Thrombocytopathy in Gaucher Disease Patients

A 1.5 Years Prospective Study Designed to Delineate the Cause of the Thrombocytopathy in Gaucher Disease Patients

In Gaucher disease type I bleeding is a common presenting symptom, that may manifest itself as frequent nose bleeds, easy bruising but can also cause substantial bleeding after surgical or dental procedures and may occur in association with pregnancy or delivery . The bleeding tendency is usually considered to be secondary to thrombocytopenia However 50,000 platelets are enough in healthy people to give a normal bleeding time but are associated with significant bleeding tendencies in Gaucher patients. Bleeding tendency might be attributed by genetic inherited or Gaucher related coagulation factors abnormalities which in some cases stabilize with ERT. However, In other cases the etiology is an abnormality of platelet function. This thrombocytopathy has not been delineated and apart from a few aggregation studies, no systematic analysis has been published that convincingly shows the cause of the disturbed function. While, experience shows that enzyme replacement (ERT, i.e: imiglucerase, Cerezyme®) reduces this bleeding tendency, in part due to the improvement in the thrombocyte count and elevation in coagulation factors, it is less clear what effect ERT has on the thrombocytopathy. This has clinical significance when patients need to be prepared for surgery or delivery or in the event of a major bleed. There is no consensus as to how patients should be prepared or treated. Different centres use different approaches. When the procedure is elective ERT is appropriate but in other situations DDAVP, fresh frozen plasma and platelet infusion are possible treatments. Even activated factor VII has been used when bleeding was not controlled. As in any other coagulation abnormality, treatment should be tailored to the specific cause of the bleeding diathesis. The aim of this study is to define the etiology of platelet dysfunction in Gaucher patients.

Hypothesis: The investigators expect to see a difference between platelets activation profile among imiglucerase treated and untreated patients with at least a partial restoration of platelets function due to treatment commencement.

Study Overview

• Status: Unknown
• Conditions: Gaucher Disease; Thrombocytopathy

Detailed Description

Objectives:

Delineating the cause of the thrombocytopathy in Gaucher disease patients:

1. Identifying thrombocytopathy among a cohort of 70 Gaucher patients managed (treated and untreated) in our clinic using a panel of platelets function tests.
2. Understanding the etiology for platelets dysfunction in Gaucher disease.
3. Evaluating the impact of Imiglucerase treatment duration and Gaucher disease severity on platelet function

• Study Type: Observational
• Enrollment (Anticipated): 70

Contacts and Locations

Study Locations

• Israel
  • Haifa, Israel
    • Not yet recruiting
    • Rambam Medical Center
    • Contact: Hagit Baris, Prof; Phone Number: 972-4-7771286; Email: HB_Feldman@rambam.health.gov.il
    • Contact: Ian J Cohen, Prof; Email: icohen@tau.ac.il
    • Principal Investigator: Hagit Baris
  • Petach Tikva, Israel, 49100
    • Recruiting
    • Rabin Medical Center
    • Contact: Monica Weisz Hubshman, MD; Phone Number: 972-3-9377522; Email: MonicaWe@clalit.org.il
    • Contact: Ian J Cohen, Prof.; Email: icohen@tau.ac.il
    • Principal Investigator: Monica Weisz Hubshman, MD
    • Sub-Investigator: Ian Cohen, Prof.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Gaucher disease patients treated and untreated wih Imiglucerase

Description

Inclusion Criteria:

• Gaucher disease patients
• Patients who do not receive any medicine that affects platlats

Exclusion Criteria:

• Treatment with enzyme replacement therapy other than Imiglucerase

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure thrombocytopathy in a cohort of 70 Gaucher patients using a set of platelet function tests.	• 70 Gaucher patients managed (treated and untreated controls) will be subjected to a panel of platelets function tests (aggregation test, closure time and FACS analysis).	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluating the impact of Imiglucerase treatment on platelet function	Platelet function during the 3 years of study will be analyzed versus Imiglucerase treatment status and duration taking into consideration genotype, age at diagnosis, spleen status and Gaucher disease severity at treatment initiation	3 years

Collaborators and Investigators

• Sponsor: Rabin Medical Center
• Collaborators: Genzyme, a Sanofi Company
• Investigators: Study Chair: Ian J Cohen, Prof., Rabin Medical Center; Study Chair: Hagit Baris, MD, Rambam Health Care Campus

Publications and helpful links

General Publications

• Baris HN, Weisz Hubshman M, Bar-Sever Z, Kornreich L, Shkalim Zemer V, Cohen IJ. Re-evaluation of bone pain in patients with type 1 Gaucher disease suggests that bone crises occur in small bones as well as long bones. Blood Cells Mol Dis. 2016 Sep;60:65-72. doi: 10.1016/j.bcmd.2015.05.003. Epub 2015 May 9.

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (ANTICIPATED): November 1, 2018
• Study Completion (ANTICIPATED): November 1, 2018

Study Registration Dates

• First Submitted: March 14, 2011
• First Submitted That Met QC Criteria: April 27, 2011
• First Posted (ESTIMATE): April 28, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): October 28, 2016
• Last Update Submitted That Met QC Criteria: October 27, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: Gaucher disease; Imiglucerase; Thrombocytopathy
• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hematologic Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Lipid Metabolism Disorders; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Lipidoses; Lipid Metabolism, Inborn Errors; Gaucher Disease; Blood Platelet Disorders
• Other Study ID Numbers: RMC6088; GZGD02507 (Genzyme)