Antiphospholipid syndrome: features of the course in pregnant women and treatment options. The cause of infertility is antiphospholipid syndrome Phospholipid syndrome during pregnancy treatment

Antiphospholipid syndrome (APS) is a set of clinical and laboratory signs 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 set of features develops, including:

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

The causes of this condition are unknown. There is some relationship with past infectious diseases. There is a hereditary predisposition to the development of APS. This syndrome can 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. Consider what symptoms can help in the diagnosis of APS before pregnancy. This is necessary in order to start treatment on time and prevent the death of the fetus.

The most common symptom of the disease is. The deep veins of the lower extremities are most often affected. But sometimes the superficial veins also suffer, as well as the vessels of the liver, adrenal glands and other organs. Deep vein thrombosis is accompanied by pain and swelling of the limb, an increase in its temperature. In this condition, a dangerous complication can develop -. It can be manifested by a persistent cough, hemoptysis, shortness of breath. In more severe cases, there is a sharp pain in the chest, severe shortness of breath, cyanosis of the skin. Thromboembolism of the pulmonary artery can lead to the death of the patient.

When a young woman develops a stroke, transient ischemic attack, episodes of severe dizziness, seizures, thrombosis of the cerebral arteries caused by APS should always be excluded. In some cases, arterial thrombosis can manifest itself as migraine or even acute mental disorders.

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

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

In the blood of patients, a decrease in the number of platelets is found. Quite often, thrombocytopenia is combined with hemolytic anemia. The tendency to bleeding is uncharacteristic and occurs most often with an overdose.

Obstetric pathology in APS

Three or more cases of spontaneous abortions at an early stage are the basis for examining a woman for antibodies to cardiolipin.

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

Developmental delay or intrauterine fetal death develops, phenomena occur. Pregnancy is interrupted most often in the II and III trimesters. Without treatment, such a sad outcome is observed in 90 - 95% of patients. With timely correct therapy, the probability of an unfavorable development of pregnancy is up to 30%.

Variants of the pathology of pregnancy:

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

Features of pregnancy management

During the planning period for pregnancy, a woman should be carefully examined by a rheumatologist, cardiologist and other specialists.

During gestation, monthly ultrasound monitoring of fetal development is necessary. Placental circulation should be assessed using dopplerometry. In the III trimester, it is necessary to regularly conduct cardiotocography in order not to miss the onset of fetal oxygen starvation due to placental insufficiency.

The determination of antibodies to phospholipids is carried out at the 6th week of pregnancy and before the planned birth.

The indicators of the blood coagulation system should be determined regularly, including after childbirth. This will help reduce the risk of thrombotic complications.
With changes indicating increased blood clotting, the dose of heparin received by the patient should be increased.

Heparin, including low molecular weight, requires the rejection 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 was diagnosed with APS before pregnancy, there are no clinical manifestations of the disease, and it is manifested only by laboratory changes, treatment may include only acetylsalicylic acid at a dose of up to 100 mg per day, but the benefit of such therapy has not been fully established.

Another treatment option for asymptomatic APS is 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 the prevention of 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 the so-called warfarin embryopathy (fetal damage). It is manifested by a violation of the development of the 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. 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. Such therapy increases the chance of pregnancy and birth by two to three times. healthy child. Enoxiparin is most often used 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 the use of low doses of glucocorticoids (5-10 mg in terms of prednisone) 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, the introduction of frozen plasma and human immunoglobulin are prescribed.

Conducted drug therapy aimed at the prevention of placental insufficiency.

After delivery, a woman with APS is put on lifelong warfarin therapy.

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

During the first trimester, the most important period for autoimmune pathology, we carry out hemostasis control every 2 weeks. From the 2nd day after ovulation in the conception cycle, the patient receives 1 t (5 mg) of prednisolone or metipre-alpha. Vitamins for pregnant women or metabolic complexes, folic acid and, if necessary, we add antiplatelet agents and / or anticoagulants. Of the antiplatelet agents in the first trimester, it is preferable to use chimes N at a dose of 25 mg 3 times a day. If signs of hypercoagulation or RKMF appear, add heparin 5,000 IU 3 times subcutaneously or LMWH (fraxiparin) 0.3 ml subcutaneously 1 time per day or fragmin 0.2 ml (2.500 IU) 2 times subcutaneously to the treatment until hemostasis parameters normalize.

An alternative option for anticoagulant and antiplatelet therapy is the use of rheopolyglucin 400.0 and 10,000 IU of heparin intravenously by drip every other day - 2-3 droppers. This therapy option can be used almost throughout pregnancy to avoid long-term use of a combination of glucocorticoids and heparin.

Based on our own extensive experience and good clinical results in the treatment of this category of patients, we should dwell on some debatable issues in the treatment of antiphospholipid syndrome during pregnancy.

Monotherapy with unfractionated heparin or even in combination with aspirin does not give such therapeutic success as we would like. Monotherapy with LMWH (fraxiparine, fragmin) is preferred over heparin. According to Shehota H. et al. (2001), where the main type of therapy for antiphospholipid syndrome is aspirin and LMWH, the incidence of preeclampsia is 18%, intrauterine growth retardation is 31% and premature birth 43%, perinatal mortality 7%.

According to studies, the frequency of complications for the fetus with different regimens of anticoagulant therapy is different. So, when using warfarin with or without heparin, pregnancy loss was 33.6%, fetal defects 6.4%; heparin during the entire pregnancy from 6 weeks - no malformations were detected, the pregnancy loss rate was 26.5%.

