Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome

Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome are acute, fulminant disorders characterized by thrombocytopenia and microangiopathic hemolytic anemia. Other manifestations include fever, altered consciousness, and renal failure. Diagnosis requires characteristic laboratory abnormalities, including Coombs-negative hemolytic anemia. Treatment is plasma exchange.

In thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS), platelet destruction occurs without immune mechanisms. Free fibrin strands are deposited in multiple small vessels, causing platelet and red blood cell damage. Platelets are also destroyed in small thrombi. Soft platelet-fibrin thrombi (without the granulocytic infiltration of the vessel wall characteristic of vasculitis) develop in many organs, localized mainly in arteriocapillary junctions, described as microangiopathies. TTP and HUS differ only in the degree of development of renal failure. Diagnosis and management in adults are the same. Therefore, in adults, TTP and HUS can be grouped together.

The following pathological conditions may cause TGP and HUS: congenital and acquired deficiency of the plasma enzyme ADAMTS13, which cleaves von Willebrand factor (vWF) and thus eliminates the abnormally large vWF multimers that cause platelet thrombi; hemorrhagic colitis resulting from the activity of Shiga toxin-producing bacteria (eg, Escherichia coli 0157:H7 and Shigella dysenteriae strains); pregnancy (in which the condition is often difficult to distinguish from severe preeclampsia or eclampsia); and certain drugs (eg, 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, and arrhythmias caused by myocardial injury. The various clinical syndromes are similar, except for childhood epidemic diseases (typical of HUS) associated with enterohemorrhagic E. coli 0157 and Shiga toxin-producing bacteria, more frequent renal complications, and spontaneous resolution.

ITP and HUS are suspected in patients with characteristic symptoms, thrombocytopenia and anemia. Patients are tested with urinalysis, peripheral blood smear, reticulocyte count, serum LDH, renal function, serum bilirubin (direct and indirect) and Coombs test. The diagnosis is confirmed by the presence of thrombocytopenia, anemia with the presence of red blood cell fragments in the blood smear (triangular-shaped red blood cells and deformed red blood cells, which is typical for microangiopathic hemolysis); evidence of hemolysis (fall in hemoglobin, polychromasia, increased reticulocyte count, increased serum LDH); negative direct Coombs test. The presence of unexplained thrombocytopenia and microangiopathic hemolytic anemia is sufficient for a presumptive diagnosis. Although the cause (eg, quinine sensitivity) or association (eg, pregnancy) is clear in some patients, in most patients ITP-HUS occurs spontaneously without apparent cause. ITP-HUS often cannot be differentiated, even by biopsy, from syndromes that cause identical thrombotic microangiopathies (eg, preeclampsia, scleroderma, rapidly progressive hypertension, acute renal allograft rejection).

Prognosis and treatment of thrombotic thrombocytopenic purpura and hemolytic uremic syndrome

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