Antiphospholipid syndrome and its significance in pregnancy. Antiphospholipid syndrome: features of the course in pregnant women and treatment options Phospholipid syndrome during pregnancy

Unfortunately, pregnancy does not always end with the birth of a child. Some women are faced with such a diagnosis as habitual miscarriage. Often it is a consequence of the antiphospholipid syndrome. This is a serious and dangerous disease that can lead to spontaneous abortion, miscarriage, fetal growth retardation, death, placental abruption, preeclampsia, etc.

If a woman does not receive medical care during pregnancy, then in 95% of cases the child dies. However, with proper treatment, it becomes possible to endure and give birth to a healthy baby.

Antiphospholipid syndrome - what is it?

Antiphospholipid syndrome (APS) or Hughes syndrome is an autoimmune disorder that results in antibodies directed to phospholipids.

Phospholipids are found in the membranes of human cells. They help transport fats and cholesterol and dissolve hydrophobic substances. Phospholipids are needed for:

maintaining the plasticity of membranes and restoring them in case of damage;
affecting blood clotting and tissue regeneration.

If there is not enough phospholipids, then cell recovery does not occur, which threatens with serious disruptions in the body.

Antibodies can not only work properly, thereby protecting against viruses or bacteria, but also attack the right elements in the body. By acting on phospholipids, they most often disrupt cell membranes in vessels or platelets. The result can be a stroke, spontaneous abortion, intrauterine fetal fading and other diseases.

Among the main reasons that can serve as the development of APS is the presence of:

infectious diseases;
polyarteritis;
cancer diseases;
lupus erythematosus;
AIDS;
some vascular diseases;
genetic predisposition;
therapy with strong hormonal or psychotropic drugs.

Most often, APS occurs in women aged 20 to 40 years, men and children are less likely to suffer from this disease.

How does APS manifest itself?

Often, the disease may not be accompanied by any symptoms, so the person does not even realize that antibodies instead of viruses begin to affect phospholipids. In this case, only laboratory tests can reveal the pathology.

Among the symptoms that appear are the following:

reduced vision as a result of the appearance of blood clots in the retina;
hypertension occurs.
kidney failure develops;
protein appears in the urine;
a vascular pattern appears on the body, mainly on the hips, ankles or feet;
miscarriages, missed pregnancies, premature births occur.

Diagnosis of antiphospholipid syndrome during pregnancy

To diagnose APS during pregnancy, laboratory confirmation of the clinical manifestation of the disease is required. The latter can be expressed in various pathologies of pregnancy - repeated spontaneous abortions, frozen at any time of pregnancy, preeclampsia and eclampsia.

A doctor may suspect antiphospholipid syndrome if a woman has a history of:

three or more miscarriages or missed pregnancies for up to ten weeks;
more than once the fetus died for periods of more than ten weeks;
preterm birth before 34 weeks as a result of preeclampsia, eclampsia or placental insufficiency.

In order to confirm the diagnosis, enzyme immunoassays are performed:

blood test for antibodies to cardiolipin classes IgG and IgM;
coagulogram with tests for lupus anticoagulant;
blood test for antibodies to beta-2-glycoprotein 1;
blood test for homocysteine.

These tests should confirm or refute the disease. They are prescribed twice during pregnancy. The first - for up to 6 weeks, and the second - not earlier than 12 weeks, but usually at the end of the term.

What to do if APS is detected already during pregnancy?

As soon as the antiphospholipid syndrome has been identified, the woman is immediately prescribed therapy. Its purpose is to improve metabolism for the prevention of various pathologies in a child.

Treatment includes drugs and vitamins that normalize redox and metabolic processes at the cellular level. The course is carried out three or four times during the bearing of the baby. It is important during APS therapy to regularly monitor the condition of the placenta and the child using Doppler ultrasound in order not to miss their deterioration.

Features of the course of antiphospholipid syndrome during pregnancy

APS can negatively affect pregnancy from the very beginning, that is, from conception. Antibodies disrupt the cells of both the embryoblast and the trophoblast, resulting in a decrease in the depth of implantation. In addition, antibodies can cause insufficient production of progesterone, which is necessary for carrying a pregnancy.

Violations of the normal course of pregnancy can be caused by:

eclampsia and preeclampsia;
premature detachment of the placenta;
thrombocytopenia;
venous thromboembolic complications;
catastrophic APS.

For a child, antiphospholipid syndrome is dangerous:

habitual miscarriage;
premature birth;
inner death;
developmental delay;
fetal thrombosis.

In addition, after birth, the baby increases the risk of thrombosis, which is often accompanied by autism, as well as asymptomatic circulation of antibodies to phospholipids.

Management of pregnancy in antiphospholipid syndrome

To manage a pregnancy complicated by antiphospholipid syndrome, the doctor chooses tactics based on the results of enzyme immunoassays, as well as a history of complicated pregnancies.

In the event that the tests for antiphospholipid antibodies and lupus anticoagulant are positive, but the woman has not previously had any thrombosis or problems with pregnancy, aspirin is prescribed until the end of the term.

In other cases, when the tests are positive, but there were miscarriages, miscarriages, premature births, thrombosis, the doctor prescribes aspirin and low molecular weight heparin. Depending on whether pregnancies were complicated by thrombosis or not, the dosage of heparins depends.

If a woman has not only APS, but also lupus erythematosus, then glucocorticoids are additionally prescribed.

In addition to these medicines, the doctor, depending on the condition of the pregnant woman, may add iron preparations, Curantil and others.

If a woman receives treatment with heparins and aspirin, then she is given immunoglobulin to prevent the activation of chronic or new infections. It is also necessary to additionally use preparations containing calcium and vitamin D to replenish the supply of calcium.

If natural childbirth is planned, then aspirin is prescribed until 37 weeks, and heparins until contractions. With cesarean section, aspirin is canceled 10 days before the operation, and heparins the day before the operation.