Another controversial issue is the use of immunoglobulin in the treatment of pregnant women with antiphospholipid syndrome. All patients with antiphospholipid syndrome have a chronic viral infection. Due to the peculiarities of the course of pregnancy, the use of glucocorticoids, even in minimal doses, reactivation of a viral infection is possible. Therefore, during pregnancy, it is recommended to carry out 3 courses of preventive therapy, which consists of intravenous administration of immunoglobulin at a dose of 25 ml (1.25 g) every other day, only 3 doses, while prescribing suppositories with viferon. Small doses of immunoglobulin do not suppress their own production of immunoglobulins, but stimulate the body's defenses.

Re-introduction of immunoglobulin is carried out at 24 weeks of pregnancy and before childbirth. This is one side of the issue - the introduction of immunoglobulin to prevent the activation of a viral infection.

There is another side, the use of large doses of immunoglobulin to suppress the production of autoantibodies.

There is evidence that large doses of immunoglobulin suppress the production of autoantibodies and this method can be used instead of glucocorticoid therapy. There is a whole series of works on the effectiveness of the use of immunoglobulin. Thus, according to studies, the combination of the use of small doses of aspirin, heparin and intravenous immunoglobulin at a dose of 1 g / 1 kg of body weight for 2 days of each month of pregnancy up to 36 weeks gave very good results - all patients successfully completed pregnancy. Immunoglobulin administration was started before 12 weeks of gestation, and these groups included patients who had the same therapy without immunoglobulin in previous pregnancies that ended adversely for the fetus. However, there are many opponents of immunoglobulin therapy and their main points are that:

• immunoglobulin is a very expensive drug, large doses must be used, and the cost of treatment is from 7,000 to 14,000 US dollars;
• there is the possibility of transmitting any viruses if the immunoglobulin is not well prepared;
• there are complications from the introduction of immunoglobulin in the form of headache, nausea, hypotension;
• the use of immunoglobulin does not significantly improve the outcome of treatment with heparin and aspirin.

Despite objections, interest in immunoglobulin therapy is extremely high. Only the excessive high cost of this drug for our patients and the impossibility of using domestic immunoglobulin in large doses due to possible anaphylactic complications limits the use of this extremely effective method therapy. With the introduction of immunoglobulin, there may be complications in the form of allergic reactions, headache, and often minor symptoms of acute respiratory disease. To prevent these complications, it is necessary to analyze the total levels of immunoglobulins in the blood of the IgG, IgM and IgA classes. With a low level of IgA, it is dangerous to administer immunoglobulin due to possible anaphylactic reactions. It is possible to recommend the introduction of antihistamines before and after the administration of immunoglobulins, prescribe plenty of fluids, tea, coffee, juices, and antipyretics in case of acute respiratory infections. As a rule, all complications pass in a day or two. An integral part of the management of pregnancy in patients with antiphospholipid syndrome is the prevention of placental insufficiency.

The state of the fetoplacental system in antiphospholipid syndrome

The pathogenetic effect of antiphospholipid antibodies is associated with thrombosis in the vessels of the placenta with the formation of infarcts in the placenta and impaired blood microcirculation. The consequence of these disorders is the development of placental insufficiency. According to ultrasound, placental insufficiency is diagnosed when there are signs of fetal hypotrophy. However, a careful examination of the placenta reveals the presence of heart attacks, cysts, thinning, placenta reduction, placental phenomena and other changes that indicate a violation of the normal functioning of the placenta. Cardiotocography data are also informative in assessing the condition of the fetus in patients with antiphospholipid syndrome. In 70% of pregnant women, despite ongoing therapy, one or another degree of chronic fetal hypoxia is detected. However, CTG data are informative only after 34 weeks of pregnancy. Doppler ultrasound of the fetal-placental blood flow has a great prognostic value in assessing the condition of the fetus. Doppler ultrasound in various pools of the fetoplacental system is a valuable diagnostic method for assessing the condition of the fetus, can serve as a criterion for the effectiveness of therapy and be one of the indicators that determine the timing and methods of delivery. The study is carried out from 16-20 weeks at intervals of 3-4 weeks before delivery. If the hemostasiogram parameters worsen, Doppler is performed weekly to assess the effectiveness of the therapy.

The conducted Doppler studies of blood flow in the umbilical artery in dynamics during miscarriage showed that "zero" and "negative" blood flow at any gestational age are extremely unfavorable signs in assessing the condition of the fetus, the therapy does not give any effect, which corresponds to the literature data. In such cases, if the duration of pregnancy allows, urgent delivery is necessary. The discrepancy between blood flow indicators and gestational age (both “leading” and “lag”) is also an unfavorable sign that requires more intensive therapy to normalize blood flow, improve placental function and combat chronic fetal hypoxia. "Advance" is considered significant when the difference is 8 or more weeks.

Thus, dopplerometry of the fetal-placental blood flow, carried out in the dynamics of pregnancy, allows you to evaluate the effectiveness of the therapy and more accurately determine the timing of delivery.

Prevention and treatment of placental insufficiency in patients with antiphospholipid syndrome should be carried out from the first trimester of pregnancy. The complex of preventive measures, in addition to antiplatelet and, if necessary, anticoagulant therapy, includes courses of metabolic therapy carried out regularly throughout pregnancy with two-week breaks.

For the treatment of placental insufficiency in patients with antiphospholipid syndrome, it is advisable to use such agents as intravenous administration of actovegin at a dose of 5 ml in 250.0 ml of physiological sodium chloride solution (course - 5 droppers every other day), alternating with instenon at a dose of 2.0 ml in 200 0 ml of physiological sodium chloride solution, also 5 droppers. It is advisable to use Essentiale Forte intravenously drip or jet slowly, or in capsules, troxevasin intravenously or in capsules.

