For Healthcare Professionals

Diagnosis of aHUS

Thrombotic microangiopathies (TMA) often share the same clinical presentations but differ in the underlying cause1-3

Factors such as a lack of identified genetic mutation or diagnosis of a coexisting disease or condition should NOT rule out a diagnosis of aHUS4

Underlying Cause

OVERLAP IN CLINICAL PRESENTATION
  • Neurological dysfunction was thought to indicate thrombotic thrombocytopenic purpura (TTP); however, 48% of atypical hemolytic uremic syndrome (aHUS) cases report having neurological dysfunction10
  • Diarrhea was thought to indicate STEC-HUS; however, up to 30% of aHUS cases present with diarrhea11
  • In one study, approximately 25% of patients diagnosed with STEC-HUS had an underlying complement mutation and should be evaluated for aHUS8


Genetic mutation identification is not required for aHUS diagnosis or management decisions4

High morbidity and mortality regardless of mutation identification12
% of patients

*Mutations consisted of membrane cofactor protein (MCP), complement factor H (CFH), and factor I (IF).12

  • Over 120 mutations have been linked with aHUS—and investigators continue to identify more4

Patients can experience aHUS as a single disease or with other coexisting diseases or conditions4

Common coexisting diseases and conditions aHUS patients with coexisting diseases or conditions, n (%)
Malignant hypertension 14 (30%)
TMA with history of transplant* 11 (23%)
TMA associated with pregnancy 10 (21%)
Glomerulopathy 8 (17%)
Systemic disease
  • Scleroderma
  • Systemic lupus erythematosus (SLE)
3 (6%)
Malignancy 1 (2%)
TOTAL 47 (100%)

* Primary cause of nephropathy unknown in 6/11 patients (3 w/mutations), 2 IgA nephropathy, 1 DM nephropathy, 1 membranoproliferative glomerulonephritis (MPGN), 1 reflux nephropathy.4 †Glomerulopathy: MPGN, nephrotic syndrome, mesangioproliferative glomerulonephritis, membranous glomerulonephritis.4 ‡Malignancy and chemotherapy.4


Diagnosis of a coexisting disease or condition should NOT rule out a diagnosis of aHUS4

1. Sadler JE, Moake JL, Miyata T, George JN. Hematology Am Soc Hematol Educ Program. 2004:407-423. 2. Zheng XL. Blood. 2010;115:1475-1476. 3. Moake JL. N Engl J Med. 2002;347:589-600. 4. Noris M, Caprioli J, Bresin E, et al. Clin J Am Soc Nephrol. 2010;5:1844-1859. 5. Tsai H-M. J Am Soc Nephrol. 2003;14:1072-1081. 6. Hirt-Minkowski P, Dickenmann M, Schifferli JA. Nephron Clin Pract. 2010;114:c219-c235. 7. Loirat C, Noris M, Fremeaux-Bacchi V. Pediatr Nephrol. 2008;23:1957-1972. 8. Bitzan M, Schaefer F, Reymond D. Semin Thromb Hemost. 2010;36:594-610. 9. Mayer SA, Aledort LM. Mt Sinai J Med. 2005;72:166-175. 10. Neuhaus TJ, Calonder S, Leumann EP. Arch Dis Child. 1997;76:518-521. 11. Zuber J, Le Quintrec M, Sberro-Soussan R, Loirat C, Frémeaux-Bacchi V, Legendre C. Nat Rev Nephrol. 2010; doi:10.1038/nrneph.2010.155. 12. Caprioli J, Noris M, Brioschi S, et al; International Registry of Recurrent and Familial HUS/TTP. Blood. 2006;108:1267-1279.

Differential diagnosis for TMAs: aHUS, TTP, and STEC-HUS

High clinical suspicion of aHUS is required in all patients presenting with TMA7

aHUS diagnosis pathway
+View Diagram