Phospholipid syndrome: causes and diagnosis. Antiphospholipid syndrome: what is dangerous? Can afs

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Antiphospholipid Syndrome (APS), or antiphospholipid antibody syndrome (SAPA), is a clinical and laboratory syndrome, the main manifestations of which are the formation of blood clots (thrombosis) in the veins and arteries of various organs and tissues, as well as the pathology of pregnancy. The specific clinical manifestations of the antiphospholipid syndrome depend on the vessels of which particular organ were clogged with blood clots. In the organ affected by thrombosis, heart attacks, strokes, tissue necrosis, gangrene, etc. can develop. Unfortunately, today there are no uniform standards for the prevention and treatment of antiphospholipid syndrome due to the fact that there is no clear understanding of the causes of the disease, and there are no laboratory and clinical signs allowing to judge the risk of recurrence with a high degree of certainty. That is why, at present, the treatment of antiphospholipid syndrome is aimed at reducing the activity of the blood coagulation system in order to reduce the risk of repeated thrombosis of organs and tissues. Such treatment is based on the use of drugs of the anticoagulant groups (Heparins, Warfarin) and antiaggregants (Aspirin, etc.), which allow preventing repeated thrombosis of various organs and tissues against the background of the disease. Anticoagulants and antiplatelet agents are usually taken for life, since such therapy only prevents thrombosis, but does not cure the disease, thus allowing to prolong life and maintain its quality at an acceptable level.

Antiphospholipid syndrome - what is it?

Antiphospholipid syndrome (APS) is also called Hughes syndrome or anticardiolipin antibody syndrome. This disease was first identified and described in 1986 in patients with systemic lupus erythematosus. Currently, antiphospholipid syndrome is classified as thrombophilia- a group of diseases characterized by increased formation of blood clots.

The antiphospholipid syndrome is non-inflammatory autoimmune disease with a peculiar complex of clinical and laboratory signs, which is based on the formation of antibodies to certain types of phospholipids, which are structural components of the membranes of platelets, cells blood vessels and nerve cells. Such antibodies are called antiphospholipid, and are produced by their own immune system, which mistakenly takes the body's own structures as foreign, and seeks to destroy them. It is precisely because the pathogenesis of the antiphospholipid syndrome is based on the production of antibodies by the immune system against the structures of the body's own cells that the disease belongs to the autoimmune group.

The immune system can produce antibodies to various phospholipids, such as phosphatidylethanolamine (PE), phosphatidylcholine (PC), phosphatidylserine (PS), phosphatidylinositol (PI), cardiolipin (diphosphatidylglycerol), phosphatidylglycerol, beta-2-glycoprotein 1, which are part of platelet membranes, cells nervous system and blood vessels. Antiphospholipid antibodies "recognize" the phospholipids against which they were developed, attach to them, forming large complexes on cell membranes that activate the blood coagulation system. Antibodies attached to the cell membranes act as a kind of irritant for the coagulation system, since they imitate trouble in the vascular wall or on the surface of platelets, which causes the activation of the blood or platelet coagulation process, as the body seeks to eliminate the defect in the vessel, "fix" it. Such activation of the coagulation system or platelets leads to the formation of numerous blood clots in the vessels of various organs and systems. Further clinical manifestations of the antiphospholipid syndrome depend on the vessels of which particular organ were clogged with blood clots.

Antiphospholipid antibodies in antiphospholipid syndrome are a laboratory sign of the disease and are determined, respectively, laboratory methods in blood serum. Some antibodies are determined qualitatively (that is, they establish only the fact whether they are present in the blood or not), others quantitatively (determine their concentration in the blood).

Antiphospholipid antibodies, which are detected using laboratory tests in blood serum, include the following:

• Lupus anticoagulant. This laboratory indicator is quantitative, that is, the concentration of lupus anticoagulant in the blood is determined. Normally, in healthy people, lupus anticoagulant may be present in the blood at a concentration of 0.8 - 1.2 c.u. An increase in the indicator above 2.0 c.u. is a sign of antiphospholipid syndrome. The lupus anticoagulant itself is not a separate substance, but is a combination of antiphospholipid antibodies of the IgG and IgM classes to various phospholipids of vascular cells.
• Antibodies to cardiolipin (IgA, IgM, IgG). This indicator is quantitative. With antiphospholipid syndrome, the level of antibodies to cardiolipin in the blood serum is more than 12 U / ml, and in normal healthy person these antibodies may be present at a concentration of less than 12 U/ml.
• Antibodies to beta-2-glycoprotein (IgA, IgM, IgG). This indicator is quantitative. In antiphospholipid syndrome, the level of antibodies to beta-2-glycoprotein rises by more than 10 U / ml, and normally in a healthy person, these antibodies may be present at a concentration of less than 10 U / ml.
• Antibodies to various phospholipids(cardiolipin, cholesterol, phosphatidylcholine). This indicator is qualitative, and is determined using the Wasserman reaction. If the Wassermann reaction is positive in the absence of syphilis, then this is a diagnostic sign of antiphospholipid syndrome.

The listed antiphospholipid antibodies cause damage to the cell membranes of the vascular wall, as a result of which the coagulation system is activated, a large number of blood clots are formed, with the help of which the body tries to "patch" vascular defects. Further, due to the large number of blood clots, thrombosis occurs, that is, the lumen of the vessels is clogged, as a result of which the blood through them cannot circulate freely. Due to thrombosis, starvation of cells occurs that do not receive oxygen and nutrients, resulting in the death of the cellular structures of any organ or tissue. It is the death of cells of organs or tissues that gives the characteristic clinical manifestations of the antiphospholipid syndrome, which can be different depending on which organ has been destroyed due to thrombosis of its vessels.

