Anti-phospholipidic syndrome

Description:

Anti-phospholipidic syndrome - a symptom complex which cornerstone development of autoimmune reaction and emergence of antibodies to the eurysynusic phospholipidic determinants which are present at membranes of thrombocytes, cells of an endothelium, nervous tissue is.

The anti-phospholipidic syndrome was for the first time in details described at a system lupus erythematosus of Hughes.

There are several classes of the membrane phospholipids differing on structure and an immunogenicity. "Neutral" phospholipids - phosphatidylethanolamine (FE) and phosphatidylsincaline (FH) are most spread in an organism. "Negatively charged" (anion) phospholipids - phosphatidylserine (FS), phosphatidylinositol (FI) and cardiolipin (дифосфатидилглицерол) are localized on an internal surface of biomembranes and exhibited at process of cellular activation.

Antibodies to phospholipids are a heterogeneous population of the antibodies reacting with negatively charged, is more rare - neutral phospholipids. The following kinds of antibodies belong to anti-phospholipidic antibodies:

    * lupoid anticoagulant - population of anti-phospholipidic antibodies of the class IgG or IgM, capable in vitro to suppress fosfolipidnozavisimy coagulative reactions by interaction with a phospholipidic component of prothrombinase of an activated complex. Lupoid anticoagulant was found in blood serum of patients with a system lupus erythematosus in the beginning. At a system lupus erythematosus products of lupoid anticoagulant are associated, unlike results of in vitro, not with bleeding, and with paradoxical increase in frequency of thromboses;
    * antibodies to cardiolipin - immunological heterogeneous population of the antibodies reacting with the immobilized negatively charged phospholipid - the cardiolipin which is the main antigen of Wassermann reaction; antibodies to cardiolipin can treats various isotypes of immunoglobulins IgG, IgM, IgA;
    * the antibodies reacting with mix of cardiolipin, cholesterol, phosphatidylsincaline, defined by an agglutination test (false positive Wassermann reaction);
    * beta2-glycoprotein-1-kofaktorzavisimye anti-phospholipidic antibodies (beta2-GP1-kofaktorzavisimye AFL) - suppressing natural anticoagulating activity beta2-GP1. At an anti-phospholipidic syndrome interaction of AFL with phospholipids depends on a cofactor of a beta2-glycoprotein-1. It has molecular weight 50.000.000 And actively contacts phospholipids, DNA, components of membranes of thrombocytes and mitochondrions, heparin. Beta2-GP1 is important natural anticoagulant, it suppresses internal activation of the anti-coagulative cascade and aggregation of thrombocytes. Suppression beta2-GP1-kofaktorzavisimykh antibodies is followed by development of thromboses.

Frequency of detection of antibodies to fofolipida in blood serum of healthy people fluctuates from 1 to 12% and can increase at elderly people.

In serum of healthy people the level of antibodies to phospholipids low, at the same time biological membranes are protected from influence of the last.

At the diseases connected with activation of V-lymphocytes concentration of antibodies to phospholipids sharply increases. Most often and in a high antiserum capacity to phospholipids are found in blood serum of patients with a system lupus erythematosus (to 70% of cases), is more rare - at other rheumatic diseases, including a pseudorheumatism, a system scleroderma, Shegren's syndrome. Excess antibody formation to phospholipids is revealed also at patients with malignant new growths, limfoproliferativny syndromes, an autoimmune Werlhof's disease, against the background of acute and persistent viral, bacterial and parasitic infections (an infectious mononucleosis, AIDS, etc.), at a number of diseases of TsNS, some forms of obstetric pathology, against the background of reception of some eurysynusic medicines (oral contraceptives, psychotropic drugs, etc.). As a rule, hyperproduction of antibodies to phospholipids leads to development of an anti-phospholipidic syndrome.

The anti-phospholipidic syndrome meets at women more often, than at men.

Symptoms of the Anti-phospholipidic syndrome:

Venous and arterial thrombosis.

