Guidelines in Russian antiphospholipid syndrome. Antiphospholipid syndrome clinical guidelines. Antiphospholipid syndrome

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

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

ICD revision 10 code - D68.8.

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

The manifestation of the syndrome occurs by the occurrence of thrombosis, miscarriage. Often, before the development of gestation, women were unaware 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 defects in hemostasis.
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 effects, infections (HIV, syphilis, malaria), at the end stage of renal failure.
Other APS options:

seronegative
catastrophic
other microangiopathic syndromes (disseminated intravascular coagulation, 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 pre-embryonic loss;
unsuccessful IVF;
miscarriages at different times;
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 has the consequences of antiphospholipid syndrome: thrombosis, neurocirculatory disorders with the formation of autism in the future. Antiphospholipid antibodies without symptoms are present in the blood in 20% of children born to mothers with APS, which indicates intrauterine transmission of APS.

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 impaired implantation mechanism. All of these mechanisms prevent pregnancy.

Diagnosis criteria

Allocate the criteria by which the diagnosis of "Antiphospholipid syndrome" is established. Among the clinical criteria, the following are highlighted:

Vascular thrombosis of any localization: both venous and arterial, confirmed by visual research methods. When using a histological study, 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 labor before 34 weeks due to significant preeclampsia, eclampsia, placental insufficiency, or
three or more cases of spontaneous abortions in a row in a period of less than 10 weeks, in the absence of pathologies of the anatomy of the uterus, genetic mutations, genital infections.

The laboratory criteria are as follows:

Antibodies to cardiolipin were detected in the blood of immunoglobulins of classes G and M 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 at least 12 months apart. The presence of VA in the blood can be suspected when the APTT in the coagulogram increases by 2 or more times.

An antibody test is considered to be highly positive - 60 IU / ml, a moderately positive response - 20-60 IU / ml, low-positive - less than 20 IU / ml.

For the 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 is manifested by miscarriage. In addition to such obvious signs, women may exhibit additional clinical criteria:

netted livedo;
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, 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 are involved in the treatment of 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 need constant laboratory monitoring and continuous anticoagulant therapy. In this group of patients, the standard prophylaxis of venous thrombosis is carried out.

Second group

In patients with a high titer of lupus anticoagulant and / or antiphospholipid antibodies of 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 have negative antibody tests, but there are confirmed cases of thrombosis and a high risk of developing them. These patients are treated with anticoagulants of low molecular weight heparin in therapeutic doses. Immediately after the diagnosis is made, 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 with 5 mg per day.

In patients of this group, heparin therapy is carried out 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 a low dose (75-100 mg) of acetylsalicylic acid are prescribed. Patients at high risk should receive lifelong anticoagulant therapy.

Pregravid preparation

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

The second stage is the direct preparation for pregnancy and its management. This requires anticoagulant therapy. It is performed individually for 1-2 menstrual cycles. To do this, you need to assign a woman to one of the following groups:

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

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

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

with a moderate AFLA titer, Aspirin 75-100 mg / day is prescribed, and with the development of pregnancy, it is canceled with replacement for dipyridomol 50-75 mg / day;
with a high and moderate titer of antiphospholipid antigen, acetylsalicylic acid 75 mg / day and low molecular weight heparin are combined subcutaneously once a day;
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 clinic of thrombosis and obstetric complications:

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

In the plasma of a woman, AFLA was detected and the lupus anticoagulant VA was determined from 1.5 to 2 conventional units. Until VA normalizes, pregnancy should be avoided. To normalize VA less than 1.2 conventional units, apply:

Clexane 100 antiXa IU / kg or Fragmin 120 antiXa IU / kg once a day subcutaneously;
recommended human immunoglobulin intravenously 25 ml every other day 3 doses, repeat the 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 subcutaneously once a day at 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 postponed for at least 6-12 months. The risk of developing thrombosis in these women is very high. The target value of VA is 1.2 conventional units. The therapy is carried out for at least 6 months.

Laboratory diagnostics and examination when planning pregnancy necessarily include the following indicators of blood coagulation:

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 monomeric complexes should be absent;
protein C - 69.1-134.1%;
antithrombin Ⅲ - 80-120%;
aggregation activity of platelets 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 analysis to determine hematuria;
control over the development of infectious diseases: lymphocytes, ESR.

Pregnancy management with APS

To prevent thrombosis and fetal loss during pregnancy, prophylaxis is necessary - non-drug and medication.

Non-drug:

physical activity stimulates its own tissue plasminogen;
elastic medical hosiery 1-2 class of compression;
a diet with a large amount 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 options for prevention, depending on the course of antiphospholipid syndrome.

There are no serological markers of BA 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 to normal 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 of less than 80%.
Before childbirth, Aspirin is canceled 3-5 days before, the evening dose of LMWH is changed to FFP 10 mg / kg with heparin 1-2 U for each ml of FFP.
At delivery - the 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 of FFP or antithrombin 3 concentrate, during the operation FFP 5 ml / kg.

With AFLA in the blood and or without thrombosis, there is no lupus anticoagulant.

1 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% 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 - an increase in the dosage of LMWH.
Before childbirth, discontinuation of Aspirin 3-5 days, LMWH is replaced with FFP 10 ml / kg + UFH 1-2 U for each ml of FFP, with an increase in antiphospholipid antibodies, Prednisolone (Methylpred) 1-1.5 mg / kg intravenously is prescribed.
At 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 3 concentrate, during surgery - FFP 5 ml / kg, with a significant increase in antibodies - Prednisolone 1.5-2 ml / kg intravenously.

With an increase in VA from 1.5 to 2 conventional units.

1 trimester - basic intake of Fragmin or Clexane in a dose, as in the previous version + folic acid + human immunoglobulin 25 ml every other day 3 doses at 7-12 weeks. If there is an increase in VA of more than 1.5 conventional units in the first trimester, then the pregnancy should be terminated.
2nd and 3rd trimester - Fragmin and Clexane in a dosage for the 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 i.v., with an increase in D-dimers - increase the dosage of LMWH, immunoglobulin 25 ml after 1 day 3 times every 24 weeks, if the VA is increased from 1.2 to 2 conventional units - Prednisolone 30-60 mg / day i.v. , from 13 to 34 weeks, it is possible to transfer to Warfarin under the supervision of the INR.
Before childbirth, if there was Warfarin, then it is canceled for 2-3 weeks, transferred to LMWH, Aspirin is canceled 3-5 days before delivery, 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 U, during surgery - FFP 10 ml / kg, Prednisolone 1.5-2 mg / kg IV.

With an increase in VA of more than 2 conventional units, the pregnancy should be terminated.

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

Postpartum period

After delivery, thromboembolism prophylaxis should be resumed after 8-12 hours 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 the consultation of a hematologist or rheumatologist to resolve the issue of hormone therapy.

Analysis price

To identify the APS, you can undergo diagnostics on a paid basis. Many private laboratories offer an antiphospholipid antibody panel. 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 - the price is 3170 rubles;
detailed serological test for APS - 4200 rubles;
laboratory criteria for APS - 3950 rubles.

In the Synevo laboratory in Moscow, the prices for analyzes of this panel vary somewhat:

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

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

27.03.2015

Antiphospholipid syndrome (APS) is a clinical and laboratory symptom complex characterized by venous and arterial thrombosis, pathology of pregnancy and some other less common clinical manifestations and laboratory disorders pathogenetically associated with the synthesis of antiphospholipid antibodies (aPL). APS prevention and treatment is a complex and underdeveloped problem. This is due to the heterogeneity of the pathogenetic mechanisms underlying the APS, the lack of reliable clinical and laboratory parameters that allow predicting the risk of recurrent thrombosis. Currently, there are no generally accepted international standards for the management of patients with various forms of APS, and the proposed recommendations are based mainly on the results of "open" trials or retrospective analysis of disease outcomes. The approaches to the prevention and treatment of atherosclerotic vascular lesions, which often develop in patients with APS, have not been sufficiently studied. Since “specific” methods of treatment of immunopathological disorders underlying APS have not been developed, the management of patients with APS (as well as with other thrombophilia) is based on the use of anticoagulant (vitamin K antagonists, heparin) and antiplatelet (acetylsalicylic acid, ASA) drugs. A characteristic feature of APS is a high risk of recurrent thrombosis. Therefore, most patients are forced to take antiplatelet and / or anticoagulant drugs for a long time, and sometimes for life.

It is believed that the risk of developing (and recurring) thrombosis in APS can be reduced by eliminating potentially controllable “risk factors”, but the true effectiveness of these recommendations is unknown. Risk factors that need to be considered when developing patient management tactics are presented in.