In addition to drug therapy, it is important to carry out:

ultrasound examinations at least once a month to assess the condition of the placenta and fetus;
cardiotocography, starting from the third trimester, for the timely detection of hypoxia in a child;
tests to determine the level of antibodies to phospholipids twice during the entire period of pregnancy;
coagulogram, it is important to regularly take a blood clotting test.

Antiphospholipid syndrome in pregnancy planning

In preparation for conception, if APS is suspected, it is necessary to take tests for blood clotting, the level of antiphospholipid antibodies, and lupus anticoagulant. If the diagnosis is confirmed, the doctor prescribes treatment with the following medications:

low molecular weight heparin preparations, for example, Clexane, Fraxiparin, Fragmin;
antiplatelet agents, for example, Clopidogrel, more often Aspirin;
hormonal agents, for example, Utrozhestan;
magnesium, for example Magne B-6 or Magnelis;
folic acid;
preparations containing omega 3-6-9 (Omega-3 Doppelherz, Linetol).

Treatment with low molecular weight heparin and antiplatelet agents is carried out for several months, if the tests do not improve, then plasmapheresis is prescribed. This procedure allows you to purify the blood with the help of special devices.

As a result of therapy, when the tests return to normal, a woman can become pregnant. It should be noted that during attempts to conceive a baby, treatment continues so that the placenta is normally formed, and the risk of fetoplacental insufficiency is low.

Finally

Antiphospholipid syndrome negatively affects the process of conception even from the implantation of the fetal egg. In the future, a woman can lose a child at any stage of pregnancy. However, if the disease is detected in a timely manner and undergo appropriate therapy, which is recommended to be started even during preparation for conception, then the disease can be kept under control. The main thing is to carefully follow the recommendations of the attending physician and believe in a positive outcome. Many women with APS have been able to experience the joy of motherhood.

Specially for- Elena Kichak

One of the reasons for non-occurrence of pregnancy, repeated miscarriages (in all trimesters of pregnancy), missed pregnancy, premature birth is antiphospholipid syndrome. Unfortunately, most women learn about antiphospholipid syndrome during pregnancy after several unsuccessful attempts to carry a child.

Antiphospholipid syndrome (APS) is an autoimmune disorder in which antiphospholipid antibodies are present in the blood plasma and certain clinical manifestations are present. Such manifestations can be: thrombosis, obstetric pathology, thrombocytopenia, neurological disorders.

Antiphospholipid antibodies:

In 2-4% of women with a healthy pregnancy, antiphospholipid antibodies are found in the blood;

Women with repeated miscarriages or multiple missed pregnancies in 27-42% of cases have antiphospholipid antibodies;

The cause of thromboembolism in 10-15% of cases are antiphospholipid antibodies;

1/3 of strokes at a young age is also a consequence of the action of antiphospholipid antibodies.

Signs of antiphospholipid syndrome

The main symptom of antiphospholipid syndrome is venous or arterial thrombosis. With venous thrombosis, the veins of the lower leg are more likely to suffer, and with arterial thrombosis, the cerebral vessels.

The diagnosis of antiphospholipid syndrome requires clinical manifestation of the disease and laboratory confirmation. The clinical manifestation of the antiphospholipid syndrome during pregnancy is the pathology of pregnancy, repeated miscarriages, a history of missed pregnancies, preeclampsia and eclampsia, vascular thrombosis.

A laboratory sign of APS during pregnancy is the presence of a high titer of antiphospholipid antibodies in the blood.

Markers (types) of antiphospholipid antibodies:
Lupus anticoagulant (LA);
Antibodies to cardiolipin (aCL);
Antibodies to ß2-glycoprotein class 1 (aß2-GP1).

Antiphospholipid antibodies are autoimmune and infectious-caused.

Doctors can talk about a possible antiphospholipid syndrome during pregnancy if:

There has been more than one death of a child in a period of more than 10 weeks of pregnancy;

If there were premature births for a period of less than 34 weeks due to eclampsia, preeclampsia or placental dysfunction;

3 or more miscarriages (missed pregnancies) for less than 10 weeks.

As for the analysis for APS, it is prescribed twice to confirm the diagnosis. The interval between them should be at least 12 weeks (previously doctors recommended 6 weeks). The titer of antibodies should be high, more than 40. But in laboratories they offer much smaller values, for example:

Ab IgM to cardiolipin 8-above normal U/mLAT IgG to ß2-glycoprotein 8-above normal U/ml

Types of antiphospholipid syndrome are: primary, secondary and catastrophic.

Manifestations of antiphospholipid syndrome during pregnancy

The diagram below shows the manifestations of antiphospholipid syndrome during pregnancy. These are spontaneous abortions, that is, natural termination of pregnancy (miscarriages); delay in fetal development; premature birth and even intrauterine fetal death.

The effect of antiphospholipid syndrome on pregnancy:

APS has a thrombotic effect - placental vascular thrombosis, fetal growth retardation, recurrent miscarriage, preeclampsia.

Non-thrombotic effect of antiphospholipid syndrome - a decrease in progesterone, suppression of hCG synthesis, damage to the embryo. Pregnancy with APS does not occur due to a violation of the implantation of the blastocyst (conception has occurred, but there is no way for the baby to firmly attach and develop).

Drugs for the treatment of APS during pregnancy

Antiphospholipid syndrome during pregnancy must be treated in order to endure and give birth to a healthy baby. There are a number of drugs that a doctor prescribes:

Glucocorticoids;
Aspirin in small doses;
unfractionated heparin;
Low-dose aspirin + unfractionated heparin (effective);
Low molecular weight heparin (effective);
Low molecular weight heparin + aspirin in small doses (effective);
Warfarin;
Hydroxychloroquine;
Plasmapheresis (not recommended during pregnancy).

Antiphospholipid syndrome is the most common cause of thrombophilic complications and associated recurrent pregnancy loss. There are primary antiphospholipid syndrome and secondary - in the presence of an autoimmune disease (most often it is systemic lupus erythematosus). There is no big difference in all parameters between the primary and secondary antiphospholipid syndrome, only the symptoms of an autoimmune disease are added to the secondary. There is also a "catastrophic antiphospholipid syndrome".

