Antiphospholipid syndrome during pregnancy. Antiphospholipid syndrome after childbirth. Video: what is AFS

Among the causes of recurrent miscarriage, special importance is given to the influence of the formation of antibodies (autoimmune reactions) to some of its own phospholipids on the processes of implantation, growth, development of the embryo and fetus, the course of pregnancy and the outcome of childbirth.

The term « Antiphospholipid syndrome"(AFS) denotes a group of autoimmune disorders characterized by a significant amount of antibodies to phospholipids contained in the blood plasma (antiphospholipid antibodies), as well as to glycoproteins associated with these phospholipids (β2-glycoprotein-I, annexin V and/or prothrombin).

APS occurs in up to 5% of cases. Among patients with recurrent miscarriage, the frequency of this pathology increases to 27-42%. The relevance of APS lies in the fact that the main complication of this pathology is thrombosis. The risk of thrombotic complications during pregnancy and the postpartum period increases significantly.

Risk factors

One of the factors causing APS is genetic predisposition to this pathology. Thus, in patients with APS, antigens of the HLA system are found more often than in the population. Familial cases of APS are also known, accounting for up to 2% of cases. Another important factor is the presence of bacterial and/or viral infection, which does not exclude the possibility of developing thrombotic complications as part of APS.

For the pathological process to occur, it is necessary to have in the body not only antibodies to phospholipids, but also so-called cofactors, upon binding with which true antigen-antibody complexes are formed. As a result of the action various factors external and internal environment(viral infection, malignant neoplasms, action medicines) AFA interacts with cofactors, which leads to serious violations in the blood coagulation system. In this case, first of all, microcirculation processes are disrupted and changes in the vascular wall occur.

Due to the fact that antiphospholipid syndrome is one of the most common types of pathology of the blood coagulation system, its recognition should be included in diagnostic process in all cases of early and, especially, recurrent venous and arterial thrombosis, thromboembolism, dynamic disturbances cerebral circulation And ischemic strokes, including those occurring with migraine syndromes, memory impairment, paresis, visual impairment and other manifestations, as well as persistent miscarriage (intrauterine fetal death, miscarriages).

Types of antiphospholipid syndrome

There are primary and secondary APS. The presence of secondary APS is due to autoimmune diseases (with systemic lupus erythematosus, periarteritis nodosa, etc.), cancer, infectious diseases, as well as exposure to a number of medicines and toxic substances. Accordingly, with primary APS listed diseases and there are no states.

In some cases, the so-called catastrophic APS is isolated, which is characterized by sudden and rapidly developing multiple organ failure, most often in response to factors such as infectious diseases or surgical interventions. Catastrophic APS manifests itself acutely respiratory distress syndrome, impaired cerebral and coronary circulation, stupor, disorientation, possible development of acute renal and adrenal failure, thrombosis of large vessels.

Symptoms and complications of the disease

One of the main and most dangerous clinical manifestations of APS is recurrent thrombosis. Most often, venous thrombosis occurs, localized in the deep veins of the legs, which is associated with the risk of developing thromboembolism of the branches pulmonary artery. However, cases of thrombosis of the renal and hepatic veins are not uncommon. Thrombotic lesions of the portal, subclavian, inferior vena cava may occur, cerebral vessels, arteries and veins of the retina, large vessels lower limbs, various parts of the aorta. Clinical manifestations of arterial thrombosis are peripheral gangrene, aortic arch syndrome, blindness, cerebrovascular accidents, etc. The danger of thrombotic complications increases with the course of pregnancy and in postpartum period.

It is known that APS leads to non-developing pregnancy, intrauterine growth retardation of the fetus, up to fetal death in the II and III trimesters. In the first trimester of pregnancy, APA can have a direct damaging effect on ovum followed by spontaneous termination of pregnancy.

WITH early dates pregnancy, there is an increase in the functional activity of platelets, a decrease in protein synthesis and hormonal functions placenta. In the absence of appropriate treatment, an increase in the activity of the blood coagulation system occurs. In this case, thrombosis occurs in the vessels of the placenta, placental insufficiency, chronic hypoxia and often fetal death due to lack of oxygen develop.

Diagnosis and treatment

For effective diagnosis of APS syndrome, it seems important comprehensive assessment anamnestic, clinical and laboratory data, which allows you to correctly assess the risk of complications and timely prescribe the necessary therapy. When managing pregnant and postpartum women suffering from APS, careful monitoring of activity is necessary autoimmune process, the state of the blood coagulation system, prevention, diagnosis and treatment of emerging disorders.

Clinical criteria for diagnosing APS are indications of episodes of venous and arterial thrombosis, confirmed by laboratory or instrumental studies. Data on the pathological course of previous pregnancies are also important: spontaneous abortions before 10 weeks of pregnancy for unknown reasons, when the death of the embryo (fetus) is unlikely due to genetic reasons; fetal death after 10 weeks, premature birth due to severe gestosis and placental insufficiency.

Laboratory criteria for antiphospholipid syndrome:

• Presence of anticardiolipin antibodies in the blood IgG class or IgM in medium or high titer at 6-week intervals.
• Detection of lupus anticoagulant (LA) in blood plasma at intervals of 6-8 weeks with an increase of at least twofold.

The development of APS can be assumed if there is autoimmune diseases, recurrent miscarriage (not associated with endocrine, genetic reasons, abnormal development of the genital organs, organic or functional isthmic-cervical insufficiency), with the early development of gestosis, especially its severe forms, placental insufficiency, fetal malnutrition during previous pregnancies, false-positive Wasserman reactions.

