What is Hemolytic Uremic Syndrome?
The term hemolytic uremic syndrome was first used by Gasser in 1955, therefore, the term Gasser’s disease is also used in the literature. Hemolytic-uremic syndrome is determined by a triad of symptoms: microangiopathic hemolytic anemia, renal failure and thrombocytopenia.
Currently, hemolytic uremic syndrome is one of the common causes of acute renal failure in young children, the timeliness of diagnosis and treatment determines the outcome of the disease.
Epidemiology. Hemolytic uremic syndrome is found throughout the world. The annual frequency in children under 5 years of age is 2-3, up to 18 years old – 0.97 cases per 100,000 children. The incidence of hemolytic-uremic syndrome tends to seasonal fluctuations with a maximum in the warm season (June – September). Hemolytic uremic syndrome is characteristic for infants and young children (from 6 months to 4 years). Age dependence is not traced in the form of D + GUS.
Symptoms of the Hemolytic Uremic Syndrome
The prodromal period of hemolytic-uremic syndrome lasts 2-14 (average 6) days and is characterized by an episode of diarrhea mixed with blood. The onset of hemolytic uremic syndrome is accompanied by a deterioration in the general condition of the child, an increase in lethargy and pallor of the skin, in some patients acquiring an icteric hue. Fever is present in 5-20% of patients. There is a decrease in diuresis, the appearance of pasty eyelids, lower legs and azotemia. 50-70% of children with D + HUS develop oligoanuric acute renal failure. Persistent arterial hypertension is observed.
In severe hemolytic uremic syndrome, extrarenal lesions are observed. Possible involvement in the central nervous system (convulsions, coma, cortical blindness), heart (ischemia with the development of insufficiency, arrhythmias), lungs (hemorrhages, edema), any gastrointestinal tract (esophagitis, enterocolitis, necrosis, perforation, intestinal invagination, hepatitis, pancreatitis) . In single patients, hemorrhage in the retina or vitreous body occurs.
Anemia is characterized by a sudden onset, a rapid decrease in hemoglobin to 60-80 g / l, sometimes to critical numbers (30-40 g / l), with reticulocytosis, anisocytosis. In addition, leukocytosis is noted.
Thrombocytopenia is moderate, sometimes short-term or recurrent, can lead to the appearance of petechiae (in 15-18% of patients), but usually occurs without bleeding.
Flow. The duration of hemolytic uremic syndrome is different and depends on its severity. With a moderate course, diuresis does not change, a decrease in renal function is moderate. The severe course of hemolytic-uremic syndrome leads to anuria requiring dialysis, and the development of extrarenal lesions. The presence of fever and leukocytosis is a risk criterion for the development of severe hemolytic uremic syndrome.
The usual duration of hemolytic-uremic syndrome is 1-2 weeks, then stabilization and gradual recovery occur. Initially, an increase in platelet count is observed, then an improvement in urine output and, lastly, resolution of anemia. Hemoglobin more often normalizes after 1 month after improvement.
Diagnosis of Hemolytic Uremic Syndrome
Diagnosis of hemolytic-uremic syndrome helps with a microscopic picture of the blood, which allows to identify fragmented red blood cells. The degree of anemia and thrombocytopenia does not correlate with the severity of renal dysfunction. There may be giant platelets in the peripheral blood.
Plasma contains free hemoglobin, which can be detected macroscopically. The direct and indirect Coombs reaction has a negative result. In the bone marrow, erythroid hyperplasia, an increase in the number of megakaryocytes are observed.
Moderate and transient indirect hyperbilirubinemia, a significant increase in urea and blood creatinine are noted. Blood transaminases may be slightly elevated. Blood complement levels (C3 and C4) are reduced. Haptoglobin is significantly reduced.
Electrolyte disturbances (hyponatremia, hyperkalemia), acidosis are detected in the oligoanuric stage of acute renal failure.
Laboratory coagulopathy is absent. This suggests that with the expanded clinical picture of hemolytic-uremic syndrome, active deposition of fibrin has already ended. Prothrombin time, partial activated thromboplastin time and blood fibrinogen are within normal limits. There may be a decrease in the level of antithrombin-III, moderate fibrinolysis with a slight increase in the products of fibrin degradation.