The cause of the antiphospholipid syndrome is still unclear, it is believed that viral infections play a role. The pathogenesis of antiphospholipid syndrome is associated with the fact that autoantibodies with heterogeneous specificity are directed against negatively charged phospholipids or phospholipid-binding proteins.

Based on numerous studies by a working group of experts in this field, at the last symposium in September 2000 in France, the following criteria for antiphospholipid syndrome were adopted in order to be able to compare studies carried out in different countries.

Criteria for classification and definition of API

Clinical Criteria

Vascular thrombosis - one or more clinical episodes of arterial, venous in any tissue or organ. Thrombosis should be confirmed by doppler or histological examination, with the exception of thrombosis of superficial small veins. For histological confirmation, thrombosis should not be accompanied by inflammatory processes in the vascular wall.

During pregnancy:

One or more indeterminate death of a morphologically normal fetus older than 10 weeks of gestation, with normal morphology filed by ultrasound or direct examination of the fetus.
One or more premature births to morphologically normal newborns before 34 weeks' gestation due to preeclampsia or eclampsia, or severe placental insufficiency.
Three or more unclear causes of spontaneous miscarriages before 10 weeks of gestation in the mother after exclusion of anatomical, hormonal and genetic causes of abortion.

Laboratory Criteria:

Anticardiolipin antibodies of IgG and / or IgM isotypes in the blood, in an average or high titer 2 or more times in a row when studied with an interval of 6 weeks, investigated by a standard enzyme immunoassay for beta2-glycoprotein-1-dependent anticardiolipin antibodies.
Lupus anticoagulant present in plasma 2 or more consecutive times, assayed 6 weeks apart, assayed according to the guidelines of the International Society for Thrombosis and Hemostasis as follows:
- Prolongation of phospholipid-dependent coagulation in coagulation tests: activated partial thromboplastin time (APTT); clotting time with goat; research with snake venom; lengthening of prothrombin time, Textarin-time.
- Failure to correct clotting time in a screening test mixed with normal platelet-poor plasma.
- Shortening or correction of prolonged coagulation time by adding excess phospholipids to the screening test.
- Exclusion of other coagulopathies, i.e. factor VIII inhibitor, heparin, etc.

Laboratory criteria excluded such tests as low levels of anticardiolipin antibodies, IgA anticardiolipin antibodies, anti-beta2-glycoprotein-1, antibodies to prothrombin, annexin or neutral phospholipids, false-positive Wasserman test.

The Working Group believes that these methods require further study. As for anti-beta2-glycoprotein-1, which, according to most researchers, plays a key role in the occurrence of thrombophilia, this test needs intralaboratory standardization and technical improvement. Perhaps in the future, this test will be the main criterion in the diagnosis of antiphospholipid syndrome.

Currently, studies have appeared on the role of anti-beta2-glycoprotein-1 IgA and IgG in the development of antiphospholipid syndrome. In groups of women with a clinical picture of antiphospholipid syndrome in the absence of cardiolipin antibodies and VA, a high level of these antibodies was detected.

According to the literature data, the incidence of antiphospholipid syndrome among patients with recurrent pregnancy loss is 27-42%.

The population frequency of this condition has not been studied in our country, and in the USA it is 5%.

There are two classes of antiphospholipid antibodies formed under the influence of endogenous stimuli:

Antiphospholipid antibodies that prolong in vitro phospholipid-dependent coagulation reactions, affecting Ca 2+ - dependent binding of prothrombin and factors Xa, Va during the assembly of the prothrombin-activator complex (prothrombinase) - lupus anticoagulant (LA);
Antiphospholipid antibodies, which are determined by immunological tests based on cardiolipin - anticardiolipin antibodies (ACA).

Autoantibodies to phospholipids can arise under the influence of exogenous and endogenous stimuli. Exogenous stimuli are associated mainly with infectious antigens, they lead to the formation of transient antibodies that do not cause thromboembolic disorders. An example of such exogenous antiphospholipid antibodies are antibodies detected by the Wasserman reaction.

Antibodies formed under the influence of endogenous stimuli are associated with impaired endothelial hemostasis. These antiphospholipid antibodies cause thromboembolic disorders, often associated with strokes, heart attacks in young people, with other thrombosis and thromboembolism, the development of Snedon's syndrome. An explanation for this phenomenon was obtained in recent years, when it was found that binding of antibodies present in the sera of patients with autoimmune, but not infectious diseases, with cardiolipin requires the presence of a plasma component (cofactor), which was identified as beta-glycoprotein-1 beta1- GP-1). In a more detailed study of this phenomenon, scientists showed that antibodies to cardiolipin isolated from the sera of patients with autoimmune diseases reacted with cardiolipin only in the presence of UGP-1, while the binding of antibodies to cardiolipin (ACA) synthesized in patients with various infectious diseases ( malaria, infectious mononucleosis, tuberculosis, hepatitis A and syphilis), did not require a cofactor in the system. Moreover, the addition of beta2-GP-1 in some cases inhibited the interaction of the sera of patients with infectious diseases with cardiolipin. In a clinical analysis of the results obtained, it turned out that the development of thrombotic complications was associated with the synthesis of cofactor-dependent antibodies to cardiolipin. However, according to other data, even in patients with antiphospholipid syndrome, despite the presence of beta2-GP-1, the ability of antibodies to phospholipids (APA) to interact with cardiolipin is also determined by a number of other factors. Thus, the binding of low-avid antiphospholipid antibodies to cardiolipin depends to a greater extent on the presence of a cofactor in the system than is required in the case of the presence of high-avid antibodies in the sera of patients. On the contrary, A.E. Gharavi (1992) emphasizes that cofactor dependence is characteristic of highly avid antibodies. Earlier, when studying the sera of patients with antiphospholipid syndrome, it was shown that in addition to antiphospholipid antibodies, their blood serum contains a large number of various phospholipid-binding proteins that react with anionic phospholipids (apolipoproteins, lipocortins, placental anticoagulant protein, coagulation inhibitors, C-reactive protein, etc.).