Recurrent venous thrombosis is most characteristic. Blood clots are usually localized in deep veins of the lower extremities, is frequent in renal and hepatic veins, leading to development of a nephrotic syndrome and Badda-Kiari's syndrome. Embolisms from deep veins of the lower extremities in a pulmonary artery, capillarites are often observed that leads to development of pulmonary hypertensia and pulmonary hemorrhages. Fibrinferments of a subclavial vein, a retina vein are described. Development of a syndrome of an upper or lower vena cava at fibrinferment of the corresponding localization is possible. Thrombosis of the central vein of adrenal glands with the subsequent development of a hemorrhage and their necrosis leads to development of chronic adrenal insufficiency.

Arterial thrombosis is clinically shown by ischemia and gangrene of the lower extremities, an aortic arch syndrome, an aseptic necrosis of a head of a hip. Fibrinferments are caused by interaction of anti-phospholipidic antibodies with endothelial cells and decrease in antitrombotichesky activity of an endothelium, suppression of products of prostacyclin and increase in aggregation of thrombocytes, decrease of the activity of the circulating anticoagulating factors (antithrombin III, protein C and S, beta2-GP1, etc.).

Defeat of TsNS.

Thrombosis of arteries of a brain leads to the tranzitorny ischemic attacks, recurrent strokes which can be shown not only by paresis and paralyzes, but also a convulsive syndrome, the progressing weak-mindedness, mental disturbances. Also other neurologic disturbances are possible: migrenepodobny headaches, chorea, cross myelitis. It is not excluded that Sneddon's syndrome (a combination of a mesh livedo, recurrent thrombosis of cerebral arteries and arterial hypertension) is also manifestation of an anti-phospholipidic syndrome.

Damage of heart.

Cardial pathology can have serious predictive value and the following clinical manifestations:
- thrombosis of coronary arteries and development of a myocardial infarction;
- acute or chronic thrombosis of small intramural branches of coronary arteries that leads to disturbance of sokratitelny ability of a myocardium;
- defeat of valves of heart (insufficiency of the mitral valve or narrowing of the left atrioventricular opening, is more rare - insufficiency of aortal or tricuspid valves). At some patients development of trombotichesky stratifications on valves (vegetation) is possible that it is difficult to differentiate from an infectious endocarditis;
- formation of intra atrial blood clots is possible that on remembers clinical manifestations of a myxoma of heart;
- often arterial hypertension labile or stable which is caused by thrombosis of renal vessels, a heart attack of kidneys, thrombosis of belly department of an aorta, intraglomerulyarny thrombosis of kidneys, development of a fibromyshechny dysplasia of renal arteries develops.

Damage of kidneys.

At an anti-phospholipidic syndrome thrombosis of a renal artery, a kidney heart attack, and also intraglomerular microthrombosis ("a renal trombotichesky mikroangiopatiya") with the subsequent development of a glomerulosclerosis and a chronic renal failure is quite often observed.

Damage of a liver.

Thrombosis of hepatic veins (Badda-Kiari's syndrome), damage of arteries with development of a heart attack of a liver, development of a nodal regenerator hyperplasia is possible.

Damage of lungs.

Thromboembolisms of a pulmonary artery less often - the trombotichesky pulmonary hypertensia caused by local thrombosis of pulmonary vessels are possible.

Damage of skin.

Skin manifestations of an anti-phospholipidic syndrome are mesh a livedo (a vascular reticulum in the form of bluish spots on shins, ступнях, hips, brushes, especially well revealed when cooling); superficial rash in the form of dot hemorrhages, reminding a vasculitis; necrosis of skin of distal departments of the lower extremities; chronic ulcers of legs; hemorrhages in a hyponychial bed (a symptom of "splinter").

Obstetric pathology.