Prevention of thrombosis

Acetylsalicylic acid

Taking into account a certain relationship between an increase in aPL titers and the risk of thrombosis in the general population, it is believed that a persistent increase in aPL level (even in the absence of clinical signs of aPS) is the basis for the prophylactic administration of low doses of ASA. Data from two retrospective studies evaluating the effectiveness of ASA have recently been published. One study studied 65 women with APS-related obstetric pathology. During 8 years of follow-up, thrombotic disorders developed only in 3 (10%) of 31 women who received ASA and in 20 (59%) of 34 women who did not receive ASA. In another study, which included 77 patients with APS or without thrombosis, but with positive results for the determination of aPL, it was shown that ASA use was clearly associated with a lower incidence of thrombosis.

Hydroxychloroquine

Aminoquinoline (antimalarial) drugs (hydroxychloroquine) can have a significant preventive effect, at least in secondary APS associated with systemic lupus erythematosus (SLE). Along with the anti-inflammatory, hydroxychloroquine has certain antithrombotic (inhibiting platelet aggregation and adhesion, reducing the size of the thrombus) and hypolipidemic effects. The use of hydroxychloroquine is undoubtedly indicated in all aPL-positive SLE patients.

Warfarin

Treatment with vitamin K antagonists (warfarin) is undoubtedly a more effective, but less safe (compared to ASA) method of preventing venous and arterial thrombosis in APS. Recall that the use of vitamin K antagonists - anticoagulants - requires careful clinical (hemorrhagic complications) and laboratory (determination of prothrombin time) control. To standardize the results of this test, the International Normalized Ratio (INR) parameter should be assessed, which takes into account the effect of the thromboplastin used in the test on the prothrombin time.

The treatment regimen with warfarin for APS is the same as for other thrombophilia, and consists in the appointment of a "saturating" dose (5 mg / day) for the first 2 days, and then in the selection of the optimal dose of the drug, focusing on the target INR. It should be remembered that in older people, to achieve the same level of anticoagulation, lower doses of warfarin should be used than in younger people.

Of particular importance is the question of the intensity and duration of anticoagulation. It is known that an increase in INR from 2-3 to 3.1-4.0 is associated with an increase in the incidence of severe hemorrhagic complications (intracranial hemorrhages or hemorrhages leading to death, requiring blood transfusion or hospitalization). Recall that the risk factors for hemorrhagic complications during treatment with warfarin include:

Advanced age (32% increase in the incidence of any bleeding and a 46% increase in the incidence of major bleeding every 10 years after 40 years);

Uncontrolled arterial hypertension (systolic blood pressure> 180 mm Hg, diastolic blood pressure> 100 mm Hg);

Stomach ulcer;

Drinking alcohol;

Taking NSAIDs (including low doses of ASA) and paracetamol;

History of stroke

Taking several medications;

Taking azathioprine;

Taking high doses of methylprednisolone;

Polymorphism of cytochrome P450CY2C2, which is responsible for heparin metabolism;

Diffuse decrease in the density of the white matter of the brain (detected by MRI or CT).

In the general population of patients with venous thrombosis, withdrawal of warfarin is associated with the same (5-10%) rate of recurrence of thrombosis, regardless of the duration of previous treatment with warfarin (6, 12 and 24 months). However, as already noted, APS is characterized by a high risk of recurrent thrombosis. Therefore, patients with APS and venous thrombosis should be treated with warfarin for a longer period (> 12 months) than patients without APS (3-6 months).

One group of authors at the risk of recurrent thrombosis (including ischemic stroke) in patients with APS recommends intensive anticoagulation with warfarin, which allows maintaining INR at> 3.1. At the same time, other authors point to the effectiveness (especially in venous thrombosis) of the average level of anticoagulation, which allows maintaining the INR at a level of 2.0-3.0. M.A. Cronwther et al. conducted a randomized, double-blind, controlled study comparing the efficacy and safety of moderately intense (INR 2-3) and high-intensity (INR 3.1-4) anticoagulation with warfarin in APS. The study included 114 patients with high / moderate levels of aPL and at least one episode of thrombosis (venous and arterial) in history; the duration of treatment was 2.7 years. During the follow-up period, recurrent thrombosis occurred in 6 of 56 (10.7%) patients receiving high-intensity therapy, and in 2 of 58 (3.4%) patients receiving moderately intensive therapy with warfarin. Interestingly, the frequency of severe bleeding in the compared groups was approximately the same (in 3 patients who underwent intensive anticoagulation, and in 4 - moderate).

Thus, at present, the most reasoned use of warfarin in medium doses (INR 2.0-3.0) in patients with the first episode of venous thrombosis in the absence of other risk factors for recurrent thromboembolic complications, while in patients with a history of recurrent thrombosis intensive anticoagulation (INR> 3.0) is probably more justified.

The question of the use of warfarin in patients with APS and ischemic stroke deserves special discussion. This is due to the fact that, according to the data of numerous controlled studies, warfarin has no advantages over ASA in the prevention of stroke recurrence in the general population of patients with cerebral strokes and often causes severe intracranial bleeding. However, according to many authors, with APS, the risk of recurrent cerebral thrombosis is higher than the risk of bleeding. At the same time, the risk of bleeding against the background of intense anticoagulation with APS can be compensated to a certain extent by the fact that patients with this syndrome are usually young. According to G. Ruiz-Irastorza et al. In patients with APS treated with warfarin, the frequency of major bleeding was 6 cases per 100 patients-year, in no case there were fatal bleeding, and intracranial hemorrhages occurred in only 1 patient. At the same time, relapses of thrombosis developed mainly in patients who had insufficient anticoagulation (INR<3,0). Таким образом, вопрос об оптимальном уровне антикоагуляции у пациентов с АФС и с ишемическими инсультами остается открытым и должен решаться индивидуально как с учетом тяжести и факторов риска рецидивов тромбоза, так и риска кровотечений .

It should be emphasized that in many patients with APS, spontaneous fluctuations in INR are observed, which complicate the selection of an effective and safe dose of warfarin. At the same time, fluctuations in INR are associated with the intake of drugs that affect the metabolism of warfarin, many of which are widely used in rheumatology (for example, cytostatics, GC, allopurinol, NSAIDs, cephalosporins, etc.). In addition, fluctuations in INR can be associated with different properties of thromboplastin used to determine prothrombin time. The dose of indirect anticoagulants is difficult to select in the presence of VA in the blood, the presence of which sometimes leads to false-positive results - to an increase in prothrombin time and INR in vitro, in the absence of effective anticoagulation in vivo. In patients with APS, resistance to warfarin is often observed, which is of a genetic nature (mutation of coagulation factors V and II).

T.M. Reshetnyak et al. studied the effectiveness of warfarin in 20 patients (5 - men and 15 - women) with APS, among whom 8 had primary APS and 12 - APS with SLE. Eighteen patients received warfarin for a year, and two for 4 years. Patients with a history of arterial thrombosis received pentoxifylline or low doses of ASA (50-100 mg / day).

Patients with APS were divided into three groups. The first group included 8 patients with a target INR of 2.0, the second - 7 with an INR of 3.0, and the third - 7 patients with an INR of 2.0 who received ASA (100 mg / day) and pentoxifylline (600 to 1200 mg / days). Recurrent venous thrombosis occurred in two patients with INR<2,0. В других группах рецидивов не отмечено. Однако у 2 пациентов 2 и 3 групп имели место «большие» кровотечения. Частота малых геморрагий в сравниваемых группах не различалась.

In case of insufficient effectiveness of monotherapy with warfarin, it is possible to carry out combined therapy with indirect anticoagulants and low doses of ASA (and / or dipyridomol), which is most justified in young people without risk factors for bleeding (secondary APS, thrombocytopenia, platelet dysfunction associated with the presence of VA, defects in prothrombin ).

In the case of excessive anticoagulation (INR> 4.0) in the absence of bleeding, it is recommended to temporarily discontinue warfarin until the INR value returns to the desired level. A faster normalization of INR can be achieved by administering small doses of vitamin K: 1 mg orally (reduces the risk of at least "minor" bleeding) or 0.5 mg intravenously. High doses of vitamin K should be avoided, as this can lead to long-term (over several days) resistance to vitamin K antagonists. Subcutaneous injections of vitamin K are not recommended because of the pronounced variability in absorption. In the case of hypocoagulation, accompanied by large bleeding, the administration of vitamin K alone is not enough, since the full effect develops only 12-24 hours after administration. In this case, it is recommended to administer fresh frozen plasma or, more preferably, a prothrombin complex concentrate.

