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

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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.

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Conflict of interest

AG, PLA, SCN, IM, BR, JM, SNK, CEE, and EE all declare that they have no conflicts of interest.

Ethics statement

The study was performed in a manner to conform with the Helsinki Declaration of 1975, as revised in 2000 and 2008 concerning Human and Animal Rights, and the authors followed the policy concerning informed consent as shown on Springer.com.

Financial support

The authors are grateful for funds received from the Fluid Research Fund at Christian Medical College, Vellore, India, for this study.

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Authors and Affiliations

  1. Department of Hepatology, Christian Medical College, Vellore, 632 004, India

    Ashish Goel, P. L. Alagammai, C. E. Eapen & Elwyn Elias

  2. Department of Transfusion Medicine and Immunohematology, Christian Medical College, Vellore, 632 004, India

    Sukesh C. Nair

  3. Haemostasis Research Unit, Haematology Department, University College London, London, UK

    Ian Mackie

  4. Department of Pathology, Christian Medical College, Vellore, 632 004, India

    Banumathi Ramakrishna

  5. Department of Community Medicine, Christian Medical College, Vellore, 632 004, India

    Jayaprakash Muliyil

  6. Department of Radiodiagnosis, Christian Medical College, Vellore, 632 004, India

    Shyamkumar N. Keshava

  7. Liver Unit, University Hospital Birmingham, Birmingham, UK

    Elwyn Elias

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  1. Ashish Goel
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  2. P. L. Alagammai
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  8. C. E. Eapen
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Corresponding author

Correspondence to C. E. Eapen.

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Goel, A., Alagammai, P.L., Nair, S.C. et al. ADAMTS13 deficiency, despite well-compensated liver functions in patients with noncirrhotic portal hypertension. Indian J Gastroenterol 33, 355–363 (2014). https://doi.org/10.1007/s12664-014-0460-4

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  • DOI: https://doi.org/10.1007/s12664-014-0460-4

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