Study of Hemostasis in Patients With Congenital Disorder of Glycosylation

Completed

• Conditions: Congenital Disorders of Glycosylation
• Interventions: Biological: Coagulation assay; Other: Clinical data collection

• Registration Number: NCT03560570
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

The purpose of this study is to investigate the coagulation balance in a cohort of congenital disorder of glycosylation (CDG) patients using conventional tests combined with an integrated approach of their coagulation disorders in using TGA in the absence or presence of sTM. Thus, investigators aimed to define if the hemostatic balance in CDG patients, is preserved despite of combined deficiencies in both procoagulant and anticoagulant factors.

Detailed Description

In CDG, coagulation abnormalities, affecting both pro and anticoagulant factors, could account for onset of acute microvascular events in these patients. In line with this hypothesis, a previous study reported a correlation between low activity of anticoagulant factors and thrombosis, although stroke-like episodes, the most frequent event, were not analyzed in this study. Moreover, the hemostatic balance is usually investigated by global coagulation tests such as the prothrombin time (PT) and the activated partial thromboplastin (aPTT). However, these tests have serious limitations. First, they explore only 5 % of the whole generated thrombin, enough to clot the plasma. In addition, global tests are insensitive to the coagulation inhibitors, especially the PC system which cannot be mobilized in the absence of thrombomodulin (TM). The thrombin generation assay (TGA), is also a global coagulation assay, but it allows exploration of the whole thrombin formation process from its generation to its inhibition. Moreover, combining different analytical conditions, all the anticoagulant systems could be investigated, including antithrombin in basal conditions and the PC system in the presence of soluble TM (sTM)

Study Timeline

• Study Start: 2014-01-01
• Primary Completion: 2017-01-31
• Study Completion: 2017-12-31
• Study First Submitted: 2018-04-06
• Status Verified: 2018-06
• Study First Submitted QC: 2018-06-06
• Study First Posted: 2018-06-18
• Last Update Submitted: 2018-08-30
• Last Update Posted: 2018-08-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 57

Inclusion Criteria

-Clinical diagnosis of Congenital Disorder of Glycosylation (CDG)

Exclusion Criteria

• no exclusion criteria

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Control	Clinical data collection	Healthy subject
Event group	Coagulation assay	CDG with antecedent of stroke-like, thrombosis or haemorrhages
Non event group	Clinical data collection	CDG without antecedent of stroke-like, thrombosis or haemorrhages
Event group	Clinical data collection	CDG with antecedent of stroke-like, thrombosis or haemorrhages
Non event group	Coagulation assay	CDG without antecedent of stroke-like, thrombosis or haemorrhages
Control	Coagulation assay	Healthy subject

Primary Outcome Measures

Name	Time	Method
Evaluation of haemostatic balance using thrombin generation assay	Up to 1 year	The assessment of thrombin generation in presence or not of soluble thrombomodulin allows to determine a ratio "R" (without units) calculated as follow : ETP (endogenous thrombin potential) with soluble thrombomodulin (nM/min)/basal ETP (nM/min). This ratio reflects the hypocoagulant or hypercoagulant profile.

Trial Locations

Locations (1)

Hôpital Necker Enfants malades; 🇫🇷 Paris, France