Antiphospholipid syndrome is an autoimmune pathology based on the formation of antibodies to phospholipids, which are the main lipid components of cell membranes. Antiphospholipid syndrome can be manifested by venous and arterial thrombosis, arterial hypertension, valvular heart defects, obstetric pathology (habitual miscarriage, fetal death, gestosis), skin lesions, thrombocytopenia, hemolytic anemia. The main diagnostic markers of antiphospholipid syndrome are At to cardiolipin and lupus anticoagulant. Treatment of antiphospholipid syndrome is reduced to the prevention of thrombosis, the appointment of anticoagulants and antiplatelet agents.
D68.6 Other thrombophilia
Antiphospholipid syndrome (APS) is a complex of disorders caused by an autoimmune reaction to phospholipid structures present on cell membranes. The disease was described in detail by the English rheumatologist Hughes in 1986. There are no data on the true prevalence of antiphospholipid syndrome; it is known that insignificant levels of AP to phospholipids in blood serum are found in 2-4% of practically healthy individuals, and high titers are found in 0.2%. Antiphospholipid syndrome is 5 times more often diagnosed among young women (20-40 years old), although men and children (including newborns) may suffer from the disease. As a multidisciplinary problem, antiphospholipid syndrome (APS) attracts the attention of specialists in the field of clinical rheumatology, obstetrics and gynecology, cardiology.
Reasons of antiphospholipid syndrome
The underlying causes of antiphospholipid syndrome are unknown. Meanwhile, factors predisposing to an increase in the level of antibodies to phospholipids have been studied and determined. Thus, a high titer of antiphospholipid antibodies is observed against the background of:
- viral and bacterial infections (hepatitis C, HIV, infectious mononucleosis, malaria, infectious endocarditis, etc.)
- autoimmune diseases (systemic lupus erythematosus, rheumatoid arthritis, Sjogren’s disease, nodular periarteritis, autoimmune thrombocytopenic purpura);
- malignant neoplasms;
- taking medications (psychotropic drugs, hormonal contraceptives, etc.), withdrawal of anticoagulants.
There is evidence of a genetic predisposition to increased synthesis of antibodies to phospholipids in individuals carrying HLA DR4, DR7, DRw53 antigens and in relatives of patients with antiphospholipid syndrome.
Depending on the structure and immunogenicity, “neutral” (phosphatidylcholine, phosphatidylethanolamine) and “negatively charged” (cardiolipin, phosphatidylserine, phosphatidylinositol) phospholipids are distinguished. The class of antiphospholipid antibodies reacting with phospholipids includes lupus anticoagulant, At to cardiolipin, beta2-glycoprotein-1-cofactor-dependent antiphospholipids, etc. Interacting with phospholipids of vascular endothelial cell membranes, platelets, neutrophils, antibodies cause hemostasis disorders, expressed in a tendency to hypercoagulation. In general, the immunobiological mechanisms of the development of antiphospholipid syndrome require further study and clarification.
Classification of antiphospholipid syndrome
Taking into account the etiopathogenesis and course, the following clinical and laboratory variants of APS are distinguished:
- primary – there is no connection with any background disease capable of inducing the formation of antiphospholipid antibodies;
- secondary – antiphospholipid syndrome develops against the background of another autoimmune pathology;
- catastrophic – acute coagulopathy occurring with multiple thrombosis of internal organs;
- AFL negative variant of antiphospholipid syndrome, in which serological markers of the disease (Ap to cardiolipin and lupus anticoagulant) are not determined.
According to modern views, antiphospholipid syndrome is an autoimmune thrombotic vasculopathy. In APS, the lesion can affect vessels of various caliber and localization (capillaries, large venous and arterial trunks), which causes an extremely diverse range of clinical manifestations, including venous and arterial thrombosis, obstetric pathology, neurological, cardiovascular, skin disorders, thrombocytopenia.
The most frequent and typical sign of antiphospholipid syndrome are recurrent venous thrombosis: thrombosis of the superficial and deep veins of the lower extremities, hepatic veins, portal veins of the liver, retinal veins. Patients with antiphospholipid syndrome may experience repeated episodes of PE, pulmonary hypertension, superior vena cava syndrome, Budd-Chiari syndrome, adrenal insufficiency.
Venous thrombosis in antiphospholipid syndrome develops 2 times more often than arterial thrombosis. Among the latter, cerebral artery thrombosis predominates, leading to transient ischemic attacks and ischemic stroke. Other neurological disorders may include migraine, hyperkinesis, convulsive syndrome, sensorineural hearing loss, ischemic optic neuropathy, transverse myelitis, dementia, mental disorders.
