October 21, 2022
2 min read
Furie RA. Antiphospholipid syndrome: Overcoming treatment challenges. Presented at: The Congress of Clinical Rheumatology West; Oct. 20-23, 2022 (hybrid meeting).
Furie reports no relevant financial disclosures.
SAN DIEGO — Primary prevention remains the biggest treatment challenge in antiphospholipid syndrome, according to a speaker at the Congress of Clinical Rheumatology West.
“If the patient has APS antibodies, what do you do?” Richard A. Furie, MD, chief of rheumatology at Northwell Health in New York, asked attendees, adding that interventions such as aspirin have not been shown to prevent a first thrombotic event in these individuals. “Predictors of thrombotic risk have to be sorted out.”
Beyond aspirin and warfarin, several potential treatment strategies for APS have been explored, including immunologic approaches and novel anticoagulants.
Immunologic approaches such as rituximab (Rituxan, Genentech) and belimumab (Benlysta, GlaxoSmithKline) have produced “not great results,” according to Furie.
Direct-acting oral anticoagulants (DOACs) like rivaroxaban (Xarelto, Janssen) also have undergone investigation, he added.
“Patients continued to have thrombotic events despite receiving rivaroxaban,” Furie said. “DOACs do not seem to be the answer.”
The clinical and research communities will continue to search for answers, but there are significant logistical obstacles to overcome.
“The thrombosis event rate is very low,” Furie said. “You are going to need a lot of patients and follow them for a long time.”
Future research is needed to develop a safe and effective therapy for primary prevention, he said.
“We certainly could use a safer, more convenient warfarin,” Furie said.
In discussing the pathogenesis, manifestations, diagnosis and management of APS, Furie raised the essential question that surrounds APS: Why does this happen?
“We have no idea why these patients clot,” he said.
One possible explanation for why thrombosis occurs is that the anti-Beta2GP1 autoantibody/Beta2GP1 complex binds to the thrombus, enhancing platelet activation. In turn, platelet activation leads to enhanced endothelium activation, which then leads to fibrin generation.
However, this hypothesis should not be taken as absolute, Furie said.
“Everybody has their pet theory about why thrombosis occurs in this syndrome,” he said. “This is just one.”
Furie added that symptomatic patients develop a “regional arterial or venous thrombotic event,” which he described as a common way to identify APS in systemic lupus erythematosus and other conditions.
Uncommon symptomatic events may include thrombotic microangiopathy, catastrophic APS, movement disorder, livedoid vasculopathy, antiphospholipid nephropathy, heart disease, adrenal insufficiency, pulmonary hypertension and osteonecrosis, among others.
For suspected APS, which occurs commonly in individuals with lupus, Furie recommended a wide battery of laboratory antibody assessments, including anticardiolipin, antiphospholipid, Beta2GP1, phosphatidylserine/prothrombin, lupus anticoagulant and rapid plasma reagin.
“If you really want to work up APS antibodies in a lupus patient, you have to work up all of these tests,” he said.
Clinicians may also use tools like dilute Russell viper venom time, platelet neutralization procedure, adsorb aPL Ab with platelet membrane and silica clotting time to determine the presence of APS antibodies.
The presence of antiphospholipid antibodies, however, does not necessarily mean that APS is present, according to Furie. Further, APS can exist alone, with SLE, or with other rheumatic diseases and infections, including Lyme disease, HIV or COVID-19.
One certainty that rheumatologists can count on, though, is that all are likely to encounter a patient who develops antiphospholipid syndrome at some point, Furie said.
He added: “APS is more common than you think.”