Acute thrombosis

The central place in the treatment of acute thrombotic complications in APS is occupied by direct anticovulants - heparin and especially drugs of low molecular weight heparin. The tactics of using direct anticoagulants in patients with APS does not differ from the generally accepted one.

1. Determine the basal APTT level, prothrombin time and complete blood count.

2. Confirm that there are no contraindications for heparin therapy.

3. Inject 5000 IU of heparin intravenously.

4. Decide on the tactics of heparin therapy.

Start continuous intravenous infusion of unfractionated heparin - 18 IU / kg / hour (average 30,000/24 hours for a man 70 kg body weight):

Determine the APTT every 6 hours during the first 24 hours, then daily;

Maintain APTT at a level of 1.5-2.5;

Continue infusion for 5-7 days.

Subcutaneous heparin: Start with 17,500 IU every 12 hours (or 250 IU / kg every 12 hours).

5. Every day to determine the level of platelets due to the possibility of developing thrombocytopenia.

6. If patients have not previously received warfarin, then it should be prescribed within the first 24-48 hours from the start of heparin therapy.

7. Continue heparin therapy for at least 4-5 days after warfarin administration. Patients with massive ileofemoral thrombosis or pulmonary thromboembolism are treated with heparin for at least 10 days.

8. Stop heparin when the INR is> 2 within 48 hours.

In patients with risk factors for recurrent thrombosis, intensive prophylaxis using low molecular weight heparin should be carried out for a long time.

Catastrophic antiphospholipid syndrome

The prognosis of a catastrophic APS largely depends on how early the diagnosis is made and how aggressive therapy is started. For the treatment of "catastrophic" APS, the entire arsenal of methods of intensive and anti-inflammatory therapy is used, which is used to treat critical conditions in rheumatic diseases ().

The effectiveness of therapy to a certain extent depends on the ability to eliminate the factors provoking its development (for example, suppression of infection and / or the activity of the underlying disease). If an infection is suspected, antibiotic therapy should be prescribed immediately, and amputation should be performed if gangrene of the extremities develops. Nonspecific intensive care is important, for example, hemodialysis in patients with rapidly developing renal failure, ventilation of the lungs, administration of inotropic drugs, etc.

Intensive glucocorticoid therapy is not aimed at treating the thrombotic disorders themselves, but is determined by the need to supervise the systemic inflammatory response syndrome. Recall that the systemic inflammatory response syndrome is characterized by diffuse inflammation of the vascular endothelium associated with overproduction of TNF-a and IL-1. A number of clinical manifestations of APS associated with both small vessel thrombosis and widespread necrosis (for example, respiratory distress syndrome in adults, etc.) are indications for the prescription of high doses of glucocorticoids. Usually, it is recommended to carry out pulse therapy according to the standard scheme (1000 mg methylprednisolone per day for 3-5 days), followed by the appointment of high doses of glucocorticoids (1-2 mg / kg / day) orally. It should be emphasized again that glucocorticoids by themselves do not affect the risk of recurrent thrombosis.

Intravenous immunoglobulin is administered at a dose of 0.4 g / kg for 4-5 days and is especially effective in the presence of thrombocytopenia. It should be remembered, however, that intravenous immunoglobulin can cause renal impairment, especially in the elderly treated with nephrotoxic drugs.

Catastrophic APS is the only absolute indication for plasmapheresis sessions (it is recommended to remove 2-3 liters of plasma for 3-5 days) in patients with APS, which should be combined with the most intensive anticoagulant therapy, use for replacement of fresh frozen plasma, and if indicated, with carrying out pulse therapy with GC and cyclophosphamide. Plasmapheresis is the method of choice for thrombotic thrombocytopenic purpura and thrombotic microangiopathic hemolytic anemia, which often complicates CAFS.

Cyclophosphamide (0.5-1.0 g per day) is indicated to a certain extent in the development of a catastrophic APS against the background of exacerbation of SLE and to prevent the "rebound" syndrome after plasmapheresis sessions.

There are no data regarding the possibility of using anticytokines (for example, a TNF-a inhibitor). The theoretical basis for their use is the data on a significant increase in the level of TNF-a in APS, including catastrophic APS. It is likely that infliximab administration can potentially be indicated in a patient with a systemic inflammatory response syndrome associated with APS.

Pathology of pregnancy

The standard for the prevention of recurrent fetal loss (as well as venous and arterial thrombosis in the postpartum period) with APS is the use of low doses of ASA (81 mg / day) in combination with unfractionated heparin or low molecular weight heparin during the entire period of pregnancy and for at least 6 months after childbirth ().

The main disadvantages of heparin are different bioavailability after subcutaneous administration and its non-specific binding to plasma proteins (AT III and coagulation factors), platelet proteins (for example, platelet factor 4) and EC. At the same time, some heparin-binding proteins are classified as proteins of the acute phase of inflammation, the concentration of which increases significantly against the background of inflammation. Finally, another limitation of heparin therapy is a decrease in the ability of heparin to inactivate thrombin, which is in a complex with fibrin and factor Xa, associated with activated platelets in the resulting thrombus. Therefore, heparin has no effect on thrombus growth, and after the termination of heparin therapy, a "rebound" increase in coagulation can be observed.

Low molecular weight heparin preparations have advantages over unfractionated heparin in the treatment of venous thrombosis and obstetric pathology in patients with APS and have almost completely replaced the latter ().

Recently, a randomized study was conducted comparing the effectiveness of low molecular weight heparin in combination with ASA and intravenous immunoglobulin. The study included 30 women with 3 or more spontaneous abortions in history. In women who received heparin and ASA, the number of successful deliveries (84%) was higher than in women who received intravenous immunoglobulin (57%).

In case of delivery by cesarean section, the administration of low molecular weight heparins is canceled in 2-3 days and resumed in the postpartum period, followed by a switch to indirect anticoagulants. Treatment with ASA and heparin reduces the risk of venous and arterial thrombosis, which often develop in patients with APS during and after pregnancy.

It should be borne in mind that long-term heparin therapy of pregnant women can lead to the development of osteoporosis, complicated by skeletal fractures. To reduce bone loss, calcium carbonate (1500 mg) in combination with vitamin D should be recommended. Treatment with low molecular weight heparin is less likely to cause osteoporosis than treatment with unfractionated heparin. One of the limitations for the use of low molecular weight heparin is the risk of developing an epidural hematoma during regional anesthesia. Therefore, if premature birth is expected, treatment with low molecular weight heparin should be discontinued no later than 36 weeks of gestation.

The use of indirect anticoagulants during pregnancy is, in principle, contraindicated, since it leads to warfarin embryopathy, characterized by impaired epiphyseal growth and hypoplasia of the nasal septum, as well as neurological disorders. However, according to a recent study, prescribing warfarin between 15 and 34 weeks of gestation in patients with APS (n = 14) was not associated with a teratogenic effect, and the rate of successful delivery (86%) was the same as in women taking low doses of ASA and low molecular weight heparin (87%). These data suggest that, in some cases, in patients requiring active anticoagulant therapy (but not tolerating heparin treatment) or having severe systemic thrombosis (stroke, etc.), warfarin may be prescribed between 14 and 34 weeks of gestation. In patients undergoing artificial conception or induction of ovulation, it is necessary to replace warfarin with heparin. Heparin should be canceled 12-24 hours before the operation, and therapy should be resumed 6-8 hours later.

Medium / high-dose glucocorticoid (GC) treatment, popular in the 1980s, is currently largely abandoned due to side effects in both the mother and the fetus and the lack of evidence of its effectiveness. Moreover, glucocorticoid therapy leads to severe side effects, including premature rupture of the membrane, premature birth, fetal growth retardation, infections, preeclampsia, diabetes, osteopenia, and osteonecrosis. However, before childbirth, GC should not be canceled in women who received it during pregnancy, and during childbirth, they need to additionally inject GC in order to avoid adrenal insufficiency. The use of HA is justified in secondary APS (in combination with SLE) and is aimed at treating the underlying disease. Only in some cases in patients in whom miscarriage cannot be overcome against the background of standard therapy with low doses of ASA and heparin (as well as intravenous immunoglobulin), it is possible to prescribe prednisolone (20-40 mg / day).

The use of intravenous immunoglobulin (0.4 g / kg for 5 days of each month) has no advantages over standard treatment with ASA and heparin and is indicated only if standard therapy with ASA and heparin is ineffective. There are several preliminary reports on the certain effectiveness of plasmapheresis, but at present this method is used extremely rarely.

It should be emphasized that the detection of aPL does not affect the outcomes of pregnancy in women who underwent artificial insemination.