It is advisable to treat placental insufficiency under the control of Doppler fetal-placental blood flow, hemostasiograms in order to assess the effectiveness of the therapy, select the optimal timing of delivery and avoid iatrogenic complications.

With placental insufficiency and the absence of the effect of drug therapy, plasmapheresis is advisable.

Such tactics of management and therapy before and during pregnancy allows us to complete pregnancy without serious complications in 95-96.7% of women with recurrent pregnancy loss due to antiphospholipid syndrome.

Thus, the combination of several differently directed drugs in a minimal but effective dose allows you to get the best effect with fewer iatrogenic complications.

In recent years, there have been reports of the use of fish oil capsules in the treatment of patients with antiphospholipid syndrome in a dosage equivalent to 5.1 g of eicosapentoic acid (EPA) and decosahexaenoic acid (DHA) in a ratio of 1:1.5. EPA and DHA are unsaturated fatty acids derived from marine plankton. They are able to competitively suppress the saturation and elongation of the alpha chain of the precursor of arachidonic acid, minoleate. Due to their ability to inhibit the formation of thromboxane A, and platelet aggregation, these acids have antithrombotic activity.

Little experience of use does not allow us to assess the preventive significance of this method of therapy.

When managing patients with antiphospholipid syndrome, it is extremely important to obtain not only a live, but also a healthy child, since almost 90% or more pregnancies die without therapy, and only 10% are born alive. Therefore, an important aspect is to assess the course of the neonatal period of children in mothers with antiphospholipid syndrome. In mothers with antiphospholipid syndrome, using modern medical and diagnostic technologies, 90.8% of children are born full-term and do not have gross violations in the functioning of vital organs and systems. The identified deviations during the early neonatal period are regarded as a strain of adaptive mechanisms due to the peculiarities of the prenatal period of development, which makes it possible to classify these children as a category of increased risk of adaptation failure. Features of the endocrine status in the form of hypocortisolemia at birth (46%) and thyroid insufficiency (24%) are transient, as a rule, do not require hormone replacement therapy and disappear within the first month of life. Changes in the immune status, such as an increase in the blood content of T-lymphocytes (CD3+), T-chelopers (CD4+), B-lymphocytes (CD19+), the proportion of cells expressing adhesion molecules (CD11 p+), an increase in the level of serum interferon in reduced interferon-producing activity of cells, are of a compensatory-adaptive nature and indicate a tense state of the immune system during early neonatal adaptation, which is consistent with a tendency to develop infectious and inflammatory pathology.

In newborns born to mothers with antiphospholipid syndrome, it is advisable to conduct control studies to assess the pituitary-thyroid-adrenal gland system in the complicated course of the period of early neonatal adaptation for timely corrective therapy. Changes in the immune status revealed during the neonatal period make it possible to recommend dispensary observation of these children for the timely prevention of infectious and inflammatory diseases.

Prevention of thromboembolic complications after childbirth

The postpartum period is the most dangerous for the health of a puerperal with antiphospholipid syndrome, since thromboembolic complications are observed more often than during pregnancy. In our practice, we had all cases of thrombophilic complications in postpartum period.

In order to prevent thromboembolic complications, it is necessary to continue taking prednisolone for two weeks at a dose of 5-10 mg. The hemostasis system is assessed 3-5 days after delivery. With severe hypercoagulation, it is advisable to conduct a short course of heparin therapy at a dose of 10 thousand or 20 thousand IU per day subcutaneously for 10-12 days (fraxiparin, fragmin is preferable) and prescribe aspirin 100 mg for a month.

When pain in the joints, fever, proteinuria and other symptoms of autoimmune diseases appear, examination by rheumatologists should be recommended, since subclinical autoimmune disorders often precede the manifest forms of autoimmune diseases.

"Catastrophic" antiphospholipid syndrome

Currently, along with the habitual and secondary antiphospholipid syndrome, clinical and serological variants of the antiphospholipid syndrome are isolated (Asherman R.A., 1997).

• "Catastrophic" antiphospholipid syndrome.
• Other microangiopathic syndromes:
  • thrombotic thrombocytopenic purpura;
  • hemolytic uremic syndrome;
  • HELLP syndrome (hemolysis, elevated liver enzymes, thrombocytopenia)
• Syndrome of hypothrombinemia;
• Disseminated intravascular coagulation;
• Antiphospholipid syndrome in combination with vasculitis.

"Catastrophic" antiphospholipid syndrome - a term proposed by Asherman R.A. in 1992, previously known as "devastating non-inflammatory vasculopathy" (Ingram S. et al., 1987), is characterized by the development of multiple organ failure due to recurrent thrombosis in various organs over a short period of time.

The combination of this syndrome with the development of DIC worsens the prognosis. The genesis of the "catastrophic" antiphospholipid syndrome is more complex than that which occurs in the antiphospholipid syndrome. It is believed that various cellular mediators (cytokines) responsible for the "explosion" of the clinically manifested inflammatory response with the development of multiple organ failure take part in its development.

This paper presents a review of data on pregnancy in some rheumatic diseases with a focus on antiphospholipid syndrome (APS). APS is a systemic autoimmune disease associated with vascular thrombosis and/or repeated episodes of fetal death under conditions of persistently elevated levels of antiphospholipid antibodies. Antiphospholipid antibodies are a heterogeneous group of antibodies that react with phospholipids, phospholipid-binding proteins, and phospholipid-protein complexes. Antiphospholipid antibodies can affect the growth and development of the fetus, and this effect can occur at any stage of pregnancy. The factors influencing the outcome of pregnancy, the development of neonatal pathology were analyzed, the risks of possible complications of rheumatic diseases in this category of patients were assessed. Particular attention is paid to planning and preparation for pregnancy. The tactics of managing pregnant women with APS, the dosage regimen largely depend on the previous history (presence / absence of non-placental thrombosis, the number of spontaneous abortions, previous therapy). In this regard, the article defines clinical groups with various types therapy.
It should be noted that some of the tools discussed drug treatment are not approved by national regulatory authorities (Roszdravnadzor, FDA, etc.) and, as a rule, are prescribed in real clinical practice without official indications (“off label”).

