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Antiphospholipid syndrome and miscarriage. APS syndrome and pregnancy: treatment and diagnosis

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

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

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

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

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

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

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

Neutral.
Anionic (negatively charged).

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

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

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

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

How common is it?

True APS is not common. Accurate epidemiology data the specified disease It is not possible to provide, since the main antibodies are lupus anticoagulant and antibodies to cardiolipin occur in healthy populations due to various causes.

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

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

Overall, secondary antiphospholipid syndrome is up to 9 times more likely to be diagnosed in women, as they are more susceptible to developing the disease connective tissue.

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

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

Classification

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

Among other forms there are:

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

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

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

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

Reasons for development

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

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

Any of stated reasons triggers a series of pathological changes which inevitably lead to thrombosis and multiorgan damage.

Development mechanisms

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

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

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

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

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

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

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

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

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

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

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

Symptoms of APS

The most common signs unique to antiphospholipid syndrome are:

Vascular thrombosis.
Obstetric pathology.

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

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

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

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

These signs of antiphospholipid syndrome can develop at any stage, often without any visible reasons when the patient does not yet know about his illness.

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

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

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

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

Antiphospholipid syndrome in children

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

Antiphospholipid syndrome in men

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

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

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

Diagnosis of APS

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

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

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

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

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

Clinical criteria for APS:

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

Laboratory criteria for API:

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

One is required to make a diagnosis. clinical sign and one laboratory.

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

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

Treatment of APS

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

Currently, new ones are beginning to be used medications, which are anticoagulants with a selective point of application on blood clotting factors. Such drugs are more effective in treating and preventing thrombosis than heparins and warfarin, and are also safer.

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

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

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

Video: Lectures on APS

What kind of problems does an expectant mother face during the entire nine months of her pregnancy? It’s one thing if at a doctor’s appointment you are only bothered by a runny nose or throat. Although this is an unpleasant matter, it is fixable. But what if, after the next analysis, you are faced with much more serious problems?

Let's talk today about antiphospholipid syndrome and pregnancy. What kind of diagnosis is this, how dangerous it can be for you and your child, and how to prevent its occurrence.

Antiphospholipid syndrome or Hughes syndrome can affect any woman who has previously had problems with pregnancy. This disease is associated with the production of female body antibodies to essential phospholipids, which leads to the formation of blood clots in the vessels of the placenta.

Naturally, such violations do not just go away: the normal development of the baby is suspended and occurs incorrectly, complications may appear, and, even worse, the woman may lose the child.

When can antiphospholipid syndrome develop and why?

The causes of antiphospholipid syndrome can be completely different. For example, if the expectant mother is ill with lupus erythematosus, scleroderma, arthritis, or is a carrier of infections chronic, malignant tumors, the likelihood that she will encounter the problem of antiphospholipid syndrome increases significantly.

How to avoid such a diagnosis, and how dangerous it is

At the stages of pregnancy planning, you must undergo a full medical examination. This is necessary in order to determine whether you have chronic diseases and the same antiphospholipid syndrome, and deal with these problems in a timely manner.

The truth does not always happen as doctors advise, and an expectant mother may find out about the presence of antiphospholipid syndrome while already pregnant. In such a situation, doctors try to prescribe the most gentle and effective therapy that would help the woman’s body restore metabolism, cope with the normalization of redox processes at the cellular level and improve blood circulation in the placenta.

Such therapy usually consists of special drugs and vitamins. During the entire course of treatment, a woman should be under the strict supervision of specialists so that they can monitor the condition of both the unborn baby and his mother.

Don’t worry too much if you hear a diagnosis of antiphospholipid syndrome at your appointment. Antiphospholipid syndrome and pregnancy, with proper therapy, are completely compatible concepts. If the problem is detected in a timely manner, most likely both pregnancy and childbirth will go well.

Signs of antiphospholipid syndrome

Antiphospholipid syndrome during pregnancy can manifest itself in completely different ways. But among the main symptoms are the appearance of vascular walls on a woman’s skin, chronic ulcers legs and peripheral gangrene. Antiphospholipid syndrome can be primary or secondary. They are not too different from each other, but the secondary one is more similar to autoimmune diseases. The appearance of this disease in the first trimester almost always leads to miscarriage.

In order to protect yourself from undesirable consequences, you must determine for yourself how necessary regular and timely examination is. Do not think that if nothing bothers you, then you are absolutely healthy.