To suppress the autoimmune process, it is advisable to prescribe glucocorticoid therapy as preparation for pregnancy. Small doses of prednisolone (5 mg) or metipred (4 mg per day) can reduce the activity of the autoimmune process and prevent the development of disorders of the blood coagulation system. Steroid therapy should be continued throughout pregnancy and for 10-15 days postpartum, followed by gradual withdrawal. To prevent the reactivation of a viral infection while taking glucocorticoids in patients with APS, intravenous drip administration of immunoglobulin is administered at a dose of 25 ml every other day (3 doses). The administration of such small doses of immunoglobulin is advisable in the first trimester of pregnancy, at 24 weeks and before childbirth.

Special attention is devoted to the correction of disorders in the blood coagulation system. When platelets are activated, antiplatelet agents are prescribed: curantil (75-150 mg daily), trental (300-600 mg) or theonicol (0.045 mg per day). Monitoring of the blood coagulation system should be carried out once every 2 weeks. In cases where pathological platelet activity is combined with an increase in plasma activity and the appearance of signs of intravascular coagulation, the use of small doses of heparin (5,000 units 2-3 times a day subcutaneously) is justified. The duration of heparin therapy is determined by the severity of hemostasiological disorders. The use of small doses of aspirin (80-100 mg per day) helps to potentiate the effect of heparin. Low molecular weight heparins are widely used to treat APS. The use of these drugs in small doses does not require strict monitoring of the state of the blood coagulation system as when using conventional heparin.

As additional method Plasmapheresis is used to treat APS. Application this method allows you to normalize the rheological properties of blood, reduce excessive activation of the blood coagulation system, reduce the dose of corticosteroid drugs and heparin, which is especially important if they are poorly tolerated. To the main therapeutic effects plasmapheresis includes: detoxification, correction of rheological properties of blood, immunocorrection, increased sensitivity to endogenous substances and medications. Special meaning in the treatment of patients with APS, it is acquired by the removal of antiphospholipid autoantibodies, immune complexes, immunogenic plasma proteins, and autoantigens during the procedure, which makes it possible to reduce the activity of the autoimmune process. Plasmapheresis can be used both as preparation for pregnancy and during it and is effective method treatment of patients with APS.

Examination and drug preparation of patients with APS should begin before pregnancy. At the same time, the patient’s complaints and medical history are carefully analyzed to identify possible signs diseases. Laboratory tests are performed to detect antibodies to cardiolipin and lupus anticoagulant. If they are detected, the study is repeated after 6-8 weeks. At the same time, an examination is carried out to identify concomitant diseases, and, if necessary, their treatment. If there are repeated positive tests for the presence of antibodies to cardiolipin and lupus anticoagulant, treatment for APS is started with individual selection of drugs.

When pregnancy occurs, from its early stages, the nature of the course of the disease is monitored using appropriate laboratory tests and necessary treatment. Using ultrasound, the fetal growth rate is monitored at intervals of 3-4 weeks, and the functional state of the fetoplacental system is also assessed. Of particular diagnostic importance is Doppler ultrasound, which is carried out from 20 weeks with an interval of 3-4 weeks before delivery. Doppler measurements allow timely diagnosis of decreased fetoplacental and uteroplacental blood flow and allow assessment of the effectiveness of therapy. Cardiotocography data after 32 weeks of pregnancy also allows us to assess the functional state of the fetus. During childbirth, careful cardiac monitoring is carried out due to the presence of chronic fetal hypoxia, as well as an increased risk of abruption of a normally located placenta, the development of acute fetal hypoxia against the background of chronic one. It is advisable to determine the state of the blood coagulation system immediately before childbirth and during childbirth.

Monitoring the condition of postpartum women is of particular importance, since it is in the postpartum period that the risk of developing thromboembolic complications increases. Steroid therapy is continued for 2 weeks with gradual withdrawal. It is advisable to monitor the hemostatic system on the 3rd and 5th days after birth. At pronounced hypercoagulability a short course of heparin of 10,000-15,000 units per day subcutaneously is required. For patients prescribed anticoagulants and antiplatelet agents, lactation is suppressed. Patients who have been diagnosed with APS during pregnancy are subject to careful observation and monitoring of the state of the blood coagulation system due to the risk of disease progression.

Thus, timely diagnosis, preparation and rational management of pregnancy in patients with APS using adequate treatment reduces the risk of complications during pregnancy and the postpartum period.

Autoimmune pathology, which is based on the formation of antibodies to phospholipids, which are the main lipid components of cell membranes. Antiphospholipid syndrome can manifest itself as venous and arterial thrombosis, arterial hypertension, valvular heart defects, obstetric pathology (recurrent miscarriage, intrauterine fetal death, preeclampsia), skin lesions, thrombocytopenia, hemolytic anemia. The main diagnostic markers of antiphospholipid syndrome are antibodies to cardiolipin and lupus anticoagulant. Treatment of antiphospholipid syndrome comes down to the prevention of thrombosis, the prescription of anticoagulants and antiplatelet agents.