The defeat of the cardiovascular system in APS is accompanied by the development of myocardial infarction, intracardiac thrombosis, ischemic cardiomyopathy, arterial hypertension. Quite often there is a lesion of the heart valves – from minor regurgitation, detected by EchoCG, to mitral, aortic, tricuspid stenosis or insufficiency. As part of the diagnosis of APS with cardiac manifestations, differential diagnosis with infectious endocarditis, myxoma of the heart is required.
Renal manifestations may include both minor proteinuria and acute renal failure. On the part of the gastrointestinal tract with antiphospholipid syndrome, hepatomegaly, gastrointestinal bleeding, occlusion of mesenteric vessels, portal hypertension, spleen infarction occur. Typical lesions of the skin and soft tissues are represented by reticular livedo, palmar and plantar erythema, trophic ulcers, gangrene of the fingers; musculoskeletal system – aseptic necrosis of the bones (femoral head). Hematological signs of antiphospholipid syndrome are thrombocytopenia, hemolytic anemia, hemorrhagic complications.
In women, APS is often detected in connection with obstetric pathology: repeated spontaneous termination of pregnancy at various times, delayed fetal development, fetoplacental insufficiency, gestosis, chronic fetal hypoxia, premature birth. When managing pregnancy in women with antiphospholipid syndrome, an obstetrician-gynecologist should take into account all possible risks.
Given the multi-organ nature of the lesion, the diagnosis and treatment require the combined efforts of doctors of various specialties: rheumatologists, cardiologists, neurologists, obstetricians, gynecologists, etc. Antiphospholipid syndrome is diagnosed on the basis of clinical (vascular thrombosis, burdened obstetric history) and laboratory data. The diagnosis is considered reliable when at least one basic clinical and laboratory criterion is combined:
- Laboratory markers. The main immunological criteria include detection in blood plasma of medium or high titers of At to IgG/IgM class cardiolipin and lupus anticoagulant twice within six weeks. Additional laboratory signs are a false positive RW, a positive Coombs reaction, an increase in the titer of antinuclear factor, rheumatoid factor, cryoglobulins, antibodies to DNA. The study of UAC, platelets, biochemical blood analysis, coagulogram is also shown.
- Instrumental diagnostics. To confirm thrombosis of internal organs, ultrasound of the vessels of the head and neck, kidney vessels, arteries and veins of the extremities, eye vessels, etc. is performed. Changes in the valves of the heart valves are detected during EchoCG.
- Examination during pregnancy. Pregnant women with antiphospholipid syndrome need monitoring of indicators of the blood coagulation system, dynamic ultrasound of the fetus and dopplerography of uteroplacental blood flow, cardiotography.
Differential diagnostic measures should be aimed at the exclusion of:
- DIC syndrome;
- hemolytic-uremic syndrome;
- thrombocytopenic purpura, etc.
Treatment of antiphospholipid syndrome
The main goal therapy is to prevent thromboembolic complications. Regime moments provide for moderate physical activity, refusal to stay in a stationary state for a long time, practicing traumatic sports and long-term air travel. Women with this disease should not be prescribed oral contraceptives, and before planning a pregnancy, it is necessary to consult an obstetrician-gynecologist. Pregnant patients during the entire gestation period are shown to take small doses of glucocorticoids and antiplatelet agents, the introduction of immunoglobulin, injections of anticoagulants under the control of hemostasiogram indicators.
Drug therapy for APS may include the appointment of indirect anticoagulants, direct anticoagulants, antiplatelet agents. Preventive anticoagulant or antiplatelet therapy for most patients with APS is carried out for a long time, and sometimes for life. In the catastrophic form of antiphospholipid syndrome, the appointment of high doses of glucocorticoids and anticoagulants, plasmapheresis sessions, transfusion of freshly frozen plasma, etc. is indicated.
Timely diagnosis and preventive therapy help to avoid the development and recurrence of thrombosis, as well as hope for a favorable outcome of pregnancy and childbirth. In secondary APS, it is important to monitor the course of the underlying pathology, prevent infections. Prognostically unfavorable factors are the combination of APS with SLE, thrombocytopenia, rapid increase in the titer of At to cardiolipin, persistent arterial hypertension. All patients diagnosed with antiphospholipid syndrome should be under the supervision of a rheumatologist with periodic monitoring of serological markers of the disease and hemostasiogram indicators.