Blood Res.  2019 Sep;54(3):218-228. 10.5045/br.2019.54.3.218.

Prognostic utility of ADAMTS13 activity for the atypical hemolytic uremic syndrome (aHUS) and comparison of complement serology between aHUS and thrombotic thrombocytopenic purpura

• Oh J
• Oh D
• Lee SJ
• Kim JO
• Kim NK
• Chong SY
• Huh JY
• Baker RI
• on behalf of the Korean TTP Registry Investigators

• KMID: 2459388
• DOI: http://doi.org/10.5045/br.2019.54.3.218

Abstract

BACKGROUND
Atypical hemolytic uremic syndrome (aHUS) involves dysregulation of the complement system, but whether this also occurs in thrombotic thrombocytopenic purpura (TTP) remains unclear. Although these conditions are difficult to differentiate clinically, TTP can be distinguished by low (<10%) ADAMTS13 activity. The aim was to identify the differences in complement activation products between TTP and aHUS and investigate ADAMTS13 activity as a prognostic factor in aHUS.
METHODS
We analyzed patients with thrombotic microangiopathy diagnosed as TTP (N=48) or aHUS (N=50), selected from a Korean registry (N=551). Complement activation products in the plasma samples collected from the patients prior to treatment and in 40 healthy controls were measured by ELISA.
RESULTS
The levels of generalized (C3a), alternate (factor Bb), and terminal (C5a and C5b-9) markers were significantly higher (all P<0.01) in the patients than in the healthy controls. Only the factor Bb levels significantly differed (P=0.008) between the two disease groups. In aHUS patients, high normal ADAMTS13 activity (≥77%) was associated with improved treatment response (OR, 6.769; 95% CI, 1.605-28.542; P=0.005), remission (OR, 6.000; 95% CI, 1.693-21.262; P=0.004), exacerbation (OR, 0.242; 95% CI, 0.064-0.916; P=0.031), and disease-associated mortality rates (OR, 0.155; 95% CI, 0.029-0.813; P=0.017).
CONCLUSION
These data suggest that complement biomarkers, except factor Bb, are similarly activated in TTP and aHUS patients, and ADAMTS13 activity can predict the treatment response and outcome in aHUS patients.

Keyword

Thrombotic thrombocytopenic purpura; Atypical hemolytic uremic syndrome; Complement; High ADAMTS13 activity; Treatment outcomes

MeSH Terms

Atypical Hemolytic Uremic Syndrome*
Biomarkers
Complement Activation
Complement System Proteins*
Enzyme-Linked Immunosorbent Assay
Humans
Mortality
Plasma
Purpura, Thrombotic Thrombocytopenic*
Thrombotic Microangiopathies
Biomarkers
Complement System Proteins

Figure

• 

  Fig. 1 CONSORT diagram of the patients included in analysis. Abbreviations: ADAMTS13, a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13; aHUS, atypical hemolytic uremic syndrome; PEX, plasma exchange; STEC-HUS, Shiga-like toxin-producing E. coli hemolytic uremic syndrome; TMA, thrombotic microangiopathy; TTP, thrombotic thrombocytopenic purpura.

• 

  Fig. 2 Summary box plots for the levels of complement activation products in healthy controls (N=40) and in patients with TTP (N=48), aHUS (N=41), or GC-aHUS (N=9) measured with ELISA. (A) C3a [ng/mL: control, 139.8 (31–473.8); TTP, 195.9 (62–404.4); aHUS, 221.3 (80.7–791.8); GC-aHUS, 266.4 (115.7–483.8); P=0.005]. (B) Factor Bb [ng/mL: control, 499 (110–2,072); TTP, 760 (1–16,557); aHUS, 1,200 (270–11,797); GC-aHUS, 1,380 (52–2490); P<0.001]. (C) C5a [ng/mL: control, 11.4 (2.7–69.1); TTP, 20.1 (2.7–68.6); aHUS, 19.9 (5.4–66.1); GC-aHUS, 22.7 (8.7 –37.4); P=0.001]. (D) C5b-9 [ng/mL: control, 155 (58–459); TTP, 292 (85–939); aHUS, 317 (82–1,415); GC-aHUS, 340 (183–515); P<0.001]. All the data represent the medians (ranges). The P-values were calculated using the Kruskal-Wallis test. Abbreviations: aHUS, atypical hemolytic uremic syndrome; GC-aHUS, genetically confirmed aHUS; NS, not significant; TTP, thrombotic thrombocytopenic purpura.

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