Phospholipid syndrome during pregnancy treatment. Antiphospholipid syndrome and pregnancy

Anti phospholipid syndrome, also abbreviated as APS, was first described only about forty years ago by London physician Graham Hughes. Sometimes APS is called Hughes syndrome (or Huge, depending on the translation of the surname).

The pathology is associated with autoimmune processes, which cannot always be adequately regulated. What is the danger of antiphospholipid syndrome? In increasing thrombus formation in blood vessels (both venous and arterial). You understand the dangers of blood clots.

Another feature of the syndrome is that women are most often affected by this pathology. And this is especially true for reproductive age (20 – 40 years). Increased thrombus formation negatively affects the pregnancy process and can provoke its premature termination with the eventual death of the fetus.

• Disturbance of the hemostasis system.
• Aggregation (gluing) of platelets.
• Changes in the walls of blood vessels.
• Blockage of blood vessels of various sizes.

It is believed that APS is the leading cause of immune thrombophilia and the basis of severe obstetric pathology.

The main target for antiphospholipid syndrome is phospholipids - one of the main components of the membranes of blood cells, blood vessels, and nervous tissue. They are also responsible for the transport of fatty acids, fats, and cholesterol.

Those phospholipids that are localized in cell membranes ah occupy an important place in the process of blood clotting. Such phospholipids act as antigens. They are different in their structure and ability to form an immune response, which divides them into two main, most common groups:

• Neutral.
• Anionic (negatively charged).

To such cellular and tissue components, when the immune response fails, antiphospholipid antibodies (APLA) are produced - these are serological markers of antiphospholipid syndrome, which are a heterogeneous group of antibodies that differ in specificity.

Based on detection methods, there are two main types of antibodies:

• , which is identified by phospholipid-dependent coagulation tests. Represented by immunoglobulins G or M.
• Antibodies that are produced to:
  • Cardiolipin – represented by immunoglobulins of classes G, M, A.
  • Phosphatidylserine.
  • Phosphatidylcholine.
  • Phosphatidylethanolamine.
  • Phosphatidylic acid.
  • Beta-2 glycoprotein – 1.
  • Annexina V.
  • Prothrombin.

A diagnosis such as APS and its identification are characterized by a gradual increase among the population, which indicates, despite modern treatment methods, the severity of the pathology.

How common is it?

True APS is not common. It is not possible to provide accurate data on the epidemiology of this disease, since the main antibodies - lupus anticoagulant and antibodies to cardiolipin - are found in healthy populations under the influence of various causes.

You can roughly estimate the number of cases of antiphospholipid syndrome using the following indicators:

• Cardiolipin antibodies in healthy people found in up to 4% of the population.
• Lupus anticoagulant can also be present in the blood serum of an absolutely healthy person.
• In situations such as taking psychotropic drugs, oral contraceptives, the presence of HIV infection, hepatitis, oncological pathology, APLA may be present in the blood, but this does not indicate the presence of antiphospholipid syndrome.
• Among all patients diagnosed with APS, up to 50% of cases are primary antiphospholipid syndrome.
• In women with obstetric pathology, which is accompanied by spontaneous abortions, miscarriage APS is diagnosed in up to 42% of cases.
• With established antiphospholipid syndrome in women of reproductive age, the incidence of pathology of conception, pregnancy, and stillbirth reaches 90%.
• In women under 50 years of age who developed a stroke, 40% confirmed a connection with the presence of antiphospholipid antibodies.
• In the presence of venous thrombosis, antiphospholipid antibodies are detected in 10% of cases.

In general, secondary antiphospholipid syndrome is up to 9 times more likely to be diagnosed in women, as they are more susceptible to developing connective tissue diseases.

Important! Unfortunately, the latest epidemiological data are not encouraging, since just a few years ago, according to rough estimates, the frequency of APS did not exceed 5%. Now this figure is confidently approaching 10%.

One of the success factors in the treatment of this disease is the correct classification of the found pathology, which in the future will make it possible to select the correct tactics for managing the patient.

Classification

• Primary antiphospholipid syndrome.
• Secondary, which occurs in the following cases:
  • Autoimmune pathology.
  • Rheumatic diseases.
  • Malignant tumors.
  • Infectious factors.
  • Other reasons.

Among other forms there are:

• Catastrophic – characterized by a sudden onset, rapid failure of organs and systems due to massive thrombosis.
• Microangiopathies such as thrombocytopenic, thrombotic purpura, hemolytic-uremic syndrome (characterized by three leading signs - thrombocytopenia, hemolytic anemia, acute renal failure), HELLP syndrome (a complication during normal pregnancy in the 2nd and 3rd trimesters with the development of severe hemolysis, liver damage, thrombocytopenia, thrombosis).
• Hypotrombinemia.
• DIC – syndrome.
• Combinations of antiphospholipid syndrome with vasculitis.
• Sneddon syndrome is a vascular pathology of non-inflammatory origin, in which recurrent thrombosis of the vessels of the head, livedo reticularis, and arterial hypertension are noted.

Depending on the serological data, the following types of APS are distinguished:

• Seropositive – anticardiolipin antibodies are detected with/without lupus anticoagulant.
• Seronegative:
  • Antibodies to phospholipids that interact with phosphatidylcholine are determined.
  • Antibodies to phospholipids that interact with phosphatidylethanolamine.

All of the above pathological conditions have their own causes, the identification of which is extremely important for understanding the situation that has arisen and what the doctor and patient should do next.

Reasons for development

The etiological factors of APS are still not well understood. The main suspected causes of the development of antiphospholipid syndrome are currently considered to be:

• Autoimmune processes.
• Bacterial infections.
• Viral pathogens.
• Genetic predisposition.
• Oncological diseases.
• Lesions of the central nervous system.
• Long-term treatment with interferons, drugs such as isoniazid, hydralazine, oral contraceptives, and various psychotropic drugs.

Any of these reasons triggers a number of pathological changes in the body, which inevitably lead to thrombosis and multi-organ damage.

Development mechanisms

Both the causes and mechanisms of development of APS have not been sufficiently studied. But, according to the conclusions of many researchers, one synthesis
antiphospholipid antibodies cannot lead to significant pathology of the hemostatic system.

Therefore, there is currently a “double strike” theory, the essence of which is:

• Elevated levels of antiphospholipid antibodies create conditions for the development of pathological coagulation processes - this is the so-called first blow.
• Under the influence of mediators, the formation of a blood clot and thrombosis is triggered, which further aggravates the activation of blood coagulation reactions, which was previously caused by APLA, which is the second blow.

In this case, antiphospholipid antibodies form complexes with proteins of the coagulation system, which are highly sensitive to phospholipids located on cell membranes.

This leads not only to disruption of the functions of phospholipids, but also to the loss of the ability of these proteins to provide normal process coagulation. This, in turn, leads to further “failures” - APLA are capable of causing an intracellular signal, which leads to transformation of the functions of target cells.

Important! Antiphospholipid antibodies affect not only phospholipids, but also proteins involved in blood clotting processes. This entails a malfunction in the blood clotting process. Moreover, APLA “send” a signal into cells, which leads to damage to target organs.

This is how the process of formation of thrombosis of arterial and venous vessels is started - the pathogenetic basis of antiphospholipid syndrome, in which the leading mechanisms are as follows:

• To ensure normal anticoagulation processes, the full functioning of protein C and S is necessary. APLA have the ability to suppress the functions of these proteins, which ensures the unimpeded formation of blood clots.
• With already developed vascular thrombosis, there is a violation between the factors that provide narrowing and dilation of blood vessels.
• Increased production and increased concentration of the main vasoconstrictor TxA2 leads to the activation of other vasoconstrictor components and substances that cause blood clotting. One of the leading components is endothelin-1.

Thus, from the onset of the disease to the appearance of the first clinical signs of antiphospholipid syndrome, the following pathological reactions appear:

• Antiphospholipid antibodies damage vascular endothelial cells. This reduces the production of prostacyclin, which dilates blood vessels and prevents platelets from sticking together.
• The activity of thrombomodulin, a protein that has an antithrombotic effect, is inhibited.
• The synthesis of coagulation factors is inhibited, production begins, and substances are released that lead to platelet aggregation.
• The interaction of antibodies with platelets further stimulates the formation of substances that also lead to their aggregation and subsequent platelet death with the development of thrombocytopenia.
• The level of anticoagulant agents in the blood gradually decreases and the effect of heparin is weakened.
• The result of this is the appearance of high blood viscosity, blood clots form in vessels of any caliber and any location, organ hypoxia develops, and clinical symptoms develop.

Such reactions at different stages lead to clinical manifestations of antiphospholipid syndrome.

Symptoms of APS

The most common signs unique to antiphospholipid syndrome are:

• Vascular thrombosis.
• Obstetric pathology.

Depending on the type of thrombosis, the symptoms of the disease develop:

• Venous – the most common species APS, especially pathology of the lower extremities. The disease very often begins with such a sign. Almost 50% of patients are diagnosed with pulmonary embolism. Pathological processes in the portal, superficial, and renal vessels are less frequently recorded. It is important that antiphospholipid syndrome ranks second in the causes of the development of Budd-Chiari syndrome, in which obstruction of the liver veins occurs, leading to impaired blood outflow and venous stagnation.
• Arterial - diagnosed less frequently than venous. The main manifestation of this process is the development of peripheral circulatory disorders, ischemia, and heart attacks. The most common localization of this pathology is the brain, a little less often – the coronary.

One of the features of antiphospholipid syndrome is the high risk of recurrence of all types of thrombosis.

