home Audience 4 Probable afs. Prevention and treatment of antiphospholipid syndrome: current recommendations and prospects. Acute thrombotic complications in APS

Probable afs. Prevention and treatment of antiphospholipid syndrome: current recommendations and prospects. Acute thrombotic complications in APS

Despite the fact that clinical recommendations for the diagnosis and treatment of antiphospholipid syndrome were developed by rheumatologists, it is directly related to obstetrics. Antiphospholipid syndrome during pregnancy leads to recurrent miscarriage, which entails childlessness for the couple.

Antiphospholipid syndrome, or APS, is a pathology that is characterized by repeated thrombosis of the venous, arterial, microvasculature, the pathology of pregnancy with fetal loss and the synthesis of antiphospholipid antibodies (aPL): cardiolipin antibodies (aCL) and/or lupus anticoagulant (LA), and/or antibodies to beta2-glycoprotein Ⅰ. APS is a variant of often acquired thrombophilia.

The ICD 10 revision code is D68.8.

The basis of the pathogenesis of antiphospholipid syndrome is the attack of cell membranes by antibodies. Most often, antiphospholipid syndrome develops in women - 5 times more often than in men.

The syndrome manifests itself through the occurrence of thrombosis and miscarriage. Often, before the development of gestation, women were not aware of the presence of this pathology and the presence of antibodies in the blood.

Classification

There are several variants of antiphospholipid syndrome. Their main classification is as follows:

Primary – associated with hereditary hemostasis defects.
Secondary APS arose against the background of autoimmune diseases (rheumatoid arthritis, systemic lupus erythematosus), vasculitis, organ-specific pathologies (diabetes mellitus, Crohn's disease), oncological processes, drug exposure, infections (HIV, syphilis, malaria), and end-stage renal failure.
Other AFS options:

seronegative
catastrophic
other microangiopathic syndromes (DIC syndrome, HELLP).

Causes of miscarriage

Pathogenesis of the development of obstetric pathology in APS.

The influence of APS in the development of such pregnancy complications has been proven:

infertility of unknown origin;
early preembryonic losses;
failed IVF;
miscarriages at different stages;
intrauterine fetal death;
postpartum fetal death;
fetal growth retardation syndrome;
preeclampsia and eclampsia;
thrombosis during pregnancy and after childbirth;
fetal malformations.

In the postpartum period, the child also experiences consequences of antiphospholipid syndrome: thrombosis, neurocirculatory disorders with the development of autism in the future. 20% of children born to mothers with APS have antiphospholipid antibodies in their blood without symptoms, which indicates intrauterine transmission of aPL.

The pathogenetic basis for the development of all manifestations of APS during pregnancy is placental decidual vasculopathy, which is caused by a lack of prostaglandin production, placental thrombosis and a violation of the implantation mechanism. All these mechanisms prevent pregnancy.

Diagnosis criteria

There are criteria by which the diagnosis of “Antiphospholipid syndrome” is established. Among the clinical criteria, the following are highlighted:

Vascular thrombosis of any location: both venous and arterial, confirmed by visual examination methods. When using histological examination, biopsy specimens should show no signs of inflammation of the vascular wall.
Complications of pregnancy:

one or more episodes of death of a normally developing fetus after 10 weeks of gestation, or
one or more episodes of preterm birth before 34 weeks due to significant preeclampsia, eclampsia, placental insufficiency, or
three or more consecutive cases of spontaneous abortions in less than 10 weeks, in the absence of pathologies of uterine anatomy, genetic mutations, or sexually transmitted infections.

Laboratory criteria are:

Antibodies to cardiolipin, immunoglobulins of classes G and M, were detected in the blood in medium and high titers, at least 2 times in 12 months.
Antibodies to b2-glycoprotein I classes G and/or M in medium or high titers, at least 2 times a year.
Plasma lupus anticoagulant VA was determined in 2 more laboratory studies over an interval of at least 12 months. The presence of VA in the blood can be suspected if the aPTT in the coagulogram increases by 2 or more times.

An antibody test is considered highly positive - 60 IU/ml, an average positive response - 20-60 IU/ml, low positive - less than 20 IU/ml.

To make a diagnosis of Antiphospholipid Syndrome, one clinical and one laboratory criterion must be present.

Symptoms

The main symptom of antiphospholipid syndrome is thrombosis. In women, this pathology manifests itself as miscarriage. In addition to these obvious signs, women may exhibit additional clinical criteria:

livedo reticularis;
a history of migraines, chorea;
trophic ulcerative defects of the lower extremities;
endocarditis and so on.

The catastrophic form of antiphospholipid syndrome is very difficult. It is accompanied by a clinical picture of acute renal failure, respiratory distress syndrome, liver failure, impaired cerebral blood flow, and thrombosis of large vessels, including the pulmonary artery. It is impossible to live with this form for a long time without urgent help.

Treatment

Many specialists treat APS: rheumatologists, hematologists, obstetricians and gynecologists, cardiologists, cardiac surgeons and others.

First group of patients

Patients who do not have laboratory signs or clinical symptoms do not require constant laboratory monitoring and continuous anticoagulant therapy. In this group of patients, standard prophylaxis of venous thrombosis is carried out.

Second group

In patients with a high titer of lupus anticoagulant and/or antiphospholipid antibodies more than 10 IU/ml without thrombosis, specific prophylaxis is required - Aspirin at a dosage of 75-100 mg once a day.

