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Antiphospholipid syndrome clinical guidelines. Antiphospholipid syndrome - what is it

Antiphospholipid syndrome (APS), or antiphospholipid antibody syndrome (SAFA), is a clinical and laboratory syndrome, the main manifestations of which are the formation of blood clots (thrombosis) in the veins and arteries of various organs and tissues, as well as the pathology of pregnancy.

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

Antiphospholipid syndrome - what is it?

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

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

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

vascular thrombosis. Presence of one or more episodes of thrombosis. Moreover, blood clots in the vessels should be detected by the histological, Doppler or visiographic method.
pathology of pregnancy. One or more deaths of a normal fetus before 10 weeks of gestation. Preterm birth before 34 weeks of gestation due to eclampsia/preeclampsia/placental insufficiency. More than two miscarriages in a row.

The laboratory criteria for APS include the following:

Anticardiolipin antibodies (IgG and/or IgM) that have been detected in the blood at least twice within 12 weeks.
Lupus anticoagulant detected in the blood at least twice within 12 weeks.
Antibodies to beta-2 glycoprotein 1 (IgG and/or IgM) that have been detected in the blood at least twice within 12 weeks.

A diagnosis of antiphospholipid syndrome is made when a person has at least one clinical and one laboratory criterion present continuously for 12 weeks. This means that it is impossible to make a diagnosis of antiphospholipid syndrome after a single examination, since for diagnosis it is necessary to conduct laboratory tests at least twice within 12 weeks and find out the presence of clinical criteria. If laboratory and clinical criteria are met both times, the diagnosis of antiphospholipid syndrome is ultimately made.

Antiphospholipid syndrome - photo

These photographs show appearance skin of a person suffering from antiphospholipid syndrome.

This photograph shows the bluish skin of the fingers in antiphospholipid syndrome.

Classification of antiphospholipid syndrome

Currently, there are two main classifications of antiphospholipid syndrome, which are based on different characteristics of the disease. So, one classification is based on whether the disease is combined with any other autoimmune, malignant, infectious or rheumatic pathologies or not. The second classification is based on the features clinical course antiphospholipid syndrome, and distinguishes several types of the disease, depending on the characteristics of the symptoms.

Primary antiphospholipid syndrome is a variant of the disease in which there are no signs of any other autoimmune, rheumatic, infectious or oncological diseases. That is, if a person has only signs of APS without a combination with other predominant diseases, then this is precisely the primary variant of the pathology. It is believed that approximately half of the cases of APS are the primary variant. In the case of primary antiphospholipid syndrome, one should constantly be on the alert, since very often this disease transforms into systemic lupus erythematosus. Some scientists even believe that primary APS is a precursor or initial stage development of lupus erythematosus.

Catastrophic antiphospholipid syndrome. With this variant of the course of the disease, thrombosis of many organs is formed within a short period of time (less than 7 hours), as a result of which multiple organ failure and clinical manifestations similar to DIC or hemolytic uremic syndrome develop.
Primary antiphospholipid syndrome, in which there are no manifestations of systemic lupus erythematosus. With this variant, the disease proceeds without any other concomitant autoimmune, rheumatic, oncological or infectious diseases.
Antiphospholipid syndrome in people with a confirmed diagnosis of systemic lupus erythematosus (secondary antiphospholipid syndrome). In this variant, the antiphospholipid syndrome is combined with systemic lupus erythematosus.
Antiphospholipid syndrome in people with lupus-like symptoms. With this variant of the course, in addition to the antiphospholipid syndrome, people have manifestations of lupus erythematosus, which, however, are not caused by lupus, but by lupus syndrome (a temporary condition in which a person has symptoms like with systemic lupus erythematosus, but passing without a trace after discontinuation of the drug that caused their development).
Antiphospholipid syndrome without antiphospholipid antibodies in the blood. With this variant of the course of APS in humans, antibodies to cardiolipin and lupus anticoagulant are not detected in the blood.
Antiphospholipid syndrome, proceeding according to the type of other thrombophilias (thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, HELLP syndrome, DIC syndrome, hypoprothrombinemic syndrome).

Depending on the presence of antiphospholipid antibodies in the blood, APS are divided into the following types:

With the presence of antibodies that react with phosphatidylcholine;
With the presence of antibodies that react with phosphatidylethanolamine;
With the presence of 32-glycoprotein-1-cofactor dependent antiphospholipid antibodies.

Causes of antiphospholipid syndrome

The exact causes of antiphospholipid syndrome are not currently known. A temporary increase in the level of antiphospholipid antibodies is observed in various bacterial and viral infections, but thrombosis almost never develops in these conditions. However, many scientists suggest that a sluggish asymptomatic infection plays a large role in the development of antiphospholipid syndrome. In addition, an increase in the level of antibodies in the blood of relatives of people suffering from antiphospholipid syndrome has been recorded, which suggests that the disease may be hereditary, genetic.

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

Antiphospholipid syndrome - signs (symptoms, clinic)

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

Symptoms of antiphospholipid syndrome

Clinical manifestations of antiphospholipid syndrome are diverse and can mimic diseases of various organs, but they are always caused by thrombosis. The appearance of specific symptoms of APS depends on the size of the vessels affected by thrombosis (small, medium, large), the speed of their blockage (rapid or slow), the type of vessels (vein or artery), and their localization (brain, skin, heart, liver, kidneys). etc.).

Symptoms of catastrophic antiphospholipid syndrome

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

Antiphospholipid syndrome in men, women and children

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

Antiphospholipid syndrome and pregnancy

What causes APS during pregnancy?

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

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

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

Management of pregnancy in antiphospholipid syndrome

Women suffering from antiphospholipid syndrome should be prepared for pregnancy at the first stage, providing optimal conditions and minimizing the risk of fetal loss in early gestation. Then it is necessary to conduct pregnancy with the obligatory use of drugs that reduce the formation of blood clots and, thereby, ensure normal gestation and the birth of a living healthy child. If pregnancy occurs without preparation, then it must simply be carried out with the use of drugs that reduce the risk of thrombosis in order to ensure normal gestation. Below we provide recommendations for the preparation and management of pregnancy, approved by the Russian Ministry of Health in 2014.

Preparations of low molecular weight heparin (Clexane, Fraxiparin, Fragmin);
Drugs of the antiplatelet group (Clopidogrel, Aspirin in low dosages of 75-80 mg per day);
Micronized progesterone (Utrozhestan 200 - 600 mg per day) vaginally;
Folic acid 4 - 6 mg per day;
Magnesium with vitamin B 6 (Magne B6);
Preparations of omega fatty acids (Linitol, Omega-3 Doppelhertz, etc.).

Low molecular weight heparin preparations and antiplatelet agents are prescribed under the control of blood coagulation parameters, adjusting their dosage until the test data return to normal.