Since the symptoms of APS are diverse, it will be easier to imagine it in the form of lesions of individual systems:

1. Damage to the central nervous system is the most common and dangerous manifestation of aniphospholipid syndrome. Manifested by the development of the following pathologies:
   • Transient ischemic attacks and encephalopathy.
   • Ischemic strokes.
   • Epileptic syndrome.
   • Chorea.
   • Multiple sclerosis.
   • Migraine.
   • Myelitis.
   • Intracranial hypertension.
   • Transient amnesia.
   • Hearing loss.
   • Parkinsonian-type hypertonicity.
   • Visual impairment up to complete loss.
   • Psychoses.
   • Dementia.
   • Depression.
2. Damages of the cardiovascular system, which manifest themselves in the form of:
   • Thrombosis of large coronary arteries.
   • Myocardial infarction.
   • Intracardiac thrombosis.
   • Repeated stenosis after coronary artery bypass grafting and percutaneous angioplasty.
   • Insufficiency/stenosis of any of the heart valves.
   • Fibrosis, thickening, calcification of valve leaflets.
   • Ischemic cardiomyopathy.
   • Arterial hypertension.
   • Pulmonary hypertension.
   • Aortic arch syndrome.
   • Atherosclerosis.
3. Kidney damage:
   • Asymptomatic proteinuria.
   • Nephrotic syndrome.
   • Acute renal failure.
   • Renal hypertension.
   • Kidney failure.
   • Hematuria.
   • Kidney infarction.
4. Pulmonary lesions:
   • Emboli.
   • Pulmonary infarction.
   • Pulmonary hypertension.
   • Spicy respiratory distress– adult syndrome.
   • Hemorrhages inside the alveoli.
   • Thrombosis of blood vessels at various levels.
   • Fibrosing alveolitis.
   • Postpartum cardiopulmonary syndrome, the main symptoms of which are pleurisy, shortness of breath, increased body temperature, and the development of infiltrates in the lungs.
   • Sustained damage to the pulmonary vessels of non-inflammatory origin.
5. Damage to the digestive tract:
   • Ischemic, necrotic lesions of any parts of the digestive organs, which lead to the development of bleeding.
   • Stomach ache.
   • Necrosis, perforation of the esophagus.
   • Uncharacteristic, large ulcerative lesions of the stomach and duodenum.
   • Acute cholecystitis.
   • Occlusive processes of the spleen with predominant damage to the veins.
6. Adrenal damage:
   • Bilateral hemorrhagic infarction.
   • Vascular thromboembolism.
7. Liver damage:
   • Budd–Chiari syndrome.
   • Portal hypertension.
   • Hepatic veno-occlusive disease.
   • Nodular hyperplasia of the liver.
   • Liver infarctions, mainly during pregnancy.
   • Hepatitis.
8. Skin damage:
   • Livedo reticularis.
   • Ulcers of various sizes.
   • Purpura.
   • Pustules.
   • Palmar, plantar erythema.
   • Nodules.
   • Gangrene of fingers and toes.
   • Superficial skin necrosis.
   • Hemorrhages in the nail bed.
   • Thrombophlebitis of the saphenous veins.
   • Atrophic papuloid lesions.
9. Bone damage:
   • Aseptic necrosis.
10. Blood disorders:
    • Thrombocytopenia.
11. Catastrophic APS:
    • Rapid development of fatal multiple organ failure.
    • Massive thrombosis of both veins and arteries.
    • Rapid development of distress syndrome.
    • Cerebral circulation disorders.
    • Stupor.
    • Disorientation in time and space.

These signs of antiphospholipid syndrome can develop at any stage, often without any apparent reason, when the patient is not yet aware of his illness.

Important. A special category consists of pregnant women, for whom antiphospholipid syndrome and the development of thrombosis, unfortunately, leave little chance of motherhood.

Increased production of antiphospholipid antibodies during pregnancy leads to the development of several types of pathology:

• Intrauterine fetal death after the 10th week of pregnancy, which leads to recurrent miscarriage.
• Early preeclampsia and severe eclampsia.
• Placental ischemia.
• Fetoplacental insufficiency.
• Fetal growth restriction, fetal arrhythmia.
• The development of three or more unexplained spontaneous miscarriages before the 10th week of pregnancy.
• Thrombosis of veins and arteries in the mother.
• Intrauterine fetal death.
• Arterial hypertension.
• Chorea.
• Hellp syndrome.
• Early placental abruption.
• Stillbirth.
• Unsuccessful IVF.

Very important! A child born to a mother suffering from APS may develop thrombosis of various localizations from the first days of life, which confirms the genetic predisposition of antiphospholipid syndrome. Such children are more at risk of developing autism and circulatory disorders.

Antiphospholipid syndrome in children

For reference. Clinical manifestations, diagnosis and treatment tactics in children are the same as in adults.

Antiphospholipid syndrome in men

This disease is less common in men. The main differences arise in systemic lupus erythematosus, since sex hormones occupy one of the places in the pathogenesis of this pathology. At the same time, almost half of men quickly develop hematological disorders.

For reference. In more than 65% of cases, males experience neuropsychiatric disorders.

This serious disease requires timely, high-quality diagnosis, since any delay can lead to death.

Diagnosis of APS

In order to determine APS in a patient, a full range of examinations is necessary, since only the detection of APS does not indicate the presence of the disease:

• Anamnesis collection.
• Physical examination.
• Laboratory diagnostics, the basis of which is the determination of lupus anticoagulant, titers of antiphospholipid antibodies, anticardiolipin antibodies. Screening diagnostics are also carried out with the study of APTT, Russell test, plasma coagulation time, prothrombin time. An important place in diagnosis is occupied by the determination of homocysteine, antibodies to beta2-glycoprotein-1, and INR.
• Instrumental diagnostics consists of ultrasound Doppler study vessels, Echo-CG, radioisotope scintigraphy lungs, ECG, cardiac catheterization, coronary angiography, MRI, CT.

It is important that every woman should exclude APS during pregnancy. If you suspect it, you need to:

• Study of the blood coagulation system.
• Echo-KG.
• Examination of the vessels of the head, neck, kidneys, lower extremities, eyes.
• Ultrasound of the fetus.
• Dopplerography of uteroplacental blood flow.

To determine antiphospholipid syndrome, special criteria have been defined, thanks to the confirmation or exclusion of which the final question of diagnosis is resolved.

Clinical criteria for APS:

• Vascular thrombosis – one or more episodes of thrombosis of any vessel, localization. This condition must be recorded instrumentally or morphologically.
• Pathology during pregnancy:
  • One or more cases of intrauterine death of a normal healthy fetus after the 10th week.
  • One or more cases premature birth healthy fetus up to 34 weeks due to severe preeclampsia/eclampsia/placental insufficiency.
• Three or more cases of spontaneous miscarriage before 10 weeks in the absence of apparent causes.

Laboratory criteria for API:

• Determination in blood serum at least twice within 12 weeks of anticardiolipin antibodies IgG or IgM, beta-2 glycoprotein-1 in medium or high concentrations.
• Determination of lupus anticoagulant in two or more tests within 12 weeks.
• Prolonged plasma clotting time in phospholipid-dependent tests: aPTT, prothrombin time, Russell tests, CBC.
• Lack of correction for prolongation of clotting time in tests with donor plasma.
• Shortening or correction by adding phospholipids.

Diagnosis requires one clinical sign and one laboratory sign.

For reference. Antiphospholipid syndrome is excluded if, before 12 weeks or more than 5 years, various levels of antiphospholipid antibodies are detected without the manifestation of clinical symptoms or there are clinical manifestations, but without the presence of antiphospholipid antibodies.

And only after this it is necessary to move on to determining patient management tactics.

Treatment of APS

1. Adults and children:
   • Anticoagulants - heparin followed by transfer to warfarin while monitoring the INR.
   • Antiplatelet agents – aspirin.
   • Immunosuppressants – hydroxychloroquine.
   • Symptomatic treatment.
2. Women during pregnancy:
   • Anticoagulants.
   • Antiplatelet agents.
   • Glucocorticosteroids (if APS is combined with systemic lupus erythematosus).
   • Plasmapheresis.
   • Immunoglobulins.
   • Immunosuppressants.

Currently, new drugs are being used that are anticoagulants with a selective point of application on blood coagulation factors. Such drugs are more effective in treating and preventing thrombosis than heparins and warfarin, and are also safer.

For reference. The main goal of treatment for antiphospholipid syndrome is to prevent and prevent thrombosis and their complications.

Signs of antiphospholipid syndrome are spontaneity and unpredictability. Today, unfortunately, there are no universal treatment methods; there is no clear understanding of the etiological factors of the disease and its pathogenesis. At this stage, everything is “tentatively, presumably, maybe.”

Hope for success in treatment is instilled by the emergence of new drugs, constant research into the causes of the disease with the ability to synthesize drugs for etiological treatment antiphospholipid syndrome.

Video: Lectures on APS

Antiphospholipid syndrome (APS) is one of the most pressing multidisciplinary problems modern medicine and is considered a unique model of autoimmune thrombotic vasculopathy.

The study of APS began about a hundred years ago in the works of A. Wassermann, dedicated to laboratory method diagnosis of syphilis. When conducting screening studies, it became obvious that a positive Wassermann reaction can be detected in many people without clinical signs of syphilitic infection. This phenomenon is called the “biological false-positive Wasserman reaction.” It was soon discovered that the main antigenic component in the Wassermann reaction was a negatively charged phospholipid called cardiolipin. The introduction of radioimmunological, and then enzyme immunoassay method(IPM) determination of antibodies to cardiolipins (aCL) contributed to a deeper understanding of their role in human diseases. By modern ideas, antiphospholipid antibodies (aPL) are a heterogeneous population of autoantibodies that interact with negatively charged, less often neutral phospholipids and/or phospholipid-binding serum proteins. Depending on the method of determination, aPL are conventionally divided into three groups: detected using IFM using cardiolipin, less often other phospholipids; antibodies detected by functional tests (lupus anticoagulant); antibodies that are not diagnosed using standard methods (antibodies to protein C, S, thrombomodulin, heparan sulfate, endothelium, etc.).