Keywords: antiphospholipid syndrome, pregnancy, prevention of exacerbations.

For citation: Trofimov E.A., Trofimova A.S. Antiphospholipid syndrome: features of the course in pregnant women and treatment options // BC. 2016. No. 15. P. 1032–1036.

For citation: Trofimov E.A., Trofimova A.S. Antiphospholipid syndrome: features of the course in pregnant women and treatment options. breast cancer. Mother and child. 2016;15:1032-1036.

The course of antiphospholipid syndrome during pregnancy and its therapy
Trofimov E.A., Trofimova A.S.

I.I. Mechnikov North-West State Medical University, St. Petersburg

The paper reviews the data on the course of the pregnancy in certain rheumatic diseases, in particular, in antiphospholipid syndrome (AFS). AFS is a systemic autoimmune disorder which is characterized by chronic increase in antiphospholipid antibody levels and manifests itself as vascular thrombosis and/or recurrent fetal loss. Antiphospholipid antibodies are a heterogeneous group antibodies reactive against phospholipids, phospholipid-binding proteins, and phospholipid-protein complexes. Antiphospholipid antibodies affect fetal growth and development during each each stage of the pregnancy. The factors which affect pregnancy outcome and neonatal pathology are analyzed. The risks of potential complications of rheumatic diseases in these patients are evaluated. Special attention is given to the planning and preparing for pregnancy. Management of pregnancy in AFS and dosing regimen mainly depend on medical history, i.e., non-placental thrombosis, the number of spontaneous abortions, and prior therapy. Considering this, clinical groups with different therapy were described in the paper. It should be noted that some of the drugs under discussion are not approved by national regulatory authorities (Russian Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing, Food and Drug Administration etc.) and are generally prescribed for an off-label use in real-world clinical practice.

key words: antiphospholipid syndrome (AFS), pregnancy, prevention of exacerbations.

For quote: Trofimov E.A., Trofimova A.S. The course of antiphospholipid syndrome during pregnancy and its therapy // RMJ. 2016. No. 15. P. 1032–1036.

The article is devoted to the features of the course of antiphospholipid syndrome in pregnant women and treatment options.

Pregnancy significantly affects the mother's immune system: depression of the cellular immunity, increased secretion of immunoglobulins, decreased function of lymphocytes due to the expression of specific PSP proteins (pregnancy-specific proteins). All these transformations are aimed at the survival of the fetus. The processes of changing the cytokine profile of T-helper type 2 are dominant in maintaining "immunotolerance" during pregnancy and can affect various autoimmune diseases. There are a number of phenomena that can be used to see the effect of rheumatic pathology on pregnancy, and vice versa. These processes are multidirectional: on the one hand, both the onset of a systemic autoimmune disease (SAD) and the exacerbation of an existing pathology (for example, an outbreak of lupus nephritis) can be noted, on the other hand, numerous cases of remission induced by pregnancy in patients with rheumatoid arthritis. In addition, the autoimmune dysfunction characteristic of SAD, the presence of antiphospholipid antibodies (APA), may lead to an increased risk of miscarriage, fetal death, and preeclampsia. Transplacental transport of pathological macromolecules, especially anti-Ro/La or SS-A, SS-B antibodies, directly affects the fetus and increases the likelihood of developing neonatal lupus. Finally, high immunoinflammatory activity, damage to internal organs within the framework of SAZ can have a significant impact on maternal and fetal mortality.
Pregnancy causes many physiological changes in the mother's body in addition to dysfunction of the immune system. Thus, there is a significant increase in the volume of circulating blood (up to 40–45%), which can aggravate the course of diseases of the kidneys or the cardiovascular system. The glomerular filtration rate (GFR) increases by about 50% during normal pregnancy, so a patient with prior proteinuria will almost certainly have some increase in protein in the urine. As a result of changes in the coagulation link of hemostasis, platelet activity, fibrinolysis, venous stasis, vascular compression of the pregnant uterus, forced bed rest increased risk of thrombotic complications. There are swelling and bleeding of the gums, gastroesophageal reflux, significant bone loss due to pregnancy, lactation, as well as the possible use of glucocorticosteroids (GCS). Thus, even a normal pregnancy can exacerbate SAD.
Physiological or pathological changes, including pregnancy-induced hypertension, can also mimic SAZ activity, which presents certain difficulties in making a differential diagnosis. For example, redness or hyperpigmentation of the face is easily confused with a centrifugal zygomatic rash of the "butterfly" type. Palmar erythema in pregnancy may look like cutaneous vasculitis. Physiological leukocytosis, anemia, and low platelets due to hemodilution, which is common in pregnant women, may mimic the hematological manifestations of SAD. As a result of an increase in the level of fibrinogen, anemia, an acceleration of the erythrocyte sedimentation rate may be noted, and this parameter cannot be an objective marker of disease activity. Many women complain of diffuse arthralgia, pain in muscles and bones, especially during the first pregnancy. Hypertension, proteinuria, renal failure, and edema associated with preeclampsia may mimic various diseases or their exacerbation, including lupus nephritis, acute scleroderma nephropathy, recurrent vasculitis, necrotizing glomerulonephritis. HELLP syndrome, a variant of preeclampsia characterized by low platelet counts, elevated liver enzymes, hemolysis, and abdominal pain, may mimic systemic lupus erythematosus (SLE) or exacerbation of systemic vasculitis. Finally, eclampsia, which includes convulsions or cerebrovascular accident, can be confused with damage to the central nervous system with SLE or neurovasculitis.