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

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

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antiphospholipid syndrome. General principles of pharmacotherapy

Venous and arterial thromboses

Patients with first venous thrombosis

Patients with recurrent thrombosis

Patients without clinical signs of APS, but with high levels of aPL

Acute thrombotic complications in APS

"Catastrophic" AFS

Rice. 15. Algorithm for the treatment of "catastrophic" APS

The "catastrophic" syndrome is the only absolute indication for plasmapheresis sessions in patients with APS, which should be combined with the most intensive anticoagulant therapy, the use of fresh frozen plasma for replacement and, in the absence of contraindications, pulse therapy with glucocorticoids and cyclosrosfamide. Separate clinical observations indicate a certain effectiveness of intravenous immunoglobulin.

Pregnant women with APS

Patients with APS without a history of non-placental thrombosis (eg, no deep vein thrombosis of the leg) and women with aPL and two or more unexplained spontaneous abortions (before 10 weeks of gestation) in history: Acetylsalicylic acid 81 mg/day from conception to delivery + Unfractionated heparin (10,000 IU every 12 hours) from documented pregnancy (usually 7 weeks after gestation) until delivery

■ echocardiography to exclude vegetation on the valves;

■ urinalysis: daily proteinuria, creatinine clearance;

■ biochemical study: liver enzymes.

■ analysis for the number of platelets every week. during the first 3 weeks, from the start of treatment with heparin, then 1 time per month;

■ training in self-identification of signs of thrombosis;

■ comparison of changes in weight, blood pressure, urine protein (for early diagnosis of preeclampsia and HELLP syndrome);

■ ultrasound procedure fetus (every 4-6 weeks, starting at 18-20 weeks of gestation) to assess fetal growth;

■ measure the number of heartbeats in the fetus from 32-34 weeks. gestation.

Hematological disorders in APS

Moderate thrombocytopenia

Resistant severe thrombocytopenia

Forecast

The sialogram allows you to determine the stages of the process, conduct dynamic monitoring and control the effectiveness of therapy. Sialography at the Institute of Rheumatology of the Russian Academy of Medical Sciences is performed for all patients with lesions of the salivary glands, since this method has proven to be the most informative. Given the systemic nature of the pores.

Raynaud's phenomenon is an excessive spastic reaction of the digital (digital) arteries and skin vessels when exposed to cold or emotional stress. The phenomenon is clinically manifested by sharply defined changes in the color of the skin of the fingers. At the heart of the increased vasospasm is a local defe.

The complexity of the prevention and treatment of APS is associated with the heterogeneity of the pathogenetic mechanisms underlying APS, the polymorphism of clinical manifestations, and the lack of reliable clinical and laboratory parameters that allow predicting relapses of thrombotic disorders.

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Rheumatology is a specialization of internal medicine dealing with the diagnosis and treatment of rheumatic diseases.

Antiphospholipid syndrome (APS) is a symptom complex that includes recurrent thrombosis (arterial and/or venous), obstetric pathology (more often fetal loss syndrome) and is associated with the synthesis of antiphospholipid antibodies (aPL): anticardiolipin antibodies (aCL) and/or lupus anticoagulant (LA) , and/or antibodies to b2-glycoprotein I (anti-b2-GP I). APS is a model of autoimmune thrombosis and belongs to acquired thrombophilias.

ICD code 10 - D68.8 (in the section other blood coagulation disorders; coagulation defects associated with the presence of "lupus anticoagulants" O00.0 spontaneous in pathological pregnancy)

One or more clinical episodes of arterial, venous, or small vessel thrombosis in any tissue or organ. Thrombosis must be confirmed by imaging or Doppler or morphologically, except for superficial venous thrombosis. Morphological confirmation should be presented without the presence of significant inflammation of the vascular wall.

a) one or more cases of intrauterine death of a morphologically normal fetus after 10 weeks of gestation (normal fetal morphological signs documented by ultrasound or direct examination of the fetus) or

b) one or more preterm deliveries of a morphologically normal fetus before 34 weeks' gestation due to severe preeclampsia or eclampsia, or severe placental insufficiency, or

c) three or more consecutive cases of spontaneous abortions before 10 weeks of gestation (exception - anatomical defects of the uterus, hormonal disorders, maternal or paternal chromosomal disorders)

1. Antibodies to cardiolipin IgG or IgM isotypes, detected in serum in medium or high titers, at least 2 times within 12 weeks, using a standardized enzyme immunoassay.

2. Antibodies to b2-glycoprotein I IgG and / or IgM isotype, detected in serum in medium or high titers, at least 2 times within 12 weeks, using a standardized enzyme immunoassay.

3. Plasma lupus anticoagulant, in two or more cases at least 12 weeks apart, determined according to the recommendations of the International Society for Thrombosis and Hemostasis (LA/phospholipid-dependent antibody study group)

a) prolongation of plasma clotting time in phospholipid-dependent coagulation tests: APTT, FAC, prothrombin time, tests with Russell's poisons, textarine time

b) no correction for prolongation of screening test clotting times in mixing tests with donor plasma

c) shortening or correction of the lengthening of the clotting time of screening tests with the addition of phospholipids

e) exclusion of other coagulopathies, such as an inhibitor of coagulation factor VIII or heparin (prolonging phospholipid-dependent blood coagulation tests)

Note. A definite APS is diagnosed by the presence of one clinical and one serological criterion. APS is excluded if aPL without clinical manifestations or clinical manifestations without aPL are detected for less than 12 weeks or more than 5 years. The presence of congenital or acquired risk factors for thrombosis does not rule out APS. Patients should be stratified with a) the presence and b) the absence of risk factors for thrombosis. Depending on aPL positivity, it is recommended to divide APS patients into the following categories: 1. detection of more than one laboratory marker (in any combination); IIa. VA only; II century only akl; only antibodies to b2-glycoprotein I.

A particular aPL profile can be identified as high or low risk for subsequent thrombosis.

Table 2. High and low risk of having different aPL for subsequent thromboses

The positivity of three types of antiphospholipid antibodies (VA + antibodies to cardiolipin (aCL) + anti-β 2-glycoprotein1 antibodies (a-β 2-GP1)

Isolated persistent AKL positivity at high and medium a levels

a Studied for systemic lupus erythematosus (SLE) only

Recommendations are graded according to the American College of Chest Phisicians (ACCP) system: strength of recommendations based on risk/benefit ratio: grade 1: “strong” recommendation = “we recommend”; grade 2 “weak” recommendation = “we advise The quality of evidence is graded: high quality = A; moderate quality = B; low or very low quality = C, so there are 6 possible grades of recommendation: 1A; 1B; 1C; 2A; 2B; 2C.

Table 3. Differential diagnosis of antiphospholipid syndrome

The differential diagnosis with thromboembolic disease depends on the vascular bed involved (venous, arterial, or both).

With venous occlusions, if only venous thrombosis or PE is determined, the differential diagnosis includes:

acquired and genetic thrombophilia;
fibrinolysis defects;
neoplastic and myeloproliferative diseases;
nephrotic syndrome.

Persons with venous thrombosis younger than 45 years of age with the presence of first-degree relatives with thrombosis at a young age should be investigated for genetic thrombophilia. Today it is clear that the study of aPL should be carried out in some endocrine diseases: Addison's disease and hypopituitarism (Sheehan's syndrome). Although the indication of venous thrombosis is an indicator of thrombophilic status, at the same time, some concomitant clinical manifestations may be a sign of a systemic disease with a higher risk of venous thrombosis. For example, a history of painful mucosal ulcers in the mouth and genitals in young patients with venous thrombosis should suggest a diagnosis of Behçet's disease, which, like APS, affects vessels of any caliber.

