Thrombotic thrombocytopenic purpura. Thrombotic thrombocytopenic purpura and hemolytic-uremic syndrome: what it is, treatment, symptoms, diagnosis, signs, causes

Circulatory system The human body has a rather complex structure. She may be attacked various diseases, including those that pose a threat to human life and health. Moreover, the causes of many of these ailments are still unknown to scientists, and specialists correct them, focusing only on the symptoms and the supposed mechanisms of development. Just such diseases include Moshkovich's disease, in which damage occurs small vessels in combination with other health problems. This disease is also classified by doctors as thrombotic thrombocytopenic purpura, the symptoms and treatment of which will be discussed further in a little more detail.

With thrombotic thrombocytopenic purpura, the patient is affected by small vessels (classified as microangiopathy), and also develops hemolytic anemia, intravascular coagulation, thrombocytopenia, purpura, kidney damage (usually acute renal failure also occurs), as well as nervous system. Similar illness is quite rare, most often it is recorded in young women. However, doctors cannot find out exact reasons its development.

Symptoms of thrombotic thrombocytopenic purpura

Thrombotic thrombocytopenic purpura in most cases is characterized by an acute onset. In some cases, the appearance of the first symptoms is preceded by respiratory or other infectious diseases, as well as intolerance medicines.

The first manifestations of the disease are headaches, a feeling of weakness and dizziness. The patient is concerned about nausea, which turns into vomiting, as well as painful sensations in the abdominal area.

Over time, thrombocytopenia develops, which is accompanied by hemorrhagic syndrome. Petichiae (purple or red pinpoint hemorrhages) and ecchymoses (large hemorrhages under the skin, the diameter of which reaches three to five centimeters, have an irregular patterned shape) appear on the patient’s skin. In addition, hemorrhage in the retina of the eyes is observed, gastrointestinal bleeding, uterine and nosebleeds.

Pathological processes lead to the development of hemolytic anemia, which in turn causes pallor and slight jaundice.

Over time, thrombotic thrombocytopenic purpura causes a number of neurological disorders, represented by seizures, paralysis cranial nerves, hemiplegia (complete unilateral paralysis of the arms and legs) and speech disorders. In some cases, coma may develop. Psychotic behavior is often observed, and delirium, stupor and confusion are possible.

In addition, thrombotic thrombocytopenic purpura leads to kidney damage, causing micro and gross hematuria, proteinuria, azotemia, hypertension, and often acute liver failure.

Common manifestations of Moshkovich's disease also include tachycardia, gallop rhythm, hepato- and splenomegaly, lymphadenopathy.

Thrombotic thrombocytopenic purpura has an undulating course. In most cases, the disease ends in the death of the patient after a few weeks or months. Sometimes the disease occurs in a fulminant form, and it can also become chronic.

How is thrombotic thrombocytopenic purpura corrected, what is its effective treatment?

The basis of therapy for thrombotic thrombocytopenic purpura lies in plasma exchange, carried out by plasmapheresis. Moreover, the frequency of such a procedure directly depends on clinical effect. In most cases, patients need daily conduct one or two plasmapheresis. Volumes of removed plasma (from one and a half to three liters) in mandatory replenish with fresh frozen donor material, which contains a platelet aggregation factor inhibitor.

If the patient has a positive reaction to such therapy, as indicated by an increase in the number of platelets, a decrease in the activity of lactate dehydrogenase, as well as the number of schizocytes, doctors can reduce the frequency of plasmapheresis. But such a procedure must necessarily be carried out over several weeks or even months.

Patients with thrombotic thrombocytopenic purpura are prescribed glucocorticoids. The practice is to use the pulse therapy technique - the patient is given ultra-high doses of such drugs over a short period of time. Methylprednisolone (1g per day intravenously for three days) becomes the drug of choice. Oral prednisolone can also be used - 1 mg per kilogram of body weight per day.

Therapy of thrombotic thrombocytopenic purpura most often involves the use of antiplatelet agents that prevent platelet aggregation (thrombosis). However, the effectiveness of such drugs has not been proven. Dipyridamole is often used as an antiaggregant - 300-400 mg per day.

It is worth noting that platelet transfusion with this diagnosis is strictly contraindicated, since similar procedure can increase thrombus formation.