A consequence of close interest in studying the role of aPL and improving methods laboratory diagnostics It was concluded that aPL are a serological marker of a unique symptom complex, including venous and/or arterial thrombosis, various forms of obstetric pathology, thrombocytopenia, as well as a wide range of neurological, skin, cardiovascular disorders. Since 1986, this symptom complex began to be designated as antiphospholipid syndrome (APS), and in 1994, at an international symposium on aPL, it was also proposed to use the term “Hughes syndrome” - after the name of the English rheumatologist who made the greatest contribution to the study of this problem.

The true prevalence of APS in the population is still unknown. Since aPL synthesis is possible under normal conditions, low level antibodies are often found in the blood of healthy people. According to various data, the frequency of detection of aCL in the population varies from 0 to 14%, on average it is 2-4%, while high titers are found quite rarely - in approximately 0.2% of donors. APL is detected somewhat more often in elderly people. Wherein clinical significance aPL in “healthy” individuals (i.e., those without obvious symptoms disease) is not entirely clear. Often, with repeated tests, the level of antibodies elevated in previous determinations normalizes.

An increase in the incidence of aPL has been noted in some inflammatory, autoimmune and infectious diseases, malignant neoplasms, against the background of reception medicines (oral contraceptives, psychotropic drugs etc.). There is evidence of an immunogenetic predisposition to increased synthesis of aPL and their more frequent detection in relatives of patients with APS.

It has been proven that aPL is not only a serological marker, but also an important “pathogenetic” mediator, developmental main clinical manifestations AFS. Antiphospholipid antibodies have the ability to influence most of the processes that form the basis of the regulation of hemostasis, the violation of which leads to hypercoagulation. The clinical significance of aPL depends on whether their presence in the blood serum is associated with the development characteristic symptoms. Thus, manifestations of APS are observed only in 30% of patients with a positive lupus anticoagulant and in 30-50% of patients with moderate or high levels of aCL. The disease develops mainly at a young age, while APS can be diagnosed in children and even newborns. Like other autoimmune rheumatic diseases, this symptom complex is more common in women than in men (5:1 ratio).

Clinical manifestations

The most common and characteristic manifestations of APS are venous and/or arterial thrombosis and obstetric pathology. With APS, vessels of any size and location can be affected - from capillaries to large venous and arterial trunks. Therefore, the range of clinical manifestations is extremely diverse and depends on the location of thrombosis. According to modern concepts, the basis of APS is a kind of vasculopathy caused by non-inflammatory and/or thrombotic damage to blood vessels and ending with their occlusion. Within the framework of APS, the pathology of the central nervous system is described, of cardio-vascular system, dysfunction of the kidneys, liver, endocrine organs, gastrointestinal tract. The development of certain forms of obstetric pathology tends to be associated with placental vascular thrombosis ( ).

Venous thrombosis, especially deep vein thrombosis of the lower extremities, is the most typical manifestation of APS, including at the onset of the disease. Thrombi are usually localized in the deep veins of the lower extremities, but can often occur in the hepatic, portal, superficial and other veins. Repeated pulmonary embolisms are typical, which can lead to the development of pulmonary hypertension. Cases of adrenal insufficiency due to thrombosis have been described. central vein adrenal glands In general, arterial thrombosis occurs approximately 2 times less frequently than venous thrombosis. They are manifested by ischemia and infarctions of the brain, coronary arteries, and peripheral circulatory disorders. Thrombosis inside cerebral arteries- the most frequent localization arterial thrombosis in APS. Rare manifestations include thrombosis of large arteries, as well as the ascending aorta (with the development of aortic arch syndrome) and abdominal aorta. A feature of APS is the high risk of recurrent thrombosis. Moreover, in patients with the first thrombosis in the arterial bed, repeated episodes also develop in the arteries. If the first thrombosis was venous, then repeated thromboses, as a rule, are observed in the venous bed.

Damage to the nervous system is one of the most severe (potentially fatal) manifestations of APS and includes transient ischemic attacks, ischemic stroke, acute ischemic encephalopathy, episyndrome, migraine, chorea, transverse myelitis, sensorineural hearing loss and other neurological and psychiatric symptoms. The leading cause of central nervous system damage is cerebral ischemia due to thrombosis of cerebral arteries, but there are a number of neurological and neuropsychiatric manifestations caused by other mechanisms. Transient ischemic attacks (TIA) are accompanied by loss of vision, paresthesia, motor weakness, dizziness, transient general amnesia and often precede a stroke by many weeks and even months. Recurrent TIA leads to multi-infarct dementia, which is manifested by cognitive impairment, decreased ability to concentrate and memory, and other symptoms nonspecific to APS. Therefore, it is often difficult to differentiate from senile dementia, metabolic (or toxic) brain damage and Alzheimer's disease. Sometimes cerebral ischemia is associated with thromboembolism, the sources of which are the valves and cavities of the heart or internal carotid artery. Overall frequency ischemic stroke higher in patients with damage to the heart valves (especially the left parts).

Headaches are traditionally considered one of the most common clinical manifestations of APS. The nature of headaches varies from classic intermittent migraines to constant, unbearable pain. There are a number of other symptoms (Guillain-Barré syndrome, idiopathic intracranial hypertension, transverse myelitis, parkinsonian hypertonicity), the development of which is also associated with the synthesis of aPL. Patients with APS often have veno-occlusive eye diseases. One of the forms of such pathology is passing loss vision (amaurosis fugax). Another manifestation, optic neuropathy is one of the most common causes of blindness in APS.

Heart damage presented wide range manifestations including myocardial infarction, damage to the valvular apparatus of the heart, chronic ischemic cardiomyopathy, intracardiac thrombosis, arterial and pulmonary hypertension. In both adults and children, thrombosis of the coronary arteries is one of the main localizations arterial occlusion with overproduction of aPL. Myocardial infarction develops in approximately 5% of aPL-positive patients, and it usually occurs in men under 50 years of age. The most common cardiac symptom of APS is damage to the heart valves. It varies from minimal abnormalities detected only by echocardiography (slight regurgitation, thickening of the valve leaflets) to heart disease (stenosis or insufficiency of the mitral, less commonly, the aortic and tricuspid valves). Despite its wide distribution, clinically significant pathology leading to heart failure and requiring surgical treatment, observed rarely (in 5% of patients). However, in some cases, very severe valve damage with vegetations caused by thrombotic deposits, indistinguishable from infective endocarditis, can quickly develop. Detection of vegetations on the valves, especially if they are combined with hemorrhages in the subungual bed and “tympanic fingers”, creates complex diagnostic problems and the need for a differential diagnosis with infective endocarditis. Within the framework of APS, the development of cardiac thrombi mimicking myxoma has been described.

Renal pathology is very diverse. Most patients experience only asymptomatic moderate proteinuria (less than 2 g per day), without renal dysfunction, but acute renal failure with severe proteinuria (up to nephrotic syndrome), active urinary sediment and arterial hypertension can develop. Renal damage is associated primarily with intraglomerular microthrombosis and is defined as “renal thrombotic microangiopathy.”

Patients with APS have clear and specific skin lesions, primarily livedo reticularis (occurring in more than 20% of patients), postthrombophlebitic ulcers, gangrene of the fingers and toes, multiple hemorrhages in the nail bed and other manifestations caused by vascular thrombosis.

In APS, there is damage to the liver (Budd-Chiari syndrome, nodular regenerative hyperplasia, portal hypertension), gastrointestinal tract (gastrointestinal bleeding, splenic infarction, thrombosis of mesenteric vessels), musculoskeletal system ( aseptic necrosis bones).

To the number characteristic manifestations APS is an obstetric pathology, the frequency of which can reach 80%. Fetal loss can occur at any stage of pregnancy, but is somewhat more common in the second and third trimester. In addition, aPL synthesis is associated with other manifestations, including late gestosis, preeclampsia and eclampsia, delayed intrauterine development fetus, premature birth. The development of thrombotic complications in newborns from mothers with APS has been described, which indicates the possibility of transplacental transfer of antibodies.

Thrombocytopenia is typical for APS. Typically, the platelet count ranges from 70 to 100 x109/l and does not require special treatment. The development of hemorrhagic complications is rare and, as a rule, is associated with a concomitant defect specific factors blood clotting, kidney pathology or overdose of anticoagulants. Coombs-positive hemolytic anemia (10%) is often observed; Evans syndrome (a combination of thrombocytopenia and hemolytic anemia) is less common.

Diagnostic criteria

The multi-organ nature of symptoms and the need for special confirmatory laboratory tests in some cases cause difficulties in diagnosing APS. In this regard, in 1999, preliminary classification criteria were proposed, according to which the diagnosis of APS is considered reliable when at least one clinical and one laboratory sign is combined.

Clinical criteria:

• Vascular thrombosis: one or more episodes of thrombosis (arterial, venous, small vessel thrombosis). Thrombosis must be confirmed using instrumental methods or morphologically (morphology - without significant inflammation of the vascular wall).
• Pregnancy pathology can have one of three options:

  One or more cases of intrauterine death of a morphologically normal fetus after 10 weeks of pregnancy;

  One or more episodes of premature birth of a morphologically normal fetus before 34 weeks of gestation due to severe preeclampsia, or eclampsia, or severe placental insufficiency;

  Three or more consecutive cases of spontaneous abortion before 10 weeks of pregnancy (with the exception of anatomical defects of the uterus, hormonal disorders, maternal and paternal chromosomal disorders).