Third group

These people test negative for antibodies, but there are confirmed cases of thrombosis and a high risk of their formation. These patients are treated with anticoagulants of low molecular weight heparin in therapeutic doses. Immediately after diagnosis, use:

Dalteparin 100 IU/kg 2 times a day;
Nadroparin 86 IU/kg or 0.1 ml per 10 kg 2 times a day subcutaneously;
Enoxaparin 1 mg/kg 2 times a day subcutaneously;
From the second day, Warfarin is prescribed at 5 mg per day.

Patients in this group undergo heparin therapy for at least 3 months. At the beginning of therapy, the INR is monitored every 4-5 days to maintain the target value of 2.0-3.0.

Fourth group

This group includes people in whom thrombosis occurs against the background of elevated titers of lupus anticoagulant and antiphospholipid antibody. In this category of patients, Warfarin and low doses (75-100 mg) of Acetylsalicylic acid are prescribed. High-risk patients should receive lifelong anticoagulation therapy.

Preconception preparation

Preparation for pregnancy with APS is carried out in 2 successive stages. At the first stage, the coagulogram is assessed, the antigenic components of the blood are determined, and infectious foci are removed and sanitized.

The second stage is the immediate preparation for pregnancy and its management. This requires anticoagulant therapy. It is carried out individually during 1-2 menstrual cycles. To do this, you need to place the woman in one of the following groups:

A seronegative variant of APS with a history of obstetric manifestations of the syndrome. Only antibodies to beta2-glycoprotein I can be detected in the serum. In this group, preparation is carried out using the following drugs:

one of the low molecular weight heparin preparations 1 time/day subcutaneously (dalteparin (Fragmin) 120 antiXa IU/kg or enoxaparin (Clexan) 100 antiXa IU/kg;
fish oil 1-2 capsules 3 times a day;
folic acid 4 mg/day;

If lupus anticoagulant is absent, but APLA is present without thrombosis and obstetric clinical manifestations:

with a moderate titer of APLA, Aspirin 75-100 mg/day is prescribed, and if pregnancy develops, it is discontinued and replaced with dipyridomole 50-75 mg/day;
with a high and moderate titer of antiphospholipid antigen, combine Acetylsalicylic acid 75 mg/day and low molecular weight heparin once a day subcutaneously;
fish oil 1-2 capsules 3 times a day;
folic acid 4 mg/day.

If there is no lupus anticoagulant in the blood, but there is a high or moderate amount of antiphospholipid antigen and there is a clinical picture of thrombosis and obstetric complications:

one of the LMWHs (Clexane, Fragmin, Fraxiparine) 1 time per day subcutaneously;
Aspirin 75 mg/day with its discontinuation during pregnancy and the prescription of Dipyridamole 50-75 mg/day;
fish oil 1-2 capsules 3 times a day;
folic acid 4 mg/day.

APLA was detected in the woman's plasma and the lupus anticoagulant VA was determined from 1.5 to 2 conventional units. Until VA normalizes, you should abstain from pregnancy. To normalize VA to less than 1.2 conventional units, the following is used:

Clexane 100 antiXa IU/kg or Fragmin 120 antiXa IU/kg once a day subcutaneously;
recommended intravenous human immunoglobulin 25 ml every other day, 3 doses, repeat administration of the drug at 7-12 weeks of pregnancy, at 24 weeks and the last administration before childbirth;
after VA is established within normal limits, Acetylsalicylic acid 75 mg/day is prescribed until pregnancy;
Clexane or Fragmin once a day subcutaneously in the same dosages;
fish oil 1-2 drops. 3 times a day;
folic acid 4 mg/kg.

If VA in the blood is more than 2 conventional units, then conception is delayed for at least 6-12 months. The risk of developing thrombosis in such women is very high. The target value of VA is 1.2 conventional units. Therapy is carried out for at least 6 months.

Laboratory diagnostics and examination when planning pregnancy necessarily includes the following blood clotting indicators:

platelets – 150-400*10 9 /l;
fibrinogen – 2-4 g/l;
INR – 0.7-1.1;
degradation products of fibrinogen and fibrin – less than 5 μg/ml;
d-dimers – less than 0.5 μg/ml;
soluble fibrin monomer complexes should be absent;
protein C – 69.1-134.1%;
antithrombin Ⅲ – 80-120%;
platelet aggregation activity with adenosine diphosphate salt – 50-80%, with adrenaline hydrochloride – 50-80%;
anticardiolipin antibodies – all classes of immunoglobulins less than 10 IU/ml;
VA – negative or less than 0.8-1.2 conventional units;
hyperhomocysteinemia – negative;
mutation FV (Leiden) of the gene responsible for the synthesis of factor V, or mutation G20210A of the gene responsible for the synthesis of factor II – absent;
general urine test to determine hematuria;
control over the development of infectious diseases: lymphocytes, ESR.

Management of pregnancy with APS

To prevent thrombosis and fetal loss during pregnancy, prevention is necessary - non-drug and medicinal.

Non-drug:

physical activity stimulates its own tissue plasminogen;
elastic medical knitwear 1-2 compression class;
a diet with plenty of vegetable oils, beets, prunes, figs, bananas, since these products have a laxative effect - it is important not to create increased pressure on the walls of the veins during bowel movements.

