Thrombotic microangiopathy and renal damage

Hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) are diseases with similar clinical presentations, which are based on thrombotic microangiopathy. The term "thrombotic microangiopathy" defines a clinical and morphological syndrome manifested by microangiopathic hemolytic anemia and thrombocytopenia, which develops as a result of occlusion of blood vessels of the microcirculatory bed (arterioles, capillaries) of various organs, including the kidneys, by thrombi containing aggregated platelets and fibrin.

Causes thrombotic microangiopathy

Thrombotic thrombocytopenic purpura was first described in 1925 by E. Moschowitz in a 16-year-old girl with fever, hemolytic anemia, petechial rash, hemiparesis, and renal damage caused by "hyaline thrombi of terminal arterioles and capillaries." In 1955, S. Gasser et al. published their observation of thrombocytopenia, Coombs-negative hemolytic anemia, and renal failure in 5 children, calling this symptom complex "hemolytic uremic syndrome." The term thrombotic microangiopathy was introduced by W. S. Symmers in 1952 to replace the term "thrombotic thrombocytopenic purpura." However, today it is used not as a name for a disease, but to define a special type of damage to microvessels (mainly arterioles and capillaries), represented by edema and/or detachment of endothelial cells from the basement membrane, expansion of the subendothelial space with accumulation of loose membrane-like material in it, formation of intravascular platelet thrombi in the absence of signs of inflammation of the vascular wall.

Hemolytic uremic syndrome and thrombotic thrombocytopenic purpura are the most common forms of thrombotic microangiopathy. Their distinction is based on differences in the predominant localization of the microangiopathic process and the age of patients. Hemolytic uremic syndrome is considered an infectious disease of children, manifested mainly by kidney damage, thrombotic thrombocytopenic purpura is a unique systemic form of thrombotic microangiopathy, developing in adults and occurring with predominant damage to the central nervous system.

However, clear differentiation of these diseases is complicated by the fact that hemolytic uremic syndrome can develop in adult patients (with neurological manifestations), and severe acute renal failure has been described in patients with thrombotic thrombocytopenic purpura. In cases where it is difficult to differentiate hemolytic uremic syndrome and thrombotic thrombocytopenic purpura, the term HUS/THP may be used.

The causes of thrombotic microangiopathy are varied. There are infectious forms of hemolytic-uremic syndrome and those not associated with infection, sporadic. Most cases of infectious hemolytic-uremic syndrome (90% in children and about 50% in adults) have an intestinal prodrome - typical, associated with diarrhea or postdiarrheal hemolytic-uremic syndrome. The most common pathogen in this form of hemolytic-uremic syndrome is E. coli, which produces verotoxin (also known as shiga-like toxin for its structural and functional similarity to the toxin of Shigella dysenteriae type I, which also causes hemolytic-uremic syndrome). Almost 90% of patients with diarrhea + hemolytic uremic syndrome in economically developed countries are infected with E. coli serotype 0157: H, but at least 10 more serotypes of this pathogen associated with the development of thrombotic microangiopathy are known. In developing countries, along with E. coli, the pathogen is often Shigella dysenteriae type I.

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Symptoms thrombotic microangiopathy

Typical postdiarrheal hemolytic uremic syndrome is preceded by a prodrome, which manifests itself in most patients as bloody diarrhea lasting from 1 to 14 days (on average 7 days). By the time of admission to hospital, 50% of patients have already stopped having diarrhea. Most children experience vomiting, moderate fever, and may have intense abdominal pain, simulating the picture of an "acute abdomen". Following the diarrheal prodrome, an asymptomatic period of varying duration may occur.

Hemolytic uremic syndrome is manifested by severe pallor, weakness, lethargy, oligoanuria, although in some cases diuresis does not change. Jaundice or skin purpura may develop.

Most patients develop oliguric acute renal failure, requiring treatment for glomerulonephritis in 50% of cases. However, cases with little or no renal impairment have been described.

Diagnostics thrombotic microangiopathy

Hemolytic anemia and thrombocytopenia are the main laboratory markers of thrombotic microangiopathy.

