Table 2.
Thrombotic microangiopathies.
| TTP | ST-HUS | aHUS | |
|---|---|---|---|
| Epidemiology | 4–11 cases per million | 6.1 cases per 100 000 children under five Overall 1–2 cases per 100 000 |
2 cases per million [62] |
| Age | Predominantly adults; rarely children | Predominantly children; less commonly adults | Predominantly children; 30% middle-aged; less common adults |
| Hereditary or acquired | Both | Acquired | Both |
| Pathogenesis | Severe deficiency of ADAMTS13 resulting in UL-vWF multimers leading to microvascular occlusive thrombi formation | Shiga toxin mediated injury to renal endothelial cells; Shiga toxin binds to Gb3 on the target cells and stimulates them leading to increased secretion of IL-1, IL-8, TNF-α, UL-vWF | Selective activation of alternative complement pathway due to congenital or rarely acquired defects in CFH, CHI, MCP, TM, and C3; result is complement mediated endothelial and platelet activation with thrombus formation |
| Potential triggers | Sporadic, surgery, acute pancreatitis, sepsis, pregnancy | Eschericia coli serotypes, Shigella dysentreae | Sporadic, infection, drugs, pregnancy |
| Clinical presentation | 50% patients with neurological problems, fever is uncommon, acute renal failure rare | Prodrome of abdominal pain and bloody diarrhea, acute renal failure | Acute kidney injury, hypertension, can have neurological symptoms |
| Laboratory features | MAHA, thrombocytopenia, < 5% ADAMTS13 activity (48–90% of patients) | MAHA, thrombocytopenia, marked derangements of renal function, Shiga toxin identification in stool | MAHA, thrombocytopenia, Decreased C3 but normal C4 level, specific hereditary defects |
| Acuity and degree of thrombocytopenia | Rapid onset of severe thrombocytopenia, direct correlation of degree of ADAMTS13 deficiency and thrombocytopenia | Generally slower than TTP, moderate to severe thrombocytopenia | Moderate to severe thrombocytopenia, Less commonly insidious onset with fluctuating thrombocytopenia for weeks to months |
| Treatment | Plasma exchange therapy, steroids, immunosuppressive therapy | Supportive, dialysis | Eculizumab, immunosuppressive therapy |
| Prognosis | Relapse is rare except when there is severe deficiency of ADAMTS13 (50%) | Good if survive the acute episode | Response to therapy, risk of relapse and progression to ESRD depend on specific mutations |
Abbreviations: TTP (thrombotic thrombocytopenic purpura), ST-HUS (Shiga toxin-mediated hemolytic uremic syndrome), aHUS (atypical hemolytic uremic syndrome), UL-vWF (ultra large von Willibrand Factor), IL (interleukin), TNF (tumor necrosis factor), CFH (complement factor H), CHI (complement factor I), MCP (membrane cofactor protein), TM (thrombomodulin), MAHA (microangiopathic hemolytic anemia), ESRD (end stage renal disease).