Drug prevention of thrombosis during pregnancy

There are several prevention options depending on the course of antiphospholipid syndrome.

There are no serological markers of VA and anticardiolipin antigen, thrombotic complications, antibodies to beta2-glycoprotein I can be detected.

In the first trimester, Clexane or Fragmin is prescribed in a dosage for optimal maintenance of d-dimers and folic acid 4 mg/kg.
Second and third trimesters - Frigmin or Clexane until normal levels of d-dimers, fish oil, Aspirin 75-100 mg/kg with increased platelet aggregation, FFP 10 ml/kg or antithrombin concentrate with a decrease in antithrombin 3 less than 80%.
Before birth, Aspirin is discontinued 3-5 days in advance, the evening dose of LMWH is changed to FFP 10 mg/kg with heparin 1-2 U for each ml of FFP.
During delivery - normal level of d-dimers FFP 10 mg/kg, with a high level before surgery - FFP 5 ml/kg plus heparin 1 U per 1 ml FFP or antithrombin concentrate 3, during surgery FFP 5 ml/kg.

If APLA is present in the blood with or without thrombosis, there is no lupus anticoagulant.

1st trimester – Klesan or Fragmin to maintain normal levels of d-dimers + folic acid 4 mg/day.
2nd and 3rd trimesters – Clexane or Fragmin in individual dosages + Aspirin 75 mg/day + fish oil 1-2 drops 3 times a day, with a decrease in antithrombin 3 less than 80% of activity – FFP 10 ml/kg or antithrombin concentrate Ⅲ – 10- 50 IU/kg, with an increase in d-dimers more than 0.5 μg/ml - increase the dosage of LMWH.
Before childbirth, Aspirin is discontinued 3-5 days in advance, LMWH is replaced with FFP 10 ml/kg + UFH 1-2 units for each ml of FFP, if antiphospholipid antibodies increase, Prednisolone (Methylpred) 1-1.5 mg/kg intravenously is prescribed.
During delivery, if D-dimers are normal - FFP 10 ml/kg; if d-dimers are elevated, then before surgery FFP 5 ml/kg + UFH 1 unit for each ml of CPG or antithrombin concentrate 3, during surgery - FFP 5 ml/kg, with a significant increase in antibodies - Prednisolone 1.5-2 ml/ kg intravenously.

When VA increases from 1.5 to 2 conventional units.

1st trimester - basic intake of Fragmin or Clexane in the same dose as in the previous version + folic acid + human immunoglobulin 25 ml every other day, 3 doses every 7-12 weeks. If there is an increase in VA by more than 1.5 conventional units in the first trimester, then the pregnancy should be terminated.
2nd and 3rd trimester – Fragmin and Clexane in dosage for normal maintenance of d-dimers + Aspirin 75 mg + fish oil 1-2 drops 3 times a day, with reduced antithrombin – FFP 10 ml/kg or antithrombin concentrate Ⅲ 10-50 IU/ kg IV, if D-dimers increase, increase the dosage of LMWH, immunoglobulin 25 ml every 1 day 3 times every 24 weeks, if VA is increased from 1.2 to 2 conventional units - Prednisolone 30-60 mg/day IV , from 13 to 34 weeks it is possible to switch to Warfarin under INR control.
Before birth, if there was Warfarin, then it is canceled 2-3 weeks before, transferred to LMWH, Aspirin is canceled 3-5 days before birth, FFP 10 ml/kg + UFH 2 units for each ml of plasma, Prednisolone - 1.5-2 ml/kg IV, with reduced antithrombin Ⅲ - antithrombin concentrate Ⅲ 10-30 IU/kg.
During childbirth - before surgery FFP 500 ml + UFH 1000 units, during surgery - FFP 10 ml/kg, Prednisolone 1.5-2 mg/kg IV.

If VA increases by more than 2 conventional units, pregnancy should be terminated.

If a woman has developed catastrophic antiphospholipid or HELLP syndrome, plasmapheresis or plasma filtration may be prescribed.

Postpartum period

After delivery, thromboembolism prevention should be resumed after 8-12 hours with Fraxiparin (Nadroparin) - 0.1 ml/10 kg, Clexane (Enoxaparin) 100 IU/kg, Fragmin (Dalteparin) 120 IU/kg, if there is no bleeding.

If a woman has a history of thrombosis, then therapeutic doses of these drugs are prescribed: Fraxiparine - 0.1 ml/10 kg 2 times a day, Clexane - 100 IU/kg 2 times a day, Fragmin - 120 IU/kg 2 times a day .

The use of LMWH must be continued for at least 10 days. And if there was an episode of proven thromboembolism, then anticoagulants are used for at least 3-6 months.

An increase in the concentration of antigens in the blood requires consultation with a hematologist or rheumatologist to decide on hormonal therapy.

Price for tests

To identify APS, you can undergo diagnostics for a fee. Many private laboratories offer a panel for the determination of antiphospholipid antibodies. In the Invitro laboratory in Moscow, prices at the end of 2018 are as follows:

detection of immunoglobulins G and M to cardiolipin costs 1990 rubles;
diagnostics of secondary APS – price 3170 rubles;
detailed serological test for APS – 4200 rubles;
laboratory criteria for APS – 3950 rub.