Nevertheless, despite the wide range of clinical signs of antiphospholipid syndrome, doctors identify the leading symptoms of the disease, which are always present in any person suffering from this pathology. The leading symptoms of antiphospholipid syndrome include venous or arterial thromboses, pathology of pregnancy(miscarriage, habitual miscarriages, placental abruption, intrauterine fetal death, etc.) and thrombocytopenia (low platelet count in the blood). All other manifestations of the antiphospholipid syndrome are combined into topical syndromes (neurological, hematological, skin, cardiovascular, etc.) depending on the affected organ.

The most common are deep vein thrombosis of the lower leg, pulmonary embolism, stroke (thrombosis of cerebral vessels) and myocardial infarction (thrombosis of the vessels of the heart muscle). Thrombosis of the veins of the extremities is manifested by pain, swelling, redness of the skin, ulcers on the skin, as well as gangrene in the area of ​​clogged vessels. Thromboembolism pulmonary artery, heart attack and stroke are life-threatening conditions that are manifested by a sharp deterioration in the condition.

In addition, thrombosis can develop in any veins and arteries, as a result of which people suffering from antiphospholipid syndrome often have skin lesions (trophic ulcers, rashes, similar to a rash, as well as blue-violet uneven skin color) and impaired cerebral circulation (memory worsens , headaches appear, dementia develops). If a woman suffering from antiphospholipid syndrome has a pregnancy, then in 90% of cases it is interrupted due to thrombosis of the vessels of the placenta. With antiphospholipid syndrome, the following complications of pregnancy are observed: spontaneous abortion, intrauterine fetal death, premature placental abruption, premature birth, HELLP syndrome, preeclampsia and eclampsia.

There are two main types of antiphospholipid syndrome - primary and secondary. Secondary antiphospholipid syndrome always develops against the background of some other autoimmune (for example, systemic lupus erythematosus, scleroderma), rheumatic ( rheumatoid arthritis etc.), oncological (malignant tumors of any localization) or infectious disease (AIDS, syphilis, hepatitis C, etc.), or after taking medicines(oral contraceptives, psychotropic drugs, Isoniazid, etc.). Primary antiphospholipid syndrome develops in the absence of other diseases, and its exact causes have not yet been established. However, it is assumed that hereditary predisposition, severe chronic long-term infections (AIDS, hepatitis, etc.) and the intake of certain drugs (Phenytoin, Hydralazine, etc.) play a role in the development of primary antiphospholipid syndrome.

Accordingly, the cause of the secondary antiphospholipid syndrome is a disease that a person has, which provoked an increase in the concentration of antiphospholipid antibodies in the blood, followed by the development of pathology. And the causes of primary antiphospholipid syndrome are unknown.

Despite the lack of knowledge about the exact causes of antiphospholipid syndrome, doctors and scientists have identified a number of factors that can be attributed to predisposing to the development of APS. That is, conditionally, these predisposing factors can be considered the causes of the antiphospholipid syndrome.

Currently, the following are among the predisposing factors of antiphospholipid syndrome:

• genetic predisposition;
• Bacterial or viral infections(staphylococcal and streptococcal infections, tuberculosis, AIDS, cytomegalovirus infection, Epstein-Barr viruses, hepatitis B and C, infectious mononucleosis, etc.);
• Autoimmune diseases (systemic lupus erythematosus, systemic scleroderma, periarteritis nodosa, autoimmune thrombocytopenic purpura, etc.);
• Rheumatic diseases (rheumatoid arthritis, etc.);
• Oncological diseases (malignant tumors of any localization);
• Some diseases of the central nervous system;
• Long-term use of certain drugs (oral contraceptives, psychotropic drugs, interferons, hydralazine, isoniazid).

Antiphospholipid syndrome - signs (symptoms, clinic)

Consider the signs of catastrophic APS and other forms of the disease separately. This approach seems rational, since according to clinical manifestations different kinds antiphospholipid syndrome are the same, and there are differences only in catastrophic APS.

If thrombosis affects small vessels, then this leads to mild disorders the functioning of the organ in which the clogged veins and arteries are located. For example, when small myocardial vessels are blocked, individual small sections of the heart muscle lose their ability to contract, which causes their degeneration, but does not provoke a heart attack or other severe damage. But if thrombosis captures the lumen of the main trunks of the coronary vessels, then a heart attack will occur.

With thrombosis of small vessels, the symptoms appear slowly, but the degree of dysfunction of the affected organ is steadily progressing. In this case, the symptoms usually resemble some chronic illness, for example, cirrhosis of the liver, Alzheimer's disease, etc. This is the course of the usual types of antiphospholipid syndrome. But with thrombosis of large vessels, a sharp disruption in the functioning of the organ occurs, which causes a catastrophic course of the antiphospholipid syndrome with multiple organ failure, DIC, and other serious life-threatening conditions.

Since thrombosis can affect the vessels of any organ and tissue, manifestations of the antiphospholipid syndrome from the side of the central nervous system, cardiovascular system, liver, kidneys, gastrointestinal tract, skin, etc. Thrombosis of placental vessels during pregnancy provokes obstetric pathology (miscarriage, premature birth, placental abruption, etc.). Consider the symptoms of antiphospholipid syndrome from various organs.