Laboratory criteria:

• positive aCL class IgG or IgM in serum in medium and high titers, determined at least twice, with an interval of at least 6 weeks, using a standardized enzyme immunoassay;
• positive lupus anticoagulant detected in plasma at least 6 weeks apart by a standardized method.

Differential diagnosis

Differential diagnosis of APS is carried out with a wide range of diseases occurring with vascular disorders. It should be remembered that with APS there is a very large number of clinical manifestations that can imitate various diseases: infective endocarditis, heart tumors, multiple sclerosis, hepatitis, nephritis, etc. APS in some cases is combined with systemic vasculitis. It is believed that APS should be suspected in the development of thrombotic disorders (especially multiple, recurrent, with unusual localization), thrombocytopenia, obstetric pathology in young and middle-aged people in the absence of risk factors for the occurrence of these pathological conditions. It should be excluded in cases of unexplained thrombosis in newborns, in cases of skin necrosis during treatment with indirect anticoagulants and in patients with a prolonged activated partial thromboplastin time in a screening study.

APS was first described as a variant of systemic lupus erythematosus (SLE). However, it was very soon established that APS can also develop in other autoimmune rheumatic and non-rheumatic diseases (secondary APS). Moreover, it turned out that the connection between overproduction of aPL and thrombotic disorders is more universal and can be observed in the absence of reliable clinical and serological signs of other diseases. This was the basis for the introduction of the term “primary APS” (PAPS). It is believed that approximately half of patients with APS suffer from the primary form of the disease. However, whether PAPS is an independent nosological form is not completely clear. Noteworthy is the high incidence of PAPS among men (the ratio of men to women is 2:1), which distinguishes PAPS from other autoimmune rheumatic diseases. Individual clinical manifestations or their combinations occur in patients with PAPS with varying frequency, which is probably due to the heterogeneity of the syndrome itself. IN currently There are three groups of patients with PAPS:

• patients with idiopathic deep vein thrombosis of the leg, which is often complicated by thromboembolism, primarily in the pulmonary artery system, leading to the development of pulmonary hypertension;
• sick young(up to 45 years) with idiopathic strokes, transient ischemic attacks, less often occlusion of other arteries, including coronary ones; most a shining example This variant of PAPS is Sneddon syndrome;
• women with obstetric pathology (repeated spontaneous abortions);

The course of APS, the severity and prevalence of thrombotic complications in it are unpredictable and in most cases do not correlate with changes in aPL levels and disease activity (in secondary APS). In some patients, APS may present as an acute, recurrent coagulopathy, often in combination with a vasculopathy affecting many vital functions. important organs and systems. This served as the basis for identifying the so-called “ catastrophic APS"(CAFS). To define this condition, the names “acute disseminated coagulopathy-vasculopathy” or “devastating non-inflammatory vasculopathy” have been proposed, which also emphasizes the acute, fulminant nature of this variant of APS. The main triggering factor for CAPS is infection. Less commonly, its development is associated with the abolition of anticoagulants or the use of certain medications. CAPS occurs in approximately 1% of patients with APS, but despite the therapy, it ends in death in 50% of cases.

Treatment of APS

Prevention and treatment of APS are complex problem. This is due to the heterogeneity of pathogenetic mechanisms, polymorphism of clinical manifestations, as well as the lack of reliable clinical and laboratory indicators to predict the recurrence of thrombotic disorders. There are no generally accepted international standards of treatment, and proposed recommendations are based primarily on the results of open-label drug trials or retrospective analyzes of disease outcomes.

Treatment with glucocorticoids and cytotoxic drugs for APS is usually ineffective, except in situations where the advisability of their use is dictated by the activity of the underlying disease (for example, SLE).

Management of patients with APS (as well as with other thrombophilias) is based on the prescription of indirect anticoagulants (warfarin, acenocoumarol) and antiplatelet agents (primarily low doses acetylsalicylic acid- ASK). This is primarily due to the fact that APS is characterized by a high risk of repeated thrombosis, which is significantly higher than that of idiopathic venous thrombosis. It is believed that most patients with APS with thrombosis require preventive antiplatelet and/or anticoagulant therapy for a long time, and sometimes for life. In addition, the risk of primary and repeated thrombosis in APS must be reduced by influencing such correctable risk factors as hyperlipidemia (statins: simvastin - simvastol, simlo; lovastatin - rovacor, cardiostatin; pravastatin - lipostat; atorvastatin - Avas, liprimar; fibrates: bezafibrate - cholestenorm; fenofibrate - nofibal, grofibrate; ciprofibrate - lipanor), arterial hypertension ( ACE inhibitors- capoten, sinopril, diroton, moex; b-blockers - atenolol, concor, egilok, betaloc ZOK, dilatrend; calcium antagonists - amlovas, norvasc, normodipine, lacidipine), hyperhomocysteinemia, sedentary lifestyle, smoking, taking oral contraceptives, etc.

In patients with high level aPL in the serum, but without clinical signs of APS (including in pregnant women without a history of obstetric pathology) should be limited to prescribing small doses of ASA (50-100 mg/day). The most preferred drugs are aspirin cardio, thrombo ACC, which have a number of advantages (convenient dosage and the presence of a shell that is resistant to the action of gastric juice). This form makes it possible to provide not only a reliable antiplatelet effect, but also to reduce the adverse effect on the stomach.

Patients with clinical signs of APS (primarily thrombosis) require more aggressive anticoagulant therapy. Treatment with vitamin K antagonists (warfarin, phenylin, acenocoumarol) is undoubtedly a more effective, but less safe (compared to ASA) method of preventing venous and arterial thrombosis. The use of vitamin K antagonists requires careful clinical and laboratory monitoring. Firstly, this is associated with an increased risk of bleeding, and the risk of developing this complication due to its severity outweighs the benefit of preventing thrombosis. Secondly, in some patients, recurrence of thrombosis is observed after cessation of anticoagulant therapy (especially during the first 6 months after discontinuation). Third, patients with APS may experience significant spontaneous fluctuations in the international normalized ratio (INR), which significantly complicates the use of this indicator for monitoring warfarin treatment. However, all of the above should not be an obstacle to active anticoagulant therapy in those patients for whom it is vitally necessary ( ).

The warfarin treatment regimen consists of prescribing a loading dose (5-10 mg of the drug per day) for the first two days, and then selecting the optimal dosage to ensure maintenance of the target INR. It is advisable to take the entire dose in the morning, before determining the INR. In elderly individuals, lower doses of warfarin should be used to achieve the same level of anticoagulation than in younger individuals. It must be borne in mind that warfarin interacts with a number of drugs that, when administered in combination, both reduce (barbiturates, estrogens, antacids, antifungal and antituberculosis drugs) and enhance its anticoagulant effect (non-steroidal anti-inflammatory drugs, antibiotics, propranolol, ranitidine, etc. .). Certain recommendations regarding diet should be given, since foods rich in vitamin K (liver, green tea, leafy vegetables - broccoli, spinach, Brussels sprouts and cabbage, turnips, lettuce) contributes to the development of warfarin resistance. Alcohol is avoided during warfarin therapy.

If warfarin monotherapy is insufficiently effective, it is possible to combination therapy indirect anticoagulants and low doses of ASA (and/or dipyridamole). This treatment is most justified in young people without risk factors for bleeding.

In case of excessive anticoagulation (INR>4) in the absence of bleeding, it is recommended to temporarily discontinue warfarin until the INR returns to the target level. In the case of hypocoagulation, accompanied by bleeding, the administration of vitamin K alone is not enough (due to the delayed onset of action - 12-24 hours after administration); Fresh frozen plasma or (preferably) prothrombin complex concentrate is recommended.

Aminoquinoline drugs (hydroxychloroquine - Plaquenil, chloroquine - Delagil) can provide quite effective prevention thrombosis (at least with secondary APS against the background of SLE). Along with the anti-inflammatory effect, hydroxychloroquine has certain antithrombotic (suppresses platelet aggregation and adhesion, reduces thrombus size) and hypolipidemic effects.

The central place in the treatment of acute thrombotic complications in APS is occupied by direct anticoagulants - heparin and especially low-molecular-weight heparin preparations (Fraxiparin, Clexane). The tactics of their use do not differ from the generally accepted ones.

For CAPS, the entire arsenal of intensive and anti-inflammatory therapy methods used for critical conditions in patients with rheumatic diseases. The effectiveness of treatment to a certain extent depends on the ability to eliminate the factors that provoke its development (infection, activity of the underlying disease). The prescription of high doses of glucocorticoids for CAPS is not aimed at treating thrombotic disorders, but is determined by the need to treat the systemic inflammatory response syndrome (widespread necrosis, adult distress syndrome, adrenal insufficiency, etc.). Pulse therapy is usually carried out according to the standard regimen (1000 mg methylprednisolone intravenously per day for 3-5 days), followed by glucocorticoids (prednisolone, methylprednisolone) orally (1-2 mg/kg/day). Intravenous immunoglobulin is administered at a dose of 0.4 g/kg for 4-5 days (it is especially effective for thrombocytopenia).

CAPS is the only absolute indication for plasmapheresis sessions, which should be combined with maximum intensive anticoagulant therapy, the use of fresh frozen plasma and pulse therapy with glucocorticoids and cytostatics. Cyclophosphamide (Cytoxan, Endoxan) (0.5-1 g/day) is indicated for the development of CAPS against the background of exacerbation of SLE and to prevent “rebound syndrome” after plasmapheresis sessions. The use of prostacyclin (5 ng/kg/min for 7 days) is justified, however, due to the possibility of developing “rebound” thrombosis, treatment should be carried out with caution.

The administration of glucocorticoids to women with obstetric pathology is currently not indicated due to the lack of data on the benefits of this type of therapy and due to the high frequency of side effects in the mother (Cushing's syndrome, diabetes, arterial hypertension) and the fetus. The use of glucocorticoids is justified only in case of secondary APS due to SLE, since it is aimed at treating the underlying disease. The use of indirect anticoagulants during pregnancy is generally contraindicated due to their teratogenic effect.

