ADAMTS13 deficiency, despite well-compensated liver functions in patients with noncirrhotic portal hypertension

Indian J Gastroenterol. 2014 Jul;33(4):355-63. doi: 10.1007/s12664-014-0460-4. Epub 2014 Apr 24.

Abstract

Background: We have reported A disintegrin and metalloprotease with thrombospondin type 1 motif, member 13 (ADAMTS13) deficiency in noncirrhotic intrahepatic portal hypertension (NCIPH) patients of European origin with preserved liver function. We aimed to study ADAMTS13-von Willebrand factor (vWF) imbalance in Indian patients with NCIPH.

Methods: Twenty-nine cases with NCIPH [22 males; 29 years (13-58); Child's A, 23; B, 6], 22 disease controls with cryptogenic chronic liver disease [15 males; 46 years (18-74); Child's A, 9; B, 9; C, 4] and 17 healthy controls [14 males; 32 years (27-45)] were enrolled in the study. We measured ADAMTS13 antigen and activity (by collagen binding assay (CBA) and by fluorescence resonance energy transfer [FRET] assay), and vWF antigen levels in plasma of study patients.

Results: ADAMTS13 activity by CBA in NCIPH patients (32 %, 5 % to 100 %; median, range; p-value <0.001) and disease controls (36 %, 5 % to 144 %; p = 0.001) was significantly lower than in healthy controls (87 %; 60 % to 148 %). ADAMTS13 antigen and activity by FRET assay were also lower in cases and disease controls. ADAMTS13 activity (by CBA) to antigen ratio was lower in NCIPH and disease controls than in healthy controls. Of 29 NCIPH patients, 3 (all in Child's A) had severe ADAMTS13 deficiency (<10 % ADAMTS13 activity), and 8 (Child's A, 7; B, 1) had moderate ADAMTS13 deficiency (10 % to 25 % activity). Conversely, vWF antigen and vWF:ADAMTS13 ratio were higher in patients with NCIPH and in disease controls than in healthy controls.

Conclusions: This study validates the finding of ADAMTS13 deficiency in NCIPH despite preserved liver functions in an Indian population suggesting its involvement in pathogenesis of NCIPH.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM Proteins / analysis
  • ADAM Proteins / blood
  • ADAM Proteins / deficiency*
  • ADAMTS13 Protein
  • Adolescent
  • Adult
  • Aged
  • Biomarkers / analysis
  • Biomarkers / blood
  • Case-Control Studies
  • Female
  • Humans
  • Hypertension, Portal / diagnosis*
  • Hypertension, Portal / genetics*
  • Hypertension, Portal / physiopathology
  • Liver / physiopathology*
  • Male
  • Middle Aged
  • Severity of Illness Index
  • Young Adult
  • von Willebrand Factor / analysis

Substances

  • Biomarkers
  • von Willebrand Factor
  • ADAM Proteins
  • ADAMTS13 Protein
  • ADAMTS13 protein, human