Asherson's syndrome – extremely rare autoimmune state which is a complication of an anti-phospholipidic syndrome (AFS) or the system red volchanka (SRV) and is followed by massive formation of blood clots. The symptomatology is various, depends on bodies injured with thrombosis – possibly development of a renal failure, necroses of skin, a pulmonary embolism, strokes, paresis, myocardial infarctions. Diagnostics is made by studying of activity of the curtailing system of blood, immunoassays and a research of the anamnesis of the patient. Treatment includes use of anticoagulants, resolvents, a plasma exchange, transfusion of freshly frozen plasma.
Asherson's syndrome or catastrophic anti-phospholipidic syndrome (KAFS) – very rare state, for all history of observations about 300 cases are authentically recorded. Usually it is registered at young faces against the background of the available autoimmune disease, the infection, surgery, pregnancy and childbirth can act as a provocative factor. Among the diseased women – their quantity among patients approximately twice higher, than men prevail. Besides, there are instructions on heavier course of pathology and the serious forecast for female patients. Any other epidemiological data on a syndrome are absent because of a rarity of this state, however its studying continues.
Reasons of a syndrome of Asherson
KAFS etiology is definitely not studied today, is established only that pathology arises against the background of AFS or hard currency. In extremely exceptional cases (no more than 3-4%) this state complicates the course of rheumatoid arthritis, a sklerodermiya, system vaskulit. Development of a syndrome against the background of diseases of connecting fabric proves its autoimmune character, also at its studying the lines characteristic of sepsis – for example, system inflammatory reaction were revealed. Several factors which are capable to provoke development of KAFS in patients with autoimmune diseases are defined:
- Infections. Very often development of a syndrome was preceded by various infectious diseases of bacterial or virus genesis. It is supposed that immunity activation by alien anti-genes at hard currency or AFS causes a peculiar answer from the curtailing system.
- Injuries. Less often pathology is diagnosed after severe injuries and in the postoperative period. How exactly the travmatization of fabrics provokes this complication – it is still unknown.
- Pregnancy. Incubation and the birth of the child is the stressful factor capable to cause development of such state in the presence of autoimmune diseases.
- Some diseases. Developing of malignant tumors, hematologic violations, diseases of a GIT, liver, kidneys sometimes too promote emergence of a syndrome. The reliable reasons and mechanisms of pathogenesis are unknown, there are only theoretical assumptions.
There were data indicating existence in blood of persons with KAFS special autoantitet, patients, uncharacteristic for the majority, with system diseases of connecting fabrics. It antibodies against a prothrombin and special protein – beta 2 - a glycoprotein. The first is directly involved in fibrillation process, the second is a receptor on a surface of cages vascular an endoteliya. Taking into account these data there is an assumption that Asherson's syndrome is a rare malignant form of autoimmune defeat of system of a hemostasis.
Because of a rarity of a syndrome of Asherson his pathogenesis is still not clear, there are only assumptions and theoretical assumptions on a number of its stages. According to the latest data, development of a disease begins with increase in a caption of antibodies to a prothrombin and beta 2 - to a glycoprotein under the influence of an infection or other stressful factors. It activates processes of formation of blood clots, significantly reduces anti-inflammatory and antitrombotichesky functions of endometrium. Dysfunction of the last, besides the facilitated formation of blood clots, promotes development of the inflammatory violations flowing in the system reaction similar that at sepsis. Cascades of immunological reactions, in turn, intensify processes of a trombogenez and adhesion of clots of blood on vascular walls even stronger.
Massive formation of blood clots happens for a short time – from several hours to 2-3 weeks, is followed by an embolism at first of the microcirculator course, and then and vessels of larger caliber. All bodies and fabrics can be surprised, kidneys, skin, lungs, a brain, digestive tract, including a liver and a pancreas are most often involved. Because of an embolism there is ischemia of sites of the struck bodies which then is replaced by necroses and heart attacks. It leads to malfunction that affects clinical manifestations of KAFS – the renal failure, a blood spitting, hemorrhages and necroses of skin, strokes is possible. Because of a massive tromboobrazovaniye the quantity of factors of folding is exhausted that leads to hypocoagulation and bleedings.
Symptoms of a syndrome of Asherson
Clinical manifestations of a syndrome are rather various as they depend on the prevailing defeat of this or that body, but also there are some the lines, general for all cases. The disease is characterized by a prompt current, blood clots in the microcirculator course are formed in only several hours or days. Two thirds of patients have distsirkulyatorny violations in kidneys which are shown waist pains, reduction of volume of the emitted urine, emergence of a smell of ammonia from a mouth because of the developed sharp renal failure. Approximately at the same number of patients crimson spots, skin necroses in the field of a nail bed, on brushes, feet, shins come to light, is more rare on other parts of the body.
At 60% of patients Asherson's syndrome is shown by defeat of vessels of lungs or a brain. In the first case speech disturbance and memories, consciousness losses, the central paralyzes are characteristic. Quite often there is an ischemic or hemorrhagic stroke. Thromboses in lungs lead to development respiratory a distress syndrome – to severe short wind, the deep speeded-up breath, feeling of shortage of air, widespread cyanosis. At a heart attack of a lung the blood spitting, rattles, cough, severe pains in a breast is observed. The last symptom is also characteristic of damage of heart which is registered in 50-55% of cases of KAFS. Stenocardia, violations of a warm rhythm is noted, the myocardial infarction symptomatology sometimes is found.