Modern methods Treatment of thrombotic thrombocytopenic purpura can achieve recovery in significant amount patients (up to 80%), but only with early therapy.

Folk remedies

Unfortunately, no method traditional medicine does not help to stop the course of thrombotic thrombocytopenic purpura, cure it or prevent its development of this disease. However, many herbs and available remedies will help patients who have suffered such a disease recover.

So, for anemia caused by such a disease, you can prepare a collection of equal parts of yarrow flowers and leaves, dried cucumber vines, and shepherd's purse grass. Brew a tablespoon of the resulting mixture with half a liter of boiling water. Leave it covered for five to six hours, then strain. Take the finished medicine one hundred and fifty milliliters three times a day, about twenty minutes before meals.

The advisability of using traditional medicine must be discussed with your doctor.

Thrombotic thrombocytopenic purpura

ICD-10: D69.4

general information

Thrombotic thrombocytopenic purpura(Moshkovich disease) - a disease characterized by hemorrhagic syndrome in the form of skin hemorrhages and increased thrombus formation leading to ischemia internal organs.

Epidemiology
Rarely seen. The predominant age is 40-60 years. The predominant gender is female (10:1).

Etiology
Not fully established. The disease can occur after infection with Mycoplasma pneumoniae, administration of a vaccine (influenza, combined, etc.), taking certain medicines(for example, penicillin, diphenine). Conditions resembling thrombotic thrombocytopenic purpura may occur with meningococcal infection, malignant neoplasms, as well as with systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome. One of the most probable causes the occurrence of thrombotic thrombocytopenic purpura - an acute deficiency (for example, against the background of an infection) of a platelet aggregation factor inhibitor, resulting in spontaneous thrombus formation.

Pathogenesis
In the pathogenesis of thrombotic thrombocytopenic purpura, several factors are distinguished: generalized Schwartzman phenomenon caused by a microorganism or endotoxin, genetic predisposition and deficiency of substances with antiplatelet properties (for example, prostacyclin). The main link in the pathogenesis is intensive thrombosis of small arteries and arterioles with hyaline thrombi, consisting of platelet granules and components of their cytoplasm with a low fibrin content. Hemolytic anemia and thrombocytopenia in thrombotic thrombocytopenic purpura are caused by mechanical destruction red blood cells and platelet consumption. Microaneurysms of affected arterioles are often encountered.

Classification

There are acute and chronic course.

Diagnostics

The advanced stage of the disease is usually preceded by weakness, headache, nausea, vomiting, abdominal pain (up to a picture resembling acute stomach), visual disturbances, the appearance of bruises and petechiae on the skin, in in rare cases Uterine, gastric and other bleeding is possible.
The advanced stage of thrombotic thrombocytopenic purpura is characterized by: fever, hemorrhagic petechial rash, cerebral and focal neurological symptoms(ataxia, hemiparesis and hemiplegia, visual impairment, convulsive syndrome), sometimes occur mental disorders, hemolytic jaundice. Ischemic lesion kidney is accompanied by proteinuria, hematuria, cylindruria. Abdominal pain due to thrombosis of mesenteric vessels (uncommon). Myocardial damage (arrhythmias, muffled tones). Arthralgia.

Mandatory laboratory tests
- General blood analysis: thrombocytopenia, anemia, leukocytosis, fragmentation of red blood cells (helmet-shaped, triangular shape of red blood cells) due to their passage through blood clots, reticulocytosis;
- biochemical analysis blood: increased urea and creatinine levels; increased concentrations of indirect and direct bilirubin fractions; increased concentration of lactate dehydrogenase; increased concentration of fibrinogen degradation products in the blood, cryofibrinogenemia (rare);
- general analysis urine: proteinuria, hematuria;
-myelogram: decreased number of megakaryocytes, increased proliferation of erythroid cells.

Differential diagnosis
It is carried out with idiopathic thrombocytopenic purpura, hepatorenal syndrome, thrombocytopenia associated with decreased platelet production, in particular with metastases malignant tumors into the bone marrow, aplastic anemia, lesion bone marrow caused, for example, by exposure to ionizing radiation; with Henoch-Schönlein disease, multiple myeloma, hemolytic-uremic syndrome.