Renal manifestations may include both mild proteinuria and acute renal failure. On the part of the gastrointestinal tract, antiphospholipid syndrome causes hepatomegaly, gastrointestinal bleeding, occlusion of mesenteric vessels, portal hypertension, and splenic infarction. Typical lesions of the skin and soft tissues are represented by livedo reticularis, palmar and plantar erythema, trophic ulcers, gangrene of the fingers; musculoskeletal system - aseptic necrosis bones (femoral head). Hematological signs of antiphospholipid syndrome are thrombocytopenia, hemolytic anemia, and hemorrhagic complications.

In women, APS is often detected in connection with obstetric pathology: repeated spontaneous abortion in different terms, intrauterine growth retardation, fetoplacental insufficiency, gestosis, chronic fetal hypoxia, premature birth. When managing pregnancy in women with antiphospholipid syndrome, the obstetrician-gynecologist must take into account all possible risks.

Diagnostics

Antiphospholipid syndrome is diagnosed based on clinical (vascular thrombosis, complicated obstetric history) and laboratory data. The main immunological criteria include the detection of medium or high titers of antibodies to cardiolipin of the IgG/IgM class and lupus anticoagulant in the blood plasma twice within six weeks. The diagnosis is considered reliable when at least one main clinical and laboratory criterion is combined. Additional laboratory signs of antiphospholipid syndrome are false-positive RW, positive reaction Coombs titer increase antinuclear factor, rheumatoid factor, cryoglobulins, antibodies to DNA. A study of CBC, platelets, biochemical blood test, and coagulogram is also indicated.

Pregnant women with antiphospholipid syndrome need monitoring of blood coagulation parameters, dynamic ultrasound of the fetus and

Treatment of antiphospholipid syndrome

The main goal of treatment for antiphospholipid syndrome is to prevent thromboembolic complications. Regular moments include moderate physical activity, refusal long stay in a stationary state, playing traumatic sports and long air flights. Women with antiphospholipid syndrome should not be prescribed oral contraceptives, and before planning a pregnancy, you must definitely contact an obstetrician-gynecologist. Pregnant patients are advised to take small doses of glucocorticoids and antiplatelet agents, administration of immunoglobulin, and heparin injections under the control of hemostasiogram parameters throughout the entire gestation period.

Drug therapy for antiphospholipid syndrome may include the prescription of indirect anticoagulants (warfarin), direct anticoagulants (heparin, nadroparin calcium, enoxaparin sodium), antiplatelet agents (acetylsalicylic acid, dipyridamole, pentoxifylline). Preventive anticoagulant or antiplatelet therapy for most patients with antiphospholipid syndrome is carried out for a long time, and sometimes for life. In the catastrophic form of antiphospholipid syndrome, the administration of high doses of glucocorticoids and anticoagulants, sessions, transfusion of fresh frozen plasma, etc. is indicated.

Forecast

Timely diagnosis and preventive therapy allow you to avoid the development and recurrence of thrombosis, and also hope for a favorable outcome of pregnancy and childbirth. In case of secondary antiphospholipid syndrome, it is important to monitor the course of the underlying pathology and prevent infections. Unfavorable prognostic factors are the combination of antiphospholipid syndrome with SLE, thrombocytopenia, rapid increase in the titer of antibodies to cardiolipin, persistent arterial hypertension. All patients diagnosed with antiphospholipid syndrome should be under the supervision of a rheumatologist with periodic monitoring serological markers diseases and hemostasiogram indicators.

Antiphospholipid syndrome (APS) is a clinical and laboratory symptom complex that includes venous and/or arterial thrombosis, various forms of obstetric pathology (primarily recurrent miscarriage), thrombocytopenia, as well as various other neurological, skin, cardiovascular and hematological disorders. A characteristic immunological feature of APS is antibodies to phospholipids - a heterogeneous group of antibodies that react with a wide range of phospholipids and phospholipid-binding proteins. APS most often develops in SLE (secondary APS) or in the absence of another leading disease (primary APS).

The true prevalence of APS in the population is still unknown. The frequency of detection of antibodies to phospholipids in the serum of healthy people varies from 0 to 14%, on average 2-4% (in high titers in less than 0.2%). The disease often develops at a young age and can occur in children and even newborns. In elderly people, the development of APS may be associated with malignant neoplasms. In the general population, APS is more often detected in women. However, among patients with primary APS, an increase in the proportion of men is noted.

ETIOLOGY

The causes of APS are not known. An increase in the level (usually transient) of antibodies to phospholipids is observed against the background wide range bacterial and viral infections. However, thrombotic complications in patients with infections develop less frequently than antibodies to phospholipids are detected. There is evidence of an immunogenetic predisposition to overproduction of antibodies to phospholipids. There was an increase in the frequency of detection of antibodies to phospholipids in families of patients with APS; Cases of APS (usually primary) have been described in members of the same family.

PATHOGENESIS

Abs to phospholipids bind to phospholipids in the presence of a cofactor, which is β2-glycoprotein I, a protein that binds to phospholipids and has anticoagulant activity. Antiphospholipid antibodies present in the serum of patients with APS react with Ags formed during the interaction of phospholipid components of the membranes of endothelial and other cells (platelets, neutrophils) and β2-glycoprotein I. As a result of this interaction, the synthesis of anticoagulants (prostacyclin, antithrombin III, Annexin V, etc.) and increased formation of procoagulant (thromboxane, tissue factor, platelet activating factor, etc.) mediators, activation of the endothelium (expression of adhesion molecules) and platelets is induced, and neutrophil degranulation occurs.

Antiphospholipid antibodies detected in the serum of patients with infectious diseases usually react with phospholipids in the absence of β2-glycoprotein I and do not have the properties described above.

