Antiphospholipid Syndrome (APS) is an autoimmune disorder where the immune system mistakenly produces antibodies that attack certain proteins and fats in the blood. This malfunction causes the blood to become excessively prone to clotting, leading to the formation of blood clots in both veins and arteries. The disorder can occur alone or in conjunction with other autoimmune diseases, such as Systemic Lupus Erythematosus (SLE).
How Frequently Antiphospholipid Syndrome Occurs
Estimates for the frequency of Antiphospholipid Syndrome vary, but it is considered a rare condition. The overall estimated prevalence typically ranges from 40 to 50 cases per 100,000 persons. The annual incidence is estimated to be approximately 2.1 to 2.84 new cases per 100,000 person-years. APS is diagnosed in women more frequently than in men, with reported ratios often ranging from 3.5:1 to 7:1, particularly when the syndrome occurs alongside other conditions.
APS is classified as either primary, occurring in isolation, or secondary, when it is found alongside another autoimmune disease, most commonly Systemic Lupus Erythematosus (SLE). Roughly half of all APS cases are considered primary, meaning they are not associated with another underlying autoimmune disorder. Although antiphospholipid antibodies are detected in 30 to 40% of patients with SLE, only about 10% of these individuals develop the full syndrome.
It is important to distinguish between having the antibodies and having the actual syndrome. Up to 5% of healthy individuals may have detectable antiphospholipid antibodies without developing clinical symptoms. The presence of these antibodies alone does not constitute a diagnosis of APS; they must be linked to clinical events like thrombosis or pregnancy complications.
The Primary Clinical Manifestations
The health issues that define Antiphospholipid Syndrome are directly related to the abnormal blood clotting that the antibodies promote. These problems fall into two major categories: blood clots (thrombosis) and complications during pregnancy. This hypercoagulable state can affect almost any blood vessel in the body.
Thrombosis can occur in either the venous system or the arterial system. In the venous system, the most common event is Deep Vein Thrombosis (DVT), typically in the legs, which can lead to a potentially life-threatening Pulmonary Embolism (PE) if the clot travels to the lungs. Arterial clots are equally serious, frequently causing ischemic stroke or transient ischemic attacks if they occur in the brain’s blood vessels. Clots can also lead to a heart attack (myocardial infarction) by blocking coronary arteries.
The second major manifestation of APS is pregnancy morbidity. This includes recurrent, unexplained miscarriages, usually before the tenth week of gestation. It also involves unexplained fetal death after the tenth week or premature birth before the 34th week, often due to severe preeclampsia or placental insufficiency. The antibodies are thought to interfere with placental blood flow, compromising the fetus’s oxygen and nutrient supply.
Establishing a Diagnosis
Confirming a diagnosis of Antiphospholipid Syndrome requires meeting a specific set of criteria that combines clinical events with persistent laboratory findings. The widely accepted classification framework, known as the revised Sapporo or Sydney criteria, requires a patient to have at least one clinical manifestation and one laboratory finding. The clinical criteria are the history of thrombosis or one of the specified pregnancy morbidities.
The laboratory criteria involve testing for the presence of three specific antiphospholipid antibodies. These are the Lupus Anticoagulant (LA), Anti-cardiolipin (aCL) antibodies, and Anti-Beta-2 Glycoprotein I (aβ2GPI) antibodies. The detection of these antibodies must be significant, usually at a medium to high titer, and must be confirmed to be persistent.
To rule out a temporary elevation of antibodies, the positive laboratory test result must be repeated and confirmed at least 12 weeks after the initial test. Transient antibody positivity can occur with certain infections or medications and is not considered diagnostic of APS.
Long-Term Management Strategies
The primary goal of long-term management for patients diagnosed with thrombotic APS is to prevent future clotting events. For individuals who have experienced a clot, treatment typically involves lifelong anticoagulation therapy with blood-thinning medications. Vitamin K Antagonists (VKA), such as Warfarin, are the standard choice, with a target intensity measured by an International Normalized Ratio (INR) of 2.0 to 3.0.
Direct Oral Anticoagulants (DOACs) may be considered for certain patients with venous clots, but they are generally avoided for those with a history of arterial clots or those who test positive for all three antiphospholipid antibodies. In cases where a clot occurs despite adequate anticoagulation, doctors may increase the Warfarin dose or add low-dose aspirin to the regimen.
For pregnant patients with APS, specialized management is necessary due to the risk of complications and the danger Warfarin poses to the developing fetus. The standard treatment involves a combination of low-dose aspirin and a form of injectable Heparin, often Low Molecular Weight Heparin (LMWH). This dual therapy helps to mitigate the risk of clotting and improves the chance of a successful pregnancy outcome.