Urinalysis revealed proteinuria from slight to severe, erythrocyturia up to macrohematuria, hemoglobinuria, hemosiderinuria. With ultrasound, the kidneys are enlarged, increased echogenicity of the parenchyma. Significant changes are observed with ultrasound dopplerography of the renal vessels.
In the examination of children, it is necessary to provide for bacteriological examination of feces, with mandatory sowing on E. coli O157: H7.
Treatment of Hemolytic Uremic Syndrome
Supportive treatment is currently underway, aimed at maintaining hematocrit within acceptable limits, normalizing serum electrolytes and maintaining water balance, as well as combating arterial hypertension and seizures. A high-calorie diet with salt restriction is indicated. With edematous syndrome, diuretics (furosemide) are used, with tachycardia – beta-blockers. In severe hypertension, continuous infusion of sodium nitroprusside with constant blood pressure monitoring is preferred. While maintaining hypertension, oral administration of antihypertensive drugs is further indicated.
Hematocrit is monitored daily. If the hematocrit is less than 20%, hemoglobin is less than 60 g / l, the erythrocyte mass is transfused. Platelet transfusion can worsen the condition of the patient, causing further damage to the kidneys, so they resort to it only in case of significant bleeding or surgery.
About 50% of patients with a typical hemolytic-uremic syndrome require dialysis (peritoneal or hemodialysis), and in its early onset. Indications for use: oliguria resistant to diuretics, severe hyperhydration, hyperkalemia, hyponatremia, acidosis. Some authors propose plasmapheresis with transfusion of freshly frozen plasma with D + HUS, as well as in the case of prolonged anuria (more than 2 weeks) or severe complications of the central nervous system with D + HUS.
D + HUS antibiotic treatment remains controversial. Their use may increase the risk of hemolytic uremic syndrome in children with? diarrhea, since in this situation the production of verotoxin increases.
According to the JAMA Editorial Board, to date there is no significant evidence of the benefits of using antibacterial drugs for the prevention or treatment of hemolytic-uremic syndrome. Many medical practitioners are likely to disagree with this conclusion and will adhere to the therapy tactics of hemolytic uremic syndrome based on their clinical experience.
The number of prospective controlled trials of the effectiveness of anticoagulant therapy is small. In most children, recovery occurs without its use. This type of therapy is associated with a significant risk of hemorrhagic complications. Some authors indicate that anticoagulant therapy does not give an immediate antithrombotic effect, but is capable in severe cases of prolonged beneficial effects on hypertension and proteinuria.
Corticosteroids, antiplatelet (dipyridamole) and antioxidant drugs also have dubious efficacy. The use of intravenous immunoglobulin (2 g / kg weight intravenously for 2-5 days) in one study in severe hemolytic uremic syndrome with central nervous system damage showed a more rapid recovery of patients.
Currently, a search is underway for means that can bind verotoxin in the intestine and prevent hemolytic-uremic syndrome. One of them – SYSNSORB Pk has been tested, but is not yet available for clinical use.
Outcomes and prognosis. The outcome of the acute stage of hemolytic uremic syndrome with a favorable course is the polyuric stage of acute renal failure, which lasts 1-1.5 months. Mortality with adequate care is 5-15%, in underdeveloped countries – up to 70%, with hereditary hemolytic uremic syndrome – 70-90%. with relapses of hemolytic uremic syndrome – 30%. The cause of deaths is damage to the central nervous system, cardiac or multiple organ failure.
Long-term studies have shown that 70-85% of patients restore renal function. Persistence of hypertension or proteinuria 1 year after hemolytic-uremic syndrome indicates a risk of chronic renal failure. After 5-7 years, CRF develops in 5%, in 10-15 years – in another 10-25% of patients. Adverse prognostic signs are: the early appearance of anuria and its duration more than 2 weeks, progressive damage to the central nervous system, microthrombi in more than 60% glomeruli, leukocytosis more than 20×109 / l, atypical form of hemolytic-uremic syndrome, age up to 6 months and older than 4 years.
Children who have had hemolytic uremic syndrome need to control blood pressure, serum creatinine, urinalysis (proteinuria level). Patients with persistent hypertension are prescribed antihypertensive drugs (ACE inhibitors).
Prevention of Hemolytic Uremic Syndrome
The best ways to prevent hemolytic-uremic syndrome are high-quality culinary processing of food products, especially meat products, personal hygiene measures (washing hands, avoiding bathing in dirty ponds), reducing fecal contamination of meat during or after slaughter of animals.