Clinical trial NCT04267406: ADAMTS-13 and Von Willebrand Factor Levels and Activities in Children With Cirrhosis and/or Portal Hypertension
Official title: Investigation of Changes in ADAMTS-13 and Von Willebrand Factor Levels and Activities in Children With Cirrhosis and/or Portal Hypertension
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Coagulation Disorder
Cirrhosis, Liver
Keywords: Von willebrand factor
ADAMTS-13
Children
Cirrhosis
Portal hypertension
Lead sponsor: Ataturk University
Sponsor class: OTHER
Collaborators: name: The Scientific and Technological Research Council of Turkey
First posted: 2020-02-12
Enrollment: 64
Sex: ALL
Minimum age (years): 3
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with cirrhosis and/or portal hypertension who were treated in Pediatric Gastroenterology Department of Ataturk University Hospital included to the study.

Brief summary: Hemostasis-related disorders are common in cirrhosis and portal hypertension. However, it is not known whether the net effect of changes in hemostasis in the sense of predisposition to hemorrhagic or thrombotic state. It is suggested that increasing the concentration and activities of Von Willebrand factor (vWF) and decline ADAMTS-13 (A Disintegrin and Metalloproteinase with Trombospondin type 1 motif, member 13) may cause thrombophilic changes in cirrhosis and portal hypertension. The aim of this study was to investigate the changes in ADAMTS-13 (A disintegrin and metalloproteinase with thrombospondin motifs 13) and von willebrand factor (vWF) levels and activities in patients with cirrhosis and portal hypertension.

Detailed description: Patients of 3 months to 18 years of age, followed-up or newly diagnosed in pediatric gastroenterology unit, who had cirrhosis or non cirrhotic portal hypertension included to the study. Written informed consent obtained from the parents and/or patients. The subjects was grouped in three. The first group consisted of patients with cirrhosis (with or without portal hypertension). The second group consisted of patients with non-cirrhotic portal hypertension (developed due thrombosis of portal vein). The last group consisted of healthy volunteers.

2 ml of EDTA blood was taken from the patients and healty volunters. Samples will be tested for vWF and ADAMTS-13 levels and activities at the end of the study.

The clinical scoring methods, PELD, MELD and Child Pugh scores, treatments received by patients, data from endoscopic, radiological screening, and blood analysis of patients were recorded.

Eligibility criteria: Inclusion Criteria:

• Patients with cirrhosis or portal hypertension aged 3 months to 18 years.

Exclusion Criteria:

* Being treated with fresh frozen plasma in the recent month.
* Patients previously diagnosed with bleeding diathesis.
* The patients who consumed vitamin K in the recent three weeks.
* Patients previously diagnosed with another chronic disease (such as renal failure, heart failure etc).
* Patients who suffer from acute or chronic infectious diseases.

Primary outcomes:
measure: Measuring ADAMTS-13 enzyme levels in collected EDTA bloods.
timeFrame: First day
measure: Measuring ADAMTS-13 activities in collected EDTA bloods.
timeFrame: First day
measure: Measuring vWF antigen levels in collected EDTA bloods.
timeFrame: First day
measure: Measuring vWF activities in collected EDTA bloods.
timeFrame: First day
Secondary outcomes:
Other outcomes:
Locations:
city: Erzurum
country: Turkey
facility: Ataturk University Hospital
Study officials:
affiliation: Ataturk University School of Medicine
name: Ali Islek, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lisman T, Caldwell SH, Burroughs AK, Northup PG, Senzolo M, Stravitz RT, Tripodi A, Trotter JF, Valla DC, Porte RJ; Coagulation in Liver Disease Study Group. Hemostasis and thrombosis in patients with liver disease: the ups and downs. J Hepatol. 2010 Aug;53(2):362-71. doi: 10.1016/j.jhep.2010.01.042. Epub 2010 May 12.
citation: Plaimauer B, Zimmermann K, Volkel D, Antoine G, Kerschbaumer R, Jenab P, Furlan M, Gerritsen H, Lammle B, Schwarz HP, Scheiflinger F. Cloning, expression, and functional characterization of the von Willebrand factor-cleaving protease (ADAMTS13). Blood. 2002 Nov 15;100(10):3626-32. doi: 10.1182/blood-2002-05-1397. Epub 2002 Jul 12.
citation: Turner NA, Nolasco L, Ruggeri ZM, Moake JL. Endothelial cell ADAMTS-13 and VWF: production, release, and VWF string cleavage. Blood. 2009 Dec 3;114(24):5102-11. doi: 10.1182/blood-2009-07-231597. Epub 2009 Oct 12.
citation: Goel A, Alagammai PL, Nair SC, Mackie I, Ramakrishna B, Muliyil J, Keshava SN, Eapen CE, Elias E. 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.
citation: Uemura M, Fujimura Y, Matsumoto M, Ishizashi H, Kato S, Matsuyama T, Isonishi A, Ishikawa M, Yagita M, Morioka C, Yoshiji H, Tsujimoto T, Kurumatani N, Fukui H. Comprehensive analysis of ADAMTS13 in patients with liver cirrhosis. Thromb Haemost. 2008 Jun;99(6):1019-29. doi: 10.1160/TH08-01-0006.
citation: Lisman T, Bongers TN, Adelmeijer J, Janssen HL, de Maat MP, de Groot PG, Leebeek FW. Elevated levels of von Willebrand Factor in cirrhosis support platelet adhesion despite reduced functional capacity. Hepatology. 2006 Jul;44(1):53-61. doi: 10.1002/hep.21231.