First, you need to know that thrombosis in APS can be venous and arterial. With venous thrombosis, thrombi are localized in the veins, and with arterial thrombosis, respectively, in the arteries. characteristic feature antiphospholipid syndrome are recurrent thrombosis. That is, if treatment is not carried out, then episodes of thrombosis of various organs will be repeated again and again, until there is an insufficiency of any organ that is incompatible with life. Also, APS has another feature - if the first thrombosis was venous, then all subsequent episodes of thrombosis are also, as a rule, venous. Accordingly, if the first thrombosis was arterial, then all subsequent ones will also capture the arteries.

Most often, APS develops venous thrombosis of various organs. In this case, most often, blood clots are localized in deep veins. lower extremities, and somewhat less often - in the veins of the kidneys and liver. Deep vein thrombosis of the legs is manifested by pain, swelling, redness, gangrene or ulcers on the affected limb. Thrombi from the veins of the lower extremities can break away from the walls of blood vessels and reach the pulmonary artery with blood flow, provoking life-threatening complications - pulmonary embolism, pulmonary hypertension, hemorrhages in the lungs. With thrombosis of the inferior or superior vena cava, the syndrome of the corresponding vein develops. Thrombosis of the adrenal vein leads to hemorrhages and necrosis of the tissues of the adrenal glands and the development of their subsequent insufficiency.

Thrombosis of the veins of the kidneys and liver leads to the development of nephrotic syndrome and Budd-Chiari syndrome. Nephrotic syndrome is manifested by the presence of protein in the urine, edema and impaired lipid and protein metabolism. Budd-Chiari syndrome is manifested by obliterating phlebitis and thrombophlebitis of the liver veins, as well as a pronounced increase in the size of the liver and spleen, ascites, increasing over time, hepatocellular insufficiency and sometimes hypokalemia (low level of potassium in the blood) and hypocholesterolemia (low level of cholesterol in the blood).

In APS, thrombosis affects not only veins, but also arteries. Moreover, arterial thrombosis develops approximately twice as often as venous ones. Such arterial thromboses are more severe downstream compared to venous ones, since they are manifested by heart attacks or hypoxia of the brain or heart, as well as peripheral blood flow disorders (blood circulation in the skin, limbs). The most common is intracerebral artery thrombosis, which results in strokes, heart attacks, hypoxia, and other CNS damage. Thrombosis of the arteries of the extremities leads to gangrene, aseptic necrosis of the femoral head. Relatively rarely, thrombosis of large arteries develops - the abdominal aorta, the ascending aorta, etc.

Damage to the nervous system is one of the most severe manifestations of the antiphospholipid syndrome. Caused by thrombosis of the cerebral arteries. Manifested by transient ischemic attacks, ischemic strokes, ischemic encephalopathy, seizures, migraine, chorea, transverse myelitis, sensorineural hearing loss, and a range of other neurological or psychiatric symptoms. Sometimes neurological symptoms in cerebral vascular thrombosis in APS resemble the clinical picture of multiple sclerosis. In some cases, cerebral thrombosis causes temporary blindness or optic neuropathy.

Transient ischemic attacks are manifested by loss of vision, paresthesia (sensation of running "goosebumps", numbness), motor weakness, dizziness and general amnesia. Often, transient ischemic attacks precede a stroke, appearing weeks or months before it. Frequent ischemic attacks lead to the development of dementia, memory loss, impaired attention and other mental disorders that are similar to Alzheimer's disease or brain toxicity.

Recurrent microstrokes in APS often occur without clear and noticeable symptoms, and may manifest themselves after some time with convulsions and the development of dementia.

Headaches are also one of the most common manifestations of antiphospholipid syndrome in the localization of thrombosis in the intracerebral arteries. At the same time, headaches can have a different character - from migraine to permanent.

In addition, a variant of CNS damage in APS is Sneddon's syndrome, which is manifested by a combination of arterial hypertension, livedo reticularis (blue-violet mesh on the skin) and cerebral vascular thrombosis.

Heart failure in antiphospholipid syndrome appears a wide range various nosologies, including myocardial infarction, valvular disease, chronic ischemic cardiomyopathy, intracardiac thrombosis, high blood pressure, and pulmonary hypertension. In rare cases, thrombosis in APS causes manifestations similar to myxoma (a tumor of the heart). Myocardial infarction develops in approximately 5% of patients with antiphospholipid syndrome, and, as a rule, in men under 50 years of age. Most often, with APS, damage to the heart valves occurs, the severity of which varies from minimal disorders (thickening of the valve leaflets, throwing back part of the blood) to defects (stenosis, insufficiency of the heart valves).

Although cardiovascular disease is common in APS, it rarely leads to heart failure and serious complications requiring surgery.

Thrombosis of the kidney vessels leads to various dysfunctions this body. So, most often with APS, proteinuria (protein in the urine) is noted, which is not accompanied by any other symptoms. Also, with APS, the development of renal failure with arterial hypertension is possible. Any disturbances in the functioning of the kidneys in APS are due to microthrombosis of the glomerular vessels, which causes glomerulosclerosis (replacement of kidney tissue by a scar). Microthrombosis of the glomerular vessels of the kidneys is referred to by the term "renal thrombotic microangiopathy".

