Interní Med. 2014; 16(1): 22-25

Atypical haemolytic-uraemic syndrome and new treatment options

prof.MUDr.Romana Ryšavá, CSc.

Klinika nefrologie 1. LF UK a VFN, Praha

Haemolytic-uraemic syndrome (HUS) is a relatively rare cause of thrombotic microangiopathy (TMA). It is typically manifested by haemolytic

anaemia with a negative Coombs test, the presence of schistocytes, thrombocytopenia, and multiple organ failure, particularly renal failure.

Damage to other organs, particularly the myocardium and organs of the alimentary tract, is frequent, as is neurological symptomatology.

Typical forms of HUS result from endothelial damage induced by Shiga toxin, produced by some E. coli serotypes in intestinal infections.

Approximately 10% of HUS result from a different cause. Secondary forms of HUS can be induced by drugs, infections, or be associated with

pregnancy or the presence of a malignancy. Atypical forms of HUS (aHUS) are caused by altered function of some complement components

when there is permanent activation of alternative complement pathway. These deviations may be of genetic origin when, due to a mutation in

various complement-regulating genes, there is impaired function of these factors or antibodies against complement components are formed.

Most commonly, mutations in the gene for complement factor H and I are encountered that are associated with a severe course of aHUS. By

contrast, mutations affecting genes for some endothelial cell−surface proteins, such as membrane protein cofactor or thrombomodulin, tend

to be least serious in terms of prognosis. The administration of frozen plasma or plasmapheresis has been well established and is aimed at

supplementing a missing factor or filtering out antibodies acting against it, which are circulating in the plasma. However, this treatment can be

associated with a number of complications and is not a causal therapy in itself. Eculizumab, a novel agent that has also been registered in the

Czech Republic, holds great promise for patients with aHUS. It is a humanized monoclonal antibody against complement factor C5 that rapidly

restores the laboratory findings to normal and improves renal function. The prognosis for patients with aHUS has improved significantly owing

to eculizumab; however, aHUS continues to be a very serious disease with a high risk of irreversible kidney damage and a high mortality rate.

Keywords: thrombotic microangiopathy, atypical haemolytic-uraemic syndrome, complement factors, renal failure

Published: March 1, 2014  Show citation