Ascher syndrome is an extremely rare autoimmune condition that is a complication of antiphospholipid syndrome (APS) or systemic lupus erythematosus (SLE) and is accompanied by massive blood clots. The symptoms are diverse, depending on the organs affected as a result of thrombosis – it is possible to develop renal failure, skin necrosis, pulmonary embolism, strokes, paresis, myocardial infarction. Diagnosis is made by studying the activity of the blood coagulation system, immunological tests and examination of the patient’s anamnesis. Treatment includes the use of anticoagulants, anti-inflammatory drugs, plasmapheresis, transfusion of freshly frozen plasma.
General information
Ascher syndrome or catastrophic antiphospholipid syndrome (CAFS) is a very rare condition, about 300 cases have been reliably recorded over the entire history of observations. It is usually registered in young people against the background of an existing autoimmune disease, the provoking factor may be infection, surgery, pregnancy and childbirth. The number of cases is dominated by women – their number among patients is about twice as high as men. In addition, there are indications of a more severe course of pathology and a serious prognosis in female patients. There are no other epidemiological data on the syndrome due to the rarity of this condition, but its study continues.
Causes
The etiology of APS has not been precisely studied to date, it has only been established that the pathology occurs against the background of APS or SLE. In extremely rare cases (no more than 3-4%), this condition complicates the course of rheumatoid arthritis, scleroderma, systemic vasculitis. The development of the syndrome against the background of connective tissue diseases proves its autoimmune nature, and its study revealed features characteristic of sepsis – for example, a systemic inflammatory reaction. Several factors have been identified that can provoke the development of CAFS in patients with autoimmune diseases:
- Infections. Very often, the development of the syndrome was preceded by various infectious diseases of bacterial or viral genesis. It is assumed that the activation of immunity by foreign antigens in SLE or APS causes a peculiar response from the coagulation system.
- Injuries. Less often, pathology is diagnosed after severe injuries and in the postoperative period. How exactly tissue traumatization provokes this complication is still unknown.
- Pregnancy. Carrying and giving birth to a child is a stressful factor that can cause the development of such a condition in the presence of autoimmune diseases.
- Some diseases. The occurrence of malignant tumors, hematological disorders, diseases of the gastrointestinal tract, liver, kidneys sometimes also contribute to the appearance of the syndrome. Reliable causes and mechanisms of pathogenesis are unknown, there are only theoretical assumptions.
There are data indicating the presence of special autoantibodies in the blood of individuals with CAFS, which are uncharacteristic for most patients with systemic connective tissue diseases. These are antibodies against prothrombin and a special protein – beta-2-glycoprotein. The first is directly involved in the process of blood clotting, the second is a receptor on the surface of vascular endothelial cells. Taking into account this information, there is an assumption that Ascher syndrome is a rare malignant form of autoimmune lesion of the hemostasis system.
Pathogenesis
Due to the rarity of Ascher syndrome, its pathogenesis is still unclear, there are only assumptions and theoretical assumptions on a number of its stages. According to recent data, the development of the disease begins with an increase in the titer of antibodies to prothrombin and beta-2-glycoprotein under the influence of infection or other stressful factors. This activates the formation of blood clots, significantly reduces the anti-inflammatory and antithrombotic functions of the endometrium. The dysfunction of the latter, in addition to the facilitated formation of blood clots, contributes to the development of inflammatory disorders that flow into a systemic reaction similar to that of sepsis. Cascades of immunological reactions, in turn, further activate the processes of thrombogenesis and adhesion of blood clots on vascular walls.
Massive formation of blood clots occurs in a short time – from several hours to 2-3 weeks, accompanied by an embolism of the microcirculatory bed first, and then of vessels of a larger caliber. All organs and tissues can be affected, most often involving the kidneys, skin, lungs, brain, gastrointestinal tract, including liver and pancreas. Due to embolism, ischemia of the affected organs occurs, which is then replaced by necrosis and heart attacks. This leads to impaired function, which affects the clinical manifestations of CAFS – possible renal failure, hemoptysis, hemorrhages and necrosis of the skin, strokes. Due to massive thrombosis, the number of clotting factors is depleted, which leads to hypocoagulation and bleeding.
Symptoms of Ascher syndrome
The clinical manifestations of the syndrome are quite diverse, since they depend on the prevailing lesion of a particular organ, but there are also some common features for all cases. The disease is characterized by a rapid course, blood clots in the microcirculatory bed are formed in just a few hours or days. Two thirds of patients have dyscirculatory disorders in the kidneys, manifested by lower back pain, a decrease in the volume of urine excreted, the appearance of ammonia from the mouth due to acute renal failure. Approximately the same number of patients have purple spots, necrosis of the skin in the area of the nail bed, on the hands, feet, shins, less often on other parts of the body.
In 60% of patients, Ascher syndrome is manifested by damage to the vessels of the lungs or brain. In the first case, speech and memory disorders, loss of consciousness, central paralysis are characteristic. Often there is an ischemic or hemorrhagic stroke. Thrombosis in the lungs leads to the development of respiratory distress syndrome – severe shortness of breath, deep rapid breathing, a feeling of lack of air, widespread cyanosis. With a lung infarction, hemoptysis, wheezing, coughing, severe chest pains are observed. The latter symptom is also characteristic of heart damage, which is recorded in 50-55% of cases of CAFS. Angina pectoris, cardiac arrhythmias are noted, and sometimes symptoms of myocardial infarction are detected.