Thrombosis of liver vessels in APS leads to the development of Budd-Chiari syndrome, liver infarction, ascites (fluid effusion into the abdominal cavity), increased activity of AST and ALT in the blood, as well as an increase in liver size due to its hyperplasia and portal hypertension ( high blood pressure in the hepatic portal vein).

In APS, in about 20% of cases, there is specific skin lesion due to thrombosis of small vessels and impaired peripheral circulation. A livedo reticularis appears on the skin (a blue-violet vascular network localized on the shins, feet, hands, thighs, and is clearly visible when cooled), ulcers, gangrene of the fingers and toes develops, as well as multiple hemorrhages in the nail bed, which appearance reminiscent of a "splinter". Also, sometimes a rash appears on the skin in the form of pinpoint hemorrhages, resembling vasculitis in appearance.

Also a frequent manifestation of antiphospholipid syndrome is obstetric pathology, which occurs in 80% of pregnant women suffering from APS. As a rule, APS causes pregnancy loss (miscarriage, miscarriage, premature birth), intrauterine growth retardation, as well as preeclampsia, preeclampsia and eclampsia.

Relatively rare manifestations of APS are pulmonary complications, such as thrombotic pulmonary hypertension(high blood pressure in the lungs), hemorrhages in the lungs and capillaritis. Thrombosis of the pulmonary veins and arteries can lead to a "shock" lung - a life-critical condition that requires immediate medical attention.

Gastrointestinal bleeding, splenic infarction, thrombosis of the mesenteric vessels of the intestine, and aseptic necrosis of the femoral head also develop rarely with APS.

With APS, there is almost always thrombocytopenia (the number of platelets in the blood is below normal), in which the number of platelets ranges from 70 to 100 g / l. This thrombocytopenia does not require treatment. Approximately 10% of APS cases develop Coombs-positive hemolytic anemia or Evans syndrome (combination hemolytic anemia and thrombocytopenia).

Symptoms of catastrophic antiphospholipid syndrome

Catastrophic antiphospholipid syndrome is a type of disease in which there is a rapid fatal increase in dysfunction of various organs due to repeated frequent episodes of massive thrombosis. At the same time, within a few days or weeks, respiratory distress syndrome develops, disorders of cerebral and cardiac circulation, stupor, disorientation in time and space, renal, cardiac, pituitary or adrenal insufficiency, which, if untreated, in 60% of cases lead to death. Usually catastrophic antiphospholipid syndrome develops in response to infection infectious disease or undergone surgery.

Antiphospholipid syndrome in men, women and children

Antiphospholipid syndrome can develop in both children and adults. At the same time, this disease is less common in children than in adults, but it is more severe. In women, antiphospholipid syndrome occurs 5 times more often than in men. Clinical manifestations and principles of treatment of the disease are the same in men, women and children.

Antiphospholipid syndrome and pregnancy

What causes APS during pregnancy?

Antiphospholipid syndrome negatively affects the course of pregnancy and childbirth, as it leads to thrombosis of the vessels of the placenta. Due to thrombosis of the placental vessels, various obstetric complications occur, such as intrauterine fetal death, fetoplacental insufficiency, fetal growth retardation, etc. In addition, APS during pregnancy, in addition to obstetric complications, can provoke thrombosis in other organs - that is, it can manifest itself with the symptoms that are characteristic of this disease even outside the gestation period. Thrombosis of other organs also negatively affects the course of pregnancy, as their functioning is disrupted.

It has now been proven that antiphospholipid syndrome can cause the following obstetric complications:

• Infertility of unknown origin;
• IVF failures;
• Miscarriages in early and late pregnancy;
• Frozen pregnancy;
• Intrauterine fetal death;
• premature birth;
• stillbirth;
• Malformations of the fetus;
• Delayed fetal development;
• Gestosis;
• Eclampsia and preeclampsia;
• Premature placental abruption;
• Thrombosis and thromboembolism.

Complications of pregnancy occurring against the background of a woman's antiphospholipid syndrome are recorded in approximately 80% of cases if APS is not treated. Most often, APS leads to pregnancy loss due to miscarriage, miscarriage, or premature birth. At the same time, the risk of pregnancy loss correlates with the level of anticardiolipin antibodies in the woman's blood. That is, the higher the concentration of anticardiolipin antibodies, the higher the risk of pregnancy loss.

After the onset of pregnancy, the doctor chooses one of the recommended tactics based on the concentration of antiphospholipid antibodies in the blood and the presence of thrombosis or complications of pregnancy in the past. In general, the gold standard for pregnancy management in women with APS is considered to be the use of low molecular weight heparins (Clexane, Fraxiparin, Fragmin), as well as Aspirin in low dosages. Glucocorticoid hormones (Dexamethasone, Metipred) are currently not recommended for pregnancy management in APS, since they have a slight therapeutic effect, but they significantly increase the risk of complications for both the woman and the fetus. The only situations where the use of glucocorticoid hormones is justified is the presence of another autoimmune disease(for example, systemic lupus erythematosus), the activity of which must be constantly suppressed.