CLASSIFICATION

The following clinical and laboratory variants of APS are distinguished.

Primary APS.

Secondary APS.

"Catastrophic" APS.

In some patients, APS manifests itself primarily as venous thrombosis, in others as a stroke, in others as obstetric pathology or thrombocytopenia. The development of APS does not correlate with the activity of the underlying disease. Approximately half of patients with APS suffer from the primary form of the disease. However, the question of the nosological independence of primary APS is not completely clear. Primary APS can sometimes be a variant of the onset of SLE. On the contrary, in some patients with classical SLE at the onset, signs of APS may subsequently come to the fore.

In some patients, APS may manifest as acute recurrent coagulopathy and vasculopathy affecting vital functions. important organs and resembling DIC or hemolytic-uremic syndrome. This condition is called "catastrophic" APS.

CLINICAL PICTURE

Since APS is based on non-inflammatory thrombotic damage to vessels of any size and location, the range of clinical manifestations is extremely diverse.

Venous thrombosis is the most common manifestation of APS. Thrombi are usually localized in the deep veins of the lower extremities, but are often found in the hepatic, portal veins, superficial veins, etc. Repeated pulmonary embolisms from the deep veins of the lower extremities are typical, sometimes leading to pulmonary hypertension. APS (more often primary than secondary) is the second most common cause of Budd-Chiari syndrome. Thrombosis of the central vein of the adrenal glands can lead to adrenal insufficiency.

Arterial thrombosis. Thrombosis inside cerebral arteries, leading to stroke and transient ischemic attacks, is the most common localization of arterial thrombosis in APS. Recurrent ischemic strokes caused by damage to small vessels sometimes occur without significant neurological disorders and can manifest as convulsive syndrome, multi-infarct dementia (resembling Alzheimer's disease), and mental disorders.

A variant of APS is Sneddon syndrome, manifested by recurrent thrombosis of cerebral vessels, livedo reticularis, hypertension and developing in young and middle-aged people. Other neurological disorders include migraine headaches, epileptiform seizures, chorea, and transverse myelitis. Sometimes neurological disorders in APS resemble those in multiple sclerosis.

Heart valve damage is one of the common cardiac manifestations of APS. It varies from minimal disturbances detected only by echocardiography (slight regurgitation, thickening of the valve leaflets) to severe heart defects (stenosis or insufficiency of the mitral, less often the aortic and tricuspid valves). Some patients quickly develop severe valve damage with vegetations caused by thrombotic overlays, similar to valve damage in infective endocarditis. Detection of vegetations on the valves, especially if they are combined with hemorrhages in the nail bed and fingers in the form of “drumsticks”, dictates the need differential diagnosis with infective endocarditis. The development of blood clots in the cardiac cavity, simulating cardiac myxoma, has been described. One of possible localizations arterial thrombosis associated with the synthesis of antibodies to phospholipids are the coronary arteries (in men with SLE this is the most common location).

Frequent complications of APS include hypertension. It can be labile and is often associated with livedo reticularis and damage to the cerebral arteries as part of Sneddon syndrome, or stable, malignant, manifested by symptoms of hypertensive encephalopathy. The development of hypertension in APS can be associated with many reasons, including thrombosis renal vessels, renal infarction, thrombosis abdominal region aorta (pseudocoarctation) and intraglomerular thrombosis. A connection has been noted between the overproduction of antibodies to phospholipids and the development of fibromuscular dysplasia of the renal arteries. A rare complication of APS is thrombotic pulmonary hypertension, which is associated with both recurrent pulmonary embolism and local ( in situ) thrombosis of the pulmonary vessels.

Kidney damage in APS is associated with intraglomerular microthrombosis and is referred to as renal thrombotic microangiopathy. Microthrombosis of the glomeruli of the kidneys is considered the cause of the subsequent development of glomerulosclerosis, leading to dysfunction of the organ.

Obstetric pathology is considered one of the most characteristic features AFS: recurrent miscarriage pregnancy, recurrent spontaneous abortion, intrauterine fetal death, preeclampsia. Fetal loss can occur at any stage of pregnancy, but more often in the second and third trimesters.

Skin lesions in APS are characterized by a variety of clinical manifestations (usually livedo reticularis). Less common are skin ulcers and pseudovasculitic lesions (purpura, palmar and plantar erythema, pustules, gangrene of the fingers).

Thrombocytopenia is a typical hematological sign of APS. The development of hemorrhagic complications is rare and, as a rule, is associated with a concomitant defect in blood coagulation factors, kidney pathology, or an overdose of anticoagulants. Hemolytic anemia with a positive Coombs test is often observed; Evans syndrome (a combination of thrombocytopenia and hemolytic anemia) is less common.

LABORATORY RESEARCH

Laboratory diagnosis of APS is based on the determination of lupus anticoagulant using functional tests and antibodies to cardiolipin using ELISA. In general, lupus anticoagulant has higher specificity, and anticardiolipin antibodies have higher sensitivity for diagnosing APS. Lupus anticoagulant and antibodies to cardiolipin are detected in 30-40% and 40-50% of patients with SLE, respectively. In the presence of antibodies to phospholipids, the risk of developing thrombosis is 40%, while in the absence of antibodies it is no higher than 15%. A method has been developed for determining antibodies that react with β2-glycoprotein I, an increase in the level of which correlates better with the development of thrombosis than an increase in the level of antibodies to phospholipids. The course of APS, the severity and prevalence of thrombotic complications in most cases do not depend on the concentration of antibodies to phospholipids.

