There are clinical and pathologic similarities between HUS and thrombotic thrombocytopenic purpura (TTP). Both conditions manifest microangiopathy with thromboses. Thrombotic microangiopathies are characterized by the involvement of widespread occlusive microvascular thromboses resulting in thrombocytopenia, microangiopathic hemolytic anemia, and variable signs and symptoms of end-organ ischemia.
The arteriolar and capillary microthrombotic process found in most cases of HUS is the result of the activity of specific toxins with ensuing injury to endothelial cells. On the other hand, most cases of TTP are the result of abnormalities of platelet function. Microangiopathic anemia is not associated with Coombs positivity in either condition.
Two predominant types of HUS are identified: one type involves diarrhea (D+) and the other, D- or atypical, does not. D+ HUS is the classic form, accounting for 95% of cases of hemolytic uremic syndrome in children. This form of hemolytic uremic syndrome occurs predominantly in children and is preceded by a prodrome of diarrhea, most commonly caused by an infection by shiga-toxin producing Escherichia coli. Specifically, E coli serotype O157:H7 has been associated with more than 80% of infections leading to hemolytic uremic syndrome. The shiga-like toxin affects endothelial cells and initiates intravascular thrombogenesis. After entering the circulation via the gastrointestinal mucosa, the toxin preferentially localizes to the kidneys, inhibiting protein synthesis and eventually leading to cell necrosis or apoptosis. Endothelial cell damage subsequently potentiates renal microvascular thrombosis by promoting activation of the blood coagulation cascade. Platelet aggregation results in a consumptive thrombocytopenia. Microangiopathic hemolytic anemia results from mechanical damage to red blood cells circulating through partially occluded microcirculation.
In contrast to hemolytic uremic syndrome, thrombotic thrombocytopenic purpura (TTP) presents with the classic pentad of microangiopathic hemolytic anemia, thrombocytopenia, prominent neurologic symptoms, fever and a milder form of renal failure. The pathophysiology of thrombotic thrombocytopenic purpura is different. As opposed to endothelial cell injury in HUS, thrombotic thrombocytopenic purpura is caused by a deficiency in the metalloprotease ADAMTS13, which is involved in the regulation of von Willebrand factor. A lack of this protein results in spontaneous platelet aggregation and the widespread deposition of platelet-rich thrombi in the microvasculature of various organs, most notably the heart, brain, and kidneys.
HUS is predominantly a disease of children younger than 5 years. TTP is predominantly a disease of adults. Renal manifestations are more prominent than neurologic ones in HUS, whereas neurologic findings are more prominent than renal findings in TTP. Fever precedes the onset of TTP more commonly than it precedes HUS. Dysentery is an important hallmark of HUS.
Platelet counts tend to be somewhat higher in HUS than in TTP because they are not consumed quickly by clot formation. However, in some cases of HUS, thrombocytopenia may be severe.
Chapter 70. Thrombotic Thrombocytopenic Purpura, Hemolytic Uremia Syndromes, and the Approach to Thrombotic Microangiopathies
o Principles of Critical Care, 3e
Chapter 286. Vascular Injury to the Kidney > Hemolytic-Uremic Syndrome (HUS)/Thrombotic Thrombocytopenic Purpura (TTP)
o Harrison's Online
Chapter 34. Thrombotic Microangiopathies > Symptoms and Signs
o CURRENT Diagnosis & Treatment: Nephrology & Hypertension