In the Sinevo laboratory in Moscow, prices for analyzes of this panel vary slightly:

immunoglobulins G and M to cardiolipin – 960 rubles;
antibodies to beta2-glycoprotein I – 720 rubles;
class G antibodies to phospholipids – 720 rubles;
class M antibodies to phospholipids – 720 rub.

Other private laboratories in Russian cities can offer approximately the same prices.

Antiphospholipid syndrome (APS) is a clinical and laboratory symptom complex that includes venous and/or arterial thrombosis, various forms of obstetric pathology (primarily recurrent miscarriage), thrombocytopenia, as well as various other neurological, skin, cardiovascular and hematological disorders. A characteristic immunological feature of APS is antibodies to phospholipids - a heterogeneous group of antibodies that react with a wide range of phospholipids and phospholipid-binding proteins. APS most often develops in SLE (secondary APS) or in the absence of another leading disease (primary APS).

The true prevalence of APS in the population is still unknown. The frequency of detection of antibodies to phospholipids in the serum of healthy people varies from 0 to 14%, on average 2-4% (in high titers in less than 0.2%). The disease often develops at a young age and can occur in children and even newborns. In elderly people, the development of APS may be associated with malignant neoplasms. In the general population, APS is more often detected in women. However, among patients with primary APS, an increase in the proportion of men is noted.

ETIOLOGY

The causes of APS are not known. An increase in the level (usually transient) of antibodies to phospholipids is observed against the background of a wide range of bacterial and viral infections. However, thrombotic complications in patients with infections develop less frequently than antibodies to phospholipids are detected. There is evidence of an immunogenetic predisposition to overproduction of antibodies to phospholipids. There was an increase in the frequency of detection of antibodies to phospholipids in families of patients with APS; Cases of APS (usually primary) have been described in members of the same family.

PATHOGENESIS

Abs to phospholipids bind to phospholipids in the presence of a cofactor, which is β 2 -glycoprotein I, a protein that binds to phospholipids and has anticoagulant activity. Antiphospholipid antibodies present in the serum of patients with APS react with Ags formed during the interaction of phospholipid components of the membranes of endothelial and other cells (platelets, neutrophils) and β 2 -glycoprotein I. As a result of this interaction, the synthesis of anticoagulants (prostacyclin, antithrombin III) is suppressed , annexin V, etc.) and increased formation of procoagulant (thromboxane, tissue factor, platelet activating factor, etc.) mediators, activation of the endothelium (expression of adhesion molecules) and platelets is induced, and neutrophil degranulation occurs.

Antiphospholipid antibodies detected in the serum of patients with infectious diseases usually react with phospholipids in the absence of β 2 -glycoprotein I and do not have the properties described above.

CLASSIFICATION

The following clinical and laboratory variants of APS are distinguished.

Primary APS.

Secondary APS.

. "Catastrophic" APS.

In some patients, APS manifests itself primarily as venous thrombosis, in others as a stroke, in others as obstetric pathology or thrombocytopenia. The development of APS does not correlate with the activity of the underlying disease. Approximately half of patients with APS suffer from the primary form of the disease. However, the question of the nosological independence of primary APS is not completely clear. Primary APS can sometimes be a variant of the onset of SLE. On the contrary, in some patients with classical SLE at the onset, signs of APS may subsequently come to the fore.

In some patients, APS may present with acute recurrent coagulopathy and vasculopathy, affecting vital organs and resembling disseminated intravascular coagulation or hemolytic uremic syndrome. This condition is called "catastrophic" APS.

CLINICAL PICTURE

Since APS is based on non-inflammatory thrombotic damage to vessels of any size and location, the range of clinical manifestations is extremely diverse.

Venous thrombosis is the most common manifestation of APS. Thrombi are usually localized in the deep veins of the lower extremities, but are often found in the hepatic, portal veins, superficial veins, etc. Repeated pulmonary embolisms from the deep veins of the lower extremities are typical, sometimes leading to pulmonary hypertension. APS (more often primary than secondary) is the second most common cause of Budd-Chiari syndrome. Thrombosis of the central vein of the adrenal glands can lead to adrenal insufficiency.

Arterial thrombosis. Thrombosis of intracerebral arteries, leading to stroke and transient ischemic attacks, is the most common localization of arterial thrombosis in APS. Recurrent ischemic strokes caused by damage to small vessels sometimes occur without significant neurological disorders and can manifest as convulsive syndrome, multi-infarct dementia (resembling Alzheimer's disease), and mental disorders.

A variant of APS is Sneddon syndrome, manifested by recurrent thrombosis of cerebral vessels, livedo reticularis, hypertension and developing in young and middle-aged people. Other neurological disorders include migraine headaches, epileptiform seizures, chorea, and transverse myelitis. Sometimes neurological disorders in APS resemble those in multiple sclerosis.

Heart valve damage is one of the common cardiac manifestations of APS. It varies from minimal disturbances detected only by echocardiography (slight regurgitation, thickening of the valve leaflets) to severe heart defects (stenosis or insufficiency of the mitral, less often the aortic and tricuspid valves). Some patients quickly develop severe valve damage with vegetations caused by thrombotic overlays, similar to valve damage in infective endocarditis. Detection of vegetations on the valves, especially if they are combined with hemorrhages in the nail bed and fingers in the form of “drumsticks”, dictates the need for differential diagnosis with infective endocarditis. The development of blood clots in the cardiac cavity, simulating cardiac myxoma, has been described. One of the possible localizations of arterial thrombosis associated with the synthesis of antibodies to phospholipids is the coronary arteries (in men with SLE this is the most common localization).