To make a reliable diagnosis of APS, a combination of at least one clinical and one laboratory criterion is necessary.

APS should be suspected in cases of thrombotic disorders (especially multiple, recurrent, with unusual localization), thrombocytopenia, obstetric pathology in young and middle-aged people, as well as in unexplained thrombosis in newborns, in case of skin necrosis during treatment with indirect anticoagulants and in patients with prolonged aPTT during a screening study. With APS, a large number of pseudo-syndromes are observed, which can imitate vasculitis, infective endocarditis, heart tumors, multiple sclerosis, hepatitis, nephritis, etc.

TREATMENT

Prevention and treatment of APS - difficult task(Table 46-2). This is due to the heterogeneity pathogenetic mechanisms underlying APS, polymorphism of clinical manifestations, lack of reliable clinical and laboratory parameters allowing to predict the recurrence of thrombotic disorders. The risk of recurrent thrombosis is especially high in patients young with persistent high levels of antibodies to cardiolipin, lupus anticoagulant and with simultaneous detection of antibodies to cardiolipin and lupus anticoagulant, as well as in the presence of recurrent thrombosis and/or obstetric pathology in the anamnesis, in the presence of other risk factors for thrombotic disorders (hypertension, hyperlipidemia, smoking, taking oral contraceptives), with high activity of SLE, with rapid withdrawal of indirect anticoagulants, with a combination of high titers of antibodies to phospholipids with other coagulation disorders.

In addition, there are a number of features in the treatment of APS.

In patients with high levels of antibodies to phospholipids in the serum, but without clinical signs of APS (including pregnant women without a history of obstetric pathology), they are limited to prescribing small doses of acetylsalicylic acid (75 mg/day). These individuals require careful follow-up, since their risk of thrombotic complications is very high. Moderate thrombocytopenia usually does not require treatment or is controlled with small doses of GCs.

Management of patients with definite APS is based on the prescription of vitamin K antagonists (warfarin) and antiplatelet agents (low doses of acetylsalicylic acid), which are widely used for the prevention of thrombosis not associated with APS. In patients with both secondary and primary APS, treatment with warfarin, which maintains the INR at a level of 2-3 (or more), leads to a significant reduction in the incidence of recurrent thrombotic complications. However, the use of warfarin is associated with a high risk of bleeding. It is advisable to prescribe antimalarial drugs, which, along with an anti-inflammatory effect, have antithrombotic (suppress platelet aggregation and adhesion, reduce the size of a blood clot) and lipid-lowering activity.

The use of warfarin during pregnancy is contraindicated, as this leads to the development of warfarin embryopathy, characterized by impaired growth of the epiphyses of the bones and hypoplasia of the nasal septum, as well as neurological disorders. Treatment with heparin (especially low molecular weight heparins in standard doses) in combination with low doses of acetylsalicylic acid in women with recurrent miscarriage can increase the frequency of successful births by approximately 2-3 times and is significantly more effective than glucocorticoid therapy.

APS syndrome and pregnancy: treatment and diagnosis

Antiphospholipid syndrome is an autoimmune thrombophilic (with a tendency to form blood clots) condition, which is caused by the presence of antibodies in the blood - APA.

These antibodies recognize and attack proteins associated with cell membranes, damaging the cell membranes themselves. APS is manifested by the development of thrombosis or pregnancy complications. Pregnancy with antiphospholipid syndrome without treatment at the planning stage and during pregnancy often has catastrophic consequences.

The presence of antiphospholipid antibodies in the blood without clinical symptoms is not antiphospholipid syndrome.

Like many autoimmune diseases, the etiology of antiphospholipid syndrome is not completely known, but there are several theories about its origin:

1. Passive transplacental transfer during pregnancy of antiphospholipid antibodies to the fetus (from the bloodstream of a pregnant woman into the bloodstream of the baby), which provokes the disease in a newborn child.
2. The genetic nature suggests familial cases of APS.
3. Phospholipids are common in nature in human tissue cells and microorganisms - viruses and bacteria. The destruction of microorganisms that have entered the body is accompanied by the destruction of the “host” cells, in our case – humans. The phenomenon is called the “Mimicry Effect”. That is, immune reactions aimed at destroying the infection lead to the launch of autoimmune processes.
4. Gene polymorphism plays a leading role in the development of APS. In the development of antiphospholipid syndrome during pregnancy, more attention is paid to antibodies of the 1st domain of beta-2-glycoprotein. This is a protein that is embedded in the cell membrane and performs its function - thromboresistance. While in the blood plasma, the protein cannot bind to antibodies, but as soon as it attaches to the phospholipids of the membrane cells, it becomes available for attack by APL antibodies. A complex of glycoprotein and antibodies is formed, which triggers most pathological reactions, encountered at APS syndrome, including during pregnancy.

A mutation in the gene encoding this beta-2-glycoprotein molecule causes the molecule to become more antigenic, autosensitization occurs, and antibodies to this protein appear.

Antiphospholipid syndrome and pregnancy

All pathological processes The effects of APS on pregnancy come down to 4 main processes:

• triggering thrombus formation in veins and arteries;
• development of the inflammatory process cascade;
• activation of apoptosis (programmed cell death);
• effects on the trophoblast - the layer of embryonic cells through which nutrition from the mother's body occurs.