The defeat of the organs of the gastrointestinal tract is manifested by abdominal pain, exacerbations of peptic ulcer disease, dyspeptic disorders (appetite disorders, nausea, vomiting). With severe thrombosis of the liver vessels, jaundice may develop, with damage to the pancreas – the formation of a clinical picture of acute pancreatitis (shingling abdominal pain, high body temperature). A serious complication is a thromboembolism of mesenteric vessels, which can provoke peritonitis or intestinal gangrene. A rare (approximately 15% of cases) consequence of the condition is adrenal insufficiency, accompanied by pigmentation of the skin, weakness, and a drop in blood pressure.
Extremely rarely, an isolated lesion of any system or organ occurs with this syndrome, usually it occurs in the form of multiple organ failure with neurological, nephrological, gastrointestinal and skin manifestations. Patients rapidly develop CNS disorders (loss of consciousness, stroke, coma), acute respiratory failure, necrosis of various skin areas, respiratory and cardiovascular insufficiency. With timely hospitalization and resuscitation, thrombosis is replaced by increased bleeding due to the occurrence of consumption coagulopathy. This is manifested by subcutaneous and intra-articular hemorrhages, bleeding in the gastrointestinal tract.
Complications
Ascher syndrome itself is a serious complication of autoimmune pathologies. Among the symptoms provoked by him, the greatest threat to the patient’s life is multiple organ failure, cerebral coma, kidney, lung or heart damage. Without timely resuscitation measures, death may occur due to the defeat of one or another vital system of the body. In hospital conditions, when the patient is stabilized in the late period, serious bleeding and hemolytic anemia may develop. After the transferred episode of CAFS, sclerotic changes occur in a number of organs, causing chronic insufficiency and violation of their functions.
Diagnostics
Diagnosis of Ascher syndrome in modern immunology is considered a rather complicated procedure, the reason for this is the rapid development of the disease and its similarity with some other pathologies (DIC syndrome, thrombocytopenic purpura). Therefore, some immunologists believe that the incidence of this condition is several times higher than the official one, but a significant number of cases are not recorded due to sudden death of patients or incorrect diagnosis. Procedures aimed at identifying specific signs of CAFS are:
- Immunological examination of blood. Patients necessarily have antiphospholipid antibodies, as well as immunoglobulins against certain plasma proteins, cell nuclei, endothelial receptors. Highly specialized laboratories can detect antibodies to beta-2-glycoprotein and prothrombin by means of enzyme immunoassay – their presence with a high degree of probability indicates Ascher syndrome.
- Study of the hemostasis system. Blood clotting time in patients with CAFS is usually somewhat reduced, which is due to consumption coagulopathy after massive thrombosis. As part of a biochemical blood test, it is possible to detect a decrease in the level of certain clotting factors.
- Biopsy of target organs. Usually, a sample of kidney tissue is taken, less often other organs (skin, spleen, gastric mucosa). Evidence of the presence of the disease are signs of thrombosis in small and medium-sized vessels, detection of thromboembolism, signs of ischemia or infarction.
An auxiliary role in the diagnosis is played by laboratory and instrumental studies aimed at studying the functions of the affected organs. These can be neurological tests, EEG, ultrasound and ultrasound of the renal vessels, electrocardiography and EchoCG, spirography and radiography of the lungs. For a more accurate determination of the diagnosis and adequate treatment, additional consultations of specialized specialists may be required – a dermatologist, a nephrologist, a cardiologist, a neurologist. Differential diagnosis is performed with other autoimmune pathologies and diseases accompanied by vascular thrombosis (DIC syndrome, HELLP syndrome).
Treatment of Ascher syndrome
Therapeutic measures are divided into two groups – procedures aimed at compensating for organ failure (stabilization of the general condition) and pathogenetic treatment itself. The first group includes a huge number of techniques – the appointment of hemodialysis, nootropic drugs, oxygen therapy and others. The pathogenetic treatment of CAFS provides for the weakening of the processes of thrombogenesis, a decrease in the severity of systemic inflammation, the elimination of provoking antibodies and other immunologically active components from the bloodstream. This is achieved by the following measures:
- Reduction of thrombosis. A decrease in the activity of the hemostasis system is produced by the appointment of traditional anticoagulants – low molecular weight heparin, warfarin. If the effect of their use is low or insufficient, fibrinolytic agents are additionally used, while the increased risk of bleeding should be taken into account.
- Decrease in the activity of inflammation. Glucocorticoid agents are used as anti-inflammatory drugs for CAFS. They effectively block the formation of a number of inflammatory mediators specific to this pathological process.
- Neutralization of aggressive antibodies. Plasmapheresis and transfusion of donor plasma contribute to the purification of blood from autoantibodies, reduce the intensity of manifestations of pathology. This also reduces the risk of certain complications, for example, hemolytic anemia.
The above methods of treatment are always used in combination, then their effectiveness is maximum. The choice of methods is carried out taking into account the general condition of the patient, the functional activity of his vital organs. There are experimental approaches to the treatment of the syndrome using prostacyclines and tumor-necrotizing factor alpha (TNF-α) antagonists. Their appointment in some cases provided a positive effect, but it is not possible to reliably assess the effectiveness of the method due to insufficient data.
Prognosis and prevention
Official statistics on the mortality of Ascher syndrome indicate a serious prognosis of the condition – more than 50% of patients die from multiple organ failure and other complications. In recent years, this figure has been decreasing due to improved methods of diagnosis and treatment of pathology. There are no specific methods of prevention, persons with proven diagnoses of APS, SLE, rheumatic diseases should be regularly checked by an immunologist. Since CAFS sometimes occurs in relatively healthy people, it is recommended to conduct an analysis for the content of antiphospholipid antibodies before surgery or during pregnancy. Their detection indicates an increased risk of this complication, which can help in its timely determination and prompt initiation of treatment.