Treatment

The main method of treatment is plasma exchange, which is carried out using plasmapheresis. The frequency of plasma exchange depends on the clinical effect. Most patients require plasmapheresis daily or even twice a day. In this case, the volume of removed plasma (from 1.5 to 3 l) must be replenished with fresh frozen donor plasma containing a platelet aggregation factor inhibitor. If there is a response to treatment (indicated by an increase in the number of platelets, a decrease in the activity of lactate dehydrogenase and the number of schizocytes), the frequency of procedures can be reduced, but they must be continued for several weeks or even months.
Glucocorticosteroids are prescribed: pulse therapy (methylprednisolone 1 g/day intravenously for 3 days in a row) or oral prednisolone 1 mg/kg/day. Antiplatelet agents (effectiveness has not been proven) - dipyridamole 300-400 mg/day.
Platelet transfusion is contraindicated as it can increase thrombus formation.

Forecast
Depends on timely diagnosis and prompt implementation therapeutic measures. The prognosis for life is unfavorable with severe ischemia of the central nervous system and myocardium.

Thrombocytopenic purpura, also known as Werlhof's disease, is a blood disease that leads to the formation of multiple blood clots in small arteries.

Thrombocytopenic purpura, what is it?

With Werlhof's disease, the number of platelets in the blood sharply decreases, since all these blood cells are involved in thrombosis of small vessels. Ischemic damage occurs to all major systems of the body: circulatory, nervous, urinary, etc.

Purpura is a companion to coagulopathy and can occur in children (including infants) and adults.

The etiology of this disease has not been fully studied. There are various hypotheses about viral and autoimmune causes, but none of them have been proven yet.

Thrombocytopenic purpura (TPP) has two main forms:

• Heteroimmune – occurs as a result of exposure to viruses and antigens. It is acute and most often affects children. After eliminating the cause, the disease passes quickly and without consequences.
• Autoimmune – occurs as a result of exposure of platelet cells to one’s own autoantibodies and antigens. The etiology is unknown. It occurs chronically, with constant relapses.

The course of Werlhof's disease is:

• Acute (period up to six months);
• Chronic (more than six months, with rare or constant relapses).

Stages of the disease:

• Crises (periods of exacerbation);
• Remissions (absence of manifestations).

Severity:

• Mild (in the presence of skin manifestations);
• Average ( skin syndrome and bleeding, platelet count in blood tests from 50 to 100 x 109/l);
• Severe (skin syndrome and heavy blood loss, anemia, platelet count in blood tests 30–50 x 109/l).

Risk factors provoking the chronic course of Werlhof's disease:

• Development of crises for no apparent reason;
• Presence of recurrent infections;
• Manifestation of the disease in teenage girls.

Idiopathic thrombocytopenic purpura

Idiopathic thrombocytopenic purpura (ITP) most often affects children. It was noted that, 3-21 days before the onset of his symptoms, the child had a viral infection.

Scientists are inclined to think that ITP has immune causes. An experiment was conducted with blood transfusion of a patient with ITP. healthy person, and the subject's platelet cell count decreased. Subsequently, it turned out that this is an immunoglobulin factor that develops activity against platelets of human cells.

Sometimes ITP occurs when using drugs, which can also be explained by the connection of the antigen with the drug, to which a negative reaction of the body is formed.

Thrombotic thrombocytopenic purpura

Thrombotic thrombocytopenic purpura (TTP) is characterized by damage to the nervous system and kidneys, edema and fibrosis.

Provoking factors may be the presence of toxic compounds in the blood, a hereditary predisposition to the disease, or the presence of unidentified microorganisms.

In TTP, kidney failure develops. Signs of Werlhof's disease include anemia of hemolytic origin, thrombocytopenia and febrile state. May appear neurological signs. These include depression of consciousness, epilepsy, and visual impairment. Damage to the central nervous system can lead to coma.

TTP is often associated with pregnancy, acquired immunodeficiency syndrome, and scleroderma. In addition, among the causes of TTP are metastases from oncological diseases and chemotherapy.

Thrombocytopenic purpura: symptoms

The main symptom to detect thrombocytopenic purpura is hemorrhage and bleeding.

Skin symptoms

Occur due to accidental and minor injuries, or at injection sites. May have the most different size– from spot to extensive. The bruise has different colors depending on the time of its occurrence. In this case, the site of hemorrhage is absolutely painless, there is no swelling.

