleeds monthly. “I had arthritis in both my knees, but my right knee was much worse,” he says. “If you looked at me from the side you could tell that my leg couldn’t straighten out all the way.”
“Hemophilia patients often have very severe erosions (defects in the joint surfaces and underlying bone) and severe deformity within the joint,” says Luck. “They have bone stock loss because of that.” They also have arthrofibrosis, or scar tissue formation. “That happens where there is bleeding or injury to the joint, and it stimulates fibroblastic activity—the cells that make scar tissue,” Luck says. He has seen arthrofibrosis so extensive that patients had very little motion left before knee surgery.
Longer Hospital Stay, More Complications
Inhibitor patients should expect a longer, costlier hospital stay and the possibility of complications after joint replacement surgery. Because NovoSeven must be given frequently—every two to three hours initially—the cost alone can be prohibitive. Wells received about 85 doses of NovoSeven during his five-day hospital stay and for 10 days afterward. “The total amount the insurance paid for was more than $900,000,” he says. “My wife calls me her ‘million dollar man.’ ”
Lowe was in the hospital three weeks, with a return visit 10 days later. “I had formed an adhesion (a band of scar tissue) on my left knee between my quad muscle and my knee capsule,” he says. He underwent a second procedure to break the adhesion so he could bend his knee fully. Lowe’s second hospital stay was nearly two weeks.
Infection is a real concern for patients post-op, even months or years after surgery. Luck co-authored a 2005 study in The Journal of Bone & Joint Surgery that showed hemophilia patients have an increased risk of late infection after total knee replacement surgery—16% vs. 1% in the general population. “It may be even higher than that in inhibitor patients, but they’re such small numbers that we can’t say that statistically,” he says. The infections result from factor product infusions under nonsterile conditions. “Bacteria love blood as a culture medium,” says Luck. They are carried in the bloodstream to the artificial joint, where they can cause infection.
Pace of Post-op PT
Post-op physical therapy for inhibitor patients, as with all patients with hemophilia, should coincide with infusions. “We can’t assume they won’t bleed,” says Funk. “Some kind of coverage is still really important.” She monitors the patient’s inhibitor before starting PT. That is the advantage of having the procedure done at an HTC, Funk says. “The entire team is aware of the increased bleeding tendency and can modify the treatment if a tolerized inhibitor recurs or if a different bypassing agent is needed.”
Most patients get moving the day after surgery. At first they may only stand next to the bed, using a walker for balance. The next day they may take a few steps. From the walker, patients transition to crutches. “That allows them a little more mobility getting in and out of rooms,” says Funk. The patient may use a walker or crutches for several months before trying a single crutch or cane, she says.
Two days after surgery, Wells walked a short distance and tried climbing some portable stairs. “I was doing physical therapy a couple of times a day for as long as I was in the hospital.” That continued for the next 10 days, while Wells stayed at his brother’s house nearby. “If I had been at home I would have been less rigorous with my PT because it would have been difficult,” says Wells. With a flat, suburban neighborhood to walk in, Wells and his wife built up to daily three-mile treks.
The PT program was a bit different for Lowe because, as he says, “I didn’t have one good leg to stand on.” Exercises in bed gradually led to use of an apparatus he likens to an adult-sized baby walker on wheels. It had an adjustable harness in the center that controlled the degree of weight bearing. “I walked up and down the halls in the hospital in that,” Lowe says. “I could exercise both of my legs without full weight bearing on either one.”
At home, Lowe used a wheelchair to get around, then crutches. “I used one crutch to assist each leg,” he says.
“As I brought my left leg forward, I would bring my right crutch forward and then vice versa.” That method spared his bad elbows.
Inhibitor patients should expect PT to last months, not weeks. “It takes six months to really get pretty stable, but you can still make progress up to a year,” says Funk. When Lowe first got out of the hospital he had PT five days a week. “It was quite a bit intense,” he says. “I learned the hard way that if you don’t keep moving, things start to heal up the way you don’t want them to and get tight.” Five months later, he was still doing PT three times weekly. By November, he walked around his college campus for the first time.
Gains and Losses
After surgery, patients will experience some gains and a few losses. “Some of the inhibitor patients have worse motion going into the procedure, which can make a difference in their ultimate outcome,” Funk says. To preserve the components in the artificial joint, running and pounding are discouraged. Most inhibitor patients don’t engage in those activities anyway, says Funk. “They tend to self-limit pretty well because they’ve lived with joint pain for so long.”
“The bleeding completely stopped once I got my knees replaced,” says Lowe. He marvels that he can now pursue his hobbies, such as carpentry and woodworking, for longer periods. “It’s not an intense workout, but it’s a lot of standing.” Lowe proudly mentions that he now cuts the grass in his small yard using a push mower. “The only complaint I have is limited flexion,” he says. Going down stairs is painful; so is sitting where there’s limited leg room, such as in a car, airplane or theater. “I can only bend my knees up to about 90 degrees, and that hurts.”
Wells has returned to cycling and working out at the gym, but with caution. “I haven’t used the seated leg press machine since surgery. It seems like a lot of extra pressure.” Wells’ new hip allows him to play with his grandchildren on the floor and commute without watching gas prices. “I walk about ¾ of a mile to work and back each day,” he says. An added bonus of Wells’ exercise regimen is that he’s reduced the amount of blood pressure medicine he takes.
Inhibitors make joint replacement surgery anything but routine. However, the surgery can be successful, especially in motivated patients. “It does take a lot of dedication and hard work, and a good support system to promote the good results that you’re seeking,” says Lowe. With all that he’s been through, he’s optimistic. “I’m hoping my new knees will last me my entire life.”