At the implantation stage, antiphospholipid antibodies disrupt the properties of embryonic cells and the structure of trophoblast cells, which continues throughout the entire implantation period, leading to a decrease in the depth of trophoblast penetration into the endometrium and increased thrombotic processes.

Antiphospholipid antibodies can cause progesterone deficiency, which itself can further cause fetal loss syndrome.

These processes occur generally (in all human organs) and locally (locally) - in the endometrium of the uterus. And for successful implantation and pregnancy, as you know, the endometrium must be healthy. Therefore, common complications of pregnancy with antiphospholipid syndrome are:

• spontaneous termination of pregnancy in the early stages;
• non-developing pregnancy;
• intrauterine growth retardation of the fetus until its death in the 2nd and 3rd trimester;
• preeclampsia.

Clinical manifestations of APS during pregnancy and diagnosis

All symptoms and manifestations of APS can be divided into 2 groups:

1. From the mother's side.
2. From the side of the fetus.

Before pregnancy, APS manifests itself as implantation disorders in natural and natural conditions. This is the answer to the question: does antiphospholipid syndrome prevent you from getting pregnant? Conception is extremely difficult. Also, before pregnancy there is an increased risk of thrombotic complications.

During pregnancy, serious complications of APS syndrome are:

• Eclapsy and preeclampsia. The risk of developing preeclampsia in a pregnant woman with APS is 16-21%, versus 2-8%, which is observed in the population.
• observed in 10% of cases. The frequency of complications in the population is 1%.
• Thrombocytopenia – complication rate 20%.
• Venous thromboembolic disorders.
• Catastrophic antiphospholipid syndrome, which is fatal in 70% of cases. Its frequency in pregnant women with APS is 1%.

After childbirth, antiphospholipid syndrome is dangerous due to venous thromboembolic disorders and catastrophic antiphospholipid syndrome.

APS during pregnancy for a child has the following complications:

• . The contribution of APS to the development of pregnancy loss is 15%, versus 1-2% in the population.
• Premature birth – 28%.
• Stillbirth or intrauterine fetal death – 7%.
• Fetal growth retardation 24-39%.
• Fetal thrombosis (thrombosis in the fetus).

After childbirth, a newborn may experience the following complications:

• Thrombosis.
• The risk of neurocirculatory thrombosis increases – 3%. Most of these disorders are accompanied by autism.
• Asymptomatic circulation of antibodies to phospholipids in 20% of cases.

APS syndrome and treatment during pregnancy

The gold standard in the management of pregnancy in women with APS is the administration of low molecular weight heparins and low doses of acetylsalicylic acid.

It has been proven that low molecular weight heparins can:

• directly bind APL antibodies, thereby reducing their concentration in the blood;
• inhibit (depress) the binding of antibodies to trophoblast;
• prevent the death of trophoblast cells by increasing the synthesis of anti-apoptotic proteins;
• have an anticoagulant (anti-clotting) effect - they prevent increased blood clotting and the formation of blood clots;
• block the production of substances that trigger inflammatory response mechanisms.

Treatment regimens for APS syndrome during pregnancy

• For APS syndrome without thrombotic complications with pregnancy losses up to 10 weeks in the past, a combination of LMWH (low molecular weight heparin) and acetylsalicylic acid is used. Clexane 40 mg is administered subcutaneously once every 24 hours.
• For APS in pregnant women without thrombotic complications with a history of pregnancy loss after term, only LMWH is recommended - Clexane 40 mg per day.
• For antiphospholipid syndrome with thrombotic complications and a history of pregnancy loss at any stage, use Clexane at a dose of 1 mg per 1 kg of weight every 12 hours.

If coagulogram parameters and uterine blood flow deteriorate, therapeutic doses are prescribed.

Take medications - low fractionated heparin (the most commonly used are Clexane, Enoxyparin) and acetylsalicylic acid in low doses is necessary even at the stage of pregnancy planning. If the blood parameters and its coagulation system improve (tests are taken - coagulograms, hemostasiogram), and uterine blood flow improves (assessed by Dopplerometry), the doctor “allows” pregnancy.

The administration of anticoagulants does not stop and continues until delivery. At the pregnancy planning stage the following is also prescribed:

• vitamins – folic acid at a dose of 400 micrograms per day;
• omega-3 polyunsaturated fatty acids;
• Utrozhestan.

The standard approach to the treatment of APS with recurrent miscarriage allows maintaining pregnancy in 70% of cases. In 30% of pregnant women with APS it is not possible to achieve positive results. In these cases, plasmapheresis and cascade plasma filtration are used. The purpose of these procedures is to remove from the bloodstream APS antibodies and a number of substances that take part in the cascade of inflammatory thrombus-forming processes.

Before a planned cesarean section, therapy is suspended to prevent bleeding and the possibility of epidural anesthesia. The drugs are discontinued one day before. At spontaneous birth and emergency caesarean section the situation is complicated, but if LMWH were administered 8-12 hours before, then epidural anesthesia is possible.

Given such difficulties with therapy, low molecular weight heparins are discontinued for women and unfractionated heparin is prescribed, its effect is shorter-term. Taking standard heparin is not a contraindication to epidural pain relief for labor.

For an emergency caesarean section, general anesthesia is used.

Antiphospholipid syndrome after childbirth

After delivery, anticoagulant therapy for antiphospholipid syndrome is resumed after 12 hours. At high risk occurrence of thrombotic complications – after 6 hours. Treatment continues for 1.5 months after birth.