The above data suggested the presence of at least two populations of cardiolipin-binding antibodies. Some of them (“infectious” antibodies) have the ability to directly recognize negatively charged epitopes of phospholipids, while others (“autoimmune” antibodies) react with a complex epitope consisting of phospholipid and beta2-GP-1, and possibly other phospholipid-binding proteins.

The development of thrombotic complications is associated with the synthesis of "autoimmune" (cofactor-dependent) antibodies.

In obstetric practice, lupus anticoagulant is of great importance. It is believed that the detection of lupus anticoagulant in the blood is a qualitative manifestation of the effect of certain levels of autoantibodies to phospholipids (cardiolipin, phosphatidylethanol, phosphatidylcholine, phosphatidylserine, phosphatidylinazitol, phosphotidylic acid) on the state of hemostasis.

An extremely interesting approach to the interpretation of the immunological aspects of miscarriage is presented in the works of A.Beer and J.Kwak (1999, 2000). The authors identify 5 categories of immune disorders that are the cause of recurrent miscarriage, IVF failures, and some forms of infertility.

I category - compatibility of spouses according to the HLA system and the relationship of the currently known antigens of the HLA system with impaired reproductive function. HLA compatibility, according to the authors, leads to ineffective "camouflage" of the placenta and makes it available to the mother's immune attack.
Category II - antiphospholipid syndrome associated with the circulation of antiphospholipid antibodies. The incidence of antiphospholipid syndrome among patients with recurrent miscarriage is 27-42%. The pathogenetic basis for the unsuccessful completion of pregnancy in APS is thrombotic complications that occur at the level of the uteroplacental pool. In addition, phosphatidylserine and phosphatidylethanalamine play an important role in the implantation process, as a "molecular glue". In the presence of antibodies to these phospholipids, the differentiation of cytotrophoblast into syncytiotrophoblast can be disrupted, which leads to the death of pregnancy in the early stages.
Category III immunological disorders include antinuclear, antihistone antibodies, which account for 22% of miscarriages of immune origin. In the presence of these antibodies, there may be no manifestations of autoimmune diseases, but inflammatory changes are found in the placenta.
IV category - the presence of antisperm antibodies. This category of immunological disorders occurs in 10% of patients with recurrent miscarriage and infertility. Antisperm antibodies are detected when women have antiphospholipid antibodies to serine or ethanolamine.
Category V is the most severe, it includes 45% of women with IVF failures with implantation failure. This category has several sections.

Section 1 is associated with an increase in the content of natural killers CD 56 in the blood over 12%. According to the authors, with an increase in CD 56+ above 18%, the death of the embryo always occurs. This type of cells is determined both in the blood and in the endometrium. In addition to their cytotoxic function, they synthesize proinflammatory cytokines, including TNFa. As a result of an excess of pro-inflammatory cytokines, implantation processes are disrupted, trophoblast cells are damaged, followed by the development of trophoblast and placental insufficiency and death of the embryo/fetus (similar data were obtained by other authors).

The 2nd section of category V is associated with the activation of CD19+5+ cells. A level above 10% is considered pathological. The main significance of these cells is associated with the production of antibodies to hormones that are essential for the normal development of pregnancy: estradiol, progesterone, human chorionic gonadotropin. In addition, the appearance of antibodies to thyroid hormones, growth hormones is possible. With pathological activation of CD 19+5+, luteal phase insufficiency develops, an inadequate response to ovulation stimulation, "resistant ovary" syndrome, premature "aging" of the ovaries, premature menopause. In addition to the direct effect on the listed hormones, with excessive activity of these cells, there is a lack of reactions preparatory to implantation in the endometrium and in the myometrium, and later in the decidual tissue. This is expressed in inflammatory and necrotic processes in the decidua, in violation of the formation of fibrinoid, in excessive deposition of fibrin.

Section 3 is associated with a high content of CD 19+5+ cells, which produce antibodies to neurotransmitters, including serotonin, endorphins, and enkephalins. These antibodies contribute to the resistance of the ovaries to stimulation, affect the development of the myometrium, and contribute to a decrease in blood circulation in the uterus during implantation. In the presence of these antibodies, patients may have depression, fibromyalgia, sleep disturbance, and panic.

Such a differentiated approach allows an individual approach to resolving the issue of the role of various immune aspects in the genesis of recurrent pregnancy loss. Unfortunately, such a clear division in clinical practice does not work. Most often, patients with antiphospholipid syndrome may have antibodies to hCG and antithyroid antibodies, etc.

In recent years, the problem of alloimmune relations regarding compatibility for antigens of the HLA system has been very widely discussed. Many researchers question the existence of this problem, given that HLA antigens are not expressed on the trophoblast. Research on this issue was raised back in the 70s. A number of researchers believed that leukocyte sensitization, like erythrocyte sensitization, is accompanied by spontaneous abortion. With Rh- and ABO-conflict pregnancy, the most common complication of the course of pregnancy is the threat of its termination. But even without sensitization, the threat of interruption is its most frequent complication. Even with severe damage to the fetus and its death from hemolytic disease, abortion often does not occur spontaneously. The work carried out by us over a number of years has shown that habitual miscarriage, as a rule, does not have a direct etiological connection with Rh and ABO sensitization. Frequent interruptions, especially after 7-8 weeks (the time of the appearance of the Rh factor in the fetus), can lead to the appearance of sensitization, which complicates the course of pregnancy. When managing such a pregnancy, complex problems arise. Is it worth examining and treating habitual miscarriage if the patient has Rh sensitization, since by maintaining the pregnancy in the early stages, you can get a fetus with an edematous form of hemolytic disease at a later date.

Particular attention in the literature is paid to the question of the role of histocompatibility antigens in miscarriage. The probability of maternal allosensitization to fetal leukocyte antigens is quite high, given their early formation and ability to cross the placenta. The question of the etiological role of leukocyte sensitization is considered extremely controversial. Many researchers etiologically associate leukosensitization with miscarriage and recommend immunosuppressive therapy.