Symptoms on the mucosa

Hemorrhages appear in the mouth, on the palate and tonsils. At severe course The disease may damage the whites of the eyes and eardrum.

Bleeding

Most often, the gums and nasal mucosa bleed, especially with minor trauma. Blood loss can also occur in the area of ​​the kidneys and stomach, but it is quite difficult to recognize because examination rarely shows pathologies of internal organs. It is extremely rare to notice a slight enlargement of the spleen.

The temperature with thrombocytopenic purpura does not rise and remains normal.

Causes of thrombocytopenic purpura

In most cases, thrombocytopenic purpura has no explainable cause. Forty percent report that TTP was preceded by a viral or viral infection. bacterial nature. These are mostly defeats. respiratory tract, as well as diseases such as chickenpox, whooping cough, rubella, measles and mononucleosis.

As a complication, TTP can occur with malaria and typhoid. There have been cases of thrombocytopenic purpura after vaccination.

TTP can be triggered by taking medications based on barbiturates, arsenic, estrogens, and exposure to radioactive isotopes.

Purpura may appear after extensive surgical intervention or trauma, prolonged solarization.

There are cases hereditary form this disease.

Thrombocytopenic purpura: treatment

Not every manifestation of Werlhof's disease requires treatment. If symptoms are caused by a viral infection, most often they will resolve during the healing process. All traces finally disappear after a couple of months. In rare cases, the disease lasts up to 6 months, but even after this period it can go away without a trace.

It is extremely rare that TTP becomes chronic. Such patients must be constantly monitored by a doctor; the treatment process can last up to 5 years. During treatment, any vaccination is contraindicated and it is not recommended to change your place of residence ( climate zone). You should try to avoid exposure to the sun and not take medications containing acetylsalicylic acid.

It is better not to take a sick child to sports activities in order to avoid the slightest injury. Even a simple ball game can become dangerous. Blood counts should be carefully monitored. With absence hemorrhagic symptoms You can let your child lead active image life.

Treatment of TTP is carried out in a hospital setting. Main types of treatment:

• Taking medications that increase blood clotting;
• Strengthening blood vessels(ascorutin, etc.);
• Hormone therapy;
• Blood and plasma transfusion;
• Herbal medicine ( herbal teas, blood thickening).

Dramatically reduces the number of deaths, exchange transfusion blood and plasmapheresis with frozen plasma.

Thrombocytopenic purpura in children

In children, TTP may appear after a history of viral infections, severe hypothermia or overheating in the sun.

Traces of hemorrhages appear on the abdomen, chest and limbs. Bleeding may come from the nose and gums

Symptom internal bleeding may be vomiting blood or unusual color urine and feces. The child may complain of pain in the abdomen and chest.

Thrombocytopenic purpura in adults

The idiopathic form of purpura is rarely observed in adults. Manifestations of thrombotic thrombocytopenic purpura mainly develop.

Multiple hemorrhages under the skin can give it the “leopard coloring”. Pulmonary, gastric and uterine bleeding.

Thrombocytopenic purpura: diagnosis

Main diagnostic symptom Werlhof's disease is considered to be thrombocytopenia. The size of platelets increases, blood clots remain loose for a long time.

In addition, blood is found in the urine and feces, and abdominal pain.

TTP should be differentiated from hemorrhagic diseases, which are not associated with thrombocytopenia: hemophilia, Glanzmann's disease, vasculitis, etc. In these cases, the sites of hemorrhage are painful; in addition, with hemophilia, blood flows into the joints.

Course and prognosis

Werlhof's disease most often ends full restoration patient within a few weeks.

Complicating the course of the disease is hemorrhage in the brain and internal organs.

If TTP has chronic nature, then it proceeds in waves, alternating stages of exacerbation and recovery.

The mortality rate for TTP is no more than 1% and is caused by hemorrhages in the central nervous system and severe anemia.

Impact on work ability

After clinical recovery, working capacity is fully restored. Exceptions are severe chronic forms diseases with frequent blood loss and anemia.

Leading specialists in the field of nephrology.