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Antiphospholipid syndrome is a complex of symptoms that includes multiple arterial and/or venous thromboses, causing disturbances in various organs, one of the most typical manifestations which is recurrent miscarriage. This condition is one of the most current problems medicine today, since it affects many organs and systems at the same time, and its diagnosis in some cases is difficult.

In this article we will try to figure out what kind of symptom complex this is, why it occurs, how it manifests itself, and also consider the principles of diagnosis, treatment and prevention of this condition.

Causes and mechanisms of development of antiphospholipid syndrome

Unfortunately, today the reliable causes of this symptom complex are unknown. It is believed that this disease in some cases is genetically determined; this variant is called primary antiphospholipid syndrome, and it is defined as an independent form of the disease. Much more often, antiphospholipid syndrome does not develop on its own, but against the background of some other diseases or pathological conditions, the main ones being:

It can also result from taking a number of medications: psychotropic drugs, oral hormonal contraceptives, hydralazine, novocainamide and others.

With antiphospholipid syndrome, the patient’s body produces a large number of autoantibodies to phospholipids, which have several varieties, located on the membranes of platelets and endothelial cells, as well as on nerve cells.

U healthy person the frequency of detection of such antibodies is 1-12%, increasing with age. In the diseases mentioned above, the production of antibodies to phospholipids sharply increases, which leads to the development of antiphospholipid syndrome.

Antibodies to phospholipids have negative impact on certain structures of the human body, namely:

• endothelial cells (endothelial cells): they reduce the synthesis of prostacyclin, which dilates blood vessels and prevents platelet aggregation; inhibit the activity of thrombomodulin, a protein substance that has an antithrombotic effect; inhibit the production of factors that prevent coagulation and initiate the synthesis and release of substances that promote platelet aggregation;
• platelets: antibodies interact with these cells, stimulating the formation of substances that enhance platelet aggregation, and also contribute to the rapid destruction of platelets, which causes thrombocytopenia;
• humoral components of the blood coagulation system: reduce the concentration in the blood of substances that prevent clotting, and also weaken the activity of heparin.

As a result of the effects described above, the blood acquires an increased ability to clot: in the vessels supplying blood various organs, blood clots form, organs experience hypoxia with the development of corresponding symptoms.

Clinical signs of antiphospholipid syndrome

The following changes may be detected in the skin:

• vascular network on the upper and lower extremities, more often on the hands, clearly visible during cooling - livedo reticularis;
• rash in the form of pinpoint hemorrhages, resembling vasculitis in appearance;
• subcutaneous hematomas;
• hemorrhages in the area of ​​the subungual bed (the so-called “splinter symptom”);
• necrosis of skin areas in the area of ​​the distal parts of the lower extremities - fingertips;
• redness of the skin of the palms and soles: plantar and palmar erythema;
• subcutaneous nodules.

The following manifestations are characteristic of damage to the vessels of the extremities:

• chronic ischemia due to disturbances in blood flow below the site blocked by a thrombus: the limb is cold to the touch, the pulse below the site of thrombosis is sharply weakened, the muscles are atrophied;
• gangrene: necrosis of limb tissue as a result of prolonged ischemia;
• deep or superficial veins of the extremities: pain in the limb area, severe swelling, disruption of its function;
• : accompanied by pronounced pain syndrome, increased body temperature, chills; Along the course of the vein, redness of the skin and painful compactions under it are determined.

If the thrombus is localized in large vessels can be determined:

• aortic arch syndrome: pressure in the upper extremities is sharply increased, diastolic (“lower”) pressure in the arms and legs varies significantly, and a murmur is detected on the aorta during auscultation;
• superior vena cava syndrome: swelling, blue discoloration, dilatation of the saphenous veins of the face, neck, upper half of the torso and upper extremities; can be determined by the esophagus, trachea or bronchi;
• inferior vena cava syndrome: severe, diffuse pain in the lower extremities, groin, buttocks, abdominal cavity; ; dilated saphenous veins.

From the outside bone tissue The following changes may be observed:

• aseptic bone necrosis: death of a section of bone tissue in the area articular surface bones; more often observed in the area of ​​the femoral head; manifests itself as a pain syndrome of uncertain localization, atrophy of the muscles adjacent to the affected area, and impaired movement in the joint;
• reversible, not associated with the use of glucocorticoids: manifested by pain in the affected area, in the absence of factors that could provoke them.

Manifestations of antiphyspholipid syndrome on the part of the organ of vision may include:

• optic nerve atrophy;
• retinal hemorrhages;
• thrombosis of arteries, arterioles or veins of the retina;
• exudation (release of inflammatory fluid) due to blockage of retinal arterioles by a thrombus.

All these conditions are manifested by varying degrees of visual impairment, which are reversible or irreversible.

On the part of the kidneys, manifestations of antiphospholipid syndrome may be the following:

• : accompanied by severe pain in the lower back, decreased diuresis, the presence of; in some cases it is asymptomatic or with minimal clinical manifestations;
• renal artery thrombosis: sudden onset sharp pains in the lumbar region, often accompanied by nausea, vomiting, decreased diuresis,;
• renal thrombotic microangiopathy - the formation of microthrombi in the glomeruli - with subsequent development.

When blood clots are localized in the vessels of the adrenal glands, acute or chronic adrenal insufficiency can develop, as well as hemorrhages and infarctions in the area of ​​the affected organ.