If these recommendations are followed, it is possible to increase the frequency of successful childbirth in women with two or more episodes of fetal loss in anamnesis to 70-80%. However, it should be emphasized that even in the case of successful delivery in patients with APS, there is an increase in the frequency of preexlampsia, fetal growth retardation, premature birth and other forms of obstetric pathology. Children in women with APS, as a rule, are born healthy, without signs of impaired physical and neuropsychic development, thrombosis, etc., for at least 5 years of follow-up.

Osteoporosis is a systemic decline of the skeleton, which is characterized by changes in the mass and damage of the architecture of the cyst tissue, which can lead to a decrease in the development of the risk of fractures. For the early detection of patients from high risk of fractures, as well as the establishment of effective methods for the prevention and treatment of osteoporosis, it is important to know the children of the old specialties, the winter of the problem of the first time. For the most important food, respect was given at the international scientific-practical conference "The development of the cyst-language system that vik", which took place on 21-22 June 2019 in Kiev. ...

24.01.2020 Cardiology Prikhovani and manifest manifestation of hypersensitivity anemia

Lack of hair loss is the most common cause of anemia in light. Zalizodeficitna anemia (ZDA) is manifested by the observance of the pink and motor development of children and the decrease in the rate of birth in older adults. Every hour of pregnancy can be the cause of perinatal death, prematurity, and low vaginosis during populations (Kasperet al., 2015). An important aspect of the problem is also comorbidity, some anemia, the patient's camp, whether it be a pathology. ...

23.01.2020 Neurology Establish the diagnosis and treatment of progressive attacks

Progressive ataxia is a group of childish and folding neurological problems, about which medical doctors are not often married. To your respect, an overview of the recommendations for diagnostics and treatment of the camp, broken up by a group of patients' responses from De Silva et al. in Great Britain (Orphanet Journal of Rare Diseases, 2019; 14 (1): 51). Ataxia can be a symptom of widespread stagnation, however, the dynasty of Nastanov focused on the progressive, fall of Fridreich's ataxies, idiopathic sporadic cerebral ataxies and specific neurodegenerative diseases. ...

For citation: E.L. Nasonov Prevention and treatment of antiphospholipid syndrome: current recommendations and prospects // BC. 2004. No. 6. P. 377

State Institution Institute of Rheumatology, Russian Academy of Medical Sciences, Moscow

State Institution Institute of Rheumatology, Russian Academy of Medical Sciences, Moscow

A antiphospholipid syndrome (APS) is a clinical and laboratory symptom complex characterized by venous and arterial thrombosis, pregnancy pathology and some other less common clinical manifestations and laboratory disorders pathogenetically associated with the synthesis of antiphospholipid antibodies (aPL).

APS prevention and treatment is a complex and underdeveloped problem ... This is due to the heterogeneity of the pathogenetic mechanisms underlying the APS, the lack of reliable clinical and laboratory parameters that allow predicting the risk of recurrent thrombosis. Currently, there are no generally accepted international standards for the management of patients with various forms of APS, and the proposed recommendations are based mainly on the results of "open" trials or retrospective analysis of disease outcomes. The approaches to the prevention and treatment of atherosclerotic vascular lesions, which often develop in patients with APS, have not been sufficiently studied. Since "specific" methods of treatment of immunopathological disorders underlying APS have not been developed, the management of patients with APS (as well as with other thrombophilia) is based on the use of anticoagulants (vitamin K antagonists, heparin) and antiplatelet drugs - acetylsalicylic acid (ASA). A characteristic feature of APS is a high risk of recurrent thrombosis ... Therefore, most patients are forced to take antiplatelet and / or anticoagulant drugs for a long time, and sometimes for life.

It is believed that the risk of developing (and recurring) thrombosis in APS can be reduced by eliminating potentially controllable “risk factors”, but the true effectiveness of these recommendations is not known. Risk factors that need to be considered when developing patient management tactics are presented in Table 1.

Prevention of thrombosis
Acetylsalicylic acid
Considering a certain relationship between an increase in aPL titers and the risk of thrombosis in the general population, it is believed that a persistent increase in aPL level (even in the absence of clinical signs of APS) is the basis for prophylactic administration of low doses of ASA. Data from two retrospective studies evaluating the effectiveness of ASA have recently been published. One study studied 65 women with APS-related obstetric pathology. During 8 years of follow-up, thrombotic disorders developed only in 3 (10%) of 31 women who received ASA and in 20 (59%) of 34 women who did not receive ASA. In another study, which included 77 patients with APS or without thrombosis, but with positive results for the determination of aPL, it was shown that ASA use was clearly associated with a lower incidence of thrombosis.
Given the definite relationship between an increase in aPL titers and the risk of thrombosis in the general population, it is believed that a persistent increase in aPL level (even in the absence of clinical signs of APS) is the basis for prophylactic administration of low doses of ASA. Data from two retrospective studies evaluating the effectiveness of ASA have recently been published. One study studied 65 women with APS-related obstetric pathology. During 8 years of follow-up, thrombotic disorders developed only in 3 (10%) of 31 women who received ASA and in 20 (59%) of 34 women who did not receive ASA. In another study, which included 77 patients with APS or without thrombosis, but with positive results for the determination of aPL, it was shown that ASA use was clearly associated with a lower incidence of thrombosis.

Hydroxychloroquine

Warfarin

Treatment with vitamin K antagonists (warfarin) is undoubtedly a more effective, but less safe (compared to ASA) method of preventing venous and arterial thrombosis in APS. Recall that the use of antagonists of vitamin K-anticoagulants requires careful clinical (hemorrhagic complications) and laboratory (determination of prothrombin time) control. To standardize the results of this test, the International Normalized Ratio (INR) parameter should be assessed, which takes into account the effect of the thromboplastin used in the test on the prothrombin time.

The treatment regimen with warfarin for APS is the same as for other thrombophilia, and consists in the appointment of a "saturating" dose (5 mg / day) for the first 2 days, and then in the selection of the optimal dose of the drug, focusing on the "target" INR ... It should be remembered that in older people, to achieve the same level of anticoagulation, lower doses of warfarin should be used than in younger people.

Of particular importance is the question of the intensity and duration of anticoagulation. It is known that an increase in INR from 2-3 to 3.1-4.0 is associated with an increase in the incidence of severe hemorrhagic complications (intracranial hemorrhages or hemorrhages leading to death, requiring blood transfusion or hospitalization). Recall that k risk factors for hemorrhagic complications during treatment with warfarin include:

advanced age (a 32% increase in the incidence of any bleeding and an increase in the incidence of "major" bleeding by 46% every 10 years after 40 years)
uncontrolled arterial hypertension (systolic blood pressure> 180 mm Hg, diastolic blood pressure> 100 mm Hg)
stomach ulcer
alcohol intake
taking NSAIDs (including low-dose ASA) and paracetamol
history of stroke
taking multiple medications
taking azathioprine
taking high doses of methylprednisolone
polymorphism of cytochrome P450CY2C2, which is responsible for heparin metabolism
a diffuse decrease in the density of the white matter of the brain (detected by MRI or CT).

One group of authors at the risk of recurrent thrombosis (including ischemic stroke) in patients with APS recommends intensive anticoagulation with warfarin, which allows maintaining INR at> 3.1. At the same time, other authors point to the effectiveness (especially in venous thrombosis) of the average level of anticoagulation, which allows maintaining the INR at a level of 2.0-3.0. M.A. Cronwther et al. conducted a randomized, double-blind, controlled study comparing the efficacy and safety of moderate intensive (INR 2-3) and high-intensity (INR 3.1-4) anticoagulation with warfarin in APS. The study included 114 patients with high / moderate levels of aPL and at least one episode of thrombosis (venous and arterial) in history; the duration of treatment was 2.7 years. During the follow-up period, recurrent thrombosis occurred in 6 of 56 (10.7%) patients receiving high-intensity therapy, and in 2 of 58 (3.4%) patients receiving moderately intensive therapy with warfarin. Interestingly, the frequency of severe bleeding in the compared groups was approximately the same (in 3 patients who underwent intensive anticoagulation, and in 4 - moderate).

The question of use of warfarin in patients with APS and ischemic stroke ... This is due to the fact that, according to the data of numerous controlled studies, warfarin has no advantages over ASA in the prevention of stroke recurrence in the general population of patients with cerebral strokes and often causes severe intracranial bleeding. However, according to many authors, with APS, the risk of recurrent cerebral thrombosis is higher than the risk of bleeding. At the same time, the risk of bleeding against the background of intense anticoagulation with APS can be compensated to a certain extent by the fact that patients with this syndrome are usually young. According to G. Ruiz-Irastorza et al. , in patients with APS on the background of warfarin treatment, the frequency of "large" bleeding was 6 cases per 100 patients-year, in no case there were fatal bleeding, and intracranial hemorrhages occurred in only 1 patient. At the same time, relapses of thrombosis developed mainly in patients who had insufficient anticoagulation (INR< 3,0). Таким образом, вопрос об оптимальном уровне антикоагуляции у пациентов с АФС и с ишемическими инсультами остается открытым и должен решаться индивидуально как с учетом тяжести и факторов риска рецидивов тромбоза, так и риска кровотечений .