Pregnancy is a delicate thing and requires special responsibility. Be sure to check yourself for antiphospholipid syndrome if you have previously encountered such a problem as premature birth And spontaneous miscarriage. Correct and accurate diagnosis is half the way to successful and effective treatment. Take care of yourself and stay healthy!

Antiphospholipid syndrome (APS) is a set of clinical and laboratory symptoms caused by the presence in the body of antibodies to phospholipids and phospholipid-binding proteins. Phospholipids are the basis of the cell membrane. Antibodies to them react with these substances and damage cell membranes. As a result, a complex of symptoms develops, including:

blockage (thrombosis) of veins or arteries;
miscarriage and other obstetric pathology;
decreased number of platelets in the blood (thrombocytopenia).

The causes of this condition are unknown. There is some correlation with transferred infectious diseases. Available hereditary predisposition to the development of APS. This syndrome may complicate the course of systemic lupus erythematosus or, conversely, precede its development.

Let's talk about how antiphospholipid syndrome and pregnancy are related.

Deep vein thrombosis in a young woman may be a sign of antiphospholipid syndrome.

Quite often, only repeated spontaneous abortions make one suspect this serious disease. Let's look at what symptoms can help diagnose APS before pregnancy. This is necessary to start treatment on time and prevent fetal death.

Most common symptom diseases – . Most often affected deep veins lower extremities. But sometimes they suffer superficial veins, as well as vessels of the liver, adrenal glands and other organs. Deep vein thrombosis is accompanied by pain and swelling of the limb, and an increase in its temperature. This condition may develop dangerous complication– . It can manifest itself as a persistent cough, hemoptysis, and shortness of breath. In more severe cases arises sharp pain in the chest, severe shortness of breath, cyanosis of the skin. Thromboembolism pulmonary artery may lead to the death of the patient.

If a young woman develops a stroke, transient ischemic attack, episodes of severe dizziness, or seizures, it is always necessary to exclude thrombosis of the cerebral arteries caused by APS. In some cases, arterial thrombosis can manifest as migraines or even acute mental disorders.

Patients may be affected the cardiovascular system. Echocardiography reveals changes in the valves with the formation of growths - vegetations. Signs or symptoms appear. The appearance of unmotivated shortness of breath, weakness, edema, and rapid heartbeat in a young woman should also be a reason for an in-depth examination and exclusion of APS.

Skin lesions are quite typical - livedo reticularis, skin ulcers, purpura, redness of the soles and palms (erythema).

A decrease in the number of platelets is detected in the blood of patients. Quite often thrombocytopenia is combined with hemolytic anemia. The tendency to bleed is uncharacteristic and occurs most often with an overdose.

Obstetric pathology in APS

Three or more cases of spontaneous abortions in the early stages are grounds for screening a woman for antibodies to cardiolipin.

In women, APS can manifest as recurrent miscarriage and spontaneous recurrent spontaneous abortions. After three spontaneous abortions, the risk of miscarriage new pregnancy in the early stages increases to 45%.

Developmental delay or intrauterine fetal death develops, and phenomena occur. Pregnancy is terminated most often in the second and third trimesters. Without treatment, such a sad outcome is observed in 90–95% of patients. With timely proper therapy the probability of unfavorable pregnancy development is up to 30%.

Variants of pregnancy pathology:

unexplained death of a healthy fetus throughout pregnancy;
death of a healthy fetus due to preeclampsia, or placental insufficiency before 34 weeks of pregnancy;
at least three spontaneous abortions before 10 weeks of pregnancy in the absence of chromosomal disorders in the parents, hormonal or anatomical disorders of the genital organs in the mother.

Features of pregnancy

During pregnancy planning, a woman should be thoroughly examined by a rheumatologist, cardiologist and other specialists.

During pregnancy, monthly ultrasonic testing for fetal development. Placental circulation should be assessed using Doppler ultrasound. In the third trimester, it is necessary to regularly conduct cardiotocography so as not to miss the onset oxygen starvation fetus due to placental insufficiency.

Determination of antibodies to phospholipids is carried out at 6 weeks of pregnancy and before the planned birth.

Blood coagulation parameters should be determined regularly, including after childbirth. This will help reduce the risk of thrombotic complications.
If changes indicate increased blood clotting, the dose of heparin received by the patient should be increased.

Heparin, including low molecular weight, requires avoidance of breastfeeding. This is the case when the threat to the health and life of the mother is disproportionately higher than any consequences for the child during artificial feeding.

Treatment of antiphospholipid syndrome during pregnancy

If a woman has been diagnosed with APS before pregnancy, there are no clinical manifestations of the disease, and it is manifested only by laboratory changes, treatment can only include acetylsalicylic acid at a dose of up to 100 mg per day, but the benefits of such therapy have not been definitively established.