• Antiphospholipid syndrome, in which a woman has elevated levels of antiphospholipid antibodies and lupus anticoagulant in the blood, but in the past there were no thrombosis and episodes of early pregnancy loss (for example, miscarriages, miscarriages before 10-12 weeks). In this case, during the entire pregnancy (until delivery), it is recommended to take only Aspirin 75 mg per day.
• Antiphospholipid syndrome, in which a woman has elevated levels of antiphospholipid antibodies and lupus anticoagulant in the blood, there were no thromboses in the past, but there were episodes of early pregnancy loss (miscarriages up to 10-12 weeks). In this case, during the entire pregnancy until childbirth, it is recommended to take Aspirin 75 mg per day, or a combination of Aspirin 75 mg per day + low molecular weight heparin preparations (Clexane, Fraxiparin, Fragmin). Clexane is injected under the skin at 5000 - 7000 IU every 12 hours, and Fraxiparine and Fragmin - 0.4 mg once a day.
• Antiphospholipid syndrome, in which a woman has elevated levels of antiphospholipid antibodies and lupus anticoagulant in the blood, there were no thromboses in the past, but there were episodes of miscarriage in the early stages (miscarriages up to 10-12 weeks) or intrauterine fetal death, or premature birth due to gestosis or placental insufficiency. In this case, during the entire pregnancy, up to childbirth, you should use low doses Aspirin (75 mg per day) + low molecular weight heparin preparations (Clexane, Fraxiparin, Fragmin). Clexane is injected under the skin at 5000-7000 IU every 12 hours, and Fraxiparine and Fragmin - at 7500-10000 IU every 12 hours in the first trimester (up to the 12th week inclusive), and then 10000 IU every 8-12 hours during second and third trimesters.
• Antiphospholipid syndrome, in which a woman has elevated levels of antiphospholipid antibodies and lupus anticoagulant in the blood, there have been thrombosis and episodes of pregnancy loss at any time in the past. In this case, during the entire pregnancy until childbirth, low doses of Aspirin (75 mg per day) + low molecular weight heparin preparations (Clexane, Fraxiparin, Fragmin) should be used. Clexane is injected under the skin at 5000-7000 IU every 12 hours, and Fraxiparine and Fragmin - at 7500-10000 IU every 8-12 hours.

Pregnancy management is carried out by a doctor who monitors the condition of the fetus, uteroplacental blood flow and the woman herself. If necessary, the doctor adjusts the dosage of drugs depending on the value of blood coagulation indicators. This therapy is mandatory for women with APS during pregnancy. However, in addition to these drugs, the doctor may additionally prescribe other medicines that are necessary for each particular woman at the current time (for example, iron preparations, Curantil, etc.).

Thus, all women with APS who receive heparins and Aspirin during pregnancy are recommended to administer prophylactic immunoglobulin intravenously at a dose of 0.4 g per 1 kg of body weight for five days at the beginning of each month, until childbirth. Immunoglobulin prevents the activation of chronic and new infections. It is also recommended that women receiving heparin take calcium and vitamin D supplements throughout pregnancy to prevent the development of osteoporosis.

The use of Aspirin is stopped at the 37th week of pregnancy, and heparins are administered until the start of regular labor activity if childbirth is carried out through natural routes. If a planned caesarean section is scheduled, then Aspirin is canceled 10 days in advance, and heparins a day before the date of the operation. If heparins were used before the onset of labor, then such women should not be given epidural anesthesia.

After delivery, the treatment carried out during pregnancy is continued for another 1-1.5 months. Moreover, they resume the use of Aspirin and heparins 6-12 hours after childbirth. Additionally, after childbirth, measures are taken to prevent thrombosis, for which it is recommended to get out of bed as early as possible and move actively, as well as bandage your legs with elastic bandages or put on compression stockings.

After 6 weeks of heparin and aspirin use postpartum further treatment antiphospholipid syndrome is carried out by a rheumatologist, whose competence is the identification and treatment of this disease. 6 weeks after the birth, the rheumatologist cancels heparins and Aspirin, and prescribes the treatment that is already necessary for later life.

In Russia, in some regions, the practice of prescribing Wobenzym to pregnant women with APS is widespread.

Antiphospholipid antibody syndrome is an autoimmune disorder in which antibodies are formed in a person's blood against particles of their own body cells, phospholipids. Pathology increases the risk of thrombosis and in 95% of cases leads to miscarriage.

A complete diagnosis of autoimmune thrombophilia is available only in a specialized laboratory for the pathology of hemostasis at the Taganka Medical Center for Women. The analysis for antiphospholipid syndrome includes 5 tests and is completed in 24 hours.

The cost of research on APS syndrome*

Why is an analysis for APS syndrome prescribed?

Antiphospholipid antibodies attack platelets and vascular membrane cells, which provokes thrombosis - blockage of veins and arteries by blood clots. The manifestations of autoimmune thrombophilia are multifaceted - these are heart attacks, strokes, thrombophlebitis, which can develop at a young age, as well as severe pregnancy complications: miscarriages, preeclampsia, fetal growth retardation syndrome, fetoplacental insufficiency, premature birth.

An analysis for the syndrome of antiphospholipid antibodies should be taken when planning a pregnancy, 2 or more cases of intrauterine fetal death, premature birth for up to 34 weeks, the presence of rheumatic and autoimmune diseases, a history of arterial or venous thrombosis.

The diagnosis is made on the basis of 1 clinical (cases of thrombosis, obstetric pathologies) and 1 laboratory criterion - a high concentration, antibody titer in a blood test.

