APS is associated with venous and arterial thromboembolism, recurrent pregnancy loss, valvular heart lesions, and thrombocytopenia. It is most often described as a comorbidity of lupus, with aPL detectable titers seen in up to 40% of lupus patients (aPL is a blanket term for lupus anticoagulant [LA], anticardiolipin antibodies [aCL], and anti-ß-glycoprotein-1 antibodies). Of note, while APS patients with lupus are usually women, the female predominance is less distinct in APS patients without other systemic autoimmune diseases (primary APS).
Importantly, the presence of an aPL does not necessarily correlate with clinical disease manifestations. “In the general population, thrombosis is multifactorial,” explains Dr. Erkan, “and we know it’s also true in APS. As many as half of these patients will have a trigger, another thrombosis risk factor at the time of their event—for example, use of birth control pills, a serious infection, or a recent surgical procedure.” Therefore, APS does not necessarily cause the clot, but it may make an individual more sensitive to clotting influences. This explains why the asymptomatic APS patient is at prothrombotic risk.
Given the variable relationship between serology and clinical manifestations, healthcare providers may be uncertain about how best to treat patients to prevent thrombotic events. “I asked this question in a survey of [congress] attendees—What are the three most important things you want know in APS?—and, overwhelmingly, everyone was interested in risk stratification.” In short, how do I know when to treat? For instance, there are APS patients with low aCL titer, says Dr. Erkan, “but we don’t think that’s clinically important. But then there are patients with very high titers in addition to positive LA test, yet the assumed increase in relative risk is not well defined.” Treating a clot is straightforward; managing risk is not.
Getting to Know You
The ideal of the CRTF in investigation is to first get everyone on the same page—a particular challenge when providers may work in different specialties. For lupus patients, APS is frequently identified by the rheumatologist, but it is the obstetrician who is following the women with an unexplained history of miscarriages; the neurologist is treating strokes; the hematologist, deep venous thrombosis; the cardiologist puzzles over valve damage in an otherwise healthy young man, and so forth. Often, APS is evidenced by an elevated activated partial thromboplastin time (aPT T) test prior to surgery. However, aPT T is not specifically informative, and the surgeon may never consider APS as a cause. “Even if you tell them that the patient has APS,” says Dr. Erkan, “they may not be aware of the risk of thrombosis associated with the disease.” This situation goes to the CRTF’s overall challenge of increasing awareness: “This is a commonly taught disease in medical school, but just a few weeks ago I got an email from a patient whose husband has been suffering multiple clots, and she’s the one who had to suggest to the physician to test for APS.”