Another treatment option for asymptomatic APS is the use of hydroxychloroquine. This drug is especially indicated if a woman has concomitant connective tissue diseases, including systemic lupus erythematosus. If there is a risk of thrombosis in asymptomatic patients (surgery, prolonged immobility), heparin is prescribed in a prophylactic dose.

Important factors in preventing thrombotic complications in asymptomatic patients are smoking cessation and normalization of body weight.

In the absence of pregnancy, the main means of preventing complications of APS is warfarin, which prevents the development of thrombosis. However, it is contraindicated during pregnancy. Its use during this period leads to the development of so-called warfarin embryopathy (damage to the fetus). It manifests itself as a developmental disorder skeletal system, nasal septum, neurological disorders.

In women with recurrent miscarriage, treatment with heparin is indicated. Studies have not shown any advantage of low molecular weight heparins over unfractionated heparins. However, low molecular weight heparins are more convenient, but more expensive. Treatment with low molecular weight heparins in combination with low doses of acetylsalicylic acid is prescribed. This therapy increases the chance of pregnancy and birth by two to three times. healthy child. The most commonly used drug is Enoxyparin at a dose of 20 mg per day subcutaneously. This drug does not cross the placenta and does not harm the unborn baby.

The use of glucocorticosteroid hormones for this purpose is much less effective. However, many scientists recommend using low doses of glucocorticoids (5-10 mg in terms of prednisolone) in addition to heparin preparations.

Glucocorticosteroids are necessarily used in the development of such complications during pregnancy as catastrophic microangiopathy. At the same time, anticoagulants, plasmapheresis, administration of frozen plasma and human immunoglobulin are prescribed.

Held drug therapy, aimed at preventing placental insufficiency.

After childbirth, a woman with APS is prescribed lifelong warfarin therapy.

Veronika Ulanova, director of the Family Source center, talks about how to diagnose and treat antiphospholipid syndrome during pregnancy:

In case of antiphospholipid syndrome (APS) in women with recurrent miscarriage, intrauterine fetal death or retardation of its development in the blood, antibodies produced by the pregnant woman’s body to its own phospholipids - special chemical structures, from which the walls and other parts of cells are built. These antibodies (AFA) become the cause of the formation of blood clots during the formation of placental vessels, which can lead to intrauterine growth retardation or fetal death, placental abruption, and the development of pregnancy complications. Also, lupus anticoagulant (a substance detected in the blood during systemic lupus erythematosus 1) is detected in the blood of women suffering from APS.

Complications of APS are miscarriage and premature birth, gestosis (complications of pregnancy, manifested by increased blood pressure, the appearance of protein in the urine, edema), fetal-placental insufficiency (in this condition, the fetus lacks oxygen).

With APS, the incidence of complications during pregnancy and childbirth is 80%. Antiphospholipid antibodies to various elements reproductive system found in 3% clinically healthy women, with miscarriage - in 7-14% of women, with a history of two or more spontaneous abortions - in every third patient.

Manifestations of antiphospholipid syndrome

At primary APS Only specific changes in the blood are detected.

At secondary APS pregnancy complications or infertility are observed in patients with autoimmune diseases such as systemic lupus erythematosus, autoimmune thyroiditis(inflammation of the thyroid gland), rheumatism, etc.

Primary and secondary APS have similar clinical manifestations: recurrent miscarriage, non-developing pregnancies in the first and second trimesters, intrauterine fetal death, premature birth, severe forms gestosis, fetal-placental insufficiency, severe complications postpartum period, thrombocytopenia (decreased platelet count). In all cases, the harbinger of the death of the ovum is the development chronic form DIC syndrome.

Observations show that without treatment, fetal death occurs in 90-95% of women with AFA.

Among patients with recurrent miscarriage, APS is detected in 27-42%. The frequency of this condition among the entire population is 5%.

Preparing for pregnancy with antiphospholipid syndrome

It is especially important to prepare for pregnancy for women who have a history of undeveloped pregnancies, spontaneous abortions (7-9 weeks), early and late toxicosis, chorionic detachment (placenta). In these cases, an examination for genital infections is carried out (using enzyme immunoassay- ELISA, polymerase chain reaction - PCR), study of hemostasis - indicators of the blood coagulation system (hemostasiogram), exclude the presence of lupus anticoagulant (LA), AFA, evaluate the immune system using special tests.

