Pathology overview and classification
Antiphospholipid syndrome is the leading cause of acquired thrombophilias—conditions in which the body demonstrates an abnormal tendency to form blood clots. The disease is caused by an immune system malfunction resulting in the production of antibodies against self phospholipid-binding proteins.
In clinical practice, two main forms of the syndrome are distinguished:
- Primary APS: occurs as an independent pathology, with the patient showing no signs of other autoimmune diseases.
- Secondary APS: develops against the background of a pre-existing autoimmune or infectious pathology. Most often, it accompanies systemic lupus erythematosus, rheumatoid arthritis, or systemic connective tissue diseases.
Pathogenesis: how thrombosis develops
Autoimmune disorders in APS directly interfere with hemostasis, shifting the balance toward hypercoagulability. The tendency toward blood clot formation is driven by three key mechanisms:
- Suppression of the anticoagulant system. Antibodies inhibit fibrinolysis and the natural anticoagulant protein C.
- Hyperactivation of platelets. Cells become more prone to aggregation.
- Endotheliosis. Antibodies attack phospholipids on the membranes of endothelial cells, damaging the vascular wall. As a result, the endothelium loses its protective anticoagulant properties and acquires pronounced procoagulant characteristics.
Clinically significant antibodies and laboratory diagnosis
A diagnosis of APS cannot be made based on symptoms alone. It is considered valid exclusively when combining at least one clinical manifestation (such as thrombosis or obstetric pathology) and one confirmed serological marker.
The main clinically significant antibodies include:
- Lupus anticoagulant (detected using Russell's viper venom or taipan venom tests).
- Anticardiolipin antibodies.
- Anti-β₂-glycoprotein I cofactor antibodies.
- Antithrombin and antiannexin antibodies.
Critical diagnostic rule: antibody detection must be persistent. Testing must be repeated after 12 weeks to rule out transient (temporary) appearance of antibodies in the blood, which can occur, for example, during infections.
Risk stratification for thrombotic complications
Depending on the autoantibody profile detected, patients are divided into groups with varying probabilities of developing thrombosis.
High risk is diagnosed in the following cases:
- The patient is positive for all three main types of antibodies simultaneously (lupus anticoagulant, anticardiolipin antibodies, anti-β₂-glycoprotein I antibodies).
- Isolated presence of lupus anticoagulant alone is detected.
- A persistent and isolated increase in anticardiolipin antibody titer to moderate or high levels is observed.
Low risk is established if the patient shows only periodic, non-persistent elevations in the levels of any specific antiphospholipid antibodies.
Catastrophic APS
This is the most severe, fulminant, and prognostically unfavorable form of the syndrome. Under conditions of extremely high antibody titers, massive microthrombi form in the microvasculature of vital organs.
Total ischemic tissue damage rapidly leads to multiple organ dysfunction syndrome. This is a critical, life-threatening condition in which the mortality rate reaches 50% despite therapy.
Distinction between APS and inherited thrombophilias
Unlike APS, which is an acquired condition, hereditary thrombophilias exist due to genetic defects. The most frequent genetic anomalies include Factor V Leiden mutation (impairing protein C function), prothrombin mutation G20210A, methylenetetrahydrofolate reductase mutation, and the PAI-1 gene polymorphism. It is important to note that with congenital defects carrying a lifelong risk (such as the Leiden mutation), additional triggers are usually required for thrombosis to manifest: pregnancy, oral contraceptives, surgical interventions, or prolonged immobilization.
To memorize the main high-risk markers, use the «LAC» triad: Lupus anticoagulant, Anticardiolipin antibodies, Cofactor anti-β₂-glycoprotein I.
Class and exam questions
Is a single positive antibody test sufficient to diagnose APS?
No. The diagnosis is confirmed only in the presence of clinical signs and a repeated positive antibody test after 12 weeks to exclude their transient nature.
Is the presence of lupus mandatory for developing this syndrome?
Not necessarily. The syndrome can be primary, meaning it develops independently without other autoimmune diseases. The secondary form frequently accompanies systemic lupus erythematosus or rheumatoid arthritis.
What is the main danger of catastrophic APS?
This form involves rapid, multiple microvascular thrombosis, causing acute multiple organ dysfunction with a mortality risk of up to 50%.
Should all patients with thrombosis be screened for thrombophilia?
According to current guidelines, routine testing for acquired or inherited thrombophilia markers is not recommended for patients who have developed provoked deep vein thrombosis.
What else to study on this topic
- Thrombotic microangiopathies (TMAs) and their pathogenesis
- Genetic causes of inherited thrombophilias (Factor V Leiden mutation, prothrombin G20210A mutation)
- Paroxysmal nocturnal hemoglobinuria (PNH): mechanism of bone marrow failure and thrombosis
- Principles of testing for inherited and acquired thrombophilias
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