If thrombosis is detected only in the arterial bed, the following diseases are excluded:

atherosclerosis;
embolism (with atrial fibrillation, atrial myxoma, endocarditis, cholesterol emboli), myocardial infarction with thrombosis of the ventricles of the heart;
decompression states (Caisson's disease);
TTP/hemolytic uremic syndrome.

Young patients with strokes require special attention, in which more than 18% of cases have aPL in the blood (Kalashnikova L.A.). Some aPL-positive patients may have clinical manifestations similar to multiple sclerosis, which are the result of multiple cerebral infarcts, confirmed by neuroimaging (MRI). A similar type of CNS damage is observed in multiple sclerosis and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. These patients should be carefully questioned about having family members with strokes and dementia at a young age. In the study of autopsies of such cases, multiple deep small cerebral infarcts and diffuse leukoencephalopathy are found. This genetic defect is linked to the 19th chromosome.

With combined thrombosis (arterial and venous), the differential diagnosis includes:

disorders in the fibrinolysis system (dysfibrinogenemia or plasminogen activator deficiency);
homocysteinemia;
myeloproliferative diseases, polycythemia;
paradoxical nocturnal hemoglobinuria;
hyperviscosity of the blood, for example, with Waldström's macroglobulinemia, sickle cell disease, etc.;
vasculitis;
paradoxical embolism.

When recurrent occlusions of the microvasculature are combined with thrombocytopenia, a differential diagnosis is made between thrombotic microangiopathies (Table 4).

Table 4. Main clinical and laboratory features associated with thrombocytopenia in antiphospholipid syndrome and thrombotic microangiopathies

Note: APS - antiphospholipid syndrome, CAPS - catastrophic APS, TTP - thrombotic thrombocytopenic purpura, DIC - disseminated intravascular coagulation, APTT - activated partial thromboplastin time, PDF - fibrinogen degradation products, ANF - antinuclear factor, aPL - antiphospholipid antibodies.

*negative mixing test (for determining lupus anticoagulant).

# positive mixing test (for determining lupus anticoagulant).

≠ TTP may be associated with SLE.

Differential diagnosis between APS and thrombotic angiopathy is often difficult. It must be taken into account that minor thrombocytopenia in APS may be associated with platelet activation and consumption; many clinical and laboratory findings may be common to SLE and TTP. TTP may develop in patients with SLE and, conversely, aPL may occur in TTP, hemolytic uremic syndrome, and HELLP syndrome, and DIC is noted in CAPS. The study of aPL as a screening test is indicated in patients with thrombocytopenia of unknown origin, especially pregnant women with thrombocytopenia, when the risk of hemorrhages due to thrombocytopenia and the risk of thrombosis due to aPL worsen the outcome, both in the fetus and in the mother.

Skin manifestations, among which livedo is the most common, can occur in various rheumatic diseases. Moreover, skin necrosis, skin ulcers, skin discoloration from pallor to redness requires the exclusion of systemic vasculitis, as well as secondary vasculitis on the background of infections. Pyoderma gangrenosum is also often a cutaneous manifestation of systemic rheumatic diseases, but there are case reports.

The pathology of the heart valves requires the exclusion of infective endocarditis, chronic rheumatic fever. Tables 5 and 6 show the signs that occur in these pathologies. As you can see, there are a number of similar features. Rheumatic fever (RF) and APS are two diseases with similar clinical picture. The triggering factor in both pathologies is infection. With LC, an infectious agent has been proven - b-hemolytic streptococcus of the Streptococcus pyogenes group. Molecular mimicry between the microbe and molecules of the heart tissue explains the etiology of LC disease; similar mechanisms also take place in APS. The timing of the development of the disease after infection in LC and APS is different. RL is induced in the first three weeks after infection, there is a clear relationship with a previous streptococcal infection, while in APS most cases develop according to the “hit and run” mechanism, i.e. the development of the disease is delayed in time. The nature of the damage to the heart valves is also different. In APS, valvular stenosis develops rarely and, in contrast to rheumatic stenosis, in these patients, according to our data, there was no adhesion of the commissures, the narrowing of the opening was due to large thromboendocardial overlays and deformation of the valves.

Table 5. Differential diagnosis of valvular heart disease in antiphospholipid syndrome, rheumatic fever, and infective endocarditis

Table 6. Similar manifestations of antiphospholipid syndrome and acute rheumatic fever (ARF) (Blank M. et al., 2005)

including T, M protein-reactive cells

including T reacting with b2 GP1

Obstetric pathology of APS also requires laboratory confirmation and exclusion of other causes of pregnancy loss. These are genetic thrombophilia, and inflammatory pathology of the genital organs. APL can be detected in infectious diseases at low or moderate positive levels, and repeated studies of aPL after 12 weeks are necessary to rule out an association with infection.

In conclusion, it should be emphasized that APS is an antibody-induced thrombosis, the basis of the diagnosis of which, along with clinical manifestations, is the mandatory presence of serological markers. Obstetric pathology in APS should be considered as a thrombotic complication. A single study of aPL does not allow verification or exclusion of APS.

The management of patients with arterial and/or venous thrombosis and aPL who do not meet the criteria for significant APS (serological markers at low levels) does not differ from the management of aPL-negative patients with similar thrombotic outcomes (level of evidence 1C)

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

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

Causes and mechanisms of development of antiphospholipid syndrome

Antiphospholipid syndrome can develop against the background of autoimmune diseases.

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

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

With antiphospholipid syndrome, a large number of autoantibodies to phospholipids are formed in the patient's body, which have several varieties located on the membranes of platelets and endotheliocytes, as well as on nerve cells.

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

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

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

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

Clinical features of antiphospholipid syndrome

Venous thrombosis may be one of the signs of antiphospholipid syndrome.

From the side of the skin, the following changes can be determined:

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

For damage to the vessels of the extremities, the following manifestations are characteristic:

chronic ischemia due to disturbances in blood flow below the site clogged with a thrombus: the limb is cold to the touch, the pulse below the site of thrombosis is sharply weakened, the muscles are atrophied;
gangrene: necrosis of limb tissues as a result of their prolonged ischemia;
deep or superficial veins of the extremities: pain in the extremity, severe swelling, impaired function;
: accompanied by severe pain, fever, chills; along the course of the vein, redness of the skin and painful seals under it are determined.

In the case of localization of a thrombus in large vessels, the following can be determined:

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

On the part of the bone tissue, the following changes can be noted:

aseptic bone necrosis: necrosis of a portion of bone tissue in the area of the articular surface of the bone; more often observed in the head of the femur; manifested by pain syndrome of indeterminate localization, atrophy of the muscles adjacent to the affected area, impaired movement in the joint;
reversible, not associated with taking glucocorticoids: manifested by pain in the affected area, in the absence of factors that could provoke them.