Professor Mikhail Mikhailovich Batyushin - Chairman of the Rostov Regional Society of Nephrologists, Deputy Director of the Research Institute of Urology and Nephrology, Head of the Nephrological Service of the State Educational Institution of Higher Professional Education Rostov State Medical University, Head of the Nephrology Department of the Rostov State Medical University Clinic

Bova Sergey Ivanovich - Honored Doctor of the Russian Federation, Head of the Urology Department - X-ray shock wave remote crushing of kidney stones and endoscopic methods treatment, State Healthcare Institution " Regional Hospital No. 2", Rostov-on-Don.

Letifov Gadzhi Mutalibovich - Head of the Department of Pediatrics with a course of neonatology of the Faculty of Pediatrics and Teaching Staff of Rostov State Medical University, Doctor of Medical Sciences, professor, member of the Presidium of the Russian Creative Society of Children's Nephrologists, member of the board of the Rostov Regional Society of Nephrologists, member of the editorial board of the "Bulletin of Pediatric Pharmacology and Nutrition", doctor of the highest category.

Page editor: Semenisty Maxim Nikolaevich.

THROMBOTIC THROMBOCYTOPENIC PURPURA (MOSHKOVICH'S DISEASE)

Thrombotic thrombocytopenic purpura - rare disease. Appearing with fever, hemolytic anemia, thrombocytopenic purpura, damage to the central nervous system and kidneys.

The disease was first described under the name “acute febrile pleiochromic anemia with hyaline thrombosis of the terminal arteries | capillaries" in 1925 by Aloschcowitz in a 16-year-old girl who suffered from fever, acute intravascular hemolysis and hemorrhagic purpura; the patient died 2 weeks after the onset of the disease. In this regard, the term “Moshkovich disease or syndrome” is often found in the literature. Other synonyms are: thrombotic microangiopathy”, “thrombotic microangiothrombosis”, “hemolytic anemia with microangiothrombosis”, “thrombohemolytic thrombocytolenic purpura”, etc.

After Moschcowitz, 11 years later, Baehr et al (1936) described 4 similar observations. In 1947, Singer et al proposed the term “thrombotic thrombocytopenic purpura.” Over the following years, the number of sightings increased significantly. According to Hill and Cooper, by 1968 more than 300 cases were known. In the domestic literature, patients with thrombotic thrombocytopenic purpura are described.M. I. 'Geodori, Yu P. Likhachev (I960), E. V. Uranova, M. Ya. Shtyren (1966), B. G. Savkiv, N. I. Golotenko (I960), T. N. Drozd (1970 ).

PATHOMORPHOLOGY

The underlying disease is widespread small vessel disease with subendothelial fibrin deposition and partial or complete vascular occlusion by amorphous eosinophilic material, described as thrombotic microangiopathy. Multiple spindle-shaped microaneurysms in the area of ​​the arteriolocapillary junction are also characteristic. Along with hemosiderin deposits, these changes are found in almost all organs, especially in the heart, adrenal glands, kidneys, and pancreas. Vascular lesions are most pronounced in the kidneys.

Macroscopically, the kidneys are enlarged and pale. Their surface is smooth with multiple pinpoint hemorrhages. At microscopic examination find characteristic lesion arterioles (usually afferent) with fibrinoid necrosis of the vessel walls and eosinophilic non-nuclear thrombi in the lumens. Some blood clots may be at various stages of organization; recanalization of blood clots is detected in many vessels (which, obviously, explains the often observed undulation of the flow). In the glomeruli (usually in places directly adjacent to capillary lesions) similar changes are found - fibrinoid necrosis of the walls of glomerular capillaries. In the lumen of many capillaries there are nuclear-free eosinophilic, PAS-positive, pyroninophilic masses that give a positive reaction to fibrin when stained according to Weigert (T. N. Drozd, 1970).

In immunohistochemical studies, fibrin is found in the walls of blood vessels and intravascular masses (Craig, Gitlin, 1957; Feldman et al., 1966). Immunoglobulin G is found in significantly smaller quantities than fibrin, complement is not detected (Feldman et al.).

Proliferative and membranous changes can be expressed in the glomeruli, up to the formation of “wire loops”, and then fibroplastic ones.

In the observations of T.N. Drozd, with a disease duration of 2 to 4 months, most of the glomeruli were reduced in size, had a palmate shape, and synechiae were visible between the capillary loops and the Shumlyansky-Bowman capsule.

Among extrarenal changes, thrombosis of large vessels and verrucous endocarditis.