Specialists

How to get tested for antiphospholipid syndrome

To diagnose autoimmune thrombophilia, examine venous blood. Before blood sampling, it is not recommended to eat food for 4-8 hours - to obtain reliable results, so the procedure is carried out in the morning:

• put a tourniquet on the patient's hand;
• perform venipuncture;
• blood is collected in a test tube and transferred to the ILC Hemostasis Pathology Laboratory for analysis.

Tests for antiphospholipid syndrome - coagulogram, lupus anticoagulant, immunoglobulins Ig G to cardiolipin and other phospholipids, are repeated after 12 weeks.

A re-analysis shows whether a person really needs treatment - taking anticoagulants, coumarins, or an increase in the concentration of antibodies was an immune response to an infection, taking certain medications and does not require correction (primary antiphospholipid antibody syndrome).

Video about the problem of APS during pregnancy

Antiphospholipid syndrome is one of the pathologies of hemostasis and the causes of miscarriage, developmental delay or death of the fetus. Makatsaria A.D. talks about the mechanism of the origin and development of APS syndrome and its manifestations, reveals the concepts of "thrombotic storm", "hypercoagulation", "hyperhomocysteinemia", explains when the presence of thrombophilia should be suspected.

obstetrician-gynecologist, hemostasiologist

Deciphering indicators

When diagnosing autoimmune thrombophilia, the value of 5 markers is taken into account:

1. Antibodies to the phospholipid cardiolipin - in APS syndrome, a high titer of Ig A and Ig G is detected, normally 0-12 U / ml.
2. Antibodies to b2-glycoprotein, a specific blood plasma protein that affects blood coagulation processes.
3. Reference values ​​of all immunoglobulins - G, M and A, are in the range of 0-10 IU / ml.
4. Lupus anticoagulant (LA) - should not exceed 0.8-1.2 U / ml. Antibodies to cardiolipin and VA are detected simultaneously in 70% of patients with antiphospholipid syndrome.
5. Antibodies to prothrombin, the 2nd blood coagulation factor - are not normally detected.
6. Annexin-5 is a placental anticoagulant protein that is the main cause of placental vascular thrombosis and intrauterine fetal death. Normally absent.

Where to take a blood test for APS syndrome

All specific tests for antiphospholipid antibody syndrome are performed in the express laboratory of the Women's Medical Center on Zemlyanoy Val.

Criteria for the diagnosis of APS have been developed since its description. Latest International diagnostic criteria include both clinical and laboratory findings. Clinical manifestations include thrombosis of a vessel of any caliber and localization (venous and / or arterial, or the smallest vessels) and obstetric pathology.

Clinical Criteria

Vascular thrombosis

• One or more cases of arterial, venous, or small vessel thrombosis in
  any organ.
• Pathology of pregnancy:
  a) one or more cases of intrauterine death of a normal fetus (without pathology) after 10 weeks of pregnancy (absence of pathology must be detected by ultrasound or during direct examination of the fetus), or
  b) one or more cases of preterm delivery of a normal fetus before 34 weeks due to severe preeclampsia, or eclampsia, or severe placental insufficiency, or
  c) three or more consecutive cases of spontaneous abortions before the 10th week (it is necessary to exclude anatomical defects of the uterus, hormonal disorders, chromosomal disorders).

Laboratory Criteria

• Antibodies to cardiolipin (aCL) detected in blood serum in medium or high concentrations at least 2 times with an interval of at least 12 weeks (!!!);
• Antibodiestoβ 2 -glycoprotein-1(anti-β2-GP1) detected in the blood serum in medium or high concentrations at least 2 times with an interval of at least 12 weeks (!!!);
• Lupus anticoagulant (LA) in two or more cases of research with an interval of at least 12 weeks (!!!).

APS is diagnosed by the presence of one clinical and one serological criterion. APS is excludedif less than 12 weeks or more than 5 years antiphospholipid antibodies WITHOUT clinical manifestations or clinical manifestations WITHOUT antibodies are detected.

APS is the only therapeutic disease whose diagnosis requires compulsory laboratory confirmation!

The detection of certain antibodies to phospholipids may indicate a high or low risk of subsequent thrombosis. A high risk of thrombosis is determined by positivity for three types of antiphospholipid antibodies (VA + aCL + anti-β2-GP1). A low risk of thrombosis is associated with isolated intermittent detection of antibodies at medium to low levels.

APS is subdivided into primary and secondary, which developed against the background of or other autoimmune diseases, lupus-like syndrome, as well as against the background of infections, tumors, the use of drugs, and. However, since primary APS may be an option for the onset of SLE, a reliable diagnosis can only be verified during long-term follow-up of patients (≥5 years from the onset of the disease). The similarity of signs of primary and secondary APS was the reason for the decision not to separate these two options. At the same time, a concomitant disease should be indicated in the diagnosis.

Probable APS. There are conditions in which subsequently develop "blockage" of the vessel, neurological manifestations, thrombocytopenia, loss of the fetus up to 10 weeks of pregnancy. Any of these conditions may precede the development of significant APS. To date, the isolation of probable APS or preAPS has been substantiated. This diagnosis may be made in patients with high or moderate levels of anti-phospholipid antibodies in the blood and one of the following: thrombocytopenia, valvular heart disease (non-infectious), kidney disease, obstetric pathology, and no other alternative disease.

Catastrophic APS - a separate and very severe form of APS, which can develop as part of both secondary and primary APS, it is characterized by widespread thrombosis, often leading to multiple organ failure and death of patients, despite treatment.

