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

• Published in: Nephrology (Carlton, Vic.) Vol. 22; no. 7; pp. 555 - 561
• Main Authors: Åkesson, Alexander, Blom, Anna M, Klintman, Jenny, Zetterberg, Eva
• Format: Journal Article
• Language: English
• Published: Australia Wiley Subscription Services, Inc 01.07.2017
• Subjects: acute kidney injury; ADAM protein; ADAMTS13 Protein - blood; Adolescent; Adult; Aged; Aged, 80 and over; Alternative pathway; anaemia, haemolytic; Anemia; Antibodies; Atypical Hemolytic Uremic Syndrome - blood; Atypical Hemolytic Uremic Syndrome - diagnosis; Atypical Hemolytic Uremic Syndrome - epidemiology; Atypical Hemolytic Uremic Syndrome - immunology; Autoantibodies - blood; Biomarkers - blood; Child; Child, Preschool; Clinical Medicine; Coagulation; Complement Activation; Complement component C3; Complement component C4; Complement factor H; complement pathway, alternative; Complement system; Complement System Proteins - analysis; Female; Hemolytic anemia; Humans; Immunoglobulins; Infant; Infant, Newborn; Kidneys; Klinisk medicin; Male; Medical and Health Sciences; Medicin och hälsovetenskap; microcirculation; Middle Aged; Morbidity; Predictive Value of Tests; Prevalence; Purpura; Rare diseases; Referral and Consultation; Renal failure; Reproducibility of Results; Retrospective Studies; Reviews; Risk Factors; Sweden - epidemiology; thrombocytopaenia; Thrombocytopenia; Thrombocytopenic purpura; Thrombospondin; Thrombotic thrombocytopenic purpura; Young Adult; Sweden; acute kidney injury; thrombocytopaenia; anaemia, haemolytic; microcirculation; complement pathway, alternative
• ISSN: 1320-5358; 1440-1797; 1440-1797
• DOI: 10.1111/nep.12818

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. Summary at a Glance Complement‐mediated atypical haemolytic uraemic syndrome (aHUS) is a rare disease and might be under diagnosed due to manifestations overlap with thrombotic thrombocytopenic purpura. Examination of serum C3 and C4, complement factor H (CFH)‐specific antibodies and associated deficiency in CFH‐related proteins may facilitate the diagnosis of aHUS.