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Platelet Glycoproteins in Inherited Thrombocytopathy: Association With Aggregation Studies and Bleeding Severity

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ClinicalTrials.gov Identifier: NCT03648190
Recruitment Status : Recruiting
First Posted : August 27, 2018
Last Update Posted : August 28, 2018
Sponsor:
Information provided by (Responsible Party):
Mohammed Ashraf, Assiut University

Brief Summary:

Disorders of platelet function are characterized by variable mucocutaneous bleeding manifestations and excessive hemorrhage following surgical procedures or trauma. Generally, most patients have mild to moderate bleeding manifestations with a prolonged bleeding time.

Platelet aggregation and secretion studies using platelet-rich plasma (PRP) provide evidence for platelet dysfunction but are neither predictive of severity of clinical manifestations nor the molecular mechanisms.

Glanzmann's thrombasthenia (GT) is a rare autosomal recessive genetic bleeding syndrome characterized by defects in platelet aggregometry. The clinical phenotype of patients with GT is variable. Some suffer from severe bleeding, while others have only mild bleeding. Some studies found bleeding severity in GT was influenced by the abundance and functioning of platelet receptors involved in aggregation and adhesion.

In addition to a complete medical history, a GT diagnosis requires a comprehensive laboratory workup, including platelet aggregation analysis, and a confirmation by flowcytometry or western blotting with monoclonal antibodies that recognize the GPIIb/IIIa complex.

Platelet flow cytometry is an emerging tool in diagnostic and therapeutic hematology. It is eminently suited to study the expression of platelet surface receptors both qualitatively as well as quantitatively.

Aim of the study:-

  • Determine the role of flowcytometry as a quantitative measurement tool of platelets surface glycoproteins in patients with inherited thrombocytopathies and its correlation with bleeding severity of these patients.
  • To compare the efficacy, advantages and disadvantages between platelets flowcytometry and aggregometer in diagnosing various inherited thrombocytopathies.

Condition or disease Intervention/treatment
Bleeding Platelet Dysfunction Diagnostic Test: Flowcytometry analysis of platelets surface receptors

Detailed Description:

This study is a case-control observational study to be done at Clinical pathology department, Assiut University hospital, Assiut University, Egypt.

Patients with inherited qualitative platelets defect with clinical manifestations in the form of mucocutaneous bleeding or hemorrhage will be included in the study. Individuals with similar age and sex distribution to the patient group will act as controls. Control group shouldn't take medications or anti-platelet drugs for the preceding two weeks. They should have normal platelet count and morphology. Bleeding patients with acquired bleeding, coagulation defects, and those on anti-platelet drugs will be excluded from the study.

All Patients with inherited platelets function disorders will be subjected to:-

I - Careful history and clinical examination data collecting including:

Clinical history of bleeding such as (Sites, Severity and frequency of bleeding, trauma related events, history of surgical procedures, history of menorrhagia in females, history of packed red cell/ platelets transfusion.

II - Family history such as consanguinity, bleeding complications in any parents/ siblings.

III - Grading of bleeding severity: according to World Health Organization (WHO) bleeding assessment scale from grade 1 to grade 4.

The following routine investigations will be done:-

  1. Complete blood count (CBC) analysis.
  2. Prothrombin time, concentration and international normalized ratio (INR) assay.
  3. Activated partial thromboplastin time assay.
  4. Fibrinogen level and thrombin time assay.

The following specific investigations:-

  1. Platelets aggregation tests by aggregometer using four different agonists (ADP, Collagen, Arachidonic acid and ristocetin) on Bio/Data PAP-8E.
  2. Flowcytometry analysis of platelets receptors (CD 41, CD 61 and CD 42b) on BD FACSCalibur flowcytometry instrument.

Data collection and analysis will be done by computer program SPSS version 21 Chicago USA. Data expressed as mean ±SD, mean±SE, number and percentage. Using Manwhitny test to determine the significance for numeric variable and chisquare to determine the significance for non-parametric variable. ROC curve was done to determine the area under curve (AUC), sensitivity and specificity for each marker.