Frequent complications of APS include hypertension. It can be labile and is often associated with livedo reticularis and damage to the cerebral arteries as part of Sneddon syndrome, or stable, malignant, manifested by symptoms of hypertensive encephalopathy. The development of hypertension in APS can be associated with many causes, including renal vascular thrombosis, renal infarction, thrombosis of the abdominal aorta (pseudocoarctation), and intraglomerular thrombosis. A connection has been noted between the overproduction of antibodies to phospholipids and the development of fibromuscular dysplasia of the renal arteries. A rare complication of APS is thrombotic pulmonary hypertension, which is associated with both recurrent pulmonary embolism and local ( in situ) thrombosis of the pulmonary vessels.

Kidney damage in APS is associated with intraglomerular microthrombosis and is referred to as renal thrombotic microangiopathy. Microthrombosis of the glomeruli of the kidneys is considered the cause of the subsequent development of glomerulosclerosis, leading to dysfunction of the organ.

Obstetric pathology is one of the most characteristic signs of APS: recurrent miscarriage, recurrent spontaneous abortions, intrauterine fetal death, preeclampsia. Fetal loss can occur at any stage of pregnancy, but more often in the second and third trimesters.

Skin lesions in APS are characterized by a variety of clinical manifestations (usually livedo reticularis). Less common are skin ulcers and pseudovasculitic lesions (purpura, palmar and plantar erythema, pustules, gangrene of the fingers).

Thrombocytopenia is a typical hematological sign of APS. The development of hemorrhagic complications is rare and, as a rule, is associated with a concomitant defect in blood coagulation factors, kidney pathology, or an overdose of anticoagulants. Hemolytic anemia with a positive Coombs test is often observed; Evans syndrome (a combination of thrombocytopenia and hemolytic anemia) is less common.

LABORATORY RESEARCH

Laboratory diagnosis of APS is based on the determination of lupus anticoagulant using functional tests and antibodies to cardiolipin using ELISA. In general, lupus anticoagulant has higher specificity, and anticardiolipin antibodies have higher sensitivity for diagnosing APS. Lupus anticoagulant and antibodies to cardiolipin are detected in 30-40% and 40-50% of patients with SLE, respectively. In the presence of antibodies to phospholipids, the risk of developing thrombosis is 40%, while in the absence of antibodies it is no higher than 15%. A method has been developed for determining antibodies that react with β 2 -glycoprotein I, an increase in the level of which correlates better with the development of thrombosis than an increase in the level of antibodies to phospholipids. The course of APS, the severity and prevalence of thrombotic complications in most cases do not depend on the concentration of antibodies to phospholipids.

DIAGNOSTICS

For diagnosis, preliminary criteria for the classification of APS should be used (Table 46-1).

Table 46-1. Criteria for diagnosing APS

. Clinical criteria

. Laboratory criteria

Vascular thrombosis

1 or more episodes of thrombosis of blood vessels supplying any organ or tissue. With the exception of superficial vein thrombosis, thrombosis must be confirmed by angiography, ultrasound or morphological method. With morphological confirmation, signs of thrombosis should be observed in the absence of pronounced inflammatory infiltration of the vascular wall.

Anticardiolipin antibodies of the IgG or IgM class in medium or high titers, determined at least 2 times within 6 weeks using an ELISA that allows the determination of antibodies to β 2 -glycoprotein

Obstetric pathology

1 or more unexplained deaths of a morphologically normal fetus before the 10th month of gestation

1 or more deaths of a morphologically normal fetus before the 34th week of gestation due to severe preeclampsia or eclampsia or severe placental insufficiency

3 or more unexplained consecutive spontaneous abortions before the 10th week of gestation, with the exception of anatomical and hormonal disorders of the maternal reproductive system or chromosomal abnormalities in the mother or father

Lupus anticoagulant detected at least 2 times within 6 weeks using a standardized method including the following steps

Prolongation of phospholipid-dependent blood coagulation using screening tests (APTT, kaolin test, Russell's viper test, prothrombin time, textarine time)

When mixed with normal plasma without platelets, the prolongation of blood clotting time according to screening tests is maintained.

Normalization of blood clotting time by adding excess phospholipids

Rule out other coagulopathies (factor VIII inhibitors or heparin)

To make a reliable diagnosis of APS, a combination of at least one clinical and one laboratory criterion is necessary.

APS should be suspected in cases of thrombotic disorders (especially multiple, recurrent, with unusual localization), thrombocytopenia, obstetric pathology in young and middle-aged people, as well as in unexplained thrombosis in newborns, in case of skin necrosis during treatment with indirect anticoagulants and in patients with prolonged aPTT during a screening study. With APS, a large number of pseudo-syndromes are observed, which can imitate vasculitis, infective endocarditis, heart tumors, multiple sclerosis, hepatitis, nephritis, etc.