Manifestations of antifispholipid syndrome on the part of the organ of vision can be:

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

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

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

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

With the localization of blood clots in the vessels of the adrenal glands, acute or chronic adrenal insufficiency can develop, as well as hemorrhages and heart attacks in the area of the affected organ can be determined.

Blood clots nervous system It usually manifests itself in the following conditions:

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

With the defeat of blood clots of the vessels of the heart are determined:

and (attacks of retrosternal pain, accompanied by);
arterial hypertension.

In case of thrombosis of the liver vessels, its heart attacks, Budd-Chiari syndrome, nodular regenerative hyperplasia are possible.

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

Diagnosis of antiphospholipid syndrome

In the blood of such patients, antibodies to cardiolipin can be detected.

In 1992, clinical and biological diagnostic criteria for antiphospholipid syndrome were proposed. Clinical criteria include:

habitual miscarriage;
arterial thromboses;
venous thrombosis;
skin lesion - livedo reticularis;
in the area of the legs;
reduced levels of platelets in the blood;
signs.

Biological criteria include elevated levels of antibodies to phospholipids - IgG or IgM.

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

In a general blood test, the following changes can be detected:

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

A biochemical blood test will reveal:

increased levels of gamma globulin;
in chronic renal failure - elevated levels of urea and creatinine;
in case of liver damage - an increased content of ALT and AST, alkaline phosphatase,;
increase in APTT in the analysis of blood coagulability.

There may also be specific immunological studies blood, in which are determined:

antibodies to cardiolipin, especially IgG in high concentration;
lupus anticoagulant (false-positive or false-negative reactions are not uncommon);
in hemolytic anemia - antibodies to erythrocytes ( positive reaction Coombs);
false positive Wasserman reaction;
increased number of T-helpers and B-lymphocytes;
antinuclear factor or antibodies to DNA;
cryoglobulins;
positive rheumatoid factor.

Treatment of antiphospholipid syndrome

In the treatment of this disease, drugs of the following groups can be used:

Antiplatelet agents and anticoagulants of indirect action: aspirin, pentoxifylline, warfarin.
(in the case of antiphospholipid syndrome that developed against the background): prednisone; combination with immunosuppressants is possible: Cyclophosphamide, Azathioprine.
Aminoquinoline drugs: Delagil, Plaquenil.
Selective non-steroidal anti-inflammatory drugs: Nimesulide, Meloxicam, Celecoxib.
In obstetric pathology: intravenous immunoglobulin.
B group vitamins.
Preparations of polyunsaturated fatty acids (Omacor).
Antioxidants (Mexicor).

Plasmapheresis is sometimes used in combination with anticoagulant therapy.

To date, they have not received wide application, but the drugs of the following groups are quite promising in the treatment of antiphospholipid syndrome:

monoclonal antibodies to platelets;
anticoagulant peptides;
apoptosis inhibitors;
preparations of systemic enzyme therapy: Wobenzym, Phlogenzym;
cytokines: mainly Interleukin-3.

Indirect anticoagulants (Warfarin) are used to prevent recurrent thrombosis.

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

Antiphospholipid syndrome and pregnancy

In 40% of women with repeated cases of intrauterine fetal death, it is the antiphospholipid syndrome that causes them. Blood clots clog the vessels of the placenta, as a result of which the fetus lacks nutrients and oxygen, its development slows down, and in 95% of cases it soon dies. In addition, this disease of the mother can lead to placental abruption or to the development of an extremely dangerous condition, both for the fetus and for the expectant mother - late preeclampsia.

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

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

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

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

Forecast

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

Which doctor to contact

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

This condition is one of the most pressing problems in medicine today, since it affects many organs and systems at the same time, and its diagnosis is difficult in some cases.

Causes and mechanisms of development of antiphospholipid syndrome

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

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

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

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

Clinical features of antiphospholipid syndrome

From the side of the skin, the following changes can be determined:

the vascular network on the upper and lower extremities, more often on the hands, is clearly visible during cooling - livedo reticularis;
rash in the form of petechial hemorrhages, resembling outwardly vasculitis;
subcutaneous hematomas;
hemorrhages in the area of the subungual bed (the so-called "symptom of a splinter");
necrosis of skin areas in the area of the distal lower extremities - fingertips;
long-term non-healing ulcerative lesions of the extremities;
redness of the skin of the palms and soles: plantar and palmar erythema;
subcutaneous nodules.

For damage to the vessels of the extremities, the following manifestations are characteristic:

chronic ischemia due to disturbances in blood flow below the site clogged with a thrombus: the limb is cold to the touch, the pulse below the site of thrombosis is sharply weakened, the muscles are atrophied;
gangrene: necrosis of limb tissues as a result of their prolonged ischemia;
thrombosis of deep or superficial veins of the extremities: pain in the extremity, severe swelling, impaired function;
thrombophlebitis: accompanied by severe pain, fever, chills; along the course of the vein, redness of the skin and painful seals under it are determined.

In the case of localization of a thrombus in large vessels, the following can be determined:

aortic arch syndrome: pressure on the upper limbs is sharply increased, diastolic (“lower”) pressure on the arms and legs varies significantly, noise is determined on the aorta during auscultation;
superior vena cava syndrome: swelling, blue discoloration, dilatation of the saphenous veins of the face, neck, upper torso and upper extremities; may be bleeding from the nose, esophagus, trachea or bronchi;
inferior vena cava syndrome: pronounced, diffuse pain in the lower extremities, groin, buttocks, abdominal cavity; swelling of these parts of the body; dilated saphenous veins.

On the part of the bone tissue, the following changes can be noted:

aseptic bone necrosis: necrosis of a portion of bone tissue in the area of the articular surface of the bone; more often observed in the head of the femur; manifested by pain syndrome of indeterminate localization, atrophy of the muscles adjacent to the affected area, impaired movement in the joint;
reversible osteoporosis, not associated with taking glucocorticoids: manifested by pain in the affected area, in the absence of factors that could provoke them.

Manifestations of antifispholipid syndrome on the part of the organ of vision can be:

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

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

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

kidney infarction: accompanied by a sharp pain in the lower back, decreased diuresis, the presence of blood in the urine; in some cases it is asymptomatic or with minimal clinical manifestations;
thrombosis of the renal artery: suddenly there are sharp pains in the lumbar region, often accompanied by nausea, vomiting, decreased diuresis, stool retention;
renal thrombotic microangiopathy - the formation of microthrombi in the glomeruli - with the subsequent development of chronic renal failure.

The defeat of the nervous system by blood clots is manifested, as a rule, by the following conditions:

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

With the defeat of blood clots of the vessels of the heart are determined:

In case of thrombosis of the liver vessels, its heart attacks, Budd-Chiari syndrome, nodular regenerative hyperplasia are possible.

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

Diagnosis of antiphospholipid syndrome

In 1992, clinical and biological diagnostic criteria for antiphospholipid syndrome were proposed. Clinical criteria include:

habitual miscarriage;
arterial thromboses;
venous thrombosis;
skin lesion - livedo reticularis;
trophic ulcers in the shins;
reduced levels of platelets in the blood;
signs of hemolytic anemia.