It should be emphasized that in many patients with APS, spontaneous fluctuations in INR are observed, which complicate the selection of an effective and safe dose of warfarin. At the same time, fluctuations in INR are associated with the intake of drugs that affect the metabolism of warfarin, many of which are widely used in rheumatology (for example, cytostatics, GC, allopurinol, NSAIDs, cephalosporins, etc.). In addition, fluctuations in INR can be associated with different properties of thromboplastin used to determine prothrombin time. The dose of indirect anticoagulants is difficult to adjust in the presence of VA in the blood, the presence of which sometimes leads to "false-positive" results - an increase in prothrombin time and INR in vitro, in the absence of effective anticoagulation in vivo... In patients with APS, resistance to warfarin is often observed, which is of a genetic nature (mutation of coagulation factors V and II).

T.M. Reshetnyak et al. the efficacy of warfarin was studied in 20 patients (5 - men and 15 - women) with APS, among whom 8 had primary APS and 12 - APS with SLE. Eighteen patients received warfarin for a year, and two for 4 years. Patients with a history of arterial thrombosis received pentoxifylline or low doses of ASA (50-100 mg / day).

Patients with APS were divided into three groups. The first group included 8 patients with a target INRЈ2.0, the second - 7 - with an INR3.0, and the third - 7 patients with an INR2.0 who received ASA (100 mg / day) and pentoxifylline (600 to 1200 mg / day. ). Recurrent venous thrombosis occurred in two patients with INR<2,0. В других группах рецидивов не отмечено. Однако у 2-х пациентов 2 и 3 групп имели место «большие» кровотечения. Частота «малых» геморрагий в сравниваемых группах не различалась.

In the case of excessive anticoagulation (INR> 4.0) in the absence of bleeding, it is recommended to temporarily discontinue warfarin until the INR value returns to the desired level. A faster normalization of INR can be achieved by administering small doses of vitamin K: 1 mg orally (reduces the risk of at least "minor" bleeding) or 0.5 mg intravenously. High doses of vitamin K should be avoided, as this can lead to long-term (over several days) resistance to vitamin K antagonists. Subcutaneous injections of vitamin K are not recommended because of the pronounced variability in absorption. In the case of hypercoagulation, accompanied by "large" bleeding, the introduction of vitamin K alone is not enough, since the full effect develops only 12-24 hours after administration. In this case, it is recommended to administer fresh frozen plasma or, more preferably, a prothrombin complex concentrate.

Acute thrombosis
The central place in the treatment of acute thrombotic complications in APS is occupied by direct anticovulants - heparin and especially drugs of low molecular weight heparin. The tactics of using direct anticoagulants in patients with APS does not differ from the generally accepted one:
The central place in the treatment of acute thrombotic complications in APS is occupied by direct anticovulants - heparin and especially drugs of low molecular weight heparin. The tactics of using direct anticoagulants in patients with APS does not differ from the generally accepted one:

1. Determine the basal APTT level, prothrombin time and complete blood count.

2. Confirm that there are no contraindications for heparin therapy.

3. Inject 5000 IU of heparin intravenously.

4. Decide on the tactics of heparin therapy.

Start continuous intravenous infusion of unfractionated heparin - 18 IU / kg / hour (on average 30,000/24 hours for a man 70 kg of weight):

Determine the APTT every 6 hours during the first 24 hours, then daily;

Maintain APTT at a level of 1.5-2.5;

Continue infusion for 5-7 days.

Subcutaneous administration of heparin: start with a dose of 17,500 IU every 12 hours (or 250 IU / kg every 12 hours).

5. Every day to determine the level of platelets due to the possibility of developing thrombocytopenia.

6. If patients have not previously received warfarin, then it should be prescribed within the first 24-48 hours from the start of heparin therapy.

8. Stop heparin when the INR is> 2 within 48 hours.

In patients with risk factors for recurrent thrombosis, intensive prophylaxis using low molecular weight heparin should be carried out for a long time.

Catastrophic antiphospholipid syndrome

The prognosis of a catastrophic APS largely depends on how early the diagnosis is made and how aggressive therapy is started. For treatment "Catastrophic" APS the entire arsenal of methods of intensive and anti-inflammatory therapy is used, used for the treatment of critical conditions in rheumatic diseases (Fig. 1).

Rice. 1. Algorithm of treatment<катастрофического>APS

The effectiveness of therapy to a certain extent depends on the ability to eliminate the factors provoking its development (for example, suppression of infection and / or the activity of the underlying disease). If an infection is suspected, antibiotic therapy should be prescribed immediately, and amputation should be performed if gangrene of the extremities develops. Of great importance is "non-specific" intensive therapy, for example, hemodialysis in patients with rapidly developing renal failure, ventilation of the lungs, administration of inotropic drugs, etc.

Intensive care glucocorticoids is not aimed at treating the "thrombotic" disorders themselves, but is determined by the need to supervise the "systemic inflammatory response" syndrome. Recall that the systemic inflammatory response syndrome is characterized by diffuse inflammation of the vascular endothelium associated with overproduction of TNF-a and IL-1. A number of clinical manifestations of APS associated with both small vessel thrombosis and widespread necrosis (for example, respiratory distress syndrome in adults, etc.) are indications for the prescription of high doses of glucocorticoids. Usually, it is recommended to carry out pulse therapy according to the standard scheme (1000 mg methylprednisolone per day for 3-5 days), followed by the appointment of high doses of glucocorticoids (1-2 mg / kg / day) orally. It should be emphasized again that glucocorticoids by themselves do not affect the risk of recurrent thrombosis.

Intravenous immunoglobulin administered at a dose of 0.4 g / kg for 4-5 days and is especially effective in the presence of thrombocytopenia. It should be remembered, however, that intravenous immunoglobulin can cause renal impairment, especially in the elderly treated with nephrotoxic drugs.

"Catastrophic" APS is the only absolute indication for sessions plasmapheresis (it is recommended to remove 2-3 liters of plasma within 3-5 days) in patients with APS, which should be combined with the most intensive anticoagulant therapy, use for replacement of fresh frozen plasma, and if indicated, with pulse therapy with GC and cyclophosphamide. Plasmapheresis is the method of choice for thrombotic thrombocytopenic purpura and thrombotic microangiopathic hemolytic anemia, which often complicates CAFS.

Cyclophosphamide (0.5-1.0 g per day) is indicated to a certain extent in the development of a catastrophic APS against the background of exacerbation of SLE and to prevent the "rebound" syndrome after plasmapheresis sessions.

Pathology of pregnancy

The use of indirect anticoagulants during pregnancy is, in principle, contraindicated, since it leads to warfarin embryopathy, characterized by impaired epiphyseal growth and hypoplasia of the nasal septum, as well as neurological disorders. However, according to a recent study, prescribing warfarin between 15 and 34 weeks of gestation in patients with APS (n = 14) was not associated with a teratogenic effect, and the rate of successful delivery (86%) was the same as in women taking low doses of ASA and low molecular weight heparin (87%). These data suggest that in some cases, in patients requiring active anticoagulant therapy (but not tolerating heparin treatment) or with severe systemic thrombosis (stroke, etc.), warfarin may be prescribed between 14 and 34 weeks of gestation. In patients undergoing artificial conception or induction of ovulation, it is necessary to replace warfarin with heparin. Heparin should be canceled 12-24 hours before the operation, and therapy should be resumed 6-8 hours later.

Medium / high-dose glucocorticoid (GC) treatment, popular in the 1980s, is currently largely abandoned due to side effects in both the mother and the fetus and lack of evidence of their effectiveness. Moreover, glucocorticoid therapy leads to severe side effects, including premature rupture of the membrane, premature birth, fetal growth retardation, infections, preeclampsia, diabetes, osteopenia, and osteonecrosis. However, before childbirth, GC should not be canceled in women who received it during pregnancy, and during childbirth, they need to additionally inject GC in order to avoid adrenal insufficiency. The use of HA is justified in secondary APS (in combination with SLE) and is aimed at treating the underlying disease. Only in some cases in patients in whom miscarriage cannot be overcome against the background of standard therapy with low doses of ASA and heparin (as well as intravenous immunoglobulin), it is possible to prescribe prednisolone (20-40 mg / day).