TREATMENT

Prevention and treatment of APS is a complex task (Table 46-2). This is due to the heterogeneity of the pathogenetic mechanisms underlying APS, the polymorphism of clinical manifestations, and the lack of reliable clinical and laboratory indicators to predict the recurrence of thrombotic disorders. The risk of recurrent thrombosis is especially high in young patients with persistent high levels of antibodies to cardiolipin, lupus anticoagulant and with simultaneous detection of antibodies to cardiolipin and lupus anticoagulant, as well as in the presence of recurrent thrombosis and/or obstetric pathology in the anamnesis, in the presence of other thrombotic risk factors disorders (hypertension, hyperlipidemia, smoking, taking oral contraceptives), with high activity of SLE, with rapid withdrawal of indirect anticoagulants, with a combination of high titers of antibodies to phospholipids with other coagulation disorders.

. Groups patients
Without clinical signs of APS, but with a high level of antibodies to phospholipids	Without risk factors - low doses of acetylsalicylic acid (less than 100 mg/day) ± hydroxychloroquine (100-200 mg/day) (for secondary APS)
	If there are risk factors - warfarin (INR less than 2) ± hydroxychloroquine (100-200 mg/day)
With venous thrombosis	Warfarin (INR=2-3) ± hydroxychloroquine (100-200 mg/day)
With arterial thrombosis	Warfarin (INR more than 3) ± hydroxychloroquine ± acetylsalicylic acid in low doses (depending on the risk of recurrent thrombosis or bleeding)
With repeated thromboses	Warfarin (INR greater than 3) ± hydroxychloroquine ± low-dose acetylsalicylic acid

In addition, there are a number of features in the treatment of APS.

In patients with high levels of antibodies to phospholipids in the serum, but without clinical signs of APS (including pregnant women without a history of obstetric pathology), they are limited to prescribing small doses of acetylsalicylic acid (75 mg/day). These individuals require careful follow-up, since their risk of thrombotic complications is very high. Moderate thrombocytopenia usually does not require treatment or is controlled with small doses of GCs.

Management of patients with definite APS is based on the prescription of vitamin K antagonists (warfarin) and antiplatelet agents (low doses of acetylsalicylic acid), which are widely used for the prevention of thrombosis not associated with APS. In patients with both secondary and primary APS, treatment with warfarin, which maintains the INR at a level of 2-3 (or more), leads to a significant reduction in the incidence of recurrent thrombotic complications. However, the use of warfarin is associated with a high risk of bleeding. It is advisable to prescribe antimalarial drugs, which, along with an anti-inflammatory effect, have antithrombotic (suppress platelet aggregation and adhesion, reduce the size of a blood clot) and lipid-lowering activity.

The use of warfarin during pregnancy is contraindicated, as this leads to the development of warfarin embryopathy, characterized by impaired growth of the epiphyses of the bones and hypoplasia of the nasal septum, as well as neurological disorders. Treatment with heparin (especially low molecular weight heparins in standard doses) in combination with low doses of acetylsalicylic acid in women with recurrent miscarriage can increase the frequency of successful births by approximately 2-3 times and is significantly more effective than glucocorticoid therapy.

Treatment with GCs and cytotoxic drugs is not recommended, except in cases of “catastrophic” APS.

FORECAST

The development of APS in SLE reduces patient survival. Prognostically unfavorable factors for recurrent thrombosis include thrombocytopenia, arterial thrombosis, and a persistent increase in the level of antibodies to cardiolipin.

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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. The specific clinical manifestations of antiphospholipid syndrome depend on which particular organ’s vessels are clogged with blood clots. In an 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 that allow us to judge the risk of relapse with a high degree of reliability. That is why the current 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. This treatment is based on the use of anticoagulant drugs (Heparins, Warfarin) and antiplatelet agents (Aspirin, etc.), which help prevent 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 one to prolong life and maintain its quality at an acceptable level.

Antiphospholipid syndrome - what is it?

Antiphospholipid syndrome (APS) is also called Huge's syndrome or anticardiolipin antibody syndrome. This disease was first identified and described in 1986 in patients suffering from systemic lupus erythematosus. Currently, antiphospholipid syndrome is classified as thrombophilias– a group of diseases characterized by increased formation of blood clots.

Antiphospholipid syndrome is non-inflammatory autoimmune disease with a unique set of clinical and laboratory signs, which is based on the formation of antibodies to certain types of phospholipids, which are structural components of the membranes of platelets, blood vessel cells and nerve cells. Such antibodies are called antiphospholipid antibodies, and are produced by the body’s own immune system, which mistakes the body’s own structures for foreign ones and seeks to destroy them. It is precisely because the pathogenesis of antiphospholipid syndrome is based on the production of antibodies by the immune system against the structures of the body’s own cells that the disease belongs to the group of autoimmune diseases.

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

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

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

Lupus anticoagulant. This laboratory indicator is quantitative, that is, the concentration of lupus anticoagulant in the blood is determined. Normally, in healthy people, a lupus anticoagulant may be present in the blood at a concentration of 0.8 - 1.2 a.u. Increasing 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. In 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 in a concentration of less than 12 U/ml.
Antibodies to beta-2-glycoprotein (IgA, IgM, IgG). This indicator is quantitative. With antiphospholipid syndrome, the level of antibodies to beta-2-glycoprotein increases by more than 10 U/ml, and normally in a healthy person these antibodies may be present in 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 becomes clogged, as a result of which blood cannot circulate freely through them. As a result of thrombosis, starvation of cells occurs that do not receive oxygen and nutrients, which results in the death of the cellular structures of any organ or tissue. It is the death of organ cells or tissues that gives rise to the characteristic clinical manifestations of antiphospholipid syndrome, which may vary depending on which organ has been destroyed due to thrombosis of its vessels.