The standard for preventing recurrent fetal losses is small doses of ASA, which are recommended to be taken before, during pregnancy and after the birth of the child (at least for 6 months). During pregnancy, it is advisable to combine small doses of ASA with low molecular weight heparin preparations. During delivery with the help caesarean section introduction low molecular weight heparins canceled 2-3 days in advance and resumed at postpartum period followed by a transition to taking indirect anticoagulants. Long-term heparin therapy in pregnant women can lead to the development of osteoporosis, therefore, to reduce bone loss, it is necessary to recommend taking calcium carbonate (1500 mg) in combination with vitamin D. It should be borne in mind that treatment with low molecular weight heparin is less likely to cause osteoporosis. One of the limitations to the use of low molecular weight heparins is the risk of developing an epidural hematoma, therefore, if there is a possibility of premature delivery, treatment with low molecular weight heparins is discontinued no later than 36 weeks of pregnancy. The use of intravenous immunoglobulin (0.4 g/kg for 5 days every month) has no advantage over standard treatment ASA and heparin, and is indicated only when standard therapy is ineffective.

Moderate thrombocytopenia in patients with APS does not require special treatment. In secondary APS, thrombocytopenia is well controlled by glucocorticoids, aminoquinoline drugs and, in some cases, low doses of ASA. Treatment tactics for resistant thrombocytopenia, which poses a risk of bleeding, include the use of glucocorticoids in high doses and intravenous immunoglobulin. If high doses of glucocorticoids are ineffective, splenectomy is the treatment of choice.

In recent years, new antithrombotic agents have been intensively developed, which include heparinoids (heparoid lecheva, emeran, sulodexide - Wessel Due), platelet receptor inhibitors (ticlopidine, tagren, ticlopidine-ratiopharm, clopidogrel, Plavix) and other drugs. Preliminary clinical data indicate the undoubted promise of these drugs.

All patients with APS should be under long-term clinical observation, the primary task of which is to assess the risk of recurrent thrombosis and their prevention. It is necessary to monitor the activity of the underlying disease (with secondary APS), timely detection and treatment of concomitant pathologies, including infectious complications, as well as impact on correctable risk factors for thrombosis. It has been established that unfavorable prognostic factors for mortality in APS are arterial thrombosis, a high incidence of thrombotic complications and thrombocytopenia, and laboratory markers include the presence of a lupus anticoagulant. The course of APS, the severity and prevalence of thrombotic complications are unpredictable; Unfortunately, there are no universal treatment regimens. The above-mentioned facts, as well as the multiorgan nature of the symptoms, require the unification of doctors of various specialties to solve problems associated with the management of this category of patients.

N. G. Klyukvina, candidate medical sciences, assistant professor
MMA im. I. M. Sechenova, Moscow

In some diseases, systemic lupus erythematosus [in 70% of cases], systemic scleroderma, rheumatoid arthritis, malignant tumors, chronic infections, etc.) antibodies are produced that can attack phospholipids - components of cell membranes. By attaching to the walls of blood vessels, platelets, and directly participating in blood coagulation reactions, such antibodies to phospholipids lead to the development of thrombosis.

In addition, some scientists believe that a direct “toxic” effect of this group of antibodies on body tissue is possible. The complex of symptoms that appears in this case is called antiphospholipid syndrome (APS), and in 1994 at the international symposium on antibodies to phospholipids it was proposed to call APS Hughes syndrome(Hughes) - named after the English rheumatologist who first described it and made the greatest contribution to the study of this problem.

There are a great variety of antibodies to phospholipids: antibodies to cardiolipin, lupus anticoagulant, b2-glycoprotein-1-cofactor-dependent antibodies, antibodies to blood coagulation factors, antibodies to substances, on the contrary, that interfere with this process, and many, many others. In practice, the first two are usually most often determined - antibodies to cardiolipin, lupus anticoagulant.

How does it manifest?

The clinical picture of antiphospholipid syndrome can be very different and will depend on:

• size of affected vessels (small, medium, large);
• the rate of blockage of the vessel (slow closure of its lumen by a thrombus that has grown in it, or fast closure by a detached thrombus that “migrated” into this vessel from another);
• their functional purpose(arteries or veins);
• locations (brain, lungs, heart, skin, kidneys, liver).

If small vessels thrombose, this leads to relatively mild disorders organ functions. Thus, when small branches of the coronary arteries in the heart are blocked, the ability of individual parts of the heart muscle to contract is impaired, while closing the lumen of the main trunk of the coronary artery will cause the development of myocardial infarction.

With thrombosis, symptoms often appear unnoticed, gradually; dysfunction of the organ increases gradually, simulating some chronic disease (cirrhosis of the liver, Alzheimer's disease). Blockage of a vessel by a detached thrombus, on the contrary, will lead to the development of “catastrophic disorders” of the organ’s functions. Thus, pulmonary embolism is manifested by attacks of suffocation, chest pain, coughing, and in most cases it leads to death.

Antiphospholipid syndrome may mimic the most various diseases, but some symptoms deserve special attention.

Quite often, with antiphospholipid syndrome, livedo reticularis (a lacy, thin network of blood vessels on the surface of the skin, which becomes better visible in the cold), chronic leg ulcers, difficult to treat, and peripheral gangrene (death of the skin or even individual fingers or toes) occur.

In men, more often than in women, a manifestation of antiphospholipid syndrome can be myocardial infarction.

In women, these are more often cerebrovascular accidents (stroke, especially before 40 years of age, migraine-like headaches).

Damage to the liver vessels can lead to an increase in its size, ascites (accumulation of fluid in the abdominal cavity), an increase in the concentration of liver enzymes (aspartate and alanine aminotransferases) in the blood. If the kidney vessels are affected, arterial hypertension develops (in this regard, require special attention people whose pressure, especially lower, high, often changes during the day).

Thrombosis of the placental arteries may result in intrauterine fetal death or premature birth. It is with antiphospholipid syndrome that women with systemic lupus erythematosus cannot “save” their pregnancy, which often ends in miscarriage.

How to suspect?

The presence of antiphospholipid syndrome can be suspected in the following cases:

• If a person suffers from systemic lupus erythematosus (the incidence of antiphospholipid syndrome in this disease is extremely high).
• If a person under the age of 40 shows signs of thrombosis of any vessels.
• If blood vessels are thrombosed, for which this is not very typical, for example, vessels supplying blood to the intestines. Their blockage leads to “abdominal toad.” This colorful name for this disease arose by analogy with angina pectoris - “angina pectoris”. “Gentic toad” is characterized by the appearance of pressing, squeezing pain in the abdomen that occurs after generous intake food. The more a person eats, the more blood the digestive tract needs to digest the food. If the lumen of the vessels is narrowed by a blood clot, then insufficient blood flows to the abdominal organs, they lack oxygen, metabolic products accumulate in them - pain appears.
• If the number of platelets in the blood is reduced and there is no hematological disease.
• If a woman has had 2 or more miscarriages, and gynecologists cannot accurately determine their cause.
• If myocardial infarction occurs in a person under 40 years of age.

Treatment

First of all, antiphospholipid syndrome is treated only under the supervision of a rheumatologist.

If antiphospholipid syndrome has developed against the background of an autoimmune disease (for example, systemic lupus erythematosus), this disease should be treated, trying to reduce its activity. If this can be achieved, the amount of antibodies to phospholipids in the blood serum will decrease. The lower their content in the blood, the lower the likelihood of thrombosis. Therefore, it is so important for the patient to take the basic therapy prescribed by the doctor (glucocorticoids, cytostatics).

If the titer (quantity, concentration) of antibodies is very high, the question of plasmapheresis (blood purification) may arise.

Perhaps the doctor will prescribe some medications that will reduce the likelihood of thrombosis by acting directly on the blood coagulation system. For their purpose you need strict indications: the benefit should significantly exceed side effects. Contraindications to taking these drugs are pregnancy (they can cause disruption of the development of the nervous system in the fetus) and peptic ulcers of the gastrointestinal tract. You should weigh the pros and cons if the patient has liver or kidney damage.

Antimalarial drugs (for example, hydroxychloroquine) combine an anti-inflammatory effect with the ability to inhibit platelet aggregation, which also helps prevent the development of thrombosis.

Women with antiphospholipid syndrome should delay pregnancy until laboratory parameters normalize. If the syndrome develops after conception, then you should consider administering immunoglobulin or small doses of heparin.

The prognosis will largely depend on the timeliness of the treatment started and the discipline of the patient.

Antiphospholipid syndrome (APS) is one of the most pressing multidisciplinary problems of modern medicine and is considered as a unique model of autoimmune thrombotic vasculopathy. The study of APS began about a hundred years ago in the works of A. Wassermann,

Antiphospholipid syndrome (APS) is one of the most pressing multidisciplinary problems of modern medicine and is considered as a unique model of autoimmune thrombotic vasculopathy.

The study of APS began about a hundred years ago in the works of A. Wassermann, devoted to the laboratory method for diagnosing syphilis. When conducting screening studies, it became obvious that a positive Wasserman reaction can be detected in many people without clinical signs of syphilitic infection. This phenomenon is called the “biological false-positive Wasserman reaction.” It was soon established that the main antigenic component in the Wassermann reaction is a negatively charged phospholipid, called cardiolipin. The introduction of radioimmunological and then enzyme-linked immunosorbent method (ELI) for the determination of antibodies to cardiolipins (aCL) contributed to a deeper understanding of their role in human diseases. According to modern concepts, antiphospholipid antibodies (aPL) are a heterogeneous population of autoantibodies that interact with negatively charged, less often neutral phospholipids and/or phospholipid-binding serum proteins. Depending on the method of determination, aPL are conventionally divided into three groups: those detected using IPM using cardiolipin, less often other phospholipids; antibodies detected using functional tests (lupus anticoagulant); antibodies that are not diagnosed using standard methods (antibodies to protein C, S, thrombomodulin, heparan sulfate, endothelium, etc.).