Antiphospholipid Syndrome
In the early 1950s antiphospholipid syndrome (APS) has been described as a variant of SLE or lupus-like syndrome. However, it was very soon established that the association between APA hyperproduction and thrombotic disorders is observed in the absence of reliable clinical and serological signs of SLE or any other leading disease. The term "primary antiphospholipid syndrome" was proposed to define this new nosological form.
The development of methods of radioimmunoassay (1983) and enzyme immunoassay for the determination of antibodies to cardiolipin contributed to the expansion of research on the role of APA in human diseases. It turned out that these antibodies are a serological marker of a peculiar symptom complex, including venous and/or arterial thrombosis, various forms obstetric pathology(primarily habitual miscarriage), thrombocytopenia, as well as various other neurological, skin, cardiovascular, hematological disorders. In 1986 G. Hughes et al. proposed to designate this symptom complex as APS. In 1994, at the VI international symposium devoted to the study of APA, it was proposed to call APS Hughes syndrome after the English rheumatologist who first described it and made the greatest contribution to the development of this problem.
In 2006, the last revision of the criteria for this disease took place in Sydney. The interpretation of clinical manifestations was somewhat changed, and antibodies to beta-2 glycoprotein I (AB2GP) were added to the laboratory criteria (Table 1). The practical diagnostics of APS is currently being built on the basis of Australian criteria.

The clinical spectrum of manifestations that are associated with APS is quite wide: migraine, arthritis/arthralgia, pulmonary hypertension, livedo reticularis, leg ulcers, etc. Although most of them were not included in the final diagnostic criteria for APS from 2006, these phenomena are discussed in the literature.
Pregnancy loss is a common complication of APS in obstetric practice, in addition, it is noteworthy that preeclampsia and eclampsia often occur in the combination of APS and SLE. HELLP-syndrome in combination with AKLA circulation is more severe and often occurs in the second rather than the third trimester. The risk of liver infarction in patients with AKLA-associated HELLP syndrome is 30 times higher than that in the seronegative variant of HELLP syndrome. In addition, other multiple thrombotic complications often develop in APS, which require more aggressive treatment than in patients with the traditional course of HELLP syndrome. Pregnancy itself is a risk factor for the development of hypercoagulability, and with the appearance of APS, the likelihood of thrombosis in the mother increases significantly. In rare cases, catastrophic APS can form during pregnancy: in the analyzed studies, 15 cases were identified, a characteristic feature of which was the fact that almost half of the patients had a history of latent APS before that. Patients may also have other hematological complications of APS, such as severe thrombocytopenia in the second and third trimesters of pregnancy.
The most common adverse events associated with APS in pregnant women are preterm birth and intrauterine growth retardation. Preterm delivery is most common in patients who have a combination of APS and SLE, and the incidence ranges from 10 to 40%. In one study, the authors attempted to determine the causes of poor neonatal outcomes (preterm birth, intrauterine growth retardation, low Apgar score). Such factors were the presence of VAK, AKLA, AB2GP antibodies, a history of vascular thrombosis before pregnancy. In the absence of these factors (even in the presence of a previous burdened obstetric history), a more favorable neonatal outcome was noted.
In rare cases, thrombosis is formed in the fetus or newborn due to transplacental transport of aPL. In such cases, we can talk about the presence of neonatal APS. The risk of thrombosis in this cohort of patients decreases along with a decrease in the concentration of maternal aPLs, however, in the future, learning difficulties, memory and other cognitive functions decrease are noted. Currently, there are registries (European registry to babies born to mothers with antiphospholipid syndrome) for monitoring the long-term neuropsychic consequences of neonatal APS.
VAK appears to be the most important risk factor for adverse pregnancy outcomes, including pregnancy loss. Currently, methods for determining the concentration of VAK are non-standardized, in contrast to tests related to the determination of anticardiolipins and beta-2 glycoprotein I. Currently, a multicenter prospective observational study PROMISSE is being completed, the main purpose of which is to monitor APS-positive and SLE-associated pregnant women . A recent analysis of interim data found that only the level of VAK is the only laboratory marker of APS associated with adverse pregnancy outcomes such as intrapartum fetal death, intrauterine growth retardation and preterm birth. On the other hand, there is evidence that only the combination of VAK, AKLA and AB2GP in a particular patient is a predictor of intrapartum fetal death. This information is somewhat reassuring for those patients who have a low or moderate titer of AKLA, AB2GP. For timely assessment of the risk of thrombosis in patients with APS, it is necessary to conduct a thorough screening for the presence of markers of hereditary thrombophilia (fibrinolysis genes: PAI-I, PLAT; platelet receptor genes: ITGA2, ITGB3, Gplba; genes of the blood coagulation system: Fl, F2, F5, F7 ), the presence of hyperhomocysteinemia. IN Lately data are emerging on the relationship between changes in serum complement levels during pregnancy and adverse outcomes. The interpretation of this phenomenon seems to be very difficult: with eclampsia and primary APS, an increase in titer is possible, and with SLE and secondary APS, hypocomplementemia. Complement is an important predictor of adverse pregnancy outcomes and mortality in a mouse model of APS, and it seems likely that activation of the complement system plays the same negative role in the human population.

