Empaveli dose adjustments thwart hemolysis in patient’s surgeries
The approved PNH therapy targets a complement protein called C3
Close monitoring and Empaveli (pegcetacoplan) dose adjustments before and after surgery effectively prevented episodes of breakthrough hemolysis,in a 67-year-old man with paroxysmal nocturnal hemoglobinuria (PNH), according to a case report in Spain.
Hemolysis is a hallmark symptom of PNH marked by the breakdown of red blood cells, which transport oxygen in the bloodstream. It may occur inside (intravascular) and outside (extravascular) blood vessels, which can both be prevented by treatment with Empaveli.
“Despite control of both extravascular and intravascular hemolysis, patients receiving [Empaveli] may still experience episodes of breakthrough hemolysis,” the researchers wrote. “Our findings highlight the need for perioperative dose adjustments to prevent breakthrough hemolysis, particularly in high-risk surgical settings.”
The case was described in “Dose Adjustments of Pegcetacoplan in a Patient With Paroxysmal Nocturnal Hemoglobinuria Undergoing Surgery: A Case Report,” in Cureus.
In PNH, a component of the immune system, known as the complement cascade, mistakenly launches an attack against blood cells because it fails to recognize them as a healthy part of the body. Complement activation leads to the destruction of red blood cells, resulting in anemia and other disease symptoms.
Treatment commonly involves blocking complement activation with therapies that target specific proteins involved in activating it. Empaveli, marketed as Aspaveli in Europe, is an approved PNH therapy that targets a complement protein called C3.
Dose adjustments, close monitoring
In this case, a 67-year-old man with PNH underwent four surgeries after starting Empaveli, but dose adjustments and close monitoring were needed to prevent breakthrough hemolysis around the time of the procedures.
The man was initially diagnosed with aplastic anemia — a condition sometimes seen with PNH wherein bone marrow is unable to produce enough new blood cells — for which he was treated with immunosuppressive medications.
Three years later, he had a first crisis of intravascular hemolysis, determined to be caused by PNH. Over 10 years, he had several hemolytic crises that required red blood cell transfusions and treatment with an artificial version of erythropoietin, a hormone that stimulates red blood cell production. The man also had other PNH symptoms, including dark urine, fatigue, difficulty swallowing, and erectile dysfunction. He received treatment to prevent thrombotic events, which occur when a blood clot blocks blood flow in an artery or vein.
Ten years after his PNH diagnosis, he started treatment with Soliris (eculizumab) due to impaired kidney function after an acute hemolytic crisis. His levels of lactate dehydrogenase (LDH) dropped, but anemia persisted and the man still needed blood transfusions. Almost all his symptoms eased, except fatigue. LDH is a marker of cell and tissue injury that’s often used as indicator of hemolysis in PNH.
The dose and frequency of Soliris were increased over the next seven years due to episodes of breakthrough hemolysis, reaching a maximum dose of 1,200 mg every two weeks. The man continued showing signs of anemia, however.
He then started treatment with Empaveli, at 1,080 mg twice weekly. The treatment eased his anemia and fatigue and reduced his LDH.
Over the next two years, he had three scheduled surgeries under general anesthesia and an emergency surgery under spinal anesthesia. To lower the risk of a hemolytic crisis triggered by the surgeries, his Empaveli dose was adjusted to 1,080 mg every three days for 10 days before and after surgery.
The emergency surgery was performed on the day the man was scheduled to receive treatment, so no additional doses were given ahead of it. After the procedure, he was monitored for hemolysis for seven days, but no more Empaveli doses were required. Because his LDH and hemoglobin were stable, no further dose adjustments were needed. Hemoglobin is the protein in red blood cells responsible for oxygen transport.
“To our knowledge, this is the first report of [Empaveli] dose adjustments in a PNH patient undergoing multiple surgeries,” the researchers wrote. “We believe that after surgery, strict monitoring of LDH and hemoglobin should be performed, and extra doses of [Empaveli] should be considered only in cases of active hemolysis.”
The researchers said more studies are needed to “establish standardized perioperative protocols for PNH patients receiving [Empaveli].”
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