Pathogenesis and clinical presentation
APS is based on non-inflammatory mechanisms leading to thrombotic vasculopathy. Thrombosis can affect absolutely any anatomical regions and vascular beds.
The clinical and laboratory symptom complex is formed by a combination of arterial or venous thromboses with the circulation of specific antibodies (Abs). These autoantibodies are directed against membrane phospholipids and associated glycoproteins (e.g., $\beta_2$-glycoprotein-1-cofactor-dependent Abs).
In addition to classic thromboses, the pathology is often accompanied by hematological abnormalities. These include thrombocytopenia and hemolytic anemia, which occur due to the destruction of blood cells by the patient's own autoantibodies.
Pediatric features
In childhood, the syndrome has a specific thrombosis pattern. Most often, it does not act as an independent disease, but manifests against the background of systemic lupus erythematosus (SLE). Vascular catastrophes can occur both during a pronounced exacerbation of lupus and at the stage of complete remission.
- Typical localization: microthromboses predominate, affecting small vessels of the skin, renal glomeruli, and brain structures.
- Rare localizations: deep vein thrombosis of the limbs, as well as involvement of the hepatic and renal veins. Hepatic vein thrombosis can trigger a severe condition—Budd-Chiari syndrome.
- Complications of arterial thrombosis: lead to profound ischemia of target organs. This manifests as myocardial, pulmonary, and renal infarctions, ischemic strokes, and gangrene of the distal limbs.
Specific laboratory diagnostics
A reliable diagnosis requires the presence of at least one clinical and one laboratory criterion.
The most important testing rule is double confirmation of results with an interval of at least 12 weeks. This is necessary to rule out transient (temporary) antibody appearance. The time window between a clinical event (thrombosis or pregnancy morbidity) and a positive test must strictly fall within the range of 12 weeks to 5 years.
The diagnostic panel includes three main markers:
- Lupus anticoagulant (LA). These are IgG or IgM class Abs directed directly against membrane phospholipids. Diagnostics is multi-stage:
- Screening: prolongation of clotting time in phospholipid-dependent tests (aPTT, dilute Russell's viper venom time, kaolin clotting time).
- Mixing test: when donor plasma is added, the time is not corrected (proves the presence of an inhibitor rather than factor deficiency).
- Confirmatory test: adding an excess of phospholipids normalizes the time (proves that the inhibitor specifically targets phospholipids).
- Exclusion: it is mandatory to rule out the presence of heparin or factor VIII inhibitors.
- Anticardiolipin antibodies (aCL). IgG and/or IgM isotypes are detected by ELISA. Only medium or high titers are diagnostically significant.
- Anti-$\beta_2$-glycoprotein I antibodies. IgG/IgM classes are assessed by ELISA. To confirm the criterion, the titer must be strictly high.
Clinical feature: antibodies to lipid mixtures (cardiolipin + cholesterol + phosphatidylcholine) may also circulate in the blood. They are responsible for the false-positive Wassermann reaction (agglutination reaction).
Routine laboratory findings
General clinical blood tests perfectly reflect the systemic nature of the involvement and the degree of inflammatory activity in APS.
Blood tests (general clinical studies):
- An elevated erythrocyte sedimentation rate (ESR) indicates the active phase of inflammation.
- Cytopenias develop: the most typical is a decrease in leukocyte count (leukopenia), which occurs predominantly at the expense of lymphocytes (lymphopenia).
- The presence of hemolytic anemia must be confirmed by a positive Coombs test.
Urine tests (markers of lupus nephritis): The severity of changes in urine sediment directly correlates with the activity of renal involvement. Laboratory findings record protein loss (proteinuria), erythrocytes (hematuria), leukocytes (leukocyturia), and the appearance of casts (cylindruria).
To confirm APS, use the "12-week rule": at least 12 weeks must pass between the first and second positive laboratory test to ensure that the antibodies have not disappeared (to rule out their transient nature).
Class and exam questions
What is the basis of APS pathogenesis?
The syndrome is based on non-inflammatory mechanisms leading to acquired autoimmune thrombophilia. This causes the development of thrombotic vasculopathy in vessels of any caliber.
Why is a plasma mixing test needed when APS is suspected?
It proves that the prolongation of clotting time is caused by the presence of a specific inhibitor in the blood, rather than a simple deficiency of coagulation factors. Upon addition of normal donor plasma, the patient's clotting time does not normalize.
What disease is most commonly associated with APS in pediatric practice?
Antiphospholipid syndrome most often accompanies systemic lupus erythematosus (SLE), being detected in approximately 33% of patients. Thrombosis in this case can develop both during the acute phase of SLE and during remission.
What else to study on this topic
- Clinical criteria of APS: classification of thromboses and pregnancy morbidities
- Mechanism of the false-positive Wassermann reaction in autoimmune pathologies
- Differential diagnosis of lupus anticoagulant and factor VIII deficiency
- Budd-Chiari syndrome as a complication of hepatic vein thrombosis
- Enzyme-linked immunosorbent assay (ELISA) in rheumatology: principles of the method
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