Recommendations for the management of pregnant women with APS
The timely establishment of the treatment of obstetric APS dates back to 1980-1985, when patients with AKLA, VAK and obstetric failures began to receive corticosteroids (prednisolone) and acetylsalicylic acid (ASA) in small doses. Moreover, the dose of corticosteroids was gradually increased until VAC or other APS markers reached acceptable levels. In the 1990s studies have shown that low doses of heparin combined with low doses of ASA were as effective as corticosteroids, but with much less side effects. To date, the combination of antiplatelet drugs and direct anticoagulants is standard: the dosage of low molecular weight heparin (LMWH) is usually 40 mg of enoxaparin daily, some experts use 30 mg 2 times a day, the dose for unfractionated heparin (UFH) is usually 5000 IU 2 times. /day
Studies show that the combination of low dose heparin and low dose ASA is more effective than ASA alone, with a success rate of about 75% versus 40%. There were no fundamental differences between low and high doses of anticoagulants, as well as UFH and LMWH heparin. This type of therapy belongs to the first line and is the most effective in terms of preventing pregnancy loss at early dates.
Second-line therapy includes the use of intravenous human immunoglobulin (IVIG). Some experts at this stage recommend increasing the dose of heparin to general therapeutic doses. In the only controlled study using IVIG, there was no significant improvement in pregnancy outcomes. However, there are a significant number of uncontrolled studies, published clinical cases with a brilliant effect with the combined use of IVIG, low doses of ASA and LMWH. With a further increase in the level of AKLA, VAK, plasmapheresis can be successfully used. The most promising methods for the treatment of APS in the future are complement inhibition, as well as the use of genetically engineered biological therapy.
Treatment with medium / high doses of corticosteroids is currently practically not used due to the lack of evidence of their effectiveness and negative impact on both mother and fetus. The use of corticosteroids is justified only if APS develops against the background of some disease (SLE, Sjögren's disease, etc.). The use of corticosteroids in these cases is aimed at treating not APS, but the underlying disease.
In the postpartum period, anticoagulant therapy should be continued for a period of 6 to 8 weeks. even in patients without a history of thrombosis.
The tactics of managing pregnant women with APS, the dosage regimen largely depend on the previous history (presence / absence of non-placental thrombosis, the number of spontaneous abortions, previous therapy). In this regard, the following subgroups can be distinguished:

1. Patients with only serological markers of APS (no previous pregnancy, with one episode of unexplained spontaneous abortion before 10 weeks of gestation), no history of thrombosis.
The tactics of managing this category of women is to use small doses of ASA, which is prescribed for the entire period of pregnancy and for 6 months. after childbirth.
If pregnant women have highly positive AKLA (more than 65 units of GPL), it is advisable to prescribe LMWH. The risk of developing thrombotic complications is high not only during pregnancy, but also in the postpartum period (within 6 months after delivery). At delivery naturally it is advisable to resume treatment with LMWH in the postpartum period. In the case of a caesarean section, the introduction of LMWH is canceled 2-3 days in advance and resumed in the postpartum period, followed by a switch to indirect anticoagulants.
2. Patients with APS without a history of non-placental thrombosis and women with a history of serological markers of APS and two or more unexplained spontaneous abortions (before 10 weeks of gestation).
The tactics of managing this category of pregnant women consists in the combined use of low doses of ASA (50-150 mg / day) from the moment of conception to delivery and UFH (enoxaparin, etc.) or UFH (5000-10,000 IU every 12 hours) from the moment of documented pregnancy and before giving birth. 12 hours after delivery, treatment with LMWH, UFH (or warfarin) should be resumed.
Long-term heparin therapy in pregnant women can lead to the development of osteoporosis. As a result, all pregnant women receiving heparin therapy must take calcium supplements (1500 mg / day) and vitamin D3 (at least 1000 IU / day).
3. Patients with APS and a history of non-placental thrombosis (who received warfarin before pregnancy).
Requires up to 6 weeks. stop warfarin during pregnancy. Subsequently, the pregnant woman takes ASA in low doses in combination with UFH.
4. With the ineffectiveness of standard therapy during the next pregnancy use immunoglobulin IV 0.4 g/kg for 5 days every month of pregnancy.

