Antiphospholipid Syndrome (APS), also known as Hughes Syndrome, is an acquired autoimmune disorder characterized by the presence of specific antibodies that mistakenly target the body’s own proteins. This leads to a hypercoagulable state, significantly increasing the risk of blood clots (thrombosis) in both arteries and veins throughout the body. APS can affect individuals of any age and also causes significant issues during pregnancy. Because its varied clinical presentation can mimic other conditions, the true prevalence of APS is often misunderstood.
Defining Antiphospholipid Syndrome
Antiphospholipid Syndrome is a systemic autoimmune disease where the immune system produces autoantibodies against plasma proteins that bind to phospholipids. The primary antibodies involved are lupus anticoagulant (LA), anticardiolipin antibodies (aCL), and anti-beta-2 glycoprotein I (anti-β2GPI). The presence of these antibodies disrupts the normal clotting process, promoting thrombosis within blood vessels. This mechanism results in the major clinical problems seen in APS, including vascular events and pregnancy complications.
APS is classified into two types. Primary APS occurs in isolation, without another underlying autoimmune disease. Secondary APS is diagnosed when the condition occurs alongside another systemic autoimmune disease, most commonly Systemic Lupus Erythematosus (SLE).
Analyzing the Prevalence of APS
While Antiphospholipid Syndrome is not common, it is not exceedingly rare. Studies suggest the prevalence of APS in the general population ranges from approximately 10 to 50 cases per 100,000 persons. Incidence rates, representing new diagnoses, are estimated to be between 1 and 2.7 cases per 100,000 person-years.
The risk of developing APS is skewed toward women, who account for approximately 83% of cases. Prevalence among women can be up to four times higher than in men, with the highest incidence rates seen in those aged 30 to 49 years. This difference is partly due to the inclusion of obstetric complications in the diagnostic criteria.
The presence of antiphospholipid antibodies is far more frequent than the syndrome itself. These antibodies are found in a higher percentage of individuals who have experienced a thrombotic event. For example, studies have found antiphospholipid antibodies in about 9.5% of patients with deep vein thrombosis (DVT) and 13.5% of patients who have had a stroke.
Clinical Manifestations and Diagnostic Criteria
APS primarily manifests as vascular thrombosis and specific pregnancy complications. Thrombosis can occur in the veins or arteries of any organ; deep vein thrombosis (DVT) is the most frequent venous event, while arterial clots often lead to strokes or transient ischemic attacks. Less common features not included in the formal criteria involve skin changes (livedo reticularis), neurological issues (migraines and seizures), and heart valve abnormalities.
A rare, life-threatening form, Catastrophic Antiphospholipid Syndrome (CAPS), involves widespread, rapid clotting in multiple small blood vessels, leading to organ failure.
Diagnosis relies on the Sydney classification criteria, requiring at least one clinical criterion and one laboratory criterion. Clinical criteria include documented episodes of thrombosis or specific pregnancy morbidity. Obstetric criteria include:
- Three or more unexplained consecutive spontaneous abortions before the 10th week of gestation.
- One or more unexplained fetal deaths after the 10th week.
- Premature birth before the 34th week due to eclampsia, severe preeclampsia, or placental insufficiency.
The laboratory component requires the persistent presence of at least one of the three antibodies (lupus anticoagulant, anticardiolipin, or anti-beta-2 glycoprotein I). Persistence means the antibody is detected at a medium or high titer on two or more occasions, spaced at least 12 weeks apart. This mandatory re-testing rules out temporary antibody positivity, ensuring the diagnosis reflects a chronic autoimmune process.
Long-Term Management and Treatment
Long-term management for diagnosed APS patients centers on anticoagulation therapy to prevent recurrent blood clots. For patients who have experienced a thrombotic event, treatment is generally lifelong, utilizing Vitamin K Antagonists (VKAs) like warfarin. The target International Normalized Ratio (INR) is typically maintained between 2.0 and 3.0 for most patients with venous thrombosis.
If clotting recurs despite standard warfarin therapy, a higher INR target (sometimes 3.0 to 4.0) or the addition of low-dose aspirin may be considered. Direct Oral Anticoagulants (DOACs) are generally not the preferred choice for APS patients, particularly those with a history of arterial thrombosis, due to limited evidence of effectiveness.
Management during pregnancy requires a specialized approach, especially for women with a history of obstetric APS. Treatment often involves a combination of low-dose aspirin and prophylactic doses of low-molecular-weight heparin (LMWH), which are safer for the developing fetus than warfarin. This regimen has significantly improved live birth rates.
Risk factor modification is also important. Patients should manage cardiovascular risks, such as quitting smoking, maintaining a healthy weight, and controlling blood pressure and cholesterol. For patients with co-occurring SLE, hydroxychloroquine may be used, as it is associated with a reduction in thrombotic events.