Antiphospholipid syndrome (APS) is an autoimmune disease characterized by the production of large amounts of antibodies to phospholipids - chemical structures from which parts of the cell are built.

Antiphospholipid syndrome occurs in approximately 5% of pregnant women. In 30% of cases, APS is the main cause of miscarriage, the most urgent problem of modern obstetrics. If certain measures are not followed, APS can lead to the most adverse and life-threatening complications during pregnancy and after childbirth.

Causes of APS

The main provoking factors leading to the development of APS include:

genetic predisposition;
- bacterial or viral infections;
- autoimmune diseases - systemic lupus erythematosus (SLE), periarteritis nodosa;
- long-term use of drugs hormonal contraceptives, psychotropic drugs);
- oncological diseases.

Symptoms of antiphospholipid syndrome

How does antiphospholipid syndrome manifest itself? Clinical manifestations of the disease are varied, but may be completely absent. The latter occurs quite often when, against the background of absolute health, a healthy woman has spontaneous miscarriages. And if not examined, then the diagnosis of APS is quite difficult to suspect. The main cause of miscarriage in APS is an increase in the activity of the blood coagulation system. For this reason, thrombosis of the vessels of the placenta occurs, which inevitably leads to termination of pregnancy.

The most “harmless” symptoms of APS include the appearance of an accentuated vascular pattern on various parts of the body. Most often, the vascular pattern is expressed on the legs, feet, and thighs.

In more severe cases, APS can manifest itself as a non-healing ulcer on the lower leg, gangrene of the toes (due to chronic deterioration of blood supply). Increased thrombus formation in vessels in APS can lead to pulmonary embolism (acute blockage of a vessel by a thrombus), which is deadly!

Less common symptoms of APS include a sudden decrease in vision, up to the appearance of blindness (due to thrombosis of the arteries and veins of the retina); development of chronic kidney failure, which may manifest as an increase blood pressure and the appearance of protein in the urine.

Pregnancy itself exacerbates the manifestations of APS, so if you have already been diagnosed with APS, you should contact an obstetrician-gynecologist even before the planned pregnancy. In the presence of the above symptoms, this should be done immediately!

Examination for APS

To confirm the diagnosis of “Antiphospholipid syndrome”, it is necessary to take a blood test from a vein for markers of APS- for lupus anticoagulant (LA) and for antibodies to cardiolipin (aCL). If the analysis turned out to be positive (that is, if APS markers were found), it should be retaken after 8-12 weeks. And if the re-analysis also turned out to be positive, then treatment is prescribed.

To determine the severity of the disease, it is necessary to prescribe general analysis blood (with APS, there is a decrease in the level of platelets) and a coagulogram (hemostasiogram) - a blood test for hemostasis (blood clotting system). In the presence of APS, a coagulogram is taken during pregnancy at least once every 2 weeks. In the postpartum period, this analysis is given on the third and fifth days after childbirth.

Ultrasound and dopplerometry (the study of blood flow in the mother-placenta-fetus system) are performed in pregnant women with APS more often than in pregnant women without pathologies. Starting from 20 weeks, these studies are carried out every month in order to anticipate and reduce the risk of developing placental insufficiency (deterioration of blood circulation in the placenta).

CTG (cardiotography) is also used to assess the condition of the fetus. This study performed without fail, starting from 32 weeks of pregnancy. In the presence of chronic fetal hypoxia, placental insufficiency (which often happens with APS), CTG is performed daily.

Treatment of antiphospholipid syndrome

What is the treatment for APS during pregnancy? As already mentioned, if you know about your diagnosis and have been examined, you should contact an obstetrician-gynecologist before planning a pregnancy.

To prevent the development of disorders of the blood coagulation system, even before pregnancy, glucocorticoids are prescribed in small doses (Prednisolone, Dexamethasone, Metipred). Further, when a woman becomes pregnant, she continues to take these drugs until the postpartum period. Only two weeks after birth, these drugs are gradually canceled.

In cases where the diagnosis of APS is established during pregnancy, the tactics of management are the same. Treatment with glucocorticoids is prescribed in any case if there is APS, even if the pregnancy is absolutely normal!

Since long-term use of glucocorticoids leads to a weakening of the immune system, immunoglobulin is prescribed in parallel in small doses.

In total, during pregnancy, immunoglobulin is administered 3 times - up to 12 weeks, at 24 weeks and immediately before childbirth.

Necessarily for the correction of the blood coagulation system, antiplatelet agents are prescribed (Trental, Curantil).

Treatment is carried out under the control of hemostasiogram parameters. In some cases, Heparin and Aspirin are additionally prescribed in small doses.

In addition to the main treatment, plasmapheresis is used (blood purification by removing plasma). This is done to improve rheological properties blood, to increase immunity, as well as to increase sensitivity to administered drugs. When using plasmapheresis, the doses of glucocorticoids and antiplatelet agents can be reduced. This is especially true for pregnant women who do not tolerate glucocorticoids well.

During childbirth, careful monitoring of the state of the blood coagulation system is carried out. Childbirth must be carried out under the control of CTG.

With timely diagnosis, careful monitoring and treatment, pregnancy and childbirth are favorable and end with the birth of healthy children. The risk of postpartum complications will be minimal.