Literature

1. Miyakis S., Lockshin M.D., Atsumi T. et al. International consensus statement on an update of the classification criteria for define antiphospholipid syndrome (APS) // J Thromb Haemost. 2006 Vol. 4. R. 295-306.
2. Tsirigotis P., Mantzios G., Pappa V. et al. Antiphospholipid syndrome: a predisposing factor for early onset HELLP syndrome // Rheumatol Int. 2007 Vol. 28. R. 171-174.
3. Gomez-Puerta J., Cervera R., Espinosa G. et al. Catastrophic antiphospholipid syndrome during pregnancy and puerperium: maternal and fetal characteristics of 15 cases // Ann Rheum Dis. 2007 Vol. 66. R. 740-746.
4. Ruffatti A., Calligaro A., Hoxha A. et al. Laboratory and clinical features of pregnant women with antiphospholipid syndrome and neonatal outcome // Arthritis Care Res. 2010 Vol. 62. R. 302-309.
5. Boffa M.C., Lachassine E. Infant perinatal thrombosis and antiphospholipid antibody: a review // Lupus. 2007 Vol. 16. R. 634–641.
6. Mekinian A., Lachassine E., Nicaise-Roland P. et al. European registry to babies born to mothers with antiphospholipid syndrome // Ann Rheum Dis. 2013. Vol. 72. R. 217-222.
7. Lockshin M.D., Kim M., Laskin C.A. et al. Prediction of adverse pregnancy outcome by the presence of lupus anticoagulant, but not anticardiolipin antibody, in patients with antiphospholipid antibody // Arthritis Rheum. 2012. Vol. 64. R. 2311-2318.
8. Ruffatti A., Tonello M., DelRoss T. et al. Antibody profile and clinical course in primary antiphospholipid syndrome with pregnancy morbidity // Thromb Haemost. 2006 Vol. 96. R. 337–341.
9. Danowski A., de Azevedo M.N., de Souza Papi J.A. et al. Determinants of risk for venous and arterial thrombosis in primary antiphospholipid syndrome and antiphospholipid syndrome with systemic lupus erythematosus // J Rheumatol. 2009 Vol. 36. R. 1195-1199.
10. Gris J.C., Perneger T.V., Quere I. et al. Antiphospholipid/antiprotein antibodies, hemostasis-related autoantibodies, and plasma homocysteine ​​as risk factors for a first early pregnancy loss: a matched case-control study // Blood. 2003 Vol. 102. R. 3504–3513.
11. Salmon J.E., Girardi G., Holers N.M. Activation of complement mediates antiphospholipid antibody-induced pregnancy loss // Lupus. 2003 Vol. 12. R. 535–538.
12. Cowchock F.S., Reece E.A., Balaban D. et al. Repeated fetal losses associated with antiphospholipid antibody: a collaborative randomized trial comparing prednisone with low-dose heparin treatment // Am JObstet Gynecol. 1992 Vol. 166. R. 1318-1323.
13. Rai R., Cohen H., Dave M. et al. Randomized controlled trial of aspirin and aspirin plus heparin in pregnant women with recurrent miscarriage associated with phospholipid antibody (or antiphospholipid antibody) // BMJ. 1997 Vol. 314. R. 253–256.
14. Kutteh W.H. Antiphospholipid antibody-associated recurrent loss pregnancy: treatment with heparin and low-dose aspirin is superior to low-dose aspirin alone // Am J Obstet Gynecol. 1996 Vol. 174. R. 1584-1589.
15. Ziakas P.D., Pavlou M., Voulgarelis M. Heparin treatment in antiphospholipid syndrome with recurrent pregnancy loss: a systematic review and meta-analysis // Obstet Gynecol. 2010 Vol. 115. R. 1256-1261.
16. Mak A., Cheung M.W.L., Cheak A.A.C. et al. Combination of heparin and aspirin is superior to aspirin alone in enhancing live births in patients with recurrent pregnancy loss and positive anti-phospholipid antibodies: a controlled meta-analysis of randomized trials and meta-regression // Rheumatology. 2010 Vol. 49. R. 281-288.
17. Fishman P., Falach-Vaknine E., Zigelman R. et al. Prevention of fetal loss in experimental anti-phospholipid syndrome by in vitro administration of recombinant interleukin-3 // J Clin Invest. 1993 Vol. 41. R. 1834-1877.

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 are looking for Additional information 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 circulatory disorders not only in the limbs - they also suffer internal organs especially the kidneys. 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 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 general analysis blood, 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, they can be carried out laboratory research for the determination of 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.

The following forms of antiphospholipid syndrome are distinguished.

• Primary antiphosolipid syndrome develops due to genetic (associated with the presence of certain genes) characteristics of the organism.
• Secondary antiphospholipid syndrome develops against the background of other diseases.
  • • (an autoimmune disease that affects all systems and organs, with the formation of antibodies to double-stranded DNA (the main component of the nucleus of all cells);
  • Infectious diseases:
  • Taking medications.

By clinical picture Separately, special forms of the disease are distinguished:

• catastrophic antiphospholipid syndrome the disease flows rapidly, failure of all systems and organs develops due to the massive formation of blood clots (blood clots) in vessels of both small and large caliber.
• Antiphospholipid syndrome associated with vasculitis (inflammatory process in vessels of various calibers).
• Syndrome of hypothrombinemia (insufficient blood levels of thrombin (a protein involved in blood coagulation and blood clot formation)).
• Microangiopathic syndromes:
  • hemolytic-uremic syndrome - characterized by (destruction of erythrocytes (red blood cells), (decreased excretory function of the kidneys) and thrombocytopenia ( low level platelets (platelets involved in the formation of a blood clot));
  • thrombotic - characterized by purpura (the formation of "spider veins" on the skin), thrombocytopenia, hemolytic anemia, impaired renal function, high temperature body and neurological disorders (convulsions);
  • - an increase in blood pressure, hepatic transaminases (enzyme proteins), a decrease in the number of platelets in pregnant women.

• - violation of the blood coagulation system with the formation of many blood clots (blood clots) and bleeding.

Exist "laboratory" options antiphospholipid syndrome:

• seropositive antiphospholipid syndrome - the main types of antibodies to phospholipids (components of the cell membrane (cell membrane)) in the patient's blood are determined by laboratory methods (anticardiolipin antibodies and / or lupus anticoagulant - one of the types of antibodies to phospholipids);
• seronegative antiphospholipid syndrome - anticardiolipin antibodies and / or lupus anticoagulant are not detected in the patient's blood.

Causes

The main reason for the development of primary antiphospholipid syndrome is the genetic characteristics of the organism, that is, the inheritance of special genes responsible for disrupting the functioning of its own immune system and the production of antibodies (protective proteins) against the membrane (cell membrane) of its own cells.

Among the reasons leading to the occurrence of secondary antiphospholipid syndrome, there are several.

• Autoimmune diseases (diseases in which the body secretes antibodies (protective proteins) that act against its own cells)):
  • (an autoimmune disease that affects all systems and organs, with the formation of antibodies to double-stranded DNA (the main component of the nucleus of all cells);
  • (an autoimmune disease affecting the external secretion glands (salivary, lacrimal, pancreas));
  • (an autoimmune disease that affects the skin, blood vessels, lungs, gastrointestinal tract);

• Infectious diseases:
  • hepatitis C virus (leads to chronic viral liver disease);
  • human immunodeficiency virus (leads to the occurrence of a chronic disease in which the death of the body's immune cells is observed);
  • (leads to the occurrence of mononucleosis - a disease manifested by fever, tonsillitis (inflammation of the tonsils), hepatosplenomegaly (inflammation of the liver and spleen), lymphadenopathy (swollen lymph nodes).