As a result of close interest in studying the role of aPL and improving laboratory diagnostic methods, the conclusion was that aPL are a serological marker of a unique symptom complex, including venous and/or arterial thrombosis, various forms of obstetric pathology, thrombocytopenia, as well as a wide range of neurological, skin, and cardiovascular disorders. Since 1986, this symptom complex began to be designated as antiphospholipid syndrome (APS), and in 1994, at an international symposium on aPL, it was also proposed to use the term “Hughes syndrome” - after the English rheumatologist who made the greatest contribution to the study of this problem.

The true prevalence of APS in the population is still unknown. Since aPL synthesis is possible and normal, low levels of antibodies are often found in the blood of healthy people. According to various data, the frequency of detection of aCL in the population varies from 0 to 14%, on average it is 2–4%, while high titers are found quite rarely - in approximately 0.2% of donors. APL is detected somewhat more often in elderly people. However, the clinical significance of aPL in “healthy” individuals (i.e., those without obvious symptoms of the disease) is not entirely clear. Often, with repeated tests, the level of antibodies that were elevated in previous determinations normalizes.

An increase in the incidence of aPL has been noted in some inflammatory, autoimmune and infectious diseases, malignant neoplasms, while taking medications (oral contraceptives, psychotropic drugs, etc.). There is evidence of an immunogenetic predisposition to increased synthesis of aPL and their more frequent detection in relatives of patients with APS.

It has been proven that aPL is not only a serological marker, but also an important “pathogenetic” mediator that causes the development of the main clinical manifestations of APS. Antiphospholipid antibodies have the ability to influence most of the processes that form the basis of the regulation of hemostasis, the violation of which leads to hypercoagulation. The clinical significance of aPL depends on whether their presence in the blood serum is associated with the development of characteristic symptoms. Thus, manifestations of APS are observed only in 30% of patients with a positive lupus anticoagulant and in 30–50% of patients with moderate or high levels of aCL. The disease develops mainly at a young age, while APS can be diagnosed in children and even newborns. Like other autoimmune rheumatic diseases, this symptom complex is more common in women than in men (5:1 ratio).

Clinical manifestations

The most common and characteristic manifestations of APS are venous and/or arterial thrombosis and obstetric pathology. With APS, vessels of any size and location can be affected - from capillaries to large venous and arterial trunks. Therefore, the range of clinical manifestations is extremely diverse and depends on the localization of thrombosis. According to modern concepts, the basis of APS is a kind of vasculopathy caused by non-inflammatory and/or thrombotic damage to blood vessels and ending with their occlusion. Within the framework of APS, the pathology of the central nervous system, cardiovascular system, dysfunction of the kidneys, liver, endocrine organs, and gastrointestinal tract are described. The development of certain forms of obstetric pathology tends to be associated with thrombosis of placental vessels ( ).

Venous thrombosis, especially deep vein thrombosis of the lower extremities, is the most typical manifestation of APS, including at the onset of the disease. Thrombi are usually localized in the deep veins of the lower extremities, but can often occur in the hepatic, portal, superficial and other veins. Repeated pulmonary embolisms are typical, which can lead to the development of pulmonary hypertension. Cases of the development of adrenal insufficiency due to thrombosis of the central vein of the adrenal glands have been described. In general, arterial thrombosis occurs approximately 2 times less frequently than venous thrombosis. They are manifested by ischemia and infarctions of the brain, coronary arteries, and peripheral circulatory disorders. Thrombosis of the intracerebral arteries is the most common location of arterial thrombosis in APS. Rare manifestations include thrombosis of large arteries, as well as the ascending aorta (with the development of arcaortic syndrome) and the abdominal aorta. A feature of APS is the high risk of recurrent thrombosis. Moreover, in patients with the first thrombosis in the arterial bed, repeated episodes also develop in the arteries. If the first thrombosis was venous, then repeated thromboses, as a rule, are observed in the venous bed.

Damage to the nervous system is one of the most severe (potentially fatal) manifestations of APS and includes transient ischemic attacks, ischemic stroke, acute ischemic encephalopathy, episyndrome, migraine, chorea, transverse myelitis, sensorineural hearing loss and other neurological and psychiatric symptoms. The leading cause of central nervous system damage is cerebral ischemia due to thrombosis of the cerebral arteries, but there are a number of neurological and neuropsychiatric manifestations caused by other mechanisms. Transient ischemic attacks (TIA) are accompanied by loss of vision, paresthesia, motor weakness, dizziness, transient general amnesia and often precede a stroke by many weeks or even months. Recurrent TIA leads to multi-infarct dementia, which is manifested by cognitive impairment, decreased ability to concentrate and memory, and other symptoms nonspecific to APS. Therefore, it is often difficult to differentiate from senile dementia, metabolic (or toxic) brain damage and Alzheimer's disease. Sometimes cerebral ischemia is associated with thromboembolism, the sources of which are the valves and cavities of the heart or the internal carotid artery. In general, the incidence of ischemic stroke is higher in patients with damage to the heart valves (especially the left side).

Headaches are traditionally considered one of the most common clinical manifestations of APS. The nature of headaches varies from classic intermittent migraine to constant, unbearable pain. There are a number of other symptoms (Guillain–Barré syndrome, idiopathic intracranial hypertension, transverse myelitis, parkinsonian hypertonicity), the development of which is also associated with the synthesis of aPL. Patients with APS often experience veno-occlusive eye diseases. One of the forms of such pathology is transient loss of vision (amaurosis fugax). Another manifestation - optic neuropathy is one of the most common causes of blindness in APS.

Heart damage is represented by a wide range of manifestations, including myocardial infarction, damage to the valvular apparatus of the heart, chronic ischemic cardiomyopathy, intracardiac thrombosis, arterial and pulmonary hypertension. In both adults and children, coronary artery thrombosis is one of the main localizations of arterial occlusion due to overproduction of aPL. Myocardial infarction occurs in approximately 5% of aPL-positive patients, and it usually occurs in men under 50 years of age. The most common cardiac symptom of APS is damage to the heart valves. It ranges from minimal disturbances detected only by echocardiography (slight regurgitation, thickening of the valve leaflets) to heart disease (stenosis or insufficiency of the mitral, less often aortic and tricuspid valves). Despite its widespread occurrence, clinically significant pathology leading to heart failure and requiring surgical treatment is rarely observed (in 5% of patients). However, in some cases, very severe damage to the valves with vegetations caused by thrombotic layers, indistinguishable from infective endocarditis, can quickly develop. Detection of vegetations on the valves, especially if they are combined with hemorrhages in the subungual bed and “tympanic fingers”, creates complex diagnostic problems and the need for a differential diagnosis with infective endocarditis . Within the framework of AFS, the development of cardiac blood clots simulating myxoma has been described.

Renal pathology is very diverse. Most patients have only asymptomatic moderate proteinuria (less than 2 g per day), without renal dysfunction, but acute renal failure may develop with severe proteinuria (up to nephrotic syndrome), active urinary sediment and arterial hypertension. Kidney damage is associated mainly with intraglomerular microthrombosis and is defined as "renal thrombotic microangiopathy".

Patients with APS have clear and specific skin lesions, primarily livedo reticularis (occurring in more than 20% of patients), postthrombophlebitic ulcers, gangrene of the fingers and toes, multiple hemorrhages in the nail bed and other manifestations caused by vascular thrombosis.

In APS, there is damage to the liver (Budd-Chiari syndrome, nodular regenerative hyperplasia, portal hypertension), the gastrointestinal tract (gastrointestinal bleeding, splenic infarction, thrombosis of mesenteric vessels), and the musculoskeletal system (aseptic bone necrosis).

Characteristic manifestations of APS include obstetric pathology, the frequency of which can reach 80%. Fetal loss can occur at any time during pregnancy, but is somewhat more common in the second and third trimesters. In addition, the synthesis of aPL is associated with other manifestations, including late gestosis, preeclampsia and eclampsia, intrauterine growth retardation, and premature birth. The development of thrombotic complications in newborns of mothers with APS has been described, which indicates the possibility of transplacental transfer of antibodies.

Thrombocytopenia is typical for APS. Typically, the platelet count ranges from 70 to 100 x109/l and does not require special treatment. The development of hemorrhagic complications is rare and, as a rule, is associated with a concomitant defect in specific blood coagulation factors, kidney pathology, or an overdose of anticoagulants. Coombs-positive hemolytic anemia is often observed (10%), Evans syndrome (a combination of thrombocytopenia and hemolytic anemia) is less common.

Diagnostic criteria

The multi-organ nature of symptoms and the need for special confirmatory laboratory tests in some cases make it difficult to diagnose APS. In this regard, in 1999, preliminary classification criteria were proposed, according to which the diagnosis of APS is considered reliable when at least one clinical and one laboratory sign is combined.

Clinical criteria:

• Vascular thrombosis: one or more episodes of thrombosis (arterial, venous, small vessel thrombosis). Thrombosis must be confirmed using instrumental methods or morphologically (morphology - without significant inflammation of the vascular wall).
• Pregnancy pathology can have one of three options:

  – one or more cases of intrauterine death of a morphologically normal fetus after 10 weeks of pregnancy;

  – one or more episodes of premature birth of a morphologically normal fetus before 34 weeks of pregnancy due to severe preeclampsia, or eclampsia, or severe placental insufficiency;

  – three or more consecutive cases of spontaneous abortions before 10 weeks of pregnancy (with the exception of anatomical defects of the uterus, hormonal disorders, maternal and paternal chromosomal disorders).