If you have been diagnosed with APS, there is no need to get upset and deprive yourself of the pleasure of being a mother. Even if a miscarriage occurs, you should not tune in to the fact that the next time it will be the same. Thanks to the possibilities of modern medicine, APS is not a sentence today. The main thing is to follow the doctor's prescriptions and be prepared for long-term treatment and numerous examinations, which are done with the sole purpose of protecting you and the unborn child from extremely unpleasant complications.

Complications of APS

Complications listed below occur in 95 out of 100 patients with APS in the absence of dynamic monitoring and treatment. These include:
- miscarriage (repeated miscarriages in the early stages of pregnancy);
- fetal growth retardation, fetal hypoxia (lack of oxygen);
- placental abruption;
- the development of severe preeclampsia (a complication of pregnancy, accompanied by an increase in blood pressure, the appearance of pronounced edema, protein in the urine). If left untreated, gestosis can lead not only to the death of the fetus, but also to the mother;
- pulmonary embolism .

Prevention of antiphospholipid syndrome

Prevention of APS includes examination before the planned pregnancy for markers of APS - lupus anticoagulant (LA), antibodies to cardiolipin (aCL).

Consultation of an obstetrician-gynecologist on APS

Question: Is it possible to use oral contraceptives in the presence of APS?
Answer: No way! Taking oral contraceptives will aggravate the course of APS.

Question: Does APS lead to infertility?
Answer: No.

Question: If the pregnancy is proceeding normally, is it worth taking for “reinsurance” on APS markers?
Answer: No, if the coagulogram is normal.

Question: How long to take antiplatelet drugs during pregnancy with APS?
Answer: The whole pregnancy, without interruptions.

Question: Can the appearance of APS provoke smoking?
Answer: Unlikely, but if you already have APS, then smoking makes it even worse.

Question: How long can I not get pregnant after a miscarriage due to APS?
Answer: At least 6 months. During this time, it is necessary to fully examine and start taking antithrombotic drugs.

Question: Is it true that pregnant women with APS should not have a caesarean section?
Answer: Yes and no. The operation itself increases the risk of thrombotic complications. But if there are indications (placental insufficiency, fetal hypoxia, etc.), then the operation is mandatory.

Obstetrician-gynecologist, Ph.D. Christina Frambos.

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. Attaching to the walls of blood vessels, platelets, directly entering into 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 tissues is possible. The complex of symptoms manifested in this case is called antiphospholipid syndrome (APS), and in 1994 at an international symposium on antibodies to phospholipids, it was proposed to name 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 many antibodies to phospholipids: antibodies to cardiolipin, lupus anticoagulant, b2-glycoprotein-1-cofactor-dependent antibodies, antibodies to blood coagulation factors, antibodies to substances that, on the contrary, interfere with this process, and many, many others. In practice, the first two are usually most often determined - antibodies to cardiolipin, lupus anticoagulant.

How is it manifested?

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

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

If small vessels are thrombosed, this leads to relatively mild dysfunction of the organ. So, when the small branches of the coronary arteries in the heart are blocked, the ability of individual sections of the heart muscle to contract is impaired, while the closure of the lumen of the main trunk of the coronary artery will cause the development of myocardial infarction.

With thrombosis, the symptoms often appear imperceptibly, gradually, the dysfunction of the organ increases gradually, imitating any chronic disease (liver cirrhosis, Alzheimer's disease). Blockage of the vessel by a detached thrombus, on the contrary, will lead to the development of "catastrophic disorders" of the functions of the organ. So, pulmonary embolism is manifested by attacks of suffocation, pain in chest, cough, in most cases it leads to death.

Antiphospholipid syndrome can mimic a variety of diseases, but some symptoms are worth paying special attention to.

Quite often, with antiphospholipid syndrome, there are livedo reticularis (lacy, thin mesh of blood vessels on the surface of the skin, which becomes better visible in the cold), chronic leg ulcers that are difficult to treat, peripheral gangrene (necrosis of the skin or even individual fingers or toes).

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

In women, it is more often cerebral circulation(stroke, especially before the age of 40, migraine-like headaches).

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

With thrombosis of the arteries of the placenta, intrauterine fetal death or premature birth may occur. It is precisely with the 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 has 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 vessels are thrombosed, for which this is not very typical, for example, vessels supplying the intestines. Their blockage leads to "abdominal toad". Such a colorful name for this disease arose by analogy with angina pectoris - "angina pectoris". "Abdominal toad" is characterized by the appearance of pressing, squeezing pain in the abdomen that occurs after a heavy meal. The more a person ate, the more blood is needed digestive tract to digest food. If the lumen of the vessels is narrowed by a thrombus, then there is not enough blood 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 a myocardial infarction occurs in a person younger than 40 years.

Treatment

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

If the 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 less the likelihood of thrombosis. Therefore, it is so important for the patient to take the basic therapy prescribed by the doctor (glucocorticoids, cytostatics).

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

Perhaps the doctor will prescribe any drugs that will reduce the likelihood of thrombosis by acting directly on the blood coagulation system. For their appointment, strict indications are needed: the benefits must significantly exceed side effects. Contraindications to taking these drugs are pregnancy (may cause a violation 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 (eg, hydroxychloroquine) combine an anti-inflammatory effect with the ability to inhibit platelet aggregation (clumping), which also helps prevent the development of thrombosis.

Women with antiphospholipid syndrome should delay pregnancy until laboratory values ​​return to normal. If the syndrome has developed after conception, then you should think about the introduction of immunoglobulin or small doses of heparin.

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