Defeat of bodies of digestive tract is shown by belly-aches, exacerbations of stomach ulcer, dispeptichesky frustration (appetite violation, nausea, vomiting). At heavy thromboses of vessels of a liver development of jaundice is possible, at damage of a pancreas – formation of a clinical picture of sharp pancreatitis (the surrounding belly-aches, high temperature of a body). A heavy complication is the thrombembolia of mezenterialny vessels which can provoke peritonitis or gangrene of intestines. Rare (about 15% of cases) a consequence of a state is the nadpochechnikovy insufficiency which is followed by pigmentation of integuments, weakness, falling of arterial pressure.
Extremely seldom at this syndrome there is an isolated defeat of any system or body, usually it proceeds in the form of polyorgan insufficiency with neurologic, nephrological, gastrointestinal and skin manifestations. At patients frustration of TsNS (consciousness loss, a stroke, a coma), OPN, necroses of various sites of skin, respiratory and cardiovascular insufficiency quickly develop. At timely hospitalization and holding resuscitation actions the tromboobrazovaniye is replaced by the raised bleeding because of emergence of a koagulopatiya of consumption. It is shown by hypodermic and intra articulate hemorrhages, bleedings in bodies of a GIT.
Asherson's syndrome in itself is the most serious complication of autoimmune pathologies. Among the symptoms provoked by it the greatest threat for life of the patient is posed by polyorgan insufficiency, a cerebral coma, damage of kidneys, lungs or heart. Without timely resuscitation actions there can come death because of defeat of this or that vital system of an organism. In the conditions of a hospital at stabilization of the patient in the late period serious bleedings and hemolytic anemia can develop. After the postponed KAFS episode in a number of bodies there are sclerous changes causing chronic insufficiency and violation of their functions.
Diagnostics of a syndrome of Asherson in modern immunology is considered rather difficult procedure, precipitancy of development of a disease and its similarity with some other pathologies is the reason of it (the DVS-syndrome, trombotsitopenichesky purpury). Therefore some immunologists consider that occurrence of this state is several times higher official, but a considerable part of cases is not fixed because of the sudden death of patients or the wrong diagnostics. The procedures directed to identification of specific signs of KAFS are:
- Immunological blood test. Anti-phospholipidic antibodies, and also immunoglobulins against some proteins of plasma, cellular kernels, receptors an endoteliya surely are found in patients. Highly specialized laboratories by means of the immunofermental analysis can define antibodies to beta 2 - a glycoprotein and to a prothrombin – their existence with high degree of probability indicates Asherson's syndrome.
- Research of system of a hemostasis. Fibrillation time at patients with KAFS is usually a little lowered that is caused by a consumption koagulopatiya after a massive tromboobrazovaniye. Within biochemical blood test identification of decrease in level of some factors of folding is possible.
- Biopsy of target organs. Usually take a sample of tissues of kidneys, is more rare than other bodies (skin, a spleen, mucous a stomach). The proof of existence of a disease are symptoms of thrombosis in vessels of small and average caliber, identification of tromboemboliya, symptoms of ischemia or heart attack.
The supporting role in diagnostics is played by the laboratory and tool researches directed to studying of functions of the struck bodies. It can be neurologic tests, EEG, ultrasonography and UZDG of vessels of kidneys, an electrocardiography and EhoKG, the spirography and a X-ray analysis of lungs. For more exact definition of the diagnosis and adequate treatment additional consultations of narrow experts – the dermatologist, the nephrologist, the cardiologist, the neuropathologist can be required. Differential diagnostics is made with other autoimmune pathologies and diseases which are followed by thromboses of vessels (the DVS-syndrome, HELLP syndrome).
Treatment of a syndrome of Asherson
Therapeutic actions divide into two groups – the procedures directed to compensation of insufficiency of bodies (stabilization of the general state) and actually pathogenetic treatment. Carry huge number of techniques to the first group – purpose of a hemodialysis, nootropic means, oxygenotherapy and others. Pathogenetic treatment of KAFS provides weakening of processes of a trombogenez, reduction of expressiveness of a system inflammation, elimination from a blood-groove of provocative antibodies and other active components in the immunological plan. It is reached by the following events:
- Reduction of a tromboobrazovaniye. Decrease of the activity of system of a hemostasis is made by purpose of traditional anticoagulants – low-molecular heparin, a varfarin. At low or insufficient effect of their application fibrinolytic means are in addition used, at the same time it is necessary to consider the increased risk of development of bleedings.
- Decrease of the activity of an inflammation. As anti-inflammatory medicines at KAFS apply glucocorticoid means. They effectively block formation of a number of the inflammatory mediators specific to this pathological process.
- Neutralization of aggressive antibodies. The plasma exchange and transfusion of donor plasma promote purification of blood from autoantitet, reduce intensity of displays of pathology. At the same time the risk of some complications – for example, hemolytic anemia also decreases.
Above-mentioned methods of treatment are always used in a complex, then their efficiency is maximum. The choice of techniques is carried out taking into account the general condition of the patient, functional activity of his vitals. There are experimental approaches to treatment of a syndrome with application of prostatsiklin and antagonists a factor tumor-nekrotiziruyushchego an alpha (TNF-α). Their appointment in some cases provided positive effect, however authentically it is not possible to estimate efficiency of a method because of the insufficient number of data.
Forecast and prevention
Official statistical data on a lethality of a syndrome of Asherson indicate the serious forecast of a state – more than 50% of patients die of polyorgan insufficiency and other complications. In recent years this figure decreases because of improvement of methods of diagnostics and treatment of pathology. Specific methods of prevention do not exist, the faces having the proved diagnoses of AFS, hard currency, rheumatic diseases need to be checked regularly at the immunologist. As sometimes KAFS arises at rather healthy people, carrying out the analysis on the maintenance of anti-phospholipidic antibodies before surgical interventions is recommended or at pregnancy. Their detection demonstrates to the increased risk of this complication that can help with its timely definition and an operational initiation of treatment.