Woman with TTP gets new hip thanks to tailored Adzynma dosing
Personalized schedule helped patient recover successfully from major surgery
A woman with the rare blood disorder congenital thrombotic thrombocytopenic purpura (TTP) safely underwent hip replacement surgery while being treated with Adzynma (ADAMTS13 recombinant-krhn), according to a case report from Germany.
Adzynma is an enzyme replacement therapy approved in the U.S., European Union, and Japan for people with congenital TTP. It delivers a lab-made form of ADAMTS13, the enzyme missing in people with TTP.
The woman’s hip replacement surgery, which typically carries a high risk of triggering a life-threatening TTP relapse, was completed without complications due to a personalized dosing schedule of the medication before and after the procedure. The case study demonstrates that individualized use of Adzynma can effectively maintain safe levels of the crucial blood-clotting enzyme ADAMTS13 through stressful medical events.
TTP background and relapses
“The present case demonstrates that a perioperative management of [congenital] TTP with an adapted dosing regimen of [Adzynma] is safe and efficient,” researchers wrote. “Individualized decisions should be made based on the clinical course and laboratory response.”
The report, “Reduced half-life of recombinant ADAMTS13 in a patient with cTTP undergoing total hip arthroplasty,” was published in the Thrombosis Journal.
Congenital TTP is caused by genetic mutations that lead to a severe deficiency of ADAMTS13, an enzyme that helps regulate blood clotting. Without enough ADAMTS13 activity, blood clots form in small vessels, restricting blood flow and damaging organs.
The disease can remain silent for long periods, but stressful events such as infection, pregnancy, or surgery may trigger a relapse, which is when symptoms rapidly worsen or reappear.
Plasma exchange, which removes and replaces the noncellular part of the blood with donor plasma containing the missing enzyme, has long been a standard preventive treatment.
More recently, Adzynma has been shown to safely raise enzyme activity to nearly normal levels, with generally mild to moderate side effects.
In this case, the 41-year-old woman with TTP underwent a total hip replacement, a major surgery known to reduce ADAMTS13 activity levels, while receiving preventive treatment with Adzynma.
She was first diagnosed with congenital TTP during her second pregnancy, after suddenly developing severe symptoms of the disease, including a minor stroke from blood clots blocking blood flow in the brain. She experienced a fetal loss at 27 weeks of gestation.
Lab tests confirmed very low ADAMTS13 activity, and genetic analysis later identified two disease-causing mutations in the ADAMTS13 gene.
After diagnosis, she was treated with regular plasma infusions every two to three weeks to prevent relapses. Her treatment schedule was intensified to once weekly in the final trimester of her third pregnancy. She gave birth to a healthy baby by cesarean section.
Switching to Adzynma
Postpartum, she continued frequent plasma infusions for several weeks. However, due to the burden of plasma exchange, she was later switched to Adzynma injections every two weeks, which successfully maintained her enzyme activity and prevented further relapses.
Months later, the woman required hip replacement surgery. To reduce the risk of relapse, Adzynma was given one week before surgery as part of her routine care and again the day before to keep ADAMTS13 activity at a safe level throughout the procedure.
The surgery went well. Afterward, however, the patient’s ADAMTS13 activity declined, likely due to inflammation and the body’s increased demand for the enzyme during the healing process, the researchers wrote. This reduced enzyme activity prompted doctors to intensify her dosing schedule temporarily. She received additional Adzynma doses on days 3, 7, and 10 due to the sustained drop in enzyme activity, and continued weekly injections for four weeks after surgery.
She recovered with no TTP relapse.
“Since post-surgical inflammatory processes are associated with an increased consumption of ADAMTS13 that can continue for several days to weeks after surgery, the [preventive] regimen should be personalized based on the clinical and laboratory parameters,” the researchers wrote, adding that further studies are needed to determine the optimal ADAMTS13 levels before and after major surgery in people with congenital TTP.
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