Biological criteria include elevated levels of antibodies to phospholipids - IgG or IgM.

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

In a general blood test, the following changes can be detected:

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

A biochemical blood test will reveal:

increased levels of gamma globulin;
in chronic renal failure - elevated levels of urea and creatinine;
in case of liver damage - an increased content of ALT and AST, alkaline phosphatase, bilirubin;
increase in APTT in the analysis of blood coagulability.

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

antibodies to cardiolipin, especially IgG in high concentration;
lupus anticoagulant (false-positive or false-negative reactions are not uncommon);
with hemolytic anemia - antibodies to erythrocytes (positive Coombs reaction);
false positive Wasserman reaction;
increased number of T-helpers and B-lymphocytes;
antinuclear factor or antibodies to DNA;
cryoglobulins;
positive rheumatoid factor.

Treatment of antiphospholipid syndrome

In the treatment of this disease, drugs of the following groups can be used:

Antiplatelet agents and anticoagulants of indirect action: aspirin, pentoxifylline, warfarin.
Glucocorticoids (in the case of antiphospholipid syndrome that developed against the background of systemic lupus erythematosus): prednisone; combination with immunosuppressants is possible: Cyclophosphamide, Azathioprine.
Aminoquinoline drugs: Delagil, Plaquenil.
Selective non-steroidal anti-inflammatory drugs: Nimesulide, Meloxicam, Celecoxib.
In obstetric pathology: intravenous immunoglobulin.
B group vitamins.
Preparations of polyunsaturated fatty acids (Omacor).
Antioxidants (Mexicor).

Plasmapheresis is sometimes used in combination with anticoagulant therapy.

To date, they have not received wide application, but the drugs of the following groups are quite promising in the treatment of antiphospholipid syndrome:

monoclonal antibodies to platelets;
anticoagulant peptides;
apoptosis inhibitors;
preparations of systemic enzyme therapy: Wobenzym, Phlogenzym;
cytokines: mainly Interleukin-3.

Indirect anticoagulants (Warfarin) are used to prevent recurrent thrombosis.

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

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

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

Forecast

Which doctor to contact

Lecture by Khasina M. Yu. on the topic "Diagnosis of antiphospholipid syndrome":

Medical Director of the Family Source Center Veronika Ulanova talks about antiphospholipid syndrome:

Help the children

Useful information

Contact the experts

Telephone appointment service for doctors in Moscow:

Information is provided for informational purposes. Do not self-medicate. At the first sign of disease, consult a doctor.

Editorial address: Moscow, 3rd Frunzenskaya st., 26

Antiphospholipid syndrome - what threatens the disease and how to deal with it?

The composition of all body cells includes esters of higher fatty acids and polyhydric alcohols. These chemical compounds are called phospholipids, they are responsible for maintaining the correct structure of tissues, are involved in metabolic processes and the breakdown of cholesterol. Depends on the concentration of these substances general state health.

APS syndrome - what is it?

About 35 years ago, rheumatologist Graham Hughes discovered a pathology in which the immune system begins to produce specific antibodies against phospholipids. They attach to platelets and vascular walls, interact with proteins, and enter into metabolic and blood coagulation reactions. Both secondary and primary antiphospholipid antibody syndrome is an autoimmune disease of unknown origin. Young women of reproductive age are more susceptible to this problem.

Antiphospholipid syndrome - causes

Rheumatologists have not yet been able to establish why the disease in question occurs. There is information that antiphospholipid syndrome is more often diagnosed in relatives with a similar disorder. In addition to heredity, experts suggest several other factors that provoke pathology. In such cases, secondary APS develops - the reasons for the production of antibodies are the progression of other diseases that affect the functioning immune system. The strategy of therapy depends on the mechanisms of the onset of the disease.

Primary antiphospholipid syndrome

This type of pathology develops independently, and not against the background of some disturbances in the body. Such a syndrome of antiphospholipid antibodies is difficult to treat due to the lack of provoking factors. Often the primary form of the disease is almost asymptomatic and is diagnosed already at the later stages of progression or when complications occur.

Secondary antiphospholipid syndrome

This variant of the autoimmune reaction develops due to the presence of other systemic diseases or certain clinical events. The impetus for the beginning of the pathological production of antibodies can even be conception. Antiphospholipid syndrome in pregnant women occurs in 5% of cases. If the disease in question was diagnosed earlier, gestation will significantly aggravate its course.

Diseases that presumably provoke antiphospholipid syndrome:

viral and bacterial infections;
oncological neoplasms;
nodular periarteritis;
systemic lupus erythematosus.

Antiphospholipid syndrome - symptoms in women

The clinical picture of the pathology is very diverse and non-specific, which makes differential diagnosis difficult. Sometimes the disorder occurs without any signs, but more often the antiphospholipid syndrome manifests itself in the form of recurrent thrombosis of superficial and deep blood vessels (arteries or veins):

Common symptoms in women:

pronounced vascular pattern on the skin (livedo reticularis);
myocardial infarction;
migraine;
suffocation;
pain in the chest;
varicose disease;
thrombophlebitis;
stroke;
arterial hypertension;
acute kidney failure;
ascites;
ischemic attacks;
strong dry cough;
necrosis of bones and soft tissues;
portal hypertension;
gastrointestinal bleeding;
severe liver damage;
spleen infarction;
intrauterine fetal death;
spontaneous miscarriage.

Antiphospholipid syndrome - diagnosis

It is difficult to confirm the presence of the described pathology, because it disguises itself as other diseases and has nonspecific signs. To diagnose a disease, doctors use 2 groups of classification criteria. Examination for antiphospholipid syndrome first involves taking an anamnesis. The first type of evaluation indicators include clinical phenomena:

vascular thrombosis. The medical history should contain one or more cases of damage to the veins or arteries, established instrumentally and laboratory.
obstetric pathology. The criterion is taken into account if there was an intrauterine death of the fetus after the 10th week of gestation or there were premature births before the 34th week of pregnancy in the absence of chromosomal, hormonal and anatomical defects on the part of the parents.

After collecting an anamnesis, the doctor prescribes additional studies. Antiphospholipid syndrome is confirmed when a combination of one is present clinical symptom and laboratory criterion (minimum). In parallel, a number of events differential diagnosis. To do this, the specialist recommends undergoing examinations that exclude diseases similar in course.

Antiphospholipid syndrome - analysis

The study of biological fluids helps to identify laboratory signs of the violation presented. The doctor prescribes a blood test for antiphospholipid syndrome to determine the presence of antibodies to cardiolipins and lupus anticoagulant in plasma and serum. Additionally, you can find:

cryoglobulins;
antibodies to erythrocytes;
T- and B-lymphocytes in high concentration;
antinuclear and rheumatoid factor.

How to treat antiphospholipid syndrome?

Therapy for this autoimmune disorder depends on its form (primary, secondary) and the severity of clinical signs. Difficulties arise if an antiphospholipid syndrome is detected in a pregnant woman - treatment should effectively stop the symptoms of the disease, prevent thrombosis, and at the same time not pose a danger to the fetus. To achieve lasting improvements, rheumatologists use a combined therapeutic approach.