Is the most characteristic manifestation of an anti-phospholipidic syndrome. The following types of obstetric pathology are possible: usual not incubation of pregnancy, the recuring spontaneous abortions (the risk of abortions increases with increase in concentration of anti-cardiolipin of the class IgG), pre-natal death of a fruit, late toxicosis of pregnancy, a preeclampsia, an eclampsia, a chorea, a delay of pre-natal fetation, premature births. The main mechanisms of obstetric pathology are: thrombosis of vessels of a placenta, development of a heart attack and insufficiency of a placenta, oppression of synthesis of prostacyclin which deficit causes a hyper tone of a uterus and an abortion.

Reasons of the Anti-phospholipidic syndrome:

The anti-phospholipidic syndrome can be primary, not connected with any previous pathology, but most often develops at the diseases called above which are followed by products of anti-phospholipidic antibodies. There is a genetic predisposition to hyperproduction of antibodies to phospholipids which is connected with a carriage of antigens HLA DR7, DQBj, DR4, and also a zero allele of the Federation Council. The main pathogenetic mechanism of an anti-phospholipidic syndrome is influence of anti-phospholipidic antibodies on vascular, cellular and humoral components of system of coagulation that leads to disturbance of balance between protrombotichesky and antitrombotichesky processes and to development of thromboses.

Anti-phospholipidic antibodies exert the following pathogenetic impacts:

    * endothelial cell: decrease in synthesis of prostacyclin - prostaglandin having anti-aggregation and vazodilatiruyushchy effect; disturbance of functional activity of thrombomodulin - the protein which is contained on a surface of the endothelium which is directly braking procoagulant activity of thrombin and accelerating activation of a protein With thrombin; geparan-sulfate decrease of the activity; induction of formation of a factor of activation of thrombocytes; disturbance of fibrinolitic activity; decrease in release of a fabric plasminogen activator; increase in release of inhibitor of a plasminogen activator 1; increase in synthesis of a factor of Villebrand necessary for normal aggregation of thrombocytes and having ability to extend an elimination half-life of a factor of VIII;
    * thrombocytes: anti-phospholipidic antibodies interact with thrombocytes, cause increase in products of thromboxane of Ag, concentration of cytosolic calcium that leads to increase in aggregation of thrombocytes; besides, anti-phospholipidic antibodies contact a membrane of the activated thrombocytes that causes more bystry destruction them the englobing mononukleara therefore thrombocytopenia develops;
    * humoral components of coagulation: decrease in activation of protein C and level of free protein S - normal the activated protein With in the presence of the cofactor of protein S selectively destroys factors of Va and VIIIa that promotes blood coagulation oppression; easing of activity of heparin and geparinoposredovanny formation of a complex antithrombin III heparin; decrease in synthesis and functional activity of placental anticoagulant; disturbance of functional activity of natural anticoagulant beta2-GP1.

Treatment of the Anti-phospholipidic syndrome:

Prevention and treatment of thromboses at AFS — not less complex challenge, than its correct diagnosis. It is connected with heterogeneity of the pathogenetic mechanisms which are the cornerstone of AFS, polymorphism of clinical manifestations, lack of the reliable clinical and laboratory indicators allowing to predict recuring of trombotichesky disturbances. Actually still the standards, standard at the international level, concerning tactics of maintaining patients with the AFS various forms, and offered now the recommendation are not developed based on results of open tests or the retrospective analysis of outcomes of a disease. It is necessary to emphasize at once that glucocorticoids (Civil Code), and also cytotoxic drugs and a plasmapheresis at AFS are applied only to suppression of activity of a basic disease (for example, hard currency) or at catastrophic AFS. In other cases they are inefficient (and are even contraindicated) as long glucocorticoid therapy can potentially increase risk of recuring of thromboses, and some cytotoxic drugs (and group of companies) increase risk of development of complications of anticoagulating therapy.

It is obvious that as the high risk of recuring of thromboses is characteristic of AFS, the vast majority of patients need performing preventive anticoagulating therapy for a long time, sometimes for life. Patients with a rack (within several years) normalization of the AFL level for lack of a recurrence of thromboses can make an exception. However and in this case the risk of recuring of thromboses cannot be completely excluded, and patients need careful dynamic observation and probably reception of low doses of aspirin.