Thus, preparation for pregnancy includes the following stages:

Assessment of the state of the reproductive system of spouses. Correction endocrine disorders(hormone therapy).
Examination of a couple in order to identify an infectious agent using PCR (detection of pathogen DNA) and serodiagnosis (detection of antibodies to this pathogen), reflecting the degree of activity of the process. Treatment of identified infections using chemotherapy and enzyme drugs (BOBEIZYM, PHLOGENZYM), immunoglobulins (IMMUNOVENIAN).
Study of the state of the immune system, its correction with the help of medications (RIDOSTIN, VIFERON, KIPFERON); lymphocytotherapy (injection of the woman’s husband’s lymphocytes); control and correction of the microcirculatory hemostasis system (CURANTIL, FRAXIPARIN, INFUL).
Revealing autoimmune processes and the impact on them (for this, glucocorticoids and alternative drugs are used: enzymes, interferon inducers).
Correction energy metabolism both spouses: metabolic therapy to reduce oxygen deficiency in tissues - tissue hypoxia (INOSIE-F, LIMONTAR, KORILIP, metabolic complexes).
Psychocorrection - elimination of anxiety, fear, irritability; antidepressants are used, MAGNE-B6(this drug improves metabolic processes, including in the brain). Application various methods psychotherapy.
If you have illnesses various organs For spouses planning a pregnancy, consultation with a specialist is necessary, followed by an assessment of the degree of damage to the diseased organ, the adaptive capabilities of the body and the prognosis of fetal development, excluding genetic abnormalities.

Most often, in the presence of APS, a chronic viral or bacterial infection is detected. Therefore, the first stage of preparation for pregnancy is antibacterial, antiviral and immunocorrective therapy. At the same time, other drugs are prescribed.

The indicators of the hemostatic system (coagulation system) in pregnant women with APS differ significantly from the indicators in women with a physiological course of pregnancy. Already in the first trimester of pregnancy, platelet hyperfunction develops, often resistant to therapy. In the second trimester, this pathology can worsen and lead to an increase in hypercoagulation (increased blood clotting) and activation of intravascular thrombus formation. Signs of developing DIC syndrome appear in the blood. These indicators are detected using a blood test - coagulogram. In the third trimester of pregnancy, hypercoagulation phenomena increase, and they can be kept within limits close to normal only with active treatment under the control of blood coagulation parameters. Similar studies are carried out in these patients also during childbirth and the postpartum period.

The second stage of preparation begins with a re-examination after treatment. It includes control of hemopelvis, lupus anticoagulant (LA), LPA. When there are changes in hemostasis, antiplatelet agents are used - drugs that prevent the formation of blood clots (ASPIRIN, CURANTIL, TRENTAL, REOPOLIGLUKIN, INFUCOL), anticoagulants (GE-PARIN, FRAXIPARIN, FRAGMIN).

When a planned pregnancy occurs (after examination and treatment), dynamic control of the formation of the fetal-placental complex is carried out, prevention of fetoplacental insufficiency and correction of placental function when it changes (ACTOVEGIN, INSTENON).

Tactics of pregnancy management with antiphospholipid syndrome

From the first trimester, the most important period for fetal development in conditions of autoimmune pathology, hemostasis is monitored every 2-3 weeks. WITH early dates, it is possible in the cycle of planned conception to prescribe treatment with hormones - glucocorticoids, which have anti-allergic, anti-inflammatory, anti-shock effects. Combination of glucocorticoids (METIPRED,DEXA-METAZONE, PREDNISOLONE etc.) with antiplatelet agents and anticoagulants deprives the activity of AFA and removes it from the body. Thanks to this, hypercoagulation is reduced and blood clotting is normalized.

All patients with APS have a chronic viral infection (virus herpes simplex, papillomavirus, cytomegalovirus, Coxsackie virus, etc.). Due to the peculiarities of pregnancy, the use of glucocorticoids even in minimal doses may activate this infection. Therefore, during pregnancy, it is recommended to carry out 3 courses of preventive therapy, which consists of intravenous administration IMMUNOGLOBULI-ON in a dose of 25 ml (1.25 g) or OKTAGAMA 50 ml (2.5 g) every other day, three doses in total; suppositories with VIFERON. Small doses of immunoglobulin do not suppress the production of immunoglobulins, but stimulate the body's defenses.

Immunoglobulin is reintroduced after 2-3 months and before childbirth. The administration of immunoglobulin is necessary to prevent the exacerbation of a viral infection and to suppress the production of autoantibodies. At the same time, protection (passive immunity) from chronic infection and autoantibodies circulating in the blood, and indirectly - and protection of the fetus from them.

