HUS is characterised by microangiopathic haemolytic anemia, thrombocytopenia and acute renal failure. It is caused by thrombi of platelets forming on the microcirculation of the kidney. HUS can be classified as associated with diarrhoea (D+HUS) and non-diarrhoea associated (D-HUS).

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Here are several links for patient information on aHUS:

The D+HUS form accounts for most childhood cases of HUS and is caused by infections with some strains of E.coli. This form of the disease is self-limiting and non-recurring and the mortality among childhood cases in the UK is now less than 3% with supportive management only (Taylor, 2001).

Alternatively the D-HUS form (also known as atypical HUS) is rare, tends to relapse and has a worse prognosis. D-HUS is associated with genetic factors that can be inherited or transmitted either dominantly or recessively. There is clear evidence of a subgroup of this form associated with genetic abnormalities within the complement regulator factor H (FH). Mutations within the FH gene have been identified in atypical HUS patients and seem to cluster in the C-terminal domains of the FH gene. Mutations have also been discovered in the Factor I (FI) and Membrane Cofactor Protein (MCP) genes of HUS patients.

HUS is a subset of a variety of diseases associated with endothelial activation, which in normal individuals is resolved spontaneously. However in disorders such as HUS, impaired regulation of the complement system, in particular the alternative pathway results in maintenance of a procoagulant-activated state (as opposed to the inactive anticoagulant phenotype ) predisposing to a thrombotic microangiopathy.

Plasma levels of FH, MCP or FI determine the outcome of local tissue damage.

1. During infection and/or inflammation the deposition of the complement component C3b on the endothelial cell lining is induced. This also results in activation of the alternative pathway cascade and the release of chomotactic anaphylatoxins C3a and C5a.
2. C3a and C5a attract effector cells, which upon activation release inflammatory mediators, TNF-α and interleukin-8 (IL-8). These mediators cause the retraction of the endothelial lining cells and exposes the subcellular extracellular matrix.
3. The exposure of the extracellular matrix allows more deposition of C3b and activation of the alternative pathway. Under normal conditions the C3bBb complex is rapidly inactivated by complement regulatory proteins such as Cr1 (complement receptor 1), Factor H, MCP (also known as CD46) and DAF (decay-accelerating factor) which bind to the Bb of the complex and displace it. The complex between the control proteins and C3b allows C3b to be cleaved by Factor I to yield inactivated iC3b. In atypical HUS cases with FH mutations, either the sub-optimal activity or the reduced concentration of FH is unanble to restrict the complement activation of the alternative pathway, and further damage the tissue occurs. Similarly, with aHUS cases involving MCP and FI mutations the alternative complement activation can not be controlled and further tissue damage occurs.

The reduced activity of FH, MCP or FI might enhance the pathological reactions and allow the generation of microthrombi of platelets which are attracted to the site of injury. The uncontrolled activation of the complement alternative pathway results in the excessive consumption of C3, as monitored by low levels of C3b.

For a list of HUS-related links click here.