Indications of underdiagnosis of atypical haemolytic uraemic syndrome in a cohort referred to the Coagulation Unit in Malmo, Sweden, for analysis of ADAMTS13 2007-2012.

AIM: Complement-mediated atypical haemolytic uraemic syndrome (aHUS) is a rare disease with high mortality and morbidity if left untreated. The diagnostic work-up is complicated and the manifestations overlap with other conditions. Therefore, we hypothesize that complement-mediated aHUS is an under diagnosed disease.

METHODS: A cohort of 768 referrals referred to the Coagulation Unit in Malmo, Sweden, for analysis of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13), 2007-2012, were retrospectively reviewed. Subjects were included on the basis of presence of haemolytic anaemia, thrombocytopaenia, renal failure and ADAMTS13 > 0.05. They were excluded if tested positive for Escherichia coli. Included subjects were categorized as "suspected HUS" with and without potential causes and triggers. Levels of C3 and C4, presence of complement factor H (CFH)-specific antibodies and associated deficiency in complement factor H related protein 1 (CFHR1) were analyzed on frozen samples.

RESULTS: In total, 134/316 (42%) unique subjects fulfilled inclusion criteria; 103 were categorized as "suspected HUS associated with potential causes/triggers" and 31 subjects categorized as "suspected HUS" without such association. One case of complement-mediated aHUS had been confirmed during the treatment period. Laboratory analyses performed showed that in total 78 cases had findings consistent with complement-mediated aHUS: 24 cases indicated presence of CFH-specific antibodies whereof five cases had isolated low C3 titres and six cases had deficiency of CFHR1. Additionally 54 cases indicated isolated alternative pathway consumption.

CONCLUSION: The results suggest that the presence of complement-mediated aHUS was under diagnosed in this cohort calling for improvement of diagnostic availability.