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Idiopathic Noncirrhotic Intrahepatic Portal Hypertension is Associated with Sustained ADAMTS13 Deficiency

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Abstract

Background

ADAMTS13 deficiency leading to excess ultralarge von Willebrand factor (VWF) multimers and platelet clumping is typically found in thrombotic thrombocytopenic purpura (a type of thrombotic microangiopathy). Idiopathic noncirrhotic intrahepatic portal hypertension (NCIPH) is a microangiopathy of portal venules associated with significant thrombocytopenia and predisposing gut disorders.

Aim

To determine whether the portal microangiopathy in NCIPH is associated with ADAMTS13 deficiency.

Methods

Plasma levels of ADAMTS13, anti-ADAMTS13 antibodies, and VWF were compared between cases (NCIPH patients) and controls (with chronic liver diseases of other etiology) matched for severity of liver dysfunction. Eighteen NCIPH patients [median (range) MELD score 12 (7–25)] and 25 controls [MELD score 11 (4–26)] were studied.

Results

ADAMTS13 activity was reduced in all 18 NCIPH patients and significantly lower than controls (median, IQR: 12.5%, 5–25% and 59.0%, 44–84%, respectively, P < 0.0001) [normal range for plasma ADAMTS13 activity (55–160%)]. ADAMTS13 activity was <5% in 5/18 NCIPH patients (28%) and 0/25 controls (P = 0.009). ADAMTS13 antigen levels were also decreased. Sustained low ADAMTS13 levels were seen in four NCIPH patients over 6 weeks to 11 months (highest ADAMTS13 level in each patient: <5%, 6%, 6%, and 25%), despite two patients having MELD score 12. Although nine cases had low titer anti-ADAMTS13 antibodies, there was no significant difference between cases and controls. Abnormally large VWF multimers were observed in 4/11 NCIPH patients (36%) and in 0/22 controls (P = 0.008).

Conclusions

Sustained deficiency of ADAMTS13 appears characteristic of NCIPH, irrespective of severity of liver disease.

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Abbreviations

NCIPH:

Idiopathic noncirrhotic intrahepatic portal hypertension

ADAMTS13:

A disintegrin and metalloprotease with a thrombospondin type 1 motif, member 13

VWF:

von Willebrand factor

MELD:

Model for end-stage liver disease

TTP:

Thrombotic thrombocytopenic purpura

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Author notes

  1. C. E. Eapen

    Present address: Department of Gastrointestinal Sciences, Christian Medical College, Vellore, Tamil Nadu, 632004, India

Authors and Affiliations

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

    Ian Mackie, Andrew S. Lawrie & Andrew Chitolie

  2. Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Edgbaston, Birmingham, B15 2QT, UK

    C. E. Eapen, Jean C. Shaw & Elwyn Elias

  3. Department of Histopathology, University of Birmingham, Birmingham, UK

    Desley Neil

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  1. Ian Mackie
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Correspondence to Elwyn Elias.

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Mackie, I., Eapen, C.E., Neil, D. et al. Idiopathic Noncirrhotic Intrahepatic Portal Hypertension is Associated with Sustained ADAMTS13 Deficiency. Dig Dis Sci 56, 2456–2465 (2011). https://doi.org/10.1007/s10620-011-1729-4

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