The use of intravenous immunoglobulin (0.4 g / kg for 5 days every month) has no advantages over standard treatment with ASA and heparin and is indicated only if the “standard” therapy with ASA and heparin is ineffective. There are several preliminary reports on the certain effectiveness of plasmapheresis, but at present this method is used extremely rarely.

It should be emphasized that the detection of aPL does not affect the outcomes of pregnancy in women who underwent artificial insemination.

Hematological disorders

Moderate thrombocytopenia, which is often observed in patients with APS, does not require special treatment. In secondary APS within SLE, thrombocytopenia is usually well controlled with HA, aminoquinoline drugs, and in resistant cases, low doses of ASA.

Treatment tactics for resistant severe thrombocytopenia (<50000/ мм 3), создающей угрозу кровотечений, до конца не разработана. Этим пациентам, наряду с применением ГК в высоких дозах, целесообразно назначение внутривенного иммуноглобулина. Имеются данные об определенной эффективности препарата даназол (слабый андроген) или дапсон.

In the case of ineffectiveness of high doses of GC, splenectomy is the method of "choice", and the overwhelming majority of patients showed stable normalization of platelet levels.

Perioperative management of patients with APS

In patients with APS, there is a significant increase in the risk of thrombosis (especially after operations on blood vessels and heart valves) and often the development of catastrophic APS. In general, patients with APS are at a very high risk of developing venous thromboembolic complications in the postoperative period.

The development of thrombosis in the pre- and postoperative period may be associated with the following factors:<

Withdrawal of indirect anticoagulants
Spontaneous increase in clotting, despite treatment with warfarin or heparin
The development of a catastrophic APS.

In addition, some patients have a very high risk of uncontrolled bleeding, the development of which may be associated with the following reasons:<

Inadequate anticoagulation therapy
Thrombocytopenia
The presence of a deficiency of coagulation factors (for example, the synthesis of high-affinity antibodies to prothrombin).

Developed by standards of anticoagulant therapy for the "high risk" group , which includes patients with APS (Table 6). However, it should be emphasized that these recommendations have not been specifically tested in the APS.

According to D. Erkan et al. , patients with APS should receive more intensive anticoagulant therapy and minimize the time during which anticoagulant therapy is suspended. In patients who have used warfarin for a long time, the drug should be prescribed immediately after surgery in the absence of surgical contraindications. Heparin treatment should be continued until the INR is stabilized at a therapeutic level.

If urgent operations are necessary in patients with APS receiving warfarin, fresh frozen plasma should be transfused (contains all coagulation factors, including vitamin K, the deficiency of which develops while taking warfarin). Patients with thrombocytopenia (<50х10 9 /Л) или кровоточивостью следует назначать ГК и/или внутривенный иммуноглобулин. Переливание тромбоцитарной массы, как правило, не эффективно и может увеличивать риск развития тромбозов.

1. Before surgery

Prolongation of APTT (or moderate lengthening of prothrombin time) is not a contraindication for surgery
When the platelet count is> 10x10 9 / l, specific therapy is not required
Thrombocytopenia does not reduce the risk of thrombosis

2 . During the operation

Minimize intravascular manipulation
Bandage limbs
Remember that any unexplained change in the patient's condition may be associated with thrombosis

3 ... Prescribing anticoagulants

Time without anticoagulant therapy should be minimized
It should be borne in mind that patients with APS may develop thrombotic complications despite anticoagulant therapy.
It should be borne in mind that "standard" anticoagulant therapy may not be effective enough for APS.
Patients with APS often require more aggressive anticoagulant therapy
Patients with APS and obstetric pathology should be managed as if they had vascular thrombosis

4 ... Kidney transplant patients

Aggressive anticoagulant therapy should be administered during surgery in all patients with APS (with a history of thrombosis)
Carefully weigh the need for anticoagulant therapy in "asymptomatic" patients with positive AFL results.
The administration of ASA can reduce the risk of thrombosis induced by cyclosporin A, at least in patients after kidney transplantation.

Atherosclerosis and arterial hypertension

Given the high risk of atherosclerotic vascular lesions in SLE, and especially in APS, prevention of atherothrombotic disorders (as in diabetes mellitus) is indicated in almost all patients (Table 7).

For the treatment of concomitant arterial hypertension and heart failure in APS, the use of ACE inhibitors is probably the most justified. It has been proven that therapy with these drugs improves the outcome in patients with hypertension, congestive heart failure and coronary artery disease.

Prospects for APS Pharmacotherapy

It is obvious that the high risk of developing coronary heart disease with APS is in itself a good reason for widespread use. statins in patients with these diseases. However, given the data on the immune mechanisms of the pathogenesis of atherothrombosis in SLE and APS, the use of statins in these pathological conditions has very important additional pathogenetic and clinical grounds. It is also known that statins have a prophylactic effect not only against myocardial infarction, but also against other vascular complications - stroke and even deep vein thrombosis of the leg, which are the most characteristic clinical manifestations of APS.

Although the efficacy of anticoagulants and platelet aggregation inhibitors in APS is beyond doubt, the practical use of these drugs has its limitations due to insufficiently high efficacy, toxicity (or both). The "standard" anticoagulants are characterized by a narrow "therapeutic window" (difficulty in achieving adequate anticoagulation without the risk of bleeding), as well as a pronounced variability in the therapeutic response in individual patients, which dictates the need for careful laboratory monitoring. All this taken together served as a powerful incentive for the development of new antithrombotic agents. These include thioperidine, which are already widely used in clinical practice. inhibitors of AFD receptors (ticlopedin and clopidogrel) and platelet (GPIIb / IIIa) receptor inhibitors and new anticoagulants - direct thrombin inhibitors, factor X inhibitors, tissue factor (TF) inhibitors, recombinant activated protein C, etc. (Table 8 and Fig. 2).

Rice. 2. Mechanisms of action of new anticoagulants

In recent years, thanks to the deciphering of the structure of antigens that are targets for aPL, real prerequisites have been created for the development of "pathogenetic" therapy for this disease. One of such fundamentally new areas of pharmacotherapy for APS, such as autoimmune thrombophilia, is associated with the possibility of induction of specific B-cell tolerance to potential autoantigens that induce the synthesis of "pathogenic" aPL. Antibodies to b 2 -glycoprotein (GP) -I can be such a "pathogenic" type of autoantibodies in APS.

The properties of b 2 -HP-I "toleragen" are possessed by the drug LJP 1082 ... It is a recombinant tetravalent molecule consisting of 4 copies of human domain 1 b 2 -HP-I (connected by polyethylene glycol bridges), which is believed to be the main B-cell "autoepitope" of this antigen. It is believed that LJP 1082 has the ability to bind to b 2 -HPI-specific B-lymphocytes and, in the absence of a T-cell signal, induce anergy or apoptosis of B cells synthesizing antibodies to b 2 -GPI. Recently, several clinical trials (in the framework of I / II phases) have been carried out, in which the high safety and tolerability of treatment with this drug has been demonstrated.

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18. Yoon KH. Sufficient evidence to consider hydroxychloroquine as an adjunct therapy in antiphospholipid antibody (Hughes`) syndrome. J. Rheumatol. 2002; 29; 1574-1575.

19. Meroni PL, Moia M, Derksen RHWM, et al. Venous thromboembolism in the antiphospholipid syndrome: management guidelines for second prophylaxis. Lupus 2003; 12: 504-507.

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21. Valentini KA, Hull RD. Clinical use of warfarin. UpToDate 2003; 12.1

22. Hirsh J, Fuster V, Ansell J, Halperin JL. American Heart Association / American College of Cardiology Foundation Guide to warfarin therapy. Circulation 2003; 107; 1692-1711.

23. van Dongen CJJ, Vink R, Hutten BA Buller HR, Prins MH. The incidence of recurrent venous thromboembolism after treatment with vitamin K antagonists in relation to time since first events. A meta-analysis. Arch Intern Med 2003; 163: 1285-1293.

24. Ruiz-Irastorza G, Khamashta MA, Caetellino G, Hughes GRV. Systemic lupus erythematosus. Lancet 2001; 357: 1027-1032.

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37. Lockwood CJ, Schur PH. Monitoring and treatment of

Today post - solid abbreviations :)))
In addition to questions, I often receive requests in private messages to write posts on a particular topic. Often the requests are too individual, so do not be offended if I do not fulfill your requests.

Still, my site is a platform for broad discussion, and too narrow topics will simply be ignored by the majority. So it is better to solve such questions individually. For example, a combination of biological drugs with antiepileptic drugs, or the course of rheumatoid arthritis in a drug addict. Well, you get the idea. Sometimes I myself have to look for literature on such "narrow" topics. Or here's another: the possibility of in vitro fertilization (IVF) in patients with and / or.