Analysis of the data showed that in healthy multiparous women, antileukocyte sensitization is observed much more often than in pregnant women with recurrent miscarriage (33.6% and 14.9%, respectively). At the same time, a number of features are revealed: in women who had multiple pregnancies that ended in normal childbirth, leukosensitization was 4 times more likely than in those whose pregnancies were interrupted by induced abortion (33.6% versus 7.2%, respectively). The frequent detection of these antibodies in the blood of healthy multiparous women testified to their harmlessness for reproductive processes. On the other hand, an increase in the frequency of occurrence of lymphocytotoxic and leukoagglutinating antibodies in the blood of healthy women with an increase in the number of normally proceeding pregnancies culminating in childbirth indicates the physiological rather than pathological significance of this type of isosensitization. The production of antileukocyte antibodies is a natural process, since the fetus necessarily contains transplantation antigens that are incompatible with the mother, and they apparently protect the fetus from the damaging effect of the mother's immune lymphocytes.

According to studies, when studying the indicators of cellular immunity in pregnant women with miscarriage, it was not possible to find noticeable differences in them from women with a physiological pregnancy. The significance of the blast transformation reaction with phytohemagglutinin, the intensity of the blast transformation reaction in a mixed culture of lymphocytes, and the content of serum immunoglobulins did not differ statistically. At the same time, in case of miscarriage, the serum of women significantly more often stimulated cellular immunity, and the serum blocking factor was detected in uncomplicated pregnancy. In the physiological course of pregnancy, 83.3% of women had lymphocyte sensitization to fetal antigens. In pregnant women with recurrent miscarriage, cell sensitization was weaker and less common, and the blocking effect of serum was usually absent.

The revealed differences indicate a weakening of the blocking properties of the serum of pregnant women with threatening spontaneous abortion. Apparently, the immunoregulatory properties of blood serum play a decisive role in the development of pregnancy. With a decrease in the blocking properties of serum, the mechanisms leading to abortion are activated. Similar data have been obtained by many researchers.

This theory about the role of serum blocking properties in maintaining pregnancy is not recognized by many researchers. Their main motivation is that there are women with normal pregnancies who do not have blocking antibodies.

Moreover, methods for detecting blocking antibodies are not standardized and have low sensitivity to accurately and in different laboratories to obtain similar results. The determination of blocking antibodies by the reaction of a mixed culture of lymphocytes also has a number of defects:

variability of responses among different patients and even the same, but carried out at different times;
difficulties in assessing the degree of suppression, relative to the blocking activity;
the sensitivity of the method is unknown;
there is no standardization of the method and standards for evaluating the result;
there is no single method in data interpretation.

Despite this, many groups of researchers consider this problem among the immunological factors of miscarriage. It is believed that blocking antibodies can act in several ways. They can be directed against antigen-specific receptors on maternal lymphocytes, which prevents their reaction to antigens of fetoplacental tissues; or they may react with antigens in fetoplacental tissues and block their recognition by maternal lymphocytes. It is also believed that blocking antibodies are anti-idiotypic antibodies directed against the antigen-specific sides (idiotypes) of other antibodies, ie. receptor antigens on the surface of T-lymphocytes can be bound and therefore prevented from acting against the germ. There is evidence that they may be associated with anti-HLA-DR antigens and with anti-Fc antibody receptors.

In addition to blocking antibodies, there is evidence of the role of lymphocytoxic antibodies against the husband's lymphocytes. Most researchers believe that they, like blocking antibodies, are the result of a normal pregnancy. In 20%, they are detected after the first normal pregnancy, and they are found in 64% of many and safely giving birth women. In women with recurrent miscarriage, they are much less common (from 9 to 23%).

Along with this, there are works indicating that the presence of neutrophil-specific antibodies against paternal antigens in the mother may be accompanied by severe neutropenia in the fetus. The neutrophil-specific antigens NA1, NA2, NB1 and NC1 were first characterized by Lalezari et al. (1960). Other neutrophil antigens NB2, ND1, NE1 were discovered by Lalezari et al. (1971), Verheugt F. et al. (1978), ClaasF. et al. (1979) respectively.

N antigens are independent of other antigens present on the surface of neutrophils, such as HLA f. The most significant antigens that cause antibody production are NA 1 and NB1 antigens. The frequency of detection of neutrophil-specific antibodies varies in different studies from 0.2% to 20%. This difference is due to the fact that methods for detecting these antibodies have only recently become available and because severe neutropenia in newborns is rare. Most often, these children develop early infection and very quickly turn into sepsis. Therefore, the authors recommend that all newborns with unclear neutropenia, especially preterm infants, have maternal blood tests for the presence of antibodies to neutrophils. In the mother, the presence of antibodies to neutrophils does not give neutropenia, like Rh antibodies, provided that they are not autoimmune.

In women with miscarriage, autoantibodies against their own lymphocytes can be detected - lymphocytotoxic autoantibodies, which in women with recurrent miscarriage are detected in 20.5% of cases, while they are not detected in physiological pregnancy.

A decrease in the blocking properties of serum is associated with the compatibility of spouses for antigens of the HLA system (Human leycocyteantigens). The HLA system or the old name "major histocompatibility complex" is a group of genes whose proteins serve as identity markers on the surface of various cells with which T-lymphocytes interact through their own receptors in an immune response. They were first identified in transplant rejection. HLA consists of a group of class I, II and III genes located on the 6th chromosome. This system has a huge polymorphism and only within one chromosome, the number of possible combinations of its genes is 3x10 6 .

The HLA class I includes the HLA-A-B and -C loci - these genes represent a family of peptides that react with T-cytotoxic (CD8+) cells.

Class II includes loci HU \ DP, -DQ and DR - they mainly interact with T-helpers (CD4+). The class III region of genes is mainly involved in inflammation processes, contains alleles of complement components C2, C4 and Bf (properdin factor), as well as TNF (tumor necrosis factor) and a number of isoenzymes. In addition, it has recently been discovered that class I molecules also interact with NK cells, preventing cell lysis.