Can antiphospholipid syndrome be cured?

It is impossible to completely get rid of the described problem until the causes of its occurrence are established. In antiphospholipid syndrome, it is necessary to use complex treatment aimed at reducing the amount of relevant antibodies in the blood and preventing thromboembolic complications. In severe cases, anti-inflammatory therapy is required.

The main way to eliminate the signs of this pathology is the use of antiplatelet agents and anticoagulants of indirect action:

acetylsalicylic acid (Aspirin and analogues);
Warfarin;
Acenocoumarol;
Phenylin;
Dipyridamole.

How to treat antiphospholipid syndrome - clinical guidelines:

Stop smoking, drinking alcohol and drugs, oral contraceptives.
Adjust the diet in favor of foods rich in vitamin K - green tea, liver, leafy green vegetables.
Fully rest, observe the regime of the day.

If standard therapy is ineffective, the appointment of additional medications is practiced:

aminoquinolines - Plaquenil, Delagil;
direct anticoagulants - Clexane, Fraxiparine;
glucocorticoids - Prednisolone, Methylprednisolone;
platelet receptor inhibitors - Tagren, Clopidogrel;
heparinoids - Emeran, Sulodexide;
cytostatics - Endoxan, Cytoxan;
immunoglobulins (intravenous administration).

Traditional medicine for antiphospholipid syndrome

There are no effective alternative methods of treatment, the only option is to replace acetylsalicylic acid with natural raw materials. Antiphospholipid syndrome cannot be treated with folk recipes because natural anticoagulants are too mild. Before using any alternative means, it is important to consult a rheumatologist. Only a specialist will help alleviate the antiphospholipid syndrome - the doctor's recommendations should be strictly followed.

Tea with the properties of aspirin

dry white willow bark - 1-2 teaspoons;
boiling water - ml.

Rinse the raw materials thoroughly and grind.
Boil willow bark with boiling water, leave for a minute.
Drink the solution as tea 3-4 times a day, you can sweeten to taste.

Antiphospholipid syndrome - prognosis

All patients with a rheumatologist with a diagnosis should be observed for a long time and regularly undergo preventive examinations. How long you can live with antiphospholipid syndrome depends on its form, severity and the presence of concomitant immunological disorders. If primary APS with moderate symptoms is detected, timely therapy and preventive treatment help to avoid complications, the prognosis in such cases is the most favorable.

Aggravating factors are the combination of the disease in question with lupus erythematosus, thrombocytopenia, persistent arterial hypertension and other pathologies. In these situations, often develops antiphospholipid complex syndrome(catastrophic), which is characterized by an increase in clinical signs and recurrent thrombosis. Some of the consequences can be fatal.

Antiphospholipid syndrome and pregnancy

The described disease is a common cause of miscarriage, so all expectant mothers should undergo a preventive examination and donate blood for a coagulogram. Antiphospholipid syndrome in obstetrics is considered a serious factor provoking fetal death and miscarriage, but its presence is not a sentence. A woman with such a diagnosis is able to bear and give birth to a healthy baby if during pregnancy she follows all the doctor's recommendations and takes antiplatelet agents.

A similar scheme is used when artificial insemination is planned. Antiphospholipid syndrome and IVF are quite compatible, you just have to first take a course of antithrombotic drugs. The use of anticoagulants and antiplatelet agents will continue throughout the gestation period. The effectiveness of such treatment is close to 100%.

/ therapy / feder recommendations / feder recommendations / federal recommendations / cardiology / Federal Clinical Guidelines for the Treatment of Antiphospholipid Syndrome

All-Russian public organization

Association of Rheumatologists of Russia

Antiphospholipid syndrome (APS) is a symptom complex that includes recurrent thrombosis (arterial and/or venous), obstetric pathology (more often fetal loss syndrome) and is associated with the synthesis of antiphospholipid antibodies (aPL): anticardiolipin antibodies (aCL) and/or lupus anticoagulant (LA) , and/or antibodies to 2-glycoprotein I (anti-2-GP I). APS is a model of autoimmune thrombosis and belongs to acquired thrombophilias.

ICD code 10 - D68.8 (in the section other blood coagulation disorders; coagulation defects associated with the presence of "lupus anticoagulants"

O00.0 spontaneous in abnormal pregnancy)

Table 1. Diagnostic criteria for APS

b) one or more preterm deliveries of a morphologically normal fetus before 34 weeks' gestation due to severe preeclampsia or eclampsia, or severe placental insufficiency, or

c) three or more consecutive cases of spontaneous abortions before 10 weeks of gestation (exception - anatomical defects of the uterus, hormonal disorders, maternal or paternal chromosomal disorders)

Antibodies to cardiolipin IgG or IgM isotypes detected in serum in medium or high titers at least 2 times within 12 weeks using a standardized enzyme immunoassay.

Antibodies to b2-glycoprotein IIgG and / or IgM isotype detected in serum in medium or high titers at least 2 times within 12 weeks using a standardized enzyme immunoassay.

Plasma lupus anticoagulant, in two or more cases at least 12 weeks apart, as determined according to the recommendations of the International Society for Thrombosis and Hemostasis (LA/phospholipid-dependent antibody study group)

a) prolongation of plasma clotting time in phospholipid-dependent coagulation tests: APTT, FAC, prothrombin time, tests with Russell's poisons, textarine time

b) no correction for prolongation of screening test clotting times in mixing tests with donor plasma

c) shortening or correction of the lengthening of the clotting time of screening tests with the addition of phospholipids

e) exclusion of other coagulopathies, such as an inhibitor of coagulation factor VIII or heparin (prolonging phospholipid-dependent blood coagulation tests)

A particular aPL profile can be identified as high or low risk for subsequent thrombosis.

Table 2. High and low risk of having different aPL for subsequent thromboses

Lupus anticoagulant (LA) positivity

The positivity of three types of antiphospholipid antibodies (VA + antibodies to cardiolipin (aCL) + anti-β 2-glycoprotein1 antibodies (a-β 2-GP1)

Isolated persistent AKL positivity at high and medium a levels

Isolated intermittent increase in each of the aPL in medium and low levels

a Studied for systemic lupus erythematosus (SLE) only

Recommendations are graded according to the American College of Chest Physicians (ACCP) system: strength of recommendation based on risk/benefit ratio: grade 1: “strong” recommendation = “we recommend”; grade 2 “weak” recommendation = “we advise”. Quality of evidence graded: high quality = A; moderate quality = B; low or very low quality = C, so there are 6 possible grades of recommendation: 1A; 1B; 1C; 2A; 2B; 2C.

The differential diagnosis of APS depends on the clinical manifestations present. There are a number of genetically determined and acquired diseases that lead to recurrent pregnancy loss, thromboembolic complications, or both (Table 3).