For a long time we did not have any medical records, and there seemed to be no histories associated with antiphospholipid syndrome at all. And this does not mean that there are no such stories, alas, they exist and there are many of them ...

By the way, in more detail about the AFS.

And this case happened at an outpatient appointment during my "exile" in a polyclinic))) Link in a good way, just before, every inpatient doctor had to sit at the clinic for some time. After 100,500 grandmothers with arthrosis and a whole delegation from places of imprisonment (I was generally lucky with them), a young man comes in. He looks, to put it mildly, very lonely. Limps, barely wanders to my table. I already suppose that now I’ll hear another story from the series “joints hurt, I drank pills, nothing helped”. And in principle, the beginning is really like this: my legs hurt, it’s difficult to walk, my head hurts, tinnitus ... In addition to everything else, he speaks as if “with cotton wool” in his mouth, cannot really remember anything, hangs on the same moments. Than he was treated, where and how - in general they tried to find out about 10 minutes !!! And this despite the fact that the guy is only 32 years old !!! Does not work, did not serve in the army, indicates that the reason is epilepsy !!! These are the times !!!

Sometimes in the description of the symptoms of "our" rheumatic diseases one can find the following - reticular livedo ... What is it and is it so dangerous ??? Let's figure it out 🙂

Livedo(lat. livedo - bruise) - a skin condition characterized by its uneven cyanotic color due to the reticular or tree-like pattern of translucent blood vessels. Synonyms: vine-shaped livedo, ring-shaped livedo, marbled leather.

Is it always pathology?

A peculiar marbled color of the skin can also occur in healthy people.

Patients with reliable APS and thrombosis should receive antithrombotic therapy for a long time (sometimes for life) !!! Patients with a definite APS and first venous thrombosis are recommended to prescribe vitamin K antagonists (for example, warfarin) with a target value of the international normalized ratio (INR) in the range of 2.0-3.0.

Patients with defined APS and arterial thrombosis should receive warfarin (with a target INR> 3.0) or be combined with low-dose aspirin (INR 2.0-3.0).

Patients with antiphospholipid antibodies detected repeatedly and in high concentrations, but without SLE and without previous thrombosis, are recommended to take long-term low-dose aspirin, especially in the presence of other risk factors for thrombosis.

The criteria for the diagnosis of APS are developed from the moment of its description. The latest international diagnostic criteria include both clinical and laboratory findings. Clinical manifestations include thrombosis of a vessel of any caliber and localization (venous and / or arterial, or the smallest vessels) and obstetric pathology.

Clinical criteria

Vascular thrombosis

One or more cases of arterial, venous or small vessel thrombosis in
any organ.
Pregnancy pathology:
a) one or more cases of intrauterine death of a normal fetus (without pathology) after 10 weeks of pregnancy (the absence of pathology should be detected by ultrasound or during direct examination of the fetus), or
b) one or more cases of premature birth of a normal fetus before 34 weeks due to severe preeclampsia, or eclampsia, or severe placental insufficiency, or
c) three or more consecutive cases of spontaneous abortions up to the 10th week (it is imperative to exclude anatomical defects of the uterus, hormonal disorders, chromosomal abnormalities).

Virtually any organ or organ system can be affected by APS. The most common and characteristic manifestations of APS are venous thrombosis (in 59% of cases), arterial thrombosis (in about 30%), and in 13% of patients, both arterial and venous thrombosis are detected.

Clinical manifestations of antiphospholipid syndrome presented below:

Large vessel thrombosis(for example, aortic arch, aortic trunk).
Neurological: cerebrovascular accidents (CVI), ischemic strokes, epilepsy, dementia, encephalopathy, migraine, pseudotumor lesions of the central nervous system, etc.
Ophthalmic: retinal artery and / or vein thrombosis, blindness.
Dermal: thrombophlebitis of superficial veins, leg ulcers, purple toe syndrome.
Cardiological: myocardial infarction, damage to the heart valves, vegetation on the valves, intracardiac thrombi.
Pulmonary: pulmonary embolism, pulmonary hypertension, pulmonary thrombosis.
Arterial: thrombosis of the aortic trunk, thrombosis of large and small main arteries.
Renal: artery / vein thrombosis of the kidney, renal infarction, acute renal failure, proteinuria, hematuria, nephrotic syndrome.
Gastrointestinal: Budd-Chiari syndrome, liver infarction, gallbladder infarction, intestinal infarction, spleen infarction, pancreatitis, ascites, esophageal perforation, ischemic colitis.
Endocrine: adrenal infarction or adrenal insufficiency, testicular infarction, prostate infarction, pituitary infarction, or hypothalamo-pituitary insufficiency.

We are starting a new section of my site dedicated to the diagnosis and treatment of antiphospholipid syndrome. This topic is very complex, but important and requires a lot of experience and attention to the patient from the doctor. I suppose that antiphospholipid syndrome will be more interesting for women who have experienced several missed pregnancies, miscarriages, or even intrauterine fetal death. For them, I am planning a separate article, where there will be a "squeeze" only on the pathology of pregnancy.

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

Dear Readers! I try to use social communication as fully as possible for the convenience of your reading and acquaintance with rheumatology. So, you can read my articles and notes on social networks, in the Live Journal (LJ), on the website. And, of course, following the fashion on the popular Instagram network. You can find me in the @revmadoctor and @ dr.voynova accounts (my personal account). If you are interested in some topics, as well as a live broadcast of a certain topic, I will gladly conduct it for you. Subscribe and follow the news: on May 12 and 13, together with a gynecologist-reproductologist, popular on Instagram, we will hold a joint consultation on a very important and necessary topic: "Miscarriage from the position of a rheumatologist." I will be glad to answer your questions! Join us!

Antiphospholipid syndrome (synonym: antiphospholipid antibody syndrome; APS) is an autoimmune condition caused by antibodies directed against phospholipids of cell membranes. The syndrome was first described in 1983 by the British rheumatologist Graham Hughes. Antiphospholipid syndrome increases the risk of blood clots (blood clots) in both arteries and veins. In the article we will analyze: APS - what it is, the causes and symptoms.

In some diseases, the body produces antibodies that can attack phospholipids - components of cell membranes, which leads to the development of thrombosis

Antiphospholipid syndrome is characterized by the formation of antibodies to components of its own cell membranes (phospholipids). Phospholipids are important building blocks of cell membranes in the human body: they are found in platelets, nerve cells and blood vessel cells. Since many pathogens are very similar to the structure of the body, it can happen that the immune system loses the ability to distinguish between "friends" and "enemies".

Studies show that up to 5% of the human population has antibodies to phospholipids in the blood. Women are significantly more likely to develop antiphospholipid syndrome than men. The average age at onset of the syndrome ranges from 25 to 45 years.

In the international classification of diseases of the 10th revision (ICD-10), the syndrome of antiphospholipid antibodies is denoted by the code D68.6.

Causes

The causes of APS are not fully understood. In medicine, there are 2 forms of antiphospholipid syndrome (APS): primary and secondary. The primary form of antiphospholipid syndrome is not due to a specific organic disease.

Much more common is secondary phospholipid syndrome, which accompanies some diseases and conditions. In this case, the APS develops due to the fact that pathogens have formations on their surface that are similar to the structures of human cells. As a result, the immune system produces antibodies that bind and eliminate both the pathogen and the body's own lipids. This process is called "molecular mimicry".

Secondary APS can be caused by:

autoimmune diseases (systemic lupus erythematosus, chronic polyarthritis, scleroderma, psoriatic arthritis, etc.);
a range of viral or bacterial infections: HIV, gonorrhea, syphilis, mumps, and Lyme disease;
rheumatoid arthritis;
deficiencies in vitamin D, vitamin E, and cysteine may increase the risk of developing autoimmune diseases;
in rare cases, APS during pregnancy appears due to multiple myeloma or hepatitis;
a very rare cause is long-term use of antiepileptic drugs, quinine and interferon.

Risk factors

People who abuse alcoholic beverages are at risk of possibly developing antiphospholipid syndrome

Main risk factors:

smoking;
overweight;
dehydration;
long-term use of contraceptives (pills);
lack of physical activity;
alcohol abuse;
eating an excess of foods rich in vitamin K - cabbage, spinach and cheese;
abuse of arachidonic acid and plant omega-6 fatty acids, which are found in edible oils.

Classification

There are four clinical and laboratory forms of APS:

Primary.
Secondary.
Catastrophic (multiple thrombosis of internal organs develops in a short time, leading to multiple organ failure).
AFL-negative (serological markers of the disease are not determined).