A large group of immunoglobulins similar to NK cell receptors was found on chromosome 19 - these are the so-called non-classical loci HLA-E, -F and G. They also take part in immune reactions, and the HLA-G locus of the fetus is expressed on the trophoblast.

Allelic variants of genes have different frequency of occurrence. The allele frequency trait is used as a genetic marker for a number of pathological conditions.

In recent years, the links between the HLA system and various diseases have been intensively studied. So it was found that autoimmune diseases such as arthritis, Reiter's disease in 95% are observed in patients who have the HLA B27 allele, i.e. almost 20 times more common than this antigen occurs in the population.

In 86.4% of patients with antiphospholipid syndrome, HLA DQ4 is determined. If the husband has HLA DQ 201, there will be anembryony in 50% of cases.

If the spouses have HLA B14, it is necessary to examine for the presence of the adrenogenital syndrome gene; with HLA B18, there is a high probability of having a child with developmental anomalies.

With habitual miscarriage, an increase in the frequency of occurrence of some alleles and HLA phenotypes was noted: A19, B8, B13, B15, B35, DR5, DR7, their occurrence is 19%, 9.5%, 19%, 17.5%, 22.2% , 69.6% and 39.1% versus 6.3%, 3.8%, 10.3%, 16.7%, 29.9% and 22.7%, respectively, in women with uncomplicated pregnancy.

In addition to the HLA phenotype, many researchers believe that the compatibility of spouses for HLA antigens plays a very important role. The main idea is that with HLA compatibility, antibodies that play the role of a blocking factor do not develop. If spouses are compatible for more than 2 HLA antigens, the risk of miscarriage is almost 100%.

Compatibility of spouses according to the HLA system and its importance in reproduction for a long time remains in the field of attention of immunologists and obstetricians. There is a whole line of research on the role of lymphocytotherapy in the treatment of recurrent miscarriage using paternal or donor lymphocytes, or both. There are many supporters of this therapy.

At the same time, there are many opponents of this therapy, who believe that compatibility is unlikely to play a role and lymphocytotherapy does not give the same effect as obtained from adherents of this therapy.

Different results have been obtained from methodologically different approaches to solving this problem: different groups of patients, different numbers of injected lymphocytes, different gestational periods at which therapy is carried out, etc.

There is also an original point of view in the literature about the HLA system. According to Chiristiansen O.B. et al. (1996), the compatibility effect of parental antigens may be of non-immunological origin. In experiments on mouse embryos, the authors showed the existence of a lethal recessive gene closely associated with HLA. Mouse embryos that are homozygous for certain HLA alleles die at different stages of embryogenesis. HLA similar complex can be in humans. If so, parental HLA compatibility may be secondary, reflecting homozygosity for the embryo for the HLA-associated lethal gene.

Phospholipid syndrome is a relatively common pathology of autoimmune origin. Against the background of the disease, lesions of blood vessels, kidneys, bones and other organs are often observed. In the absence of therapy, the disease can lead to dangerous complications up to the death of the patient. Moreover, often the disease is detected in women during pregnancy, which endangers the health of the mother and child.

Of course, many people seek additional information by asking questions about the causes of the development of the disease. What symptoms should you look out for? Is there an analysis for phospholipid syndrome? Can medicine offer effective treatments?

Phospholipid syndrome: what is it?

For the first time this disease was described not so long ago. Official information about him was published in the 1980s. Since the English rheumatologist Graham Hughes worked on the study, the disease is often called Hughes syndrome. There are other names - antiphospholipid syndrome and syndrome

Phospholipid syndrome is an autoimmune disease in which the immune system begins to produce antibodies that attack the body's own phospholipids. Since these substances are part of the membrane walls of many cells, the lesions in such a disease are significant:

Antibodies attack healthy endothelial cells, reducing the synthesis of growth factors and prostacyclin, which is responsible for the expansion of the walls of blood vessels. Against the background of the disease, there is a violation of platelet aggregation.
Phospholipids are also contained in the walls of the platelets themselves, which leads to increased aggregation of platelets, as well as rapid destruction.
In the presence of antibodies, a weakening of heparin activity is also observed.
The process of destruction does not bypass the nerve cells.

The blood begins to clot in the vessels, forming blood clots that disrupt the blood flow and, consequently, the functions of various organs - this is how the phospholipid syndrome develops. The causes and symptoms of this disease are of interest to many people. After all, the earlier the disease is detected, the fewer complications will develop in the patient.

The main causes of the development of the disease

Why do people develop phospholipid syndrome? The reasons may be different. It is known that quite often patients have a genetic predisposition. The disease develops in case of malfunctioning of the immune system, which for one reason or another begins to produce antibodies to the cells of its own body. In any case, the disease must be provoked by something. To date, scientists have been able to identify several risk factors:

Often, phospholipid syndrome develops against the background of microangiopathy, in particular trobocytopenia, hemolytic-uremic syndrome.
Risk factors include other autoimmune diseases, such as lupus erythematosus, vasculitis, and scleroderma.
The disease often develops in the presence of malignant tumors in the patient's body.
Risk factors include infectious diseases. Of particular danger is infectious mononucleosis and AIDS.
Antibodies may appear in DIC.
It is known that the disease can develop while taking certain medications, including hormonal contraceptives, psychotropic drugs, Novocainamide, etc.

Naturally, it is important to find out why the patient developed phospholipid syndrome. Diagnosis and treatment should identify and, if possible, eliminate the root cause of the disease.

Cardiovascular lesions in phospholipid syndrome

Blood and vessels are the first "targets" that the phospholipid syndrome affects. Its symptoms depend on the stage of development of the disease. Thrombi usually form first in the small vessels of the extremities. They disrupt the blood flow, which is accompanied by tissue ischemia. The affected limb is always colder to the touch, the skin turns pale, and the muscles gradually atrophy. Prolonged tissue malnutrition leads to necrosis and subsequent gangrene.

