Thrombotic thrombocytopenic purpura and hemolytic-uremic syndrome

Thrombotic thrombocytopenic purpura and hemolytic-uremic syndrome are acute, fulminant diseases characterized by the development of thrombocytopenia and microangiopathic hemolytic anemia. Other manifestations include fever, impaired consciousness and kidney failure. The diagnosis requires the presence of characteristic laboratory abnormalities, including Coombs-negative hemolytic anemia. Treatment consists in plasma exchange.

With thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome (HUS), platelet destruction is not caused by immune mechanisms. Free filaments of fibrin are deposited in multiple small vessels, resulting in damage to platelets and erythrocytes. Platelets also break down in small thrombi. In many organs, soft platelet-fibrin thrombi develop (without granulocyte infiltration of the vascular wall, characteristic of vasculitis), localized mainly in arteriocapillary compounds, described as microangiopathies. TTP and HUS differ only in the degree of development of renal insufficiency. Diagnosis and management in adults is the same. Therefore, in adults, TTPs and HUS can be grouped together.

The causes of TGP and HUS may be the following pathological conditions: congenital and acquired deficiency of the plasma enzyme ADAMTS13, which cleaves the vWF and thus eliminates abnormally large Willebrand factor (FV) multimers that cause platelet thrombi; hemorrhagic colitis resulting from the activity of bacteria producing shiga toxin (eg, Escherichia coli 0157: H7 and strains of Shigella dysenteriae); pregnancy (the condition is often difficult to distinguish from severe preeclampsia or eclampsia) and some medications (such as quinine, cyclosporine, mitomycin C). Many cases are idiopathic.

Symptoms of thrombotic thrombocytopenic purpura and hemolytic-uremic syndrome

Fever and ischemia of varying severity develop in many organs. These manifestations include confusion or coma, abdominal pain, arrhythmias caused by myocardial damage. A variety of clinical syndromes are similar, except for childhood epidemics (typical of HUS) associated with the enterohemorrhagic strain E. Coli 0157 and bacteria producing Shiga toxin, more frequent complications from the kidneys and spontaneously passing.

ITP and HUS are suspected in patients with characteristic symptoms, thrombocytopenia and anemia. Patients undergo urine analysis, a peripheral blood smear, a number of reticulocytes, serum LDH, kidney function, serum bilirubin (direct and indirect) and Coombs test. The diagnosis is confirmed in the presence of thrombocytopenia, anemia with the presence of fragments of erythrocytes in the blood smear (triangular erythrocytes and deformed erythrocytes, which is typical for microangiopathic hemolysis); evidence of hemolysis (a drop in hemoglobin, polychromasia, an increase in the number of reticulocytes, an increase in serum LDH); a negative direct test of Coombs. For the expected diagnosis, the presence of unexplained thrombocytopenia and microangiopathic hemolytic anemia is sufficient. Although the causes (eg, sensitivity to quinine) or the relationship (eg, pregnancy) are clear in some patients, most ITP-HUS patients show up spontaneously for no apparent reason. IPT-HUS often fails to differentiate even from biopsies from syndromes that cause identical thrombotic microangiopathies (eg, preeclampsia, scleroderma, fast-progressive hypertension, acute rejection of the renal allograft).

Prognosis and treatment of thrombotic thrombocytopenic purpura and hemolytic-uremic syndrome

Epidemic HUS in children associated with enterohemorrhagic infection is usually spontaneously resolved, treated with symptomatic therapy and does not require plasmapheresis. In other cases, ITP-HUS in the absence of treatment is almost always fatal. Conduction of plasmapheresis is effective in almost 85% of patients. Plasmapheresis is performed daily until the signs of disease activity disappear, which can be from several days to many weeks. Glucocorticoids and antiplatelet agents (eg, aspirin) can also be used, but their effectiveness is questionable. Many patients, as a rule, showed one episode of ITP-HUS. However, relapses may occur after years, and if suspected of relapse, the patient should perform all necessary examinations as soon as possible.