Laboratory criteria:

• positive aCL class IgG or IgM in serum in medium and high titers, determined at least twice, with an interval of at least 6 weeks, using a standardized enzyme immunoassay;
• a positive lupus anticoagulant detected in plasma at least at an interval of at least 6 weeks using a standardized method.

Differential diagnosis

Differential diagnosis of APS is carried out with a wide range of diseases occurring with vascular disorders. It should be remembered that with APS there is a very large number of clinical manifestations that can imitate various diseases: infective endocarditis, heart tumors, multiple sclerosis, hepatitis, nephritis, etc. APS in some cases is combined with systemic vasculitis. It is believed that APS should be suspected when the development of thrombotic disorders (especially multiple, recurrent, with unusual localization), thrombocytopenia, obstetric pathology in young and middle-aged people in the absence of risk factors for the occurrence of these pathological conditions. It should be excluded in cases of unexplained thrombosis in newborns, in cases of skin necrosis during treatment with indirect anticoagulants, and in patients with a prolonged activated partial thromboplastin time in a screening study.

APS was first described as a variant of systemic lupus erythematosus (SLE). However, it was soon discovered that APS can also develop in other autoimmune rheumatic and non-rheumatic diseases (secondary APS). Moreover, it turned out that the connection between overproduction of aPL and thrombotic disorders is more universal and can be observed in the absence of reliable clinical and serological signs of other diseases. This served as the basis for the introduction of the term “primary APS” (PAPS). It is believed that approximately half of patients with APS suffer from the primary form of the disease. However, whether PAPS is an independent nosological form is not completely clear. Noteworthy is the high incidence of PAPS among men (the ratio of men to women is 2:1), which distinguishes PAPS from other autoimmune rheumatic diseases. Individual clinical manifestations or their combinations occur in patients with PAPS with varying frequencies, which is probably due to the heterogeneity of the syndrome itself. Currently, three groups of patients with PAPS are conventionally distinguished:

• patients with idiopathic deep vein thrombosis of the leg, which is often complicated by thromboembolism, primarily in the pulmonary artery system, leading to the development of pulmonary hypertension;
• young patients (up to 45 years) with idiopathic strokes, transient ischemic attacks, less often occlusion of other arteries, including coronary ones; the most striking example of this variant of PAF is Sneddon syndrome;
• women with obstetric pathology (repeated spontaneous abortions);

The course of APS, the severity and prevalence of thrombotic complications are unpredictable and in most cases do not correlate with changes in aPL levels and disease activity (in secondary APS). In some patients, APS may manifest as acute, recurrent coagulopathy, often in combination with vasculopathy, affecting many vital organs and systems. This served as the basis for identifying the so-called “catastrophic APS” (CAPS). To define this condition, the names “acute disseminated coagulopathy–vasculopathy” or “devastating non-inflammatory vasculopathy” have been proposed, which also emphasizes the acute, fulminant nature of this variant of APS. The main triggering factor for CAPS is infection. Less commonly, its development is associated with the abolition of anticoagulants or the use of certain medications. CAPS occurs in approximately 1% of patients with APS, but despite therapy, in 50% of cases it ends in death.

Treatment of APS

Prevention and treatment of APS are challenging. This is due to the heterogeneity of pathogenetic mechanisms, polymorphism of clinical manifestations, as well as the lack of reliable clinical and laboratory indicators to predict the recurrence of thrombotic disorders. There are no generally accepted international standards of treatment, and proposed recommendations are based mainly on the results of open-label drug trials or retrospective analyzes of disease outcomes.

Treatment with glucocorticoids and cytotoxic drugs for APS is usually ineffective, except in situations where the advisability of their use is dictated by the activity of the underlying disease (for example, SLE).

Management of patients with APS (as with other thrombophilias) is based on the prescription of indirect anticoagulants (warfarin, acenocoumarol) and antiplatelet agents (primarily low-dose acetylsalicylic acid - ASA). This is primarily due to the fact that APS is characterized by a high risk of repeated thrombosis, which significantly exceeds that of idiopathic venous thrombosis. It is believed that most patients with APS with thrombosis require prophylactic antiplatelet and/or anticoagulant therapy for a long time, and sometimes for life. In addition, the risk of primary and recurrent thrombosis in APS must be reduced by influencing such correctable risk factors as hyperlipidemia (statins: simvastin - simvastol, simlo; lovastatin - rovacor, cardiostatin; pravastatin - lipostat; atorvastatin - Avas, liprimar; fibrates: bezafibrate - cholestenorm ; fenofibrate - nofibal, grofibrate; ciprofibrate - lipanor), arterial hypertension (ACE inhibitors - capoten, sinopril, diroton, moex; b-blockers - atenolol, concor, egilok, betaloc ZOK, dilatrend; calcium antagonists - amlovas, norvasc, normodipine, lacidipine), hyperhomocysteinemia, sedentary lifestyle, smoking, oral contraceptives, etc.

In patients with high levels of aPL in the serum, but without clinical signs of APS (including pregnant women without obstetric pathology and medical history), one should limit oneself to the administration of small doses of ASA (50–100 mg/day). The most preferred drugs are aspirin cardio, thrombo ACC, which have a number of advantages (convenient dosage and the presence of a shell that is resistant to the action of gastric juice). This form makes it possible to provide not only a reliable antiplatelet effect, but also to reduce the adverse effect on the stomach.

Patients with clinical signs of APS (primarily thromboses) require more aggressive anticoagulant therapy. Treatment with vitamin K antagonists (warfarin, phenylin, acenocoumarol) is undoubtedly a more effective, but less safe (compared to ASA) method of preventing venous and arterial thrombosis. The use of vitamin K antagonists requires careful clinical and laboratory monitoring. Firstly, this is associated with an increased risk of bleeding, and the risk of developing this complication due to its severity outweighs the benefit of preventing thrombosis. Secondly, in some patients, recurrence of thrombosis is observed after cessation of anticoagulant therapy (especially during the first 6 months after discontinuation). Thirdly, patients with APS may experience pronounced spontaneous fluctuations in the international normalized ratio (INR), which significantly complicates the use of this indicator for monitoring warfarin treatment. However, all of the above should not be an obstacle to active anticoagulant therapy in those patients for whom it is vitally necessary ( ).

The warfarin treatment regimen consists of prescribing a loading dose (5–10 mg of the drug per day) for the first two days, and then selecting the optimal dosage to ensure maintenance of the target INR. It is advisable to take every dose in the morning, before determining the INR. In older people, lower doses of warfarin should be used to achieve the same level of anticoagulation than in younger people. It is necessary to keep in mind that warfarin interacts with a number of medications, which, when administered in combination, both reduce (barbiturates, estrogens, antacids, antifungal and antituberculosis drugs) and enhance its anticoagulant effect (non-steroidal anti-inflammatory drugs, antibiotics, propranolol, ranitidine, etc.). Certain dietary recommendations should be given, since foods rich in vitamin K (liver, green tea, leafy vegetables - broccoli, spinach, Brussels sprouts, cabbage, turnips, lettuce) contribute to the development of warfarin resistance. Alcohol is avoided during warfarin therapy.

If warfarin monotherapy is insufficiently effective, combination therapy with indirect anticoagulants and low-dose ASA (and/or dipyridamole) is possible. This treatment is most justified in young people without risk factors for bleeding.

In case of excessive anticoagulation (INR>4) in the absence of bleeding, it is recommended to temporarily discontinue warfarin until the INR returns to the target level. In the case of hypocoagulation accompanied by bleeding, it is not enough to prescribe vitamin K alone (due to the delayed onset of action - 12–24 hours after administration); fresh frozen plasma or (preferably) prothrombin complex concentrate is recommended.

Aminoquinoline drugs (hydroxychloroquine - Plaquenil, chloroquine - Delagil) can provide quite effective prevention of thrombosis (at least in secondary APS against the background of SLE). Along with the anti-inflammatory effect, hydroxychloroquine has certain antithrombotic (suppresses platelet aggregation and adhesion, reduces thrombus size) and lipid-lowering effects.

A central place in the treatment of acute thrombotic complications in APS is occupied by direct anticoagulants - heparin and especially low-molecular-weight heparin preparations (Fraxiparin, Clexane). The tactics of their use do not differ from the generally accepted ones.

In CAPS, the entire arsenal of intensive and anti-inflammatory therapy methods used in critical conditions of patients with rheumatic diseases is used. The effectiveness of treatment to a certain extent depends on the ability to eliminate the factors that provoke its development (infection, activity of the underlying disease). The prescription of high doses of glucocorticoids for CAPS is not aimed at treating thrombotic disorders, but is determined by the need for treatment of systemic inflammatory response syndrome (widespread necrosis, adult distress syndrome, adrenal insufficiency, etc.). Pulse therapy is usually carried out according to a standard regimen (1000 mg methylprednisolone intravenously per day for 3–5 days), followed by glucocorticoids (prednisolone, methylprednisolone) orally (1–2 mg/kg/day). Intravenous immunoglobulin is administered at a dose of 0.4 g/kg for 4–5 days (it is especially effective for thrombocytopenia).

CAPS is the only absolute indication for plasmapheresis sessions, which should be combined with maximum intensive anticoagulant therapy, the use of fresh frozen plasma and pulse therapy with glucocorticoids and cytostatics. Cyclophosphamide (Cytoxan, Endoxan) (0.5–1 g/day) is indicated for the development of CAPS against the background of exacerbation SLE and to prevent “rebound syndrome” after plasmapheresis sessions. The use of prostacyclin (5 ng/kg/min for 7 days) is justified, however, due to the possibility of “rebound” thrombosis, treatment should be carried out with caution.