Deep vein thrombosis of the extremities is also possible, which is accompanied by the appearance of edema, pain, and impaired mobility. Phospholipid syndrome can be complicated by thrombophlebitis (inflammation of the vascular walls), which is accompanied by fever, chills, redness of the skin in the affected area and acute, sharp pain.

The formation of blood clots in large vessels can lead to the development of the following pathologies:

aortic syndrome (accompanied by a sharp increase in pressure in the vessels of the upper body);
syndrome (this condition is characterized by swelling, cyanosis of the skin, bleeding from the nose, trachea and esophagus);
(accompanied by impaired circulation in the lower body, swelling of the limbs, pain in the legs, buttocks, abdominal cavity and groin).

Thrombosis also affects the work of the heart. Often the disease is accompanied by the development of angina pectoris, persistent arterial hypertension, myocardial infarction.

Kidney damage and main symptoms

The formation of blood clots leads to a violation of blood circulation not only in the limbs - internal organs, in particular the kidneys, also suffer. With prolonged development of phospholipid syndrome, the so-called kidney infarction is possible. This condition is accompanied by pain in the lower back, a decrease in the amount of urine and the presence of blood impurities in it.

A thrombus can block the renal artery, which is accompanied by severe pain, nausea and vomiting. This is a dangerous condition - if left untreated, a necrotic process may develop. The dangerous consequences of the phospholipid syndrome include renal microangiopathy, in which small blood clots form directly in the renal glomeruli. This condition often leads to the development of chronic renal failure.

Sometimes there is a violation of blood circulation in the adrenal glands, which leads to a violation of the hormonal background.

What other organs can be affected?

Phospholipid syndrome is a disease that affects many organs. As already mentioned, antibodies affect the membranes of nerve cells, which cannot do without consequences. Many patients complain of constant severe headaches, which are often accompanied by dizziness, nausea and vomiting. There is a possibility of developing various mental disorders.

In some patients, blood clots are found in the vessels that supply the visual analyzer with blood. Prolonged deficiency of oxygen and nutrients leads to atrophy of the optic nerve. Possible thrombosis of the retinal vessels with subsequent hemorrhage. Some of the eye pathologies, unfortunately, are irreversible: visual impairments remain with the patient for life.

Bones may also be involved in the pathological process. People are often diagnosed with reversible osteoporosis, which is accompanied by skeletal deformity and frequent fractures. More dangerous is aseptic bone necrosis.

Skin lesions are also characteristic of the disease. Often, spider veins form on the skin of the upper and lower extremities. Sometimes you can notice a very characteristic rash that resembles small, pinpoint hemorrhages. Some patients develop erythema on the soles of the feet and palms. There is frequent formation of subcutaneous hematomas (for no apparent reason) and hemorrhages under the nail plate. A long-term violation of tissue trophism leads to the appearance of ulcers that take a long time to heal and are difficult to treat.

We found out what constitutes a phospholipid syndrome. The causes and symptoms of the disease are extremely important questions. After all, the treatment regimen chosen by the doctor will depend on these factors.

Phospholipid Syndrome: Diagnosis

Of course, in this case it is extremely important to detect the presence of the disease in time. A doctor can suspect phospholipid syndrome even during the collection of anamnesis. The presence of thrombosis and trophic ulcers in the patient, frequent miscarriages, signs of anemia can lead to this thought. Of course, further examinations are carried out in the future.

Analysis for phospholipid syndrome consists in determining the level of antibodies to phospholipids in the blood of patients. In the general blood test, you can notice a decrease in the level of platelets, an increase in ESR, an increase in the number of leukocytes. Often, the syndrome is accompanied by hemolytic anemia, which can also be seen during a laboratory study.

Additionally, blood is taken. Patients have an increase in the amount of gamma globulins. If the liver was damaged against the background of pathology, then the amount of bilirubin and alkaline phosphatase increases in the blood. In the presence of kidney disease, an increase in the level of creatinine and urea can be observed.

Some patients are also recommended specific immunological blood tests. For example, laboratory tests may be performed to determine rheumatoid factor and lupus coagulant. With phospholipid syndrome in the blood, the presence of antibodies to erythrocytes, an increase in the level of lymphocytes can be detected. If there are suspicions of severe damage to the liver, kidneys, bones, then instrumental examinations are performed, including x-ray, ultrasound, tomography.

What complications are associated with the disease?

Left untreated, phospholipid syndrome can lead to extremely dangerous complications. Against the background of the disease, blood clots form in the vessels, which in itself is dangerous. Blood clots clog blood vessels, disrupting normal blood circulation - tissues and organs do not receive enough nutrients and oxygen.

Often, against the background of an illness, patients develop a stroke and myocardial infarction. Blockage of the vessels of the extremities can lead to the development of gangrene. As mentioned above, patients have impaired functioning of the kidneys and adrenal glands. The most dangerous consequence is pulmonary embolism - this pathology develops acutely, and not in all cases the patient can be delivered to the hospital on time.

Pregnancy in patients with phospholipid syndrome

As already mentioned, phospholipid syndrome is diagnosed during pregnancy. What is the danger of the disease and what to do in such a situation?

Due to the phospholipid syndrome, blood clots form in the vessels, which clog the arteries that carry blood to the placenta. The embryo does not receive enough oxygen and nutrients, in 95% of cases this leads to miscarriage. Even if the pregnancy is not interrupted, there is a risk of early placental abruption and the development of late gestosis, which is very dangerous for both the mother and the child.

Ideally, a woman should be tested at the planning stage. However, phospholipid syndrome is often diagnosed during pregnancy. In such cases, it is very important to notice the presence of the disease in time and take the necessary measures. For the expectant mother, small doses of anticoagulants may be prescribed. In addition, a woman should regularly undergo examinations so that the doctor can notice the onset of placental abruption in time. Every few months, expectant mothers undergo a course of general strengthening therapy, taking preparations containing vitamins, minerals and antioxidants. With the right approach, pregnancy often ends safely.

What does the treatment look like?