Symptoms

The two main symptoms associated with antiphospholipid syndrome are:

arterial and venous thrombosis;
thrombocytopenia.

Venous thrombosis most commonly occurs in the lower extremities, but can also occur in other parts of the venous system. Arterial thrombosis occurs mainly in the vessels of the brain, but can also appear in the arteries of other organs.

Depending on the location of the thrombosis, phospholipid syndrome leads to various complications: pulmonary embolism, heart attacks, kidney infarctions and strokes. The exact mechanisms of blood clot formation are not fully understood.

Another common symptom, especially in the case of primary antiphospholipid syndrome, is thrombocytopenia - a decrease in platelet count, which is characterized by an increased tendency to bleed. Patients may experience paradoxical bleeding in the skin. Women with phospholipid syndrome have an increased risk of early miscarriage.

Visual signs of AFL include bluish discoloration of the limbs and skin ulcers that can occur in various parts of the body.

Antiphospholipid syndrome is a common cause of stroke in young patients. If a patient under the age of 45 has a stroke in the absence of risk factors (arterial hypertension, lipid metabolism disorders), antiphospholipid syndrome should be excluded.

It is important to understand that not all patients with antiphospholipid antibodies suffer from thrombotic complications. In a large study in which 360 patients with phospholipid antibodies were followed over a 4-year period, only 9% had venous thrombosis. Other studies have reported a higher incidence of venous and arterial thrombosis.

Diagnostics

The main way to diagnose antiphospholipid syndrome is to detect antibodies in blood plasma.

The symptoms of antiphospholipid syndrome do not allow for an accurate diagnosis, as they can also be associated with other diseases. To detect antiphospholipid syndrome, additional laboratory tests are required.

In 2006, a panel of experts listed criteria that are still relevant and should be used for the definitive diagnosis of antiphospholipid syndrome:

one or more arterial and venous thrombosis in a tissue or organ. Blood clots should be confirmed by imaging or histological examination;
one or more unexplained intrauterine fetal deaths after the 10th week of pregnancy;
multiple preterm births of morphologically normal newborns at 34 weeks gestation or later;
three or more unexplained spontaneous abortions in a woman before the 10th week of pregnancy.

Laboratory tests and indicators of antiphospholipid syndrome:

increased concentration of anticardiolipin antibodies in the blood in at least two analyzes with an interval of at least 12 weeks;
a positive test for lupus anticoagulant (in accordance with the recommendations of the international medical community) in blood plasma;
increased concentration of antibodies against beta-2-glycoprotein-1 in two dimensions with an interval of 3 months.

In 30-50% of patients, the number of platelets in the blood decreases moderately (70,000-120,000 / μl); only in 5-10% of cases the platelet count is below 50,000 / μl. Hemolytic anemia and thrombocytopenic purpura develop in 1% of patients.

The final diagnosis of antiphospholipid syndrome can be made only if at least one clinical and laboratory criterion is observed.

Treatment of antiphospholipid syndrome

Aspirin prevents platelet clotting and prevents the development of thrombosis and embolism

Due to the lack of large and thus relevant clinical studies on the causes of disease, risk of thrombosis and therapy, there is a lack of clarity regarding the correct treatment strategies, even in the expert community.

The main directions in the therapy of APS are the treatment of acute thrombosis and the prevention of re-thrombosis of blood vessels. Patients should be treated promptly as paradoxical bleeding may occur. Late treatment can complicate the course of the disease.

If there are no absolute contraindications, treatment with low dose acetylsalicylic acid is recommended. Aspirin prevents platelet clotting and thus can counteract the development of thrombosis and embolism. However, there are still no clear research results.

Aspirin is supplemented with heparin, which prevents blood from clotting. For this purpose, Marcumar (indirect anticoagulant) is also used.

Long-term anticoagulant therapy should be used to prevent further thrombosis and embolism. The most effective remedies are coumarins, which are associated with an increased risk of complications. Lifelong anticoagulation with coumarins is recommended only for patients with phospholipid syndrome and severe thromboembolic complications.

In all patients with antiphospholipid syndrome, it is important to eliminate possible factors that increase the risk of thrombosis: it is recommended to completely quit smoking.

Secondary forms require effective treatment of the underlying disease.

The risk of recurrent thrombosis and occlusion is unfortunately high in patients with confirmed phospholipid syndrome. Therefore, they need to take an anticoagulant with a vitamin K antagonist in the long term (sometimes for life).

Statins are thought to have a moderate anti-thrombotic effect. Statins are recommended for patients with phospholipid syndrome if they have elevated blood lipids.

Women with antiphospholipid syndrome should refrain from using estrogen-containing medications, which are used to prevent unwanted pregnancies and treat menopausal problems. The use of estrogen significantly increases the risk of vascular blockage.

Treatment of pregnant women with AFL

For girls with complications of pregnancy, low molecular weight Heparin is administered once a day

Pregnant women are high-risk patients who need to be handled with extreme caution. If the woman with antiphospholipid syndrome has not had thrombosis or complications from previous pregnancies, treatment with acetylsalicylic acid is recommended.

Research shows that combination treatment (Aspirin + heparin) can reduce the risk of further spontaneous abortion. Some international research groups recommend the use of low molecular weight heparin.

Sometimes low doses of heparin and Aspirin (100 mg per day) are required. Although heparin has a much shorter duration of action than Marcumar and must be injected under the skin, it is much more effective.

Two to three days after delivery, heparin therapy is resumed and continues for 6 weeks if thromboembolic complications have occurred in the past. If amniocentesis or caesarean section is being performed, heparin therapy should be interrupted the evening before the procedure.

In addition to heparin therapy, the gynecologist often prescribes progestins to compensate for the deficiency of the corpus luteum. In addition, consistent wearing of Grade 2 compression stockings can improve a woman's condition.

For patients with complications of pregnancy, low molecular weight heparin is also administered once a day. Low molecular weight heparin, unlike Marcumar, does not cross the placenta and therefore does not affect the fetus.

Complications

Antiphospholipid syndrome is one of the relatively common autoimmune diseases. Complications of APL mainly develop during pregnancy due to the development of placental vascular thrombosis. These complications include:

miscarriages and premature birth;
freezing of the fetus and its intrauterine death;
premature placental abruption;
fetal malformations;
female infertility;
eclampsia;
gestosis.

In the absence of treatment, complications of pregnancy against the background of AFL occur in 80% of cases.

Smoking is contraindicated in people with antiphospholipid syndrome

Regardless of the form of antiphospholipid syndrome, all patients with this diagnosis should lead a lifestyle that reduces the risk of thromboembolic complications: it is recommended to stop smoking and use other psychotropic drugs.

It is necessary to move more in the fresh air, take enough fluids and not abuse alcohol. Clinical recommendations largely depend on the patient's condition.

Patients with phospholipid syndrome should refrain from using estrogen-containing contraceptives, as they can contribute to the development of thrombosis.

Pregnancy must be carefully planned due to the increased risk of miscarriage. Treatment of the syndrome must be adjusted during pregnancy to prevent spontaneous abortion and not endanger the fetus. Women who want to get pregnant should be aware of the possible risks and treatment options during pregnancy.

Forecast and prevention

Antiphospholipid syndrome is correlated with dementia in the elderly. The disease also increases the risk of developing renal disease (renal failure, renal infarction), stroke, and myocardial ischemia.

The mortality rate within 10 years among patients with APL is 10%, which means that 10% of patients will die as a result of complications of antiphospholipid antibody syndrome within the next 10 years.

The prognosis is less favorable in women suffering from multiple vascular thrombosis soon after childbirth. There is a danger of multiple narrowing of large and smaller vessels. Massive vasoconstriction can impair the delivery of blood to vital organs. If the organ fails as a result of narrowing of the vascular lumen, the patient may die. The more often a patient experiences thrombosis during their lifetime, the worse the prognosis.

There are no methods to prevent antiphospholipid syndrome. Only the development of complications can be indirectly prevented. When using anticoagulants, avoid competitive sports, use soft toothbrushes or an electric razor. The use of new drugs should be reported to the doctor in advance, as some of them may affect blood clotting.

In the event of a stroke, heart attack, or pulmonary hemorrhage, call an ambulance. A sudden appearance of urine in underwear indicates a kidney infarction, which should also be treated immediately.

Advice! If in any doubt, seek the advice of a qualified professional. The earlier treatment begins, the better the prognosis, since with each new thrombosis, the risk of death increases.

Timely referral to a specialist will help prevent complications and, in some cases (secondary antiphospholipid syndrome), completely get rid of the disease.