In the pathogenesis of thrombotic thrombocytopenic purpura, immunological disorders undoubtedly play a dominant role. Currently, the most common concept is primary damage to the vascular endothelium with subsequent deposition of acellular material consisting of fibrinogen derivatives and the formation of blood clots. Immunohistochemical and electron microscopic studies have confirmed that thrombocytopenic purpura is a disease with widespread vascular damage, in which fibrin precipitates both in the walls and in the lumen of blood vessels.

Fibrin is deposited first in the subendothelial region, which is accompanied by swelling of the endothelium and narrowing of the lumen of blood vessels. The passage of red blood cells through the narrowed lumen of the capillaries and repeated contact of red blood cells with pathologically altered vessels lead to fragmentation of red blood cells and intravascular hemolysis.

The English hematologist Dacie (1962, 1967) brings together the mechanism of hemolytic anemia in thrombotic thrombocytopenic purpura with the mechanism of hemolysis in some patients with prosthetic heart valves, which is based on mechanical damage to erythrocytes. Opportunity mechanical damage of erythrocytes was proven by Bull et al (1968) in in vitro experiments with the forced passage of erythrocytes through loose fibrin thrombi or even through a network of non-fibrin fibers. Dacie proposes to combine hemolytic anemias with a similar mechanism into the group of hemolytic microangioiatic anemias, considering the picture peripheral blood quite characteristic. Damage to the vascular endothelium and destruction of red blood cells lead to the release of tissue and cellular thromboplastins with a subsequent increase in thrombin content, platelet aggregation and intravascular coagulation. The accumulation of platelets inside the affected vessels and their gluing, which is a secondary phenomenon, lead to thrombocytopenia.

From the point of view of primacy vascular changes One of the observations of Distenfeld and Oppenheim (1966) is of interest. The patient had a cholecystectomy long before the development of thrombotic thrombocytopenic purpura. A retrospective study of a gallbladder specimen revealed vascular changes typical of thrombotic thrombocytopenic purpura.

Some authors attribute thrombotic thrombocytopenic purpura to hemopathy of autoimmune origin and explain the development of acute hemolysis and thrombocytopenia by the action of anti-erythrocyte and anti-platelet antibodies, and damage vascular wall considered as secondary, associated with thrombosis and vasospasm. However, this is only an assumption, since specific antibodies are detected only in isolated cases. Ritz et al (1956), based on an analysis of literary data, found that among 55 patients described before 1956, only 2 had a positive Coombs test.

The absence of complement in the walls of affected vessels, in the glomerular basement membrane and in intravascular thrombi, and the frequent detection in affected areas of only fibrin without immunoglobulin G (Feldman et al.) obviously exclude the role of the antigen-antibody reaction as a trigger of the disease.

The literature draws attention to some similar morphological features of thrombotic thrombocytopenic purpura and systemic lupus erythematosus: fibrinoid necrosis of the walls of blood vessels and glomerular capillaries, thickening basement membrane glomerular capillaries in the form of “wire loops”, warty endocarditis, etc. There are also isolated observations of a combination of thrombotic thrombocytopenic purpura and systemic lupus erythematosus. Thus, Levine and Shearn (1964) summarized the literature data regarding 117 cases of purpura and 34 cases of a combination of it and systemic lupus erythematosus. They assume that vascular lesions with systemic lupus erythematosus can lead to the development of purpura. This point of view seems more correct than the attempt to explain the combination by generality.” pathogenetic mechanisms named diseases. However, when observing 268 patients with systemic lupus erythematosus, we were never able to note the development of thrombotic thrombocytopenic purpura.

The disease develops more often in young and middle age and equally often affects men and women.

The onset is usually acute. Sometimes the disease is preceded by respiratory or other infectious diseases, drug intolerance (penicillin, sulfonamides, iodine preparations). Cases of the development of thrombotic thrombocytopenic purpura during pregnancy have been described. The first signs are usually weakness, headache, dizziness, nausea, vomiting, and abdominal pain. Soon, thrombocytopenia develops with hemorrhagic syndrome (petechiae, ecchymoses, retinal hemorrhages, gastrointestinal, nasal*, uterine bleeding) and hemolytic anemia (pallor, slight jaundice skin), then neurological disorders are added - convulsions, cranial nerve palsies, hemiplegia, speech disorders, sometimes coma, psychotic behavior, delirium, stupor, confused consciousness. Tachycardia, gallop rhythm, hepatomegaly, splenomegaly, and lymphadenopathy are common.