When immunoglobulin is administered, there may be complications in the form of allergic reactions, headaches, and sometimes cold-like symptoms occur (runny nose, etc.). To prevent these complications, it is necessary to check the immune, interferon status by determining immunoglobulins of the IgG, IgM, and IgA classes in the blood (IgM and IgA antibodies are produced when the infectious agent first enters the body and during exacerbation infectious process, IgG remain in the body after an infection). When IgA levels are low, administering immunoglobulin is dangerous due to possible allergic reactions. In order to prevent such complications, a woman is given antihistamines, after which they prescribe drinking plenty of fluids, tea, juices, and for symptoms similar to colds, antipyretics. These drugs should not be administered on an empty stomach; the patient should eat food shortly before the procedure.

IN last years studies have appeared in which one of the promising directions recognized in the treatment of APS infusion therapy solutions of hydroxyethylated starches (HES), leading to improved blood microcirculation in the vessels. Clinical studies of hydroxyethyl starch solutions of the second generation (INFUKOL-GEC) Many clinics in the Russian Federation have shown their effectiveness and safety.

It is known that thrombosis and ischemia of placental vessels (the appearance of areas where there is no blood circulation) in pregnant women with the presence of APS begins in the early stages of pregnancy, therefore treatment and prevention of placental insufficiency is carried out from the first trimester of pregnancy under control -lem of hemostasis. From 6-8 weeks of pregnancy, a gradual prescription of antiplatelet agents and anticoagulants is used against the background of glucocorticoid therapy (CURANTIL, THEONICOL, ASPIRIN, HEPARIN, FRAXIPARIN). In case of changes in hemostasis (hyperfunction of platelets, etc.) and resistance to antiplatelet agents, a course is prescribed in combination with this therapy INFUCOLA every other day intravenously.

Pregnant women with APS are at risk for developing fetoplacental insufficiency. They require careful monitoring of the state of blood circulation in the placenta, fetal-placental blood flow, which is possible during ultrasonic Dopplerometry. This study is carried out in the 2nd and 3rd trimesters of pregnancy, starting from 16 weeks, with an interval of 4-6 weeks. This makes it possible to timely diagnose the developmental features of the placenta, its condition, impaired blood flow in it, and also evaluate the effectiveness of the therapy, which is important when identifying fetal malnutrition and placental insufficiency.

To prevent fetal pathology, women with APS are prescribed therapy that improves metabolism from early pregnancy. This complex (which cannot be replaced by taking regular multivitamins for pregnant women) includes drugs and vitamins that normalize redox and metabolic processes at the cellular level of the body. During pregnancy, it is recommended to use a course of such therapy 3-4 times lasting 14 days (2 regimens of 7 days each). While taking these medications, multivitamins are discontinued, and between courses it is recommended to continue taking multivitamins.

To prevent placental insufficiency in women with APS, it is also recommended in the second trimester of pregnancy, from 16-18 weeks. AKTOVEGINA orally in the form of tablets or intravenously. If signs of fetal-placental insufficiency appear, drugs such as TROXEVAZIN, ESSENTIALE, LIMONTAR, COGITUM. If there is a suspicion of fetal developmental delay (hypotrophy), a course of special therapy is carried out (INFESOL and other drugs).

The tactics for managing pregnant women with APS, outlined in this article, have been tested in practice and have shown high efficiency: in 90-95% of women, pregnancy ends in a timely and safe manner, provided that the patients follow all necessary research and appointments.

Newborns in women with APS are examined only if the course of the early neonatal period is complicated (in the maternity hospital). In this case, a study is carried out immune status, and hormonal assessment child's condition.

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 fully known, but there are several theories of its origin:

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.
The genetic nature suggests familial cases of APS.
Phospholipids are common in nature human cells tissues 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.
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 of the pathological reactions occurring in 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 of the impact 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:

From the mother's side.
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, formidable 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.

It is necessary to take medications - low fractionated heparin (Clexane, Enoxyparin are most often used) and acetylsalicylic acid in low doses 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 in 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. With spontaneous birth and emergency cesarean, the situation becomes more complicated, but if LMWH were administered 8-12 hours in advance, 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.

In case of emergency caesarean section general anesthesia is used.

Antiphospholipid syndrome after childbirth

After delivery, anticoagulant therapy for antiphospholipid syndrome is resumed after 12 hours. If there is a high risk of thrombotic complications - after 6 hours. Treatment continues for 1.5 months after birth.