• Tumors (ovarian tumors, lymphoproliferative diseases (tumors of precursors of lymphocytes (white blood cells)).
• Taking medications:
  • hormonal contraceptives - drugs for contraception (exclusion of unwanted pregnancy) containing estrogens and progesterones (female sex hormones);
  • hydralazine - a drug for lowering blood pressure;
  • novocainamide - a drug that restores the rhythm of the heart;
  • quinidine - a drug for the treatment of malaria (an infectious disease, accompanied by a wave-like alternation of fever and sweating with periods of well-being) and the treatment of autoimmune diseases.

Diagnostics

• Analysis of the anamnesis of the disease and complaints - when (how long ago) swelling of the legs, ulcers on the legs, headaches, increased blood pressure and other symptoms appeared, with which the patient associates their occurrence.
• Analysis of the anamnesis of life - were there:
  • (death of part of the heart muscle due to the formation of a thrombus (blood clot) in the heart vessels);
  • (death of part of the brain due to the formation of a blood clot in the cerebral arteries);
  • thrombosis (the formation of blood clots in the arteries of the upper or lower extremities of the body (numbness, pain, their coldness, lack of movement)).

• Analysis of family history - did any of the close relatives have had myocardial infarctions, ischemic strokes, thrombosis of the vessels of the extremities, etc.
• Analysis of obstetric and gynecological history - pregnancies, how they proceeded, their outcomes.
• Availability of clinical criteria for diagnosis:
  • one or more episodes of blood clots in the arteries or veins of any localization (location), confirmed by dopplerometry (a study of blood flow in the vessels);
  • one or more unexplained intrauterine death of a normal fetus after 10 weeks of gestation;
  • one or more healthy child up to 34 weeks of pregnancy due to (increased blood pressure in a pregnant woman, dysfunction of the central nervous system (headaches, dizziness));
  • three or more unexplained spontaneous events before 10 weeks of gestation.

• Complete blood count - counting the number of erythrocytes (red blood cells), platelets (platelets involved in the formation of a blood clot), leukocytes (white blood cells), etc.
• Indirect Coombs test - determination of the presence and amount of antibodies to erythrocytes (red blood cells). Standard washed erythrocytes are introduced into the patient's blood serum. In the presence of antibodies in the serum, agglutination (gluing of red blood cells) will occur.
• Enzyme immunoassay for the detection of anticardiolipin (antiphospholipid) antibodies in the blood. In the laboratory, with the help of "labeled" enzymes (special proteins), the presence of anticardiolipin antibodies in the blood is determined. The analysis is carried out twice with a difference of 6 weeks.
• Immuno-enzymatic analysis for the detection of lupus anticoagulant in the blood (a type of antiphospholipid antibodies). In the laboratory, with the help of "labeled" enzymes (special proteins), the presence of lupus anticoagulant in the blood is determined. The analysis is carried out twice with a difference of 6 weeks.
• Ultrasonic fetometry - the dimensions of the parts of the fetus are determined, their compliance with the norm.
• Cardiotocography (synchronous recording of the fetal heart rate, its motor activity and uterine contractions to assess the condition of the fetus).
• A consultation with a hemostasiologist is also possible.

Treatment of antiphospholipid syndrome of pregnancy

Treatment of antiphospholipid syndrome is difficult due to the variety of factors that lead to its occurrence.
The main goal of treating patients with antiphospholipid syndrome is to correct the parameters of the blood coagulation system.

• Reception:
  • glucocorticoids (steroid hormones of the adrenal cortex that reduce the production of autoantibodies (special protective proteins against their own cells));
  • indirect anticoagulants (drugs that prevent the formation of a blood clot (blood clot));
  • antiplatelet agents (drugs that block the aggregation (gluing) of erythrocytes (red blood cells)).

• Plasmapheresis (taking plasma (the liquid part of the blood free from cells) of the patient). During the procedure, a system is inserted into the vein that takes blood and filters it. Then the cellular components of the blood are returned back to the vein together with the plasma-substituting solution (saline solution), the filtered plasma (the liquid part of the blood free of cells) is removed.

The elements of the treatment of antiphospholipid syndrome in pregnant women are the following methods for controlling the development of possible complications.

• Complete blood count (counting the number of red blood cells, platelets (platelets involved in the formation of a blood clot), leukocytes (white blood cells), etc.) once every 2 weeks.
• Coagulogram - a study of the blood coagulation system. Measurement of blood parameters responsible for the formation of blood clots and stopping bleeding. Determination of D-dimer (a product of the breakdown of blood clots).
• Ultrasonic fetometry (the dimensions of the parts of the fetus are determined, their compliance with the norm) is carried out once a month.
• Regular study of liver and kidney function (determination of liver enzymes, levels of urea and creatinine (products of nitrogen metabolism excreted through the kidneys)).
• Prophylactic intake of iron, folic acid and fatty acids.
• Consultation
• Timely registration of a pregnant woman in a antenatal clinic (up to 12 weeks of pregnancy).
• Regular visits (1 time per month in the 1st trimester, 1 time in 2-3 weeks in the 2nd trimester, 1 time in 7-10 days in the 3rd trimester).
• Rational and balanced nutrition of a pregnant woman (eating foods high in fiber (vegetables, fruits, herbs), avoiding fried, canned, too hot and spicy foods).
• Complete sleep.
• Taking vitamins and sedatives (if necessary).
• Quit smoking, alcohol and drug use.
• Exclusion of excessive physical and psycho-emotional stress.