Table 3. Differential diagnosis of antiphospholipid syndrome

SL, distal limb gangrene, skin ulcers, skin necrosis, CNS, kidney damage

Thromboangiitis obliterans (Buerger-Winivarter disease)

Recurrent migratory phlebitis, distal limb gangrene, skin ulcers, skin necrosis, myocardial infarction, mesenteric vascular thrombosis, CNS involvement

Hemorrhagic rashes on the skin, ulcers and necrosis of the skin, kidney damage

Temporal arteritis (Horton's disease)

Retinal artery thrombosis, headaches

Nonspecific aortoarteritis (Takayasu's disease)

Aortic arch syndrome, heart valve disease

TTP (Moszkowitz's disease)

Recurrent thrombosis of vessels of various sizes, thrombocytopenia, hemolytic autoimmune anemia

Recurrent thrombosis of vessels of various sizes, kidney damage, hemolytic anemia, hemorrhages

Ulcers and necrosis of the skin, livedo-vasculitis

Acute rheumatic fever

Formation of heart defects, thrombosis of vessels of various localization (usually CNS and limbs) according to the mechanism of cardiogenic thromboembolism

Thrombosis, hematological disorders, livedo

Livedo, distal limb gangrene, skin ulcers

Hereditary (as a result of mutations in clotting factors, plasma anticoagulants)

Recurrent thrombosis of vessels of various caliber and localization, skin ulcers

Thromboembolic complications, thrombocytopenia, skin ulcers

Tuberculosis, viral hepatitis, etc.

Thromboembolism, transverse myelitis, livedo

The differential diagnosis with thromboembolic disease depends on the vascular bed involved (venous, arterial, or both).

With venous occlusions, if only venous thrombosis or PE is determined, the differential diagnosis includes:

acquired and genetic thrombophilia;

neoplastic and myeloproliferative diseases;

If thrombosis is detected only in the arterial bed, the following diseases are excluded:

embolism (with atrial fibrillation, atrial myxoma, endocarditis, cholesterol emboli), myocardial infarction with thrombosis of the ventricles of the heart;

decompression states (Caisson's disease);

With combined thrombosis (arterial and venous), the differential diagnosis includes:

disorders in the fibrinolysis system (dysfibrinogenemia or plasminogen activator deficiency);

myeloproliferative diseases, polycythemia;

paradoxical nocturnal hemoglobinuria;

hyperviscosity of the blood, for example, with Waldström's macroglobulinemia, sickle cell disease, etc.;

When recurrent occlusions of the microvasculature are combined with thrombocytopenia, a differential diagnosis is made between thrombotic microangiopathies (Table 4).

Table 4. Main clinical and laboratory features associated with thrombocytopenia in antiphospholipid syndrome and thrombotic microangiopathies

Antibodies to platelets

Direct Coombs reaction is positive

*negative mixing test (for determining lupus anticoagulant).

# a positive mixing test (when determining lupus anticoagulant).

≠ TTP may be associated with SLE.

§ DIC may be associated with CAPS.

The pathology of the heart valves requires the exclusion of infective endocarditis, chronic rheumatic fever. Tables 5 and 6 show the signs that occur in these pathologies. As you can see, there are a number of similar features. Rheumatic fever (RF) and APS are two diseases with a similar clinical presentation. The triggering factor in both pathologies is infection. With RL, an infectious agent has been proven - group b-hemolytic streptococcus Streptococcus pyogenes. Molecular mimicry between the microbe and molecules of the heart tissue explains the etiology of LC disease; similar mechanisms also take place in APS. The timing of the development of the disease after infection in LC and APS is different. RL is induced in the first three weeks after infection, there is a clear relationship with a previous streptococcal infection, while in APS most cases develop according to the “hit and run” mechanism, i.e. the development of the disease is delayed in time. The nature of the damage to the heart valves is also different. In APS, valvular stenosis develops rarely and, in contrast to rheumatic stenosis, in these patients, according to our data, there was no adhesion of the commissures, the narrowing of the opening was due to large thromboendocardial overlays and deformation of the valves.

Table 5. Differential diagnosis of valvular heart disease in antiphospholipid syndrome, rheumatic fever, and infective endocarditis

Diffuse thickening or local thickening of the middle part of the valve or its base

Limited valve thickening with superior involvement, chord thickening and fusion, valve calcification

Limited overlays on the atrial or aortic or atrioventricular surface with valve rupture

Table 6. Similar manifestations of antiphospholipid syndrome and acute rheumatic fever (ARF) (Blank M. et al., 2005)

Heart valve deformity

Fibrosis (collagen IV)

CNS damage (chorea)

Streptococcus pyogenes and etc.

Tissue infiltration with lymphocytes

Including T, M protein-reactive cells

Including T reacting with b2 GP1

Expression of adhesion molecules

M-protein and myosin, GlcNA, laminin, b2 GP1

b2 GP1 to cardiolipin and prothrombin, annexin-V, M-protein

The management of patients with arterial and/or venous thrombosis and aPL who do not meet the criteria for significant APS (serological markers at low levels) does not differ from the management of aPL-negative patients with similar thrombotic outcomes (level of evidence 1C)

Comments. Data from a systematic review suggest that patients with venous thromboembolism and aPL, even if they do not meet laboratory criteria for the diagnosis of APS, treatment with anticoagulants does not differ from the management of patients with non-aPL thrombosis. Heparins are usually prescribed first: unfractionated (regular), or low molecular weight, or pentasaccharides, followed by a switch to vitamin K antagonists (VKA) (warfarin).

A vitamin K antagonist (VKA) with an international normalized ratio (INR) target of 2.0-3.0 is recommended for patients with defined APS and first venous thrombosis (LE: 1B)

Autoimmune pathology, which is based on the formation of antibodies to phospholipids, which are the main lipid components of cell membranes. Antiphospholipid syndrome can be manifested by venous and arterial thrombosis, arterial hypertension, valvular heart disease, obstetric pathology (recurrent miscarriage, intrauterine death of the fetus, preeclampsia), skin lesions, thrombocytopenia, hemolytic anemia. The main diagnostic markers of antiphospholipid syndrome are antibodies to cardiolipin and lupus anticoagulant. Treatment of antiphospholipid syndrome is reduced to the prevention of thrombosis, the appointment of anticoagulants and antiplatelet agents.

General information

Antiphospholipid syndrome (APS) is a complex of disorders caused by an autoimmune reaction to phospholipid structures present on cell membranes. The disease was described in detail by the English rheumatologist Hughes in 1986. Data on the true prevalence of antiphospholipid syndrome are not available; it is known that insignificant levels of antibodies to phospholipids in the blood serum are found in 2-4% of practically healthy individuals, and high titers - in 0.2%. Antiphospholipid syndrome is 5 times more likely to be diagnosed among young women (20-40 years old), although men and children (including newborns) can suffer from the disease. As a multidisciplinary problem, antiphospholipid syndrome (APS) attracts the attention of specialists in the field of rheumatology, obstetrics and gynecology, and cardiology.

Causes

The underlying causes of the development of antiphospholipid syndrome are unknown. Meanwhile, factors predisposing to an increase in the level of antibodies to phospholipids have been studied and identified. Thus, a transient increase in antiphospholipid antibodies is observed against the background of viral and bacterial infections (hepatitis C, HIV, infectious mononucleosis, malaria, infective endocarditis, etc.). High titers of antibodies to phospholipids are found in patients with systemic lupus erythematosus, rheumatoid arthritis, Sjögren's disease, periarteritis nodosa, autoimmune thrombocytopenic purpura.

