Diagnosis of aHUS

A clinical diagnosis of aHUS in a patient with signs of TMA requires exclusion of other underlying causes1,2

Severe ADAMTS13 deficiency (TTP)

The underlying cause in TTP is a severe deficiency in ADAMTS13 activity (≤5%)1,2

Insufficient ADAMTS13 activity (≤5%) leaves von Willebrand (vWF) factor uncleaved, causing excessive platelet aggregation1,2

Genetic, complement-mediated TMA (aHUS)

aHUS is caused by chronic, uncontrolled complement activation6-8

Genetic defects in natural inhibitors lead to chronic, uncontrolled activation of the complement system, causing continuous endothelial cell damage and platelet aggregation6-8

Early identification of aHUS allows for rapid and improved disease management1,2

A patient with a TMA presenting with SCr >1.7 mg/dL OR platelet count >30,000/mm3 is 21.8 times less likely to have severe ADAMTS13 deficiency (TTP) than those who meet neither criteria9

  • In a national registry of 214 TMA patients, baseline SCr and platelet count were identified as independently predictive values of ADAMTS13 deficiency9.
  • Multiple studies on a total of 806 patients with TMA have demonstrated that baseline values of SCr and platelets at clinical presentation can rapidly and efficiently distinguish between sufficient and severely deficient ADAMTS13 activity9-14

When you suspect TMA:

  • Rapidly test ADAMTS13 activity PRIOR TO intervention to ensure accurate test results1,2
  • Confirm non-immune hemolysis with a negative Coombs test2
  • Get medical history including previous TMA and unexplained renal disease2
  • Obtain family history of TMA or renal impairment2,7

Complement-amplifying conditions place patients with aHUS at high risk for TMA manifestations1,15,16

  • TMA is very rare among the general population17-19
  • A patient who presents with TMA and an identifiable complement-amplifying condition may have a defect in complement regulation15,16,20,21

70% of patients with aHUS presented their first clinical manifestations while experiencing a complement-amplifying condition (191/273)3

Complement amplification occurs frequently and is not always apparent20, 22-24

If the signs and symptoms of TMA do not rapidly resolve in response to complement-amplifying condition management, continue to evaluate following the differential diagnostic pathway of TMAs1

1. Laurence J, et al. Clin Adv Hematol Oncol. 2016;14 Suppl 11(11):2-15. 2. Azoulay E, et al. Chest. 2017;152(2):424-434. 3. Noris M, et al. Clin J Am Soc Nephrol. 2010;5(10):1844-1859. 4. Fremeaux-Bacchi V, et al. Clin J Am Soc Nephrol. 2013;8(4):554-562. 5. Bresin E, et al. J Am Soc Nephrol. 2013;24(3):475-486. 6. Goodship THJ, et al. Kidney Int. 2017;91(3):539-551. 7. Kato H, et al. Pediatr Int. 2016;58(7):549-555. 8. Loirat C, et al. Pediatr Nephrol. 2016;31(1):15-39. 9. Coppo P, et al. PLOS ONE. 2010;5(4):e10208. 10. Bentley MJ, et al. Transfusion. 2010;50(8):1654-1664. 11. Kremer Hovinga JA, et al. Blood. 2010;115(8):1500-1511. 12. George JN. Blood. 2010;116(20):4060-4069. 13. Cataland SR, et al. Br J Haematol. 2012;157(4):501-503. 14. Shah N, Rutherford C, et al. Br J Haematol. 2013;163(4):514-519. 15. Campistol JM, et al. Nefrologia. 2015;35(5):421-447. 16. Noris M, et al. Nat Rev Nephrol. 2012;8(11):622-633. 17. Chen MH, et al. Rheumatology (Oxford). 2011;50(4):768-775. 18. Ardalan MR. Saudi J Kidney Dis Transplant. 2006;17(2):235-244. 19. lzzedine H, et al. Nephrol Dial Transplant. 2006;21(11):3038-3045. 20. Liszewski MK, Atkinson JP. Hematology Am Soc Hematol Educ Program. 2011 ;2011 :9-14. 21. Fang CJ, et al. Br J Haematol. 2008;143(3):336-348. 22. Hirt-Minkowski P, et al. Nephron Clin Pract. 2010;114(4):c219-c235. 23. Ricklin D, et al. Nat lmmunol. 2010;11(9):785-797. 24. Wagner E, Frank MM. Nat Rev Drug Discov. 2010;9(1):43-56.