The administration of glucocorticoids to women with obstetric pathology is currently not indicated, due to the lack of data on the advantages of this type of therapy and due to the high frequency of side effects in the mother (Cushing's syndrome, diabetes, arterial hypertension) and fetus. The use of glucocorticoids is justified only in case of secondary APS against the background of SLE, since it is aimed at treating the underlying disease. The use of indirect anticoagulants during pregnancy is in principle contraindicated due to their teratogenic effect.

The standard for preventing recurrent fetal losses is small doses of ASA, which are recommended to be taken before, during pregnancy and after the birth of the child (at least for 6 months). During pregnancy, it is advisable to combine small doses of ASA with low molecular weight heparin preparations. During delivery by cesarean section, the administration of low molecular weight heparins is canceled for 2–3 days and resumed in the postpartum period, followed by a transition to indirect anticoagulants. Long-term heparin therapy in pregnant women can lead to the development of osteoporosis, therefore, to reduce bone loss, it is necessary to recommend taking calcium carbonate (1500 mg) in combination with vitamin D. It should be borne in mind that treatment with low molecular weight heparin is less likely to cause osteoporosis. One of the limitations to the use of low molecular weight heparins is the risk of developing an epidural hematoma, therefore, if there is a possibility of premature delivery, treatment with low molecular weight heparins is discontinued no later than 36 weeks of pregnancy. The use of intravenous immunoglobulin (0.4 g/kg for 5 days every month) has no advantages over standard treatment with ASA and heparin, and is indicated only if standard therapy is ineffective.

Moderate thrombocytopenia in patients with APS does not require special treatment. In secondary APS, thrombocytopenia is well controlled by glucocorticoids, aminoquinoline drugs and, in some cases, low doses of ASA. Treatment tactics for resistant thrombocytopenia, which poses a risk of bleeding, include the use of glucocorticoids in high doses and intravenous immunoglobulin. If high doses of glucocorticoids are ineffective, splenectomy is the treatment of choice.

In recent years, new antithrombotic agents have been intensively developed, which include heparinoids (heparoid lecheva, emeran, sulodexide - Wessel Due), platelet receptor inhibitors (ticlopidine, tagren, ticlopidine-ratiopharm, clopidogrel, Plavix) and other drugs. Preliminary clinical data indicate the undoubted promise of these drugs.

All patients with APS should be under long-term clinical observation, the primary task of which is to assess the risk of recurrent thrombosis and their prevention. It is necessary to control the activity of the underlying disease (in case of secondary APS), timely detection and treatment of concomitant pathologies, including infectious complications, as well as an impact on correctable risk factors for thrombosis. It has been established that prognostically unfavorable factors with regard to mortality in APS are arterial thrombosis, a high frequency of thrombotic complications and thrombocytopenia, and among laboratory markers - the presence of lupus anticoagulant. The course of APS, the severity and prevalence of thrombotic complications are unpredictable; unfortunately, there are no universal treatment regimens. The above-mentioned facts, as well as the multiorgan nature of symptoms, require the unification of doctors of various specialties to solve problems associated with the management of this category of patients.

N. G. Klyukvina, Candidate of Medical Sciences, Associate Professor
MMA im. I. M. Sechenova, Moscow

Autoimmune diseases are difficult to treat successfully because immune cells fight against certain vital structures of the body. Common health problems include phospholipid syndrome, where the immune system perceives the structural component of bone as foreign body, trying to destroy.

What is antiphospholipid syndrome

Any treatment must begin with diagnosis. Antiphospholipid syndrome is an autoimmune pathology with persistent resistance of the immune system to phospholipids. Because these are indispensable structures for the formation and strengthening skeletal system, wrong actions immunity can negatively affect the health and functioning of the entire body. If antiphospholipid antibodies are observed in the blood, the disease does not occur alone; it is accompanied by venous thrombosis, myocardial infarction, stroke, and chronic miscarriage.

This disease may predominate in the primary form, i.e. develops independently, as a single ailment of the body. Antiphospholipid syndrome also has a secondary form (VAPS), i.e. becomes a complication of another chronic disease of the body. Alternatively, it could be Budd-Chiari syndrome (hepatic vein thrombosis), superior vena cava syndrome and other pathogenic factors.

Antiphospholipid syndrome in men

Extensive medical practice describes cases of illness among representatives of the stronger sex, although these are much less common. Antiphospholipid syndrome in men is represented by blockage of the lumen of the veins, as a result of which systemic blood flow in individual internal organs and systems is disrupted. Insufficient blood supply can lead to such serious problems with health, like:

• pulmonary embolism;
• pulmonary hypertension;
• episodes of pulmonary embolism;
• thrombosis of the central vein of the adrenal glands;
• gradual death of lung, liver tissue, liver parenchyma;
• Arterial thrombosis and disorders of the central nervous system cannot be excluded.

Antiphospholipid syndrome in women

The disease entails catastrophic consequences, so doctors insist on immediate diagnosis and effective treatment. In most clinical pictures, the patients are representatives of the weaker sex, and not always pregnant. Antiphospholipid syndrome in women is the cause of diagnosed infertility, and the results of an examination for APS show that a huge number of blood clots are concentrated in the blood. The international code ICD 10 includes the specified diagnosis, which often progresses during pregnancy.

Antiphospholipid syndrome in pregnant women

During pregnancy, the danger lies in the fact that during the formation of blood vessels in the placenta, thrombosis develops and rapidly progresses, which disrupts the blood supply to the fetus. The blood is not sufficiently enriched with oxygen, and the embryo suffers from oxygen starvation and does not receive nutrients valuable for intrauterine development. The disease can be identified through routine screening.

If antiphospholipid syndrome develops in pregnant women, this is fraught with premature and pathological birth, early miscarriage, feto-placental insufficiency, late gestosis, placental abruption, congenital diseases newborns. APS during pregnancy is a dangerous pathology at any time. obstetric period, which may result in diagnosed infertility.

Causes of antiphospholipid syndrome

It is difficult to determine the etiology of the pathological process, and modern scientists are still at a loss. It has been established that Sneddon syndrome (also called antiphospholipid syndrome) may have a genetic predisposition in the presence of the DR7, DRw53, HLA DR4 loci. In addition, it is possible that the disease will develop against the background infectious processes body. Other causes of antiphospholipid syndrome are detailed below:

• autoimmune diseases;
• long-term use of medications;
• oncological diseases;
• pathological pregnancy;
• pathologies of the cardiovascular system.

Symptoms of antiphospholipid syndrome

The disease can be determined by a blood test, but a number of additional tests still need to be carried out. laboratory research for antigen detection. Normal in biological fluid it should not exist, and its appearance only indicates that in the body goes fight against own phospholipids. The main symptoms of antiphospholipid syndrome are detailed below:

• diagnosis of APS by vascular pattern on sensitive skin;
• convulsive syndrome;
• severe migraine attacks;
• deep vein thrombosis;
• mental disorders;
• thrombosis of the lower extremities;
• decreased visual acuity;
• superficial vein thrombosis;
• adrenal insufficiency;
• retinal vein thrombosis;
• ischemic optic neuropathy;
• thrombosis portal vein liver;
• sensorineural hearing loss;
• acute coagulopathy;
• recurrent hyperkinesis;
• dementia syndrome;
• transverse myelitis;
• thrombosis of cerebral arteries.

Diagnosis of antiphospholipid syndrome

To determine the pathogenesis of the disease, it is necessary to undergo an examination for APS, which requires a blood test for serological markers - lupus anticoagulant and Ab antibodies to cardiolipin. Diagnosis of antiphospholipid syndrome, in addition to testing, includes an anticardiolipin test, aPL, coagulogram, Dopplerometry, CTG. The diagnosis is based on blood counts. To increase the reliability of the results, on the recommendation of the attending physician, an integrated approach to the problem is indicated. So, pay attention to the following symptom complex:

• lupus anticoagulant increases the number of thromboses, while it itself was first diagnosed with systemic lupus erythematosus;
• Antibodies to cardiolipin resist natural phospholipids and contribute to their rapid destruction;
• antibodies in contact with cardiolipin, cholesterol, phosphatidylcholine are determined by the false-positive Wasserman reaction;
• beta2-glycoprotein-1-cofactor-dependent antiphospholipid antibodies become main reason symptoms of thrombosis;
• antibodies to beta-2-glycoprotein, limiting the patient’s chances of successfully becoming pregnant.
• APL-negative subtype without detection of antibodies to phospholipids.

Treatment of antiphospholipid syndrome

If AFLS or VAFS is diagnosed, and the signs of the disease are clearly expressed without additional clinical examinations, this means that treatment must be started in a timely manner. The approach to the problem is complex, includes taking several medications pharmacological groups. The main goal is to normalize systemic circulation, prevent the formation of blood clots with subsequent stagnation body. So, the main treatment for antiphospholipid syndrome is presented below:

1. Glucocorticoids in small doses to prevent increased blood clotting. It is advisable to choose medications Prednisolone, Dexamethasone, Metypred.
2. Immunoglobulin for the correction of immunity weakened by long-term drug therapy.
3. Antiplatelet agents are necessary to prevent blood clotting. Medicines such as Curantil and Trental are especially relevant. It will not be superfluous to take aspirin and heparin.
4. Indirect anticoagulants to control blood viscosity. Doctors recommend medical drug Warfarin.
5. Plasmapheresis provides blood purification in a hospital setting, but the doses of these medications should be reduced.

In case of catastrophic antiphospholipid syndrome, it is necessary to increase daily dose glucocorticoids and antiplatelet agents, in mandatory carry out blood cleansing with an increased concentration of glycoprotein. Pregnancy should proceed under strict medical supervision, otherwise the clinical outcome for the pregnant woman and her child is not the most favorable.

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