In the peripheral blood, leukocytosis (often with a shift to the left), single platelets, and hemolytic anemia with increased reticulocytosis are observed. Particularly characteristic is a sharp change in the shape of erythrocytes - anisocytosis, poikilocytosis, fragments of erythrocytes and so-called helmet-shaped erythrocytes, which, according to Dacie, characterizes microangiopathic hemolytic anemia. Bilirubin content is slightly increased, bleeding time is prolonged, retraction blood clot slowed down, the Coombs reaction is usually negative.

Kidney damage is observed in the vast majority of patients, manifested by proteinuria, micro- or macrohematuria, cylindriuria, azotemia, and sometimes hypertension. In some cases, acute renal failure with anuria develops. The course of the disease is undulating, usually leading to death from renal failure over several weeks or months. Fulminant and chronic forms have been described.

The prognosis is extremely unfavorable. Thus, according to Hill and Cooper, of the more than 300 patients described in the literature from 1925 to 1968, only 20 people remained alive.

DIAGNOSTICS

When making a diagnosis, in addition to the characteristic clinical picture a biopsy may help lymph nodes, skin, muscles, kidneys, trephine biopsy with detection of typical vascular changes.

Differential diagnosis should be made with systemic erythematosus, lupus, periarteritis nodosa, rheumatism, prolonged septic endocarditis, hemorrhagic vasculitis Henoch-Schönlein Werlhof disease, hemolytic anemias, nephropathy of pregnancy, etc.

33 treatment is dominated by corticosteroids, splenectomy, dialysis (hemo- or peritoneal) and anticoagulants. Based on the recognition of the leading role of immunological disorders, it is necessary to apply large doses corticosteroid hormones. However, corticosteroid therapy alone rarely produces beneficial results. Somewhat more often it is possible to achieve remissions with a combination of massive corticosteroid therapy and splenectomy.

Hill and Cooper observed recovery in 3 patients after massive corticosteroid therapy and splenectomy. When analyzing the literature, they noted that more than half of the patients who survived received similar treatment. The authors emphasize that due to the often fulminant course of the disease, it is necessary to begin steroid therapy and perform splenectomy immediately after diagnosis.

With the development of acute renal failure, hemodialysis or peritoneal dialysis is indicated.

In some cases, anticoagulants are effective (despite the apparent paradox of such therapy in hemorrhagic syndrome), mainly heparin. The mechanism of action of heparin is not entirely clear: heparin prevents platelet aggregation and has a fibrinolytic effect.

The observations of Brain et al (1968), who treated 7 patients with thrombotic thrombocytopenic purpura with heparin, are quite convincing; 4 patients for whom heparin therapy was started in the first 10 days of illness recovered (only 2 of them underwent peritoneal dialysis); of the 3 patients for whom treatment was started later (days 18-31 of illness), only one survived, and her kidney function did not fully recover.

Allanby et al (1966), based on the assumption of the antagonism of magnesium and calcium in coagulation processes, achieved recovery of the patient when treated with heparin and magnesium salts (magnesium sulfate, magnesium carbonate).

Monnens and Schretlen (1968), based on experimental data on reverse development kidney damage with the Sanarelli-Shvartsman phenomenon (with histological picture, close to thrombotic thrombocytopenic purpura) under the influence of streptokinase, streptokinase was successfully used in one patient.

Finally, the observation of Giromini and Laperronza is of interest<1969), описавших 23-летнюю больную тромботической тромбоцитопени­ческой пурпурой с синдромом злокачественной гипертонии, безуспешно леченную кортикостероидами, гепарином и гемодиализом. Лишь после спленэктомии и двусторонней нефрэктомии исчезли гемолиз и гиперто­нический синдром.

TTP is a TMA caused by the presence of autoantibodies to the plasma metalloproteinase ADAMTS 13, which cleaves “unusually large” von Willebrand factor (ULvWF) multimers. Significantly reduced activity of ADAMTS 13 leads to the appearance of ULvWF in the plasma, which combines with glycoproteins on the surface of platelets, which leads to their aggregation. As a result, intravascular blood clots and consumption thrombocytopenia are formed. Due to microcirculation disorders, hemolytic anemia and symptoms of ischemia of various organs, most often the central nervous system, develop. Clinical symptoms usually occur after an additional factor, such as infection or pregnancy.