What to do if a person has phospholipid syndrome? Treatment in this case is complex, and it depends on the presence of certain complications in the patient. Since blood clots form against the background of the disease, the therapy is primarily aimed at thinning the blood. The treatment regimen, as a rule, includes the use of several groups of drugs:

First of all, anticoagulants of indirect action and antiplatelet agents ("Aspirin", "Warfarin") are prescribed.
Often, therapy includes selective non-steroidal anti-inflammatory drugs, in particular Nimesulide or Celecoxib.
If the disease is associated with systemic lupus erythematosus and some other autoimmune diseases, the doctor may prescribe glucocorticoids (hormonal anti-inflammatory drugs). Along with this, immunosuppressive drugs can be used to suppress the activity of the immune system and reduce the production of dangerous antibodies.
Immunoglobulin is sometimes given intravenously to pregnant women.
Patients periodically take drugs containing B vitamins.
For general health improvement, protection of blood vessels and cell membranes, antioxidant drugs are used, as well as drugs that contain a complex of polyunsaturated fatty acids (Omacor, Mexicor).

Electrophoresis procedures have a beneficial effect on the patient's condition. When it comes to secondary phospholipid syndrome, it is important to control the primary disease. For example, patients with vasculitis and lupus should receive adequate treatment for these pathologies. It is also important to detect infectious diseases in time and carry out appropriate therapy until complete recovery (if possible).

Patient Predictions

If the phospholipid syndrome was diagnosed on time and the patient received the necessary assistance, then the prognosis is very favorable. Unfortunately, it is impossible to get rid of the disease forever, but with the help of medicines it is possible to control its exacerbations and carry out preventive treatment of thrombosis. Situations in which the disease is associated with thrombocytopenia and high blood pressure are considered dangerous.

In any case, all patients diagnosed with phospholipid syndrome should be under the control of a rheumatologist. How many times the analysis is repeated, how often you need to undergo examinations with other doctors, what drugs you need to take, how to monitor the state of your own body - the attending physician will tell you about all this.

Such an unpleasant condition as antiphospholipid syndrome, or as it is also called Hughes syndrome, is considered to be a fairly common disease among those women who have already repeatedly or even several times do not carry a normal pregnancy. It should be noted that with the development of this syndrome in the body of a woman, antibodies can be produced to special components of cell walls (or, more correctly, to phospholipids), and as a result, blood clots can form directly during the formation of placental vessels. And then everything will develop, to put it mildly, not very pleasant. Usually this can lead to a real delay in the development of the fetus itself, and sometimes, perhaps even to its death. This is followed by other complications of this pregnancy.

It should be said that antiphospholipid syndrome, first of all, can occur due to the development of a variety of diseases - it can be lupus erythematosus, systemic scleroderma, and even arthritis. Also, the real causes of this extremely unpleasant and dangerous syndrome can be various chronic infections, and even malignant tumors. Among all the listed diseases, most often, namely, in more than 70% of all cases, phospholipid bodies will be produced precisely in such a disease as systemic lupus erythematosus.

It will be best at a time when you, in order to avoid such extremely unpleasant consequences, go through the most complete and high-quality, including, of course, the presence of this syndrome. However, most often, unfortunately, it turns out that this disease is found in a woman after conception. And then in this case, in order to be able to save the fetus, experienced doctors prescribe a completely special therapy. As a rule, with its help, it is still possible to somewhat improve metabolism, since this set of therapeutic measures includes various drugs and vitamins that can almost completely normalize all redox processes at the cellular level. I must say that this whole procedure is a rather complicated and responsible process, in which the blood circulation of the unborn baby and the maternal placenta will also have to be monitored without fail. Usually a full course of therapy consists of three or even four stages throughout the pregnancy.

However, we hasten to reassure you - such a diagnosis as antiphospholipid syndrome does not mean at all that you are not capable or will not be able to give birth to an absolutely healthy, normally developed child. In cases where the disease is detected in a timely manner, and the woman herself is ready to almost unquestioningly adhere to all the recommendations of her doctors, then both pregnancy and childbirth are likely to be successful.

But the main signs of antiphospholipid syndrome will depend on so many different factors. Moreover, the most important symptom of this syndrome is that a very thin network of vessels becomes noticeable directly on the skin of a woman, which is much more clearly and strongly visible precisely in the cold. And among other symptoms - these are chronic ulcers on the legs and even peripheral gangrene.

Among doctors, it is customary to divide the antiphospholipid syndrome into its individual forms. As a rule, it is divided into primary and also secondary syndromes. We can say that between them in general, there is no particular big difference. However, it is the secondary syndrome that will necessarily have the symptoms of a specific autoimmune disease. In addition, it sometimes happens that a simply catastrophic antiphospholipid syndrome begins to develop. And already such a condition usually proceeds suddenly and can be characterized by multiple organ failure.

In addition, it is important to know that the antiphospholipid syndrome manifested precisely in can have the most direct negative and even damaging effect on the fetal egg itself. As a rule, this can lead to a subsequent completely spontaneous or miscarriage.

But in order to clearly diagnose this syndrome, it will be necessary to conduct a comprehensive qualified assessment of both anamnestic, clinical and, of course, laboratory data. And in those cases, if you still have phospholipid antibodies, do not rush to panic, just contact an experienced specialist right away. He then will have to observe you literally throughout the pregnancy. He will also be able to monitor the activity of the so-called autoimmune process, as well as the state of the entire blood coagulation system. With such a specialist, you will be able to timely carry out prevention, diagnosis and the necessary adequate treatment of all possible disorders.

For yourself, you must remember that during observation, as well as during treatment, the course of all your previous pregnancies will be of great importance. Especially if you have previously experienced spontaneous abortions that occur before the tenth week of pregnancy, the causes of which were not clearly clarified then. Or in those cases when you had those that occurred due to too severe preeclampsia or due to placental insufficiency.

In any case, the most important thing for a pregnant woman is not to panic right away if, for example, you have such an unpleasant antiphospholipid syndrome. Remember, modern technologies really allow, with the exact and careful observance of all the necessary medical recommendations, to give birth to an absolutely healthy child, and without the slightest complications.