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

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

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

There are two main types of antiphospholipid syndrome – primary and secondary. Secondary antiphospholipid syndrome always develops against the background of some other autoimmune (for example, systemic lupus erythematosus, scleroderma), rheumatic (rheumatoid arthritis, etc.), oncological (malignant tumors of any localization) or infectious disease (AIDS, syphilis, hepatitis C, etc. .d.), or after taking medications (oral contraceptives, psychotropic drugs, Isoniazid, etc.). Primary antiphospholipid syndrome develops in the absence of other diseases, and its exact causes are currently unknown. However, it is assumed that hereditary predisposition, severe chronic long-term infections (AIDS, hepatitis, etc.) and the use of certain medications (Phenytoin, Hydralazine, etc.) play a role in the development of primary antiphospholipid syndrome.

Accordingly, the cause of secondary antiphospholipid syndrome is a person’s existing disease, which provoked an increase in the concentration of antiphospholipid antibodies in the blood with the subsequent development of pathology. And the causes of primary antiphospholipid syndrome are unknown.

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

Currently, predisposing factors for antiphospholipid syndrome include the following:

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 location);
Some diseases of the central nervous system;
Long-term use of certain medications (oral contraceptives, psychotropic drugs, interferons, Hydralazine, Isoniazid).

Antiphospholipid syndrome - signs (symptoms, clinic)

Let's look at the signs of catastrophic APS and other forms of the disease separately. This approach seems rational, since the clinical manifestations of various types of antiphospholipid syndrome are the same, and only catastrophic APS has differences.

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

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

Since thrombosis can affect the vessels of any organ and tissue, manifestations of antiphospholipid syndrome in the central nervous system, cardiovascular system, liver, kidneys, gastrointestinal tract, skin, etc. are currently described. Thrombosis of placental vessels during pregnancy provokes obstetric pathology ( miscarriages, premature birth, placental abruption, etc.). Let us consider the symptoms of antiphospholipid syndrome from various organs.

Firstly, you need to know that thrombosis in APS can be venous and arterial. With venous thrombosis, the blood clots are localized in the veins, and with arterial thrombosis, respectively, in the arteries. A characteristic feature of antiphospholipid syndrome is recurrent thrombosis. That is, if treatment is not carried out, then episodes of thrombosis of various organs will be repeated again and again, until failure of any organ occurs, incompatible with life. APS also has one more feature - if the first thrombosis was venous, then all subsequent episodes of thrombosis are also, as a rule, venous. Accordingly, if the first thrombosis was arterial, then all subsequent ones will also involve the arteries.

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

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

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

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

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

Recurrent microstrokes in APS often occur without clear and noticeable symptoms, and can manifest themselves after some time as seizures and the development of dementia.

Headaches are also one of the most common manifestations of antiphospholipid syndrome when thrombosis is localized in intracerebral arteries. In this case, headaches can have a different character - from migraine to constant.

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

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

Despite the fact that damage to the cardiovascular system in APS develops frequently, it rarely leads to heart failure and severe consequences requiring surgery.

Renal vascular thrombosis leads to various disorders of the functioning of this organ. Thus, the most common symptom of APS is proteinuria (protein in the urine), which is not accompanied by any other symptoms. Also, with APS, the development of renal failure with arterial hypertension is possible. Any disturbances in kidney function in APS are caused by microthrombosis of the glomerular vessels, which causes glomerulosclerosis (replacement of kidney tissue with scar). Microthrombosis of the glomerular vessels of the kidneys is designated by the term “renal thrombotic microangiopathy.”

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

With APS, in approximately 20% of cases, specific skin lesion due to thrombosis of small vessels and peripheral circulation disorders. Livedo reticularis appears on the skin (a vascular network of blue-violet color, localized on the legs, feet, hands, thighs, and clearly visible when cooled), ulcers, gangrene of the fingers and toes develops, as well as multiple hemorrhages in the nail bed, which in appearance they look like a "thorn". Also, sometimes a rash appears on the skin in the form of pinpoint hemorrhages, which in appearance resembles vasculitis.

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

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

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

With APS, there is almost always thrombocytopenia (the number of platelets in the blood is lower than normal), in which the platelet count ranges from 70 to 100 G/L. This thrombocytopenia does not require treatment. In approximately 10% of cases with APS, Coombs-positive hemolytic anemia or Evans syndrome (a combination of hemolytic anemia and thrombocytopenia) develops.

Symptoms of catastrophic antiphospholipid syndrome

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

Antiphospholipid syndrome in men, women and children

Antiphospholipid syndrome can develop in both children and adults. In children, this disease occurs less frequently than in adults, but is more severe. Antiphospholipid syndrome occurs 5 times more often in women 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 placental vessels. Due to thrombosis of the placental vessels, various obstetric complications arise, such as intrauterine fetal death, fetoplacental insufficiency, delayed fetal development, etc. In addition, APS during pregnancy, in addition to obstetric complications, can provoke thrombosis in other organs - that is, manifest itself with symptoms that are characteristic of this disease even outside the gestation period. Thrombosis of other organs also negatively affects the course of pregnancy, since their functioning is disrupted.

