Antiphospholipid Syndrome

Antiphospholipid syndrome (APS) is a systemic autoimmune disease in which particular clinical manifestations coexist with persistently positive antiphospholipid antibodies. Its main manifestations are venous or arterial thrombosis and certain pregnancy complications. APS may occur independently or alongside systemic lupus erythematosus and other diseases. Antibodies alone, without corresponding clinical manifestations, do not establish APS.

Antibodies and Disease Mechanisms

The principal laboratory markers are lupus anticoagulant (LA), IgG/IgM anticardiolipin antibodies (aCL) and antibodies to β2-glycoprotein I (anti-β2GPI). Many pathogenic antibodies target phospholipid-binding proteins rather than simply all of the body's own phospholipids. Antibodies to phosphatidylserine and other antigens may be investigated in special circumstances but do not replace the standard panel.

Cellular phospholipid surfaces help organize coagulation reactions. Antiphospholipid antibodies can affect endothelium, platelets, and cellular and humoral mechanisms of hemostasis and inflammation, increasing the tendency to thrombosis. The mechanism is more complex than simply switching off one anticoagulant factor.

The term lupus anticoagulant reflects the history of these antibodies and their ability to prolong certain phospholipid-dependent clotting tests in vitro. It does not mean the patient necessarily has lupus or that the antibodies protect against thrombosis in vivo.

Clinical Manifestations and Risk Factors

Thrombosis may affect various organs and vascular territories, causing DVT, PE, ischemic stroke and other vascular events. Risk differs between antibody carriers: persistence, profile, level and other risk factors matter. LA, double or triple positivity and persistently high antibody levels are features of a high-risk profile.

Smoking, arterial hypertension, dyslipidemia, diabetes, surgery, prolonged immobility, pregnancy and the postpartum period may add risk. Another risk factor is not required for APS to manifest, but can increase the likelihood of thrombosis. There is no reliable basis for stating that APS affects 5% of the entire population or accounts for fixed high percentages of all pregnancy losses.

APS and Pregnancy

Obstetric manifestations may include recurrent early pregnancy loss, unexplained fetal death later in pregnancy, and preterm delivery due to severe preeclampsia or placental insufficiency. Placental damage involves thrombotic and inflammatory mechanisms; not every complication in an antibody-positive patient is caused by APS.

Individual assessment by an obstetrician and the relevant specialist is needed before and during pregnancy. Thrombosis history, previous pregnancy outcomes and antibody profile influence monitoring and treatment. Postpartum risk is not limited to the first 2–3 weeks. A positive test is not a reason to start aspirin or anticoagulants without medical advice.

Laboratory Diagnosis

• IgG/IgM aCL and IgG/IgM anti-β2GPI are measured using validated immunoassays. Antibody level, method and laboratory cutoff matter.
• LA is assessed using functional coagulation methods, usually a sensitive activated partial thromboplastin time (aPTT) and dilute Russell's viper venom time (dRVVT).
• Positive results must be confirmed on repeat testing at least 12 weeks later to distinguish persistent antibodies from transient positivity, for example during an infection.

A prolonged aPTT or prothrombin time alone does not prove LA. Laboratories use screening, mixing assessment and confirmation of phospholipid dependence; factor deficiencies and other inhibitors must be considered. Anticoagulants can interfere with results, so testing should be coordinated with the clinician without stopping treatment independently.

The diagram illustrates the principle of LA testing; the actual algorithm depends on current recommendations and the laboratory's reagents.

Persistent positivity for at least one standard marker may be significant, but diagnosis requires laboratory and clinical findings together. ACR/EULAR classification criteria are primarily intended for research and do not replace individual clinical diagnosis.

When Testing Is Considered

• Unexplained, early or recurrent venous or arterial thrombosis, particularly at unusual sites.
• Selected adverse obstetric outcomes. Classical clinical criteria include unexplained death of a morphologically normal fetus at 10 weeks or later; delivery of a morphologically normal infant before 34 weeks because of severe preeclampsia/eclampsia or placental insufficiency; or three or more unexplained consecutive losses before 10 weeks after relevant alternative causes have been excluded.

A clinician may also request testing in other justified situations. Memory or visual symptoms without a confirmed vascular event are nonspecific and do not themselves establish APS.