CLINICAL PICTURE AND NATURAL COURSE The onset of the disease is sudden, most often in a young, previously unill adult patient. Symptoms of thrombocytopenic hemorrhagic diathesis and hemolysis (anemia and jaundice), symptoms of central nervous system ischemia (in ≈65% of patients; often benign, such as amentia and headache, transient focal symptoms [visual disturbances and paresthesia, aphasia], less often seizures, stroke, coma), fever, abdominal pain (often), less often chest pain, renal failure.

Mortality in untreated patients is 90%. TTP can recur, which is more common in young patients with low ADAMTS-13 activity (<5–10 %) и антителами анти ADAMTS-13, сохраняющимися после достижения ремиссии.

Additional research methods

1. General analysis of peripheral blood: normocytic anemia, erythroblasts and schistocytes in the smear, increased number of reticulocytes, significant thrombocytopenia.

2. Biochemical blood test: increased levels of free bilirubin and LDH activity, decreased concentration of haptoglobin; Some patients have signs of renal dysfunction.

3. Urine examination: proteinuria, hematuria and casts in the sediment (in some patients).

4. Study of the blood coagulation system: signs of DIC → (in 15%, especially during the period of increased hemolysis or in the case of sepsis).

5. Others: ADAMTS-13 levels and activity are usually significantly reduced (<10 %), определяются антитела к ADAMTS-13; отрицательные пробы Кумбса.

Diagnostic criteria Diagnosis is usually made based on clinical findings. Confirmation of MAGA (with the presence of schizocytes) and thrombocytopenia without any other apparent cause is sufficient. Detection of reduced ADAMTS-13 activity and the presence of antibodies to ADAMTS-13 is useful.

Differential diagnosis

Other thrombotic microangiopathies →above, Evans syndrome.

Begin immediately after preliminary diagnosis of TTP and collection of a patient's blood sample for ADAMTS-13 activity testing.

1.  First line treatment:

1) exchange plasmapheresis in the amount of 1–1.5 plasma volumes per day, compensates for ADAMTS-13 deficiency and removes anti-ADAMTS-13 autoantibodies. When preparing for plasmapheresis, transfuse FFP at a dose of 30 ml/kg/day. Continue treatment until neurological manifestations resolve, platelet counts and LDH activity normalize. Use plasmapheresis for an additional 2 days after platelet counts >150,000/µL.

2) GCS (in combination with plasmapheresis) - prednisone 1 mg/kg/day po for ≥5 days, and in the absence of complete remission - even for 3–4 weeks, or methylprednisolone 1 g/day i.v. within 3 days;

3) rituximab - 375 mg/m2 IV 1 ×/week. within 4 weeks, consider treatment with plasmapheresis and corticosteroids, especially in patients with a severe clinical course and/or without a rapid response to treatment.

2. Treatment of resistant and recurrent disease:

1) search for other causes of MAHA and thrombocytopenia (infections, drugs);

2) continue or restart exchange plasmapheresis (in case of resistance, consider increasing the volume of exchanged plasma to 1.5 L/day or performing 2 procedures during the day);

3) GCS - methylprednisolone 1 g/day IV for 3 days;

4) rituximab - 375 mg/m2 IV 1 ×/week. within 4 weeks;

5) in patients with resistance to the above methods, consider splenectomy, immunosuppressive drugs (cyclosporine, cyclophosphamide, vincristine, mycophenolate mofetil), experimental treatments (bortezomib, acetylcysteine, caplacizumab, recombined ADAMTS-13 and its non-antibody-reactive variant);

3. Prevention of relapse:

1) rituximab - consider in patients with a history of TTP with persistent low ADAMTS-13 activity;

2) splenectomy - consider during the period of remission after the first relapse.

4. Maintenance therapy:

1) anemia → EV transfusions;

2) transfusion of TM only in case of life-threatening bleeding;

3) heparin in therapeutic doses is contraindicated; may consider LMWH at prophylactic doses if platelet count >50,000/µL.