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

Infertility of unknown origin;
IVF failures;
Miscarriages in early and late pregnancy;
Frozen pregnancy;
Intrauterine fetal death;
Premature birth;
Stillbirth;
Fetal malformations;
Fetal growth retardation;
Preeclampsia;
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 missed abortion, miscarriage, or premature birth. Moreover, the risk of pregnancy loss correlates with the level of anticardiolipin antibodies in a woman’s blood. That is, the higher the concentration of anticardiolipin antibodies, the higher the risk of pregnancy loss.

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

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 clotting indicators. This therapy is mandatory for women with APS during pregnancy. However, in addition to these drugs, the doctor may additionally prescribe other medications that are necessary for each specific woman at the current time (for example, iron supplements, Curantil, etc.).

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

The use of Aspirin is stopped at the 37th week of pregnancy, and heparins are administered until the onset of regular labor if childbirth is vaginal. If a planned cesarean section is scheduled, then Aspirin is canceled 10 days, and heparins one day before the date of surgery. If heparins were used before the onset of labor, then such women should not be given epidural anesthesia.

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

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

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

Antiphospholipid syndrome is a complex of symptoms that includes multiple arterial and/or venous thrombosis, causing 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 this 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, today 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 some other diseases or pathological conditions, the main of which are:

It can also be a consequence of taking a number of medications: psychotropic drugs, oral hormonal contraceptives, hydralazine, procainamide and others.

With antiphospholipid syndrome, the patient’s body produces a large number of autoantibodies to phospholipids, which have several varieties, located on the membranes of platelets and endothelial cells, 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 antiphospholipid syndrome.

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

endothelial cells (endothelial cells): they reduce the synthesis of prostacyclin, 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 coagulation 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 clotting, and also weaken the activity of heparin.

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

Clinical signs of antiphospholipid syndrome

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

The following changes may be detected in the skin:

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

The following manifestations are characteristic of damage to the vessels of the extremities:

chronic ischemia due to disturbances in blood flow below the site blocked by 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 tissue as a result of prolonged ischemia;
deep or superficial veins of the extremities: pain in the limb area, severe swelling, disruption of its function;
: accompanied by severe pain, increased body temperature, chills; Along the course of the vein, redness of the skin and painful compactions under it are determined.

If a thrombus is localized in large vessels, the following may be determined:

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

The following changes may be observed in bone tissue:

aseptic bone necrosis: necrosis of a section of bone tissue in the area of the articular surface of the bone; more often observed in the area of the femoral head; manifests itself as a pain syndrome of uncertain localization, atrophy of the muscles adjacent to the affected area, and impaired movement in the joint;
reversible, not associated with the use of glucocorticoids: manifested by pain in the affected area, in the absence of factors that could provoke them.

Manifestations of antiphyspholipid syndrome on the part of the organ of vision may include:

optic nerve atrophy;
retinal hemorrhages;
thrombosis of arteries, arterioles or veins of the retina;
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 are reversible or irreversible.

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

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

When blood clots are localized in the vessels of the adrenal glands, acute or chronic adrenal insufficiency can develop, as well as hemorrhages and infarctions in the area of the affected organ.

Damage to the nervous system by blood clots is usually manifested by the following conditions:

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

When blood vessels in the heart are affected by blood clots, the following are determined:

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

In case of thrombosis of liver vessels, liver infarctions, Budd-Chiari syndrome, and nodular regenerative hyperplasia are possible.

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

Diagnosis of antiphospholipid syndrome

Antibodies to cardiolipin may be detected in the blood of such patients.

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

recurrent miscarriage;
arterial thrombosis;
venous thrombosis;
skin lesion – livedo reticularis;
in the area of the legs;
decreased level of platelets in the blood;
signs .

Biological criteria include an increased level 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.

A general blood test may reveal the following changes:

increased ESR;
reduced platelet level (within 70-120*10 9 /l);
increased white blood cell count;
sometimes – signs of hemolytic anemia.

A biochemical blood test will reveal:

increased gamma globulin levels;
in chronic renal failure - increased levels of urea and creatinine;
in case of liver damage - increased levels of ALT and AST, alkaline phosphatase,;
increase in aPTT in the blood clotting test.

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 common);
for hemolytic anemia - antibodies to red blood cells (positive Coombs test);
false-positive Wasserman reaction;
increased number of T helper cells and B lymphocytes;
antinuclear factor or antibodies to DNA;
cryoglobulins;
positive rheumatoid factor.

Treatment of antiphospholipid syndrome

The following groups of drugs can be used in the treatment of this disease:

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

In some cases, plasmapheresis is used in combination with anticoagulant therapy.

To date, they have not been widely used, but the following groups of drugs are quite promising in the treatment of antiphospholipid syndrome:

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

To prevent recurrent thrombosis, indirect anticoagulants (Warfarin) are used.

In the case of the secondary nature of 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, the cause is antiphospholipid syndrome. Blood clots clog the blood 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 the development of an extremely dangerous condition for both the fetus and the expectant mother - late gestosis.

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

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

In order to monitor the condition of the placenta and the blood circulation of the fetus, a woman undergoes a study such as Doppler ultrasound several times during pregnancy. In addition, in order to prevent thrombus formation 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, the woman may be given immunoglobulin or heparin in small doses.

Forecast

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

Which doctor should I contact?

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