Hyperproduction of antiphospholipid antibodies can be observed with malignant neoplasms, taking medications (psychotropic drugs, hormonal contraceptives, etc.), the abolition of anticoagulants. There is evidence of a genetic predisposition to increased synthesis of antibodies to phospholipids in persons carrying HLA DR4, DR7, DRw53 antigens and in relatives of patients with antiphospholipid syndrome. In general, the immunobiological mechanisms of the development of the antiphospholipid syndrome require further study and clarification.

Depending on the structure and immunogenicity, "neutral" (phosphatidylcholine, phosphatidylethanolamine) and "negatively charged" (cardiolipin, phosphatidylserine, phosphatidylinositol) phospholipids are distinguished. The class of antiphospholipid antibodies that react with phospholipids includes lupus anticoagulant, antibodies to cardiolipin, beta2-glycoprotein-1-cofactor-dependent antiphospholipids, etc. Interacting with phospholipids of membranes of vascular endothelial cells, platelets, neutrophils, antibodies cause a hemostasis disorder, expressed in a tendency to hypercoagulation.

Classification

Taking into account the etiopathogenesis and course, the following clinical and laboratory variants of the antiphospholipid syndrome are distinguished:

primary- there is no connection with any underlying disease capable of inducing the formation of antiphospholipid antibodies;
secondary- antiphospholipid syndrome develops against the background of another autoimmune pathology;
catastrophic- acute coagulopathy, occurring with multiple thrombosis of internal organs;
AFL-negative a variant of the antiphospholipid syndrome, in which serological markers of the disease (Ab to cardiolipin and lupus anticoagulant) are not detected.

Symptoms of antiphospholipid syndrome

According to modern views, antiphospholipid syndrome is an autoimmune thrombotic vasculopathy. In APS, the lesion can affect vessels of various caliber and localization (capillaries, large venous and arterial trunks), which causes an extremely diverse range of clinical manifestations, including venous and arterial thrombosis, obstetric pathology, neurological, cardiovascular, skin disorders, thrombocytopenia.

The most common and typical sign of antiphospholipid syndrome is recurrent venous thrombosis: thrombosis of the superficial and deep veins of the lower extremities, hepatic veins, portal vein of the liver, retinal veins. Patients with antiphospholipid syndrome may experience repeated episodes of PE, pulmonary hypertension, superior vena cava syndrome, Budd-Chiari syndrome, adrenal insufficiency. Venous thrombosis in antiphospholipid syndrome develop 2 times more often than arterial. Among the latter, cerebral artery thrombosis predominates, leading to transient ischemic attacks and ischemic stroke. Other neurological disorders may include migraine, hyperkinesis, seizures, sensorineural hearing loss, ischemic optic neuropathy, transverse myelitis, dementia, mental disorders.

The defeat of the cardiovascular system in antiphospholipid syndrome is accompanied by the development of myocardial infarction, intracardiac thrombosis, ischemic cardiomyopathy, arterial hypertension. Quite often, there is damage to the heart valves - from minor regurgitation, detected by echocardiography, to mitral, aortic, tricuspid stenosis or insufficiency. As part of the diagnosis of antiphospholipid syndrome with cardiac manifestations, differential diagnosis with infective endocarditis, cardiac myxoma is required.

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

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

Diagnostics

Antiphospholipid syndrome is diagnosed on the basis of clinical (vascular thrombosis, aggravated obstetric history) and laboratory data. The main immunological criteria include the detection in plasma of medium or high titers of antibodies to cardiolipin class IgG / IgM and lupus anticoagulant twice within six weeks. The diagnosis is considered certain when at least one major clinical and laboratory criterion is combined. Additional laboratory signs of antiphospholipid syndrome are false positive RW, positive Coombs test, increased titer of antinuclear factor, rheumatoid factor, cryoglobulins, antibodies to DNA. Also shown is the study of KLA, platelets, biochemical analysis blood, coagulograms.

Pregnant women with antiphospholipid syndrome need to monitor the parameters of the blood coagulation system, conduct dynamic ultrasound of the fetus and

Treatment of antiphospholipid syndrome

The main goal of therapy for antiphospholipid syndrome is to prevent thromboembolic complications. Regime moments provide for moderate physical activity, the rejection of a long stay in a stationary state, practicing traumatic sports and long flights. Women with antiphospholipid syndrome should not be prescribed oral contraceptives, and before planning pregnancy, it is imperative to contact an obstetrician-gynecologist. Pregnant patients during the entire gestation period are shown taking small doses of glucocorticoids and antiplatelet agents, the introduction of immunoglobulin, heparin injections under the control of hemostasiogram parameters.

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

Forecast

Timely diagnosis and preventive therapy can avoid the development and recurrence of thrombosis, as well as hope for a favorable outcome of pregnancy and childbirth. In secondary antiphospholipid syndrome, it is important to control the course of the underlying pathology and prevent infections. Prognostically unfavorable factors are the combination of antiphospholipid syndrome with SLE, thrombocytopenia, a rapid increase in Ab titer to cardiolipin, and persistent arterial hypertension. All patients diagnosed with antiphospholipid syndrome should be under the supervision of a rheumatologist with periodic monitoring of serological markers of the disease and hemostasiogram parameters.

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Symptoms of antiphospholipid syndrome

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antiphospholipid syndrome. General principles of pharmacotherapy

Venous and arterial thromboses

Patients with first venous thrombosis

Patients with recurrent thrombosis

Patients without clinical signs of APS, but with high levels of aPL

Acute thrombotic complications in APS

"Catastrophic" AFS

Pregnant women with APS

Hematological disorders in APS

Moderate thrombocytopenia

Resistant severe thrombocytopenia

Forecast

Causes and mechanisms of development of antiphospholipid syndrome

Clinical features of antiphospholipid syndrome

Diagnosis of antiphospholipid syndrome

Treatment of antiphospholipid syndrome

Antiphospholipid syndrome and pregnancy

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Which doctor to contact

Causes and mechanisms of development of antiphospholipid syndrome

Clinical features of antiphospholipid syndrome

Diagnosis of antiphospholipid syndrome

Treatment of antiphospholipid syndrome

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Antiphospholipid syndrome - what threatens the disease and how to deal with it?

APS syndrome - what is it?

Antiphospholipid syndrome - causes

Primary antiphospholipid syndrome

Secondary antiphospholipid syndrome

Antiphospholipid syndrome - symptoms in women

Antiphospholipid syndrome - diagnosis

Antiphospholipid syndrome - analysis

How to treat antiphospholipid syndrome?

Can antiphospholipid syndrome be cured?

Traditional medicine for antiphospholipid syndrome

Antiphospholipid syndrome - prognosis

Antiphospholipid syndrome and pregnancy

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General information

Causes

Classification

Symptoms of antiphospholipid syndrome

Diagnostics

Treatment of antiphospholipid syndrome

Forecast