Damage to the nervous system by blood clots is usually manifested by the following conditions:

• ischemic stroke: accompanied by weakness, paresis or paralysis of skeletal muscles;
• migraine: characterized by intense paroxysmal pain in one half of the head, accompanied by vomiting;
• constant painful;
• psychiatric syndromes.

When blood vessels in the heart are affected by blood clots, the following are determined:

• and (attacks of chest pain accompanied by);
• arterial hypertension.

In case of thrombosis of liver vessels, liver infarctions, Budd-Chiari syndrome, and nodular regenerative hyperplasia are possible.

Very often, with antiphospholipid syndrome, all kinds of obstetric pathologies are noted, but this will be discussed below in a separate subsection of the article.

Diagnosis of antiphospholipid syndrome

In 1992, clinical and biological diagnostic criteria antiphospholipid syndrome. TO clinical criteria relate:

• recurrent miscarriage;
• arterial thrombosis;
• venous thrombosis;
• skin lesion – livedo reticularis;
• in the area of ​​the legs;
• decreased level of platelets in the blood;
• signs .

Biological criteria include increased level antibodies to phospholipids - IgG or IgM.

A reliable diagnosis of “antiphospholipid syndrome” is considered if the patient has 2 or more clinical and biological criterion. In other cases, this diagnosis is possible or not confirmed.

IN general analysis blood, the following changes can be detected:

• increased ESR;
• reduced platelet level (within 70-120*10 9 /l);
• increased content leukocytes;
• sometimes – signs of hemolytic anemia.

A biochemical blood test will reveal:

• increased gamma globulin levels;
• for chronic renal failure– increased levels of urea and creatinine;
• in case of liver damage – increased levels of ALT and AST, alkaline phosphatase, ;
• increase in aPTT in the blood clotting test.

Specific tests can also be carried out immunological studies blood, which determines:

• antibodies to cardiolipin, especially IgG in high concentration;
• lupus anticoagulant (false-positive or false-negative reactions are common);
• for hemolytic anemia - antibodies to red blood cells (positive Coombs test);
• false-positive Wasserman reaction;
• increased number of T helper cells and B lymphocytes;
• antinuclear factor or antibodies to DNA;
• cryoglobulins;
• positive rheumatoid factor.

Treatment of antiphospholipid syndrome

The following groups of drugs can be used in the treatment of this disease:

1. Antiplatelet agents and anticoagulants indirect action: aspirin, pentoxifylline, warfarin.
2. (in the case of antiphospholipid syndrome developed against the background): prednisolone; possible combination with immunosuppressants: Cyclophosphamide, Azathioprine.
3. Aminoquinoline drugs: Delagil, Plaquenil.
4. Selective non-steroidal anti-inflammatory drugs: Nimesulide, Meloxicam, Celecoxib.
5. For obstetric pathology: intravenous immunoglobulin.
6. B vitamins.
7. Preparations of polyunsaturated fatty acids (Omacor).
8. Antioxidants (Mexico).

In some cases, plasmapheresis is used in combination with anticoagulant therapy.

To date, they have not been widely used, but the following groups of drugs are quite promising in the treatment of antiphospholipid syndrome:

• monoclonal antibodies to platelets;
• anticoagulant peptides;
• apoptosis inhibitors;
• systemic enzyme therapy drugs: Wobenzym, Phlogenzyme;
• cytokines: mainly Interleukin-3.

To prevent recurrent thrombosis, use indirect anticoagulants(Warfarin).

In the case of the secondary nature of antiphospholipid syndrome, it is treated against the background of adequate therapy for the underlying disease.

Antiphospholipid syndrome and pregnancy

In 40% of women with repeated cases of intrauterine fetal death, the cause is antiphospholipid syndrome. Blood clots clog the blood vessels of the placenta, causing the fetus to lack nutrients and oxygen, its development slows down, and in 95% of cases it soon dies. In addition, this disease of the mother can lead to placental abruption or the development of extreme dangerous condition, both for the fetus and for the expectant mother - late gestosis.

Clinical manifestations of antiphospholipid syndrome during pregnancy are the same as outside this period. Ideally, if this disease was detected in a woman before pregnancy: in this case, with adequate recommendations from doctors and the woman’s diligence, the likelihood of having a healthy child is high.

First of all, pregnancy should be planned after blood counts normalize as a result of treatment.

In order to monitor the condition of the placenta and the blood circulation of the fetus, a woman undergoes a study such as Doppler ultrasound several times during pregnancy. In addition, in order to prevent thrombus formation in the vessels of the placenta and in general, 3-4 times during pregnancy she is prescribed a course of drugs that improve metabolic processes: vitamins, microelements, antihypoxants and antioxidants.

If antiphospholipid syndrome is diagnosed after conception, the woman may be given immunoglobulin or heparin in small doses.

Forecast

The prognosis for antiphospholipid syndrome is ambiguous and directly depends on the timeliness of the start and adequacy of therapy, and on the discipline of the patient, on his compliance with all the doctor’s instructions.

Which doctor should I contact?

Antiphospholipid syndrome is treated by a rheumatologist. Since most cases of the disease are associated with pregnancy pathology, an obstetrician-gynecologist is involved in therapy. Since the disease affects many organs, consultation with relevant specialists is required - a neurologist, nephrologist, ophthalmologist, dermatologist, vascular surgeon, phlebologist, cardiologist.