Anemia develops within 1 to 3 weeks from the onset of the disease, is significantly expressed in most patients and requires blood transfusions in 75% of cases. In patients with hemolytic uremic syndrome, the average hemoglobin level is 70-90 g / l, although it can quickly decrease to 30 g / l. The severity of anemia does not correlate with the degree of acute renal failure. High reticulocytosis, an increase in the level of unconjugated bilirubin, and a decrease in blood haptoglobin indicate the presence of hemolysis. The most sensitive marker of hemolysis, directly correlating with its severity, is an increase in the level of LDH. However, in thrombotic microangiopathy, an increase in LDH activity is due not only to the release of the enzyme from erythrocytes, but also to ischemic damage to organs. The microangiopathic nature of hemolysis in HUS/TTP is confirmed by a negative Coombs reaction and the detection of deformed, altered erythrocytes (schistocytes) in a peripheral blood smear.

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Treatment thrombotic microangiopathy

Treatment of thrombotic microangiopathy includes the use of fresh frozen plasma, the purpose of which is to prevent or limit intravascular thrombus formation and tissue damage, and supportive therapy aimed at eliminating or limiting the severity of the main clinical manifestations. However, the ratio of these types of treatment in hemolytic uremic syndrome and thrombotic thrombocytopenic purpura is different.

The basis of treatment of post-diarrheal hemolytic uremic syndrome is supportive therapy: correction of water-electrolyte disturbances, anemia, renal failure. In case of severe manifestations of hemorrhagic colitis in children, parenteral nutrition is necessary.

Forecast

The risk of developing typical hemolytic uremic syndrome after E. Coli infection increases many times with the use of antidiarrheal drugs and antibacterial drugs, bloody diarrhea, fever, vomiting and high leukocytosis, especially in young children (under 2 years) and the elderly.

Postdiarrheal hemolytic uremic syndrome has a favorable prognosis: complete recovery occurs in 90% of cases. Mortality during the acute episode is 3-5% (a sharp decrease in mortality, which was 50% in the 1960s, occurred as a result of significant progress in the treatment of acute renal failure, anemia, arterial hypertension, electrolyte disorders achieved over the past 40 years). Almost 5% of patients who survive the acute stage of the disease develop chronic renal failure or severe extrarenal manifestations, and 40% have a long-term decrease in SCF.

Anuria lasting more than 10 days, the need for hemodialysis during the acute stage of the disease, proteinuria persisting for a year after the acute episode has been stopped are associated with the risk of developing chronic renal failure in the future. Morphological risk factors for an unfavorable prognosis for renal function are focal cortical necrosis, damage to more than 50% of the glomeruli, and the arteriolar type of damage.

There are 2 variants of the course of atypical hemolytic uremic syndrome.

The first is characterized by a pronounced gastrointestinal prodrome, anuric acute renal failure, and malignant arterial hypertension. In the acute period, high mortality is observed as a result of severe damage to the gastrointestinal tract and central nervous system. Recovery of renal function is possible in less than 50% of patients. The second variant is characterized by progressive deterioration of renal function and neurological symptoms resembling thrombotic thrombocytopenic purpura. This form can be hereditary, usually recurs, steadily leading to chronic renal failure or death.

Acute thrombotic thrombocytopenic purpura in the early 60s was a virtually fatal disease with a mortality rate of 90%. However, at present, thanks to early diagnosis, the development of new therapeutic approaches (treatment with fresh frozen plasma), and modern intensive care methods, mortality has decreased to 15-30%.

Recurrent episodes of thrombotic thrombocytopenic purpura occur at intervals of 4 weeks or more after complete recovery. They must be distinguished from continuation of an acute episode after too rapid cessation of fresh frozen plasma, which causes a new wave of thrombocytopenia and hemolysis. The recurrence rate has now increased to 30%, which is associated with a decrease in mortality during the first acute episode as a result of improved treatment. Relapses may occur months or even years after onset. Although exacerbations respond to treatment as well as the first episode, the long-term prognosis for recurrent thrombotic thrombocytopenic purpura is generally poor.

In acute thrombotic thrombocytopenic purpura, timely treatment with fresh frozen plasma helps prevent the development of terminal renal failure in the future.

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