Study of Hemostasis in Patients With Congenital Disorder of Glycosylation

Study Overview
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Brief Summary
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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
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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)

Official Title
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Evaluation of Global Coagulation Balance of 57 Patients With Congenital Disorder of Glycosylation Using the Thrombin Generation Assay

Conditions
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Congenital Disorders of Glycosylation

Intervention / Treatment
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* Biological: Coagulation assay
* Other: Clinical data collection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: -Clinical diagnosis of Congenital Disorder of Glycosylation (CDG) Exclusion Criteria: - no exclusion criteria
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Event group<br>CDG with antecedent of stroke-like, thrombosis or haemorrhages | Biological: Coagulation assay<br>* Conventional coagulation assays: prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, factor II, FV, FVII, FX, FVIII, FIX, FXI, FXII, d-dimers, antithrombin, protein C, protein S Thrombin generation assay: in presence or not of soluble thrombomodulin<br>Other: Clinical data collection<br>* At inclusion, we recorded clinical data about the disease (type and form of congenital disorder of glycosylation, and antecedent of microvascular event: thrombosis, stroke-like or hemorrhages)<br>|
| Non event group<br>CDG without antecedent of stroke-like, thrombosis or haemorrhages | Biological: Coagulation assay<br>* Conventional coagulation assays: prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, factor II, FV, FVII, FX, FVIII, FIX, FXI, FXII, d-dimers, antithrombin, protein C, protein S Thrombin generation assay: in presence or not of soluble thrombomodulin<br>Other: Clinical data collection<br>* At inclusion, we recorded clinical data about the disease (type and form of congenital disorder of glycosylation, and antecedent of microvascular event: thrombosis, stroke-like or hemorrhages)<br>|
| Control<br>Healthy subject | Biological: Coagulation assay<br>* Conventional coagulation assays: prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, factor II, FV, FVII, FX, FVIII, FIX, FXI, FXII, d-dimers, antithrombin, protein C, protein S Thrombin generation assay: in presence or not of soluble thrombomodulin<br>Other: Clinical data collection<br>* At inclusion, we recorded clinical data about the disease (type and form of congenital disorder of glycosylation, and antecedent of microvascular event: thrombosis, stroke-like or hemorrhages)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of haemostatic balance using thrombin generation assay | 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. | Up to 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stroke-like, thrombosis, haemorrhages