Study Type : Observational
Estimated Enrollment : 50 participants
Observational Model: Case-Control
Time Perspective: Cross-Sectional
Official Title: Evaluation of Platelet Surface Glycoproteins in Patients With Inherited Thrombocytopathy: Association With Aggregation Studies and Bleeding Severity
Estimated Study Start Date : December 1, 2018
Estimated Primary Completion Date : December 30, 2019
Estimated Study Completion Date : August 30, 2020

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
Inherited qualitative platelets defect

Clinical manifestations in the form of mucocutaneous bleeding or hemorrhage.

Bleeding patients with acquired bleeding disorders, coagulation defects, and those on antiplatelet drugs will be excluded from the study.

Diagnostic Test: Flowcytometry analysis of platelets surface receptors

BD FACSCalibur flowcytometry instrument.

Platelet flow cytometry is an emerging tool in diagnostic and therapeutic hematology. It is eminently suited to study the expression of platelet surface receptors both qualitatively as well as quantitatively.

Flow cytometry rapidly measures the specific characteristics of a large number of cells in suspension. Typically, the cells are labeled with fluorescently conjugated monoclonal antibodies (mAbs).

Other Name: Platelets aggregation tests by aggregometer

Control
Normal healthy participants, with no manifestations of bleeding disorders.
Diagnostic Test: Flowcytometry analysis of platelets surface receptors

BD FACSCalibur flowcytometry instrument.

Platelet flow cytometry is an emerging tool in diagnostic and therapeutic hematology. It is eminently suited to study the expression of platelet surface receptors both qualitatively as well as quantitatively.

Flow cytometry rapidly measures the specific characteristics of a large number of cells in suspension. Typically, the cells are labeled with fluorescently conjugated monoclonal antibodies (mAbs).

Other Name: Platelets aggregation tests by aggregometer




Primary Outcome Measures :
  1. Establishment of a protocol for Flowcytometry device to be used in routinely diagnosing cases with inherited platelets function defects. [ Time Frame: 6 Weeks ]
    Determine the ability of flowcytometry to assay (determine the levels of expression of each surface marker in percent) platelets surface glycoproteins (CD 41, CD 61 and CD 42b) using BD FACSCalibur flowcytometry instrument in patients with inherited thrombocytopathies and its correlation with bleeding severity of these patients with establishment of a protocol for it to be used in routinely diagnosing these cases.



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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population
Bleeding patients suffering from inherited qualitative platelets defect, with the exclusion of coagulation defects, acquired bleeding disorders and anti-platelet drugs intake. Both male and females are eligible with no age limits.
Criteria

Inclusion Criteria:

  • Bleeding patients.

Exclusion Criteria:

  • Coagulation defects, and those on anti-platelet drugs.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03648190


Contacts
Contact: Mohammed Ashraf, M.Sc +201002867611 M1111a1111@yahoo.com

Locations
Egypt
Assiut University Hospital Recruiting
Assiut, Egypt, 71515
Contact: Mohammed Ashraf, M.Sc    +201002867611    M1111a1111@yahoo.com   
Sponsors and Collaborators
Assiut University
Investigators
Principal Investigator: Hanan Galal, MD Assiut University
Study Chair: Madleen Adel, MD Assiut University
Study Chair: Eman Nasr-Eldin, MD Assiut University
Study Director: Mohammed Ashraf, M.Sc Assiut University

Publications:
Responsible Party: Mohammed Ashraf, Assistant Lecturer, Assiut University
ClinicalTrials.gov Identifier: NCT03648190     History of Changes
Other Study ID Numbers: 17200237
First Posted: August 27, 2018    Key Record Dates
Last Update Posted: August 28, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Mohammed Ashraf, Assiut University:
GT
CD

Additional relevant MeSH terms:
Hemorrhage
Blood Platelet Disorders
Pathologic Processes
Hematologic Diseases
Krestin
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Interferon Inducers
Radiation-Protective Agents
Protective Agents