Ignite Creation Date:
2024-05-05 @ 11:35 AM
Last Modification Date:
2024-10-26 @ 9:10 AM
Study NCT ID:
NCT00086476
Status:
COMPLETED
Last Update Posted:
2017-07-02
First Post:
2004-07-01
Brief Title:
Study of Megakaryocytes From Patients With Abnormal Platelet Vesicles
Sponsor:
National Human Genome Research Institute NHGRI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Investigations of Megakaryocytes From Patients With Abnormal Platelet Vesicles
Status:
COMPLETED
Status Verified Date:
2011-06-13
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Congenital bleeding disorders characterized by abnormal platelet granules include Gray Platelet syndrome GPS defective alpha-granules Hermansky-Pudlak syndrome HPS defective delta-granules and combined alpha delta-storage pool deficiency alpha delta-SPD Other diseases associated with variable defects in platelet gamma-granules include Chediak-Higashi Griscelli Wiskott-Aldrich and Thrombocytopenia Absent Radius syndromes These disorders are models for the study of organelle formation in megakaryocytes and platelets Characteristics of megakaryocytopoiesis in these disorders have not been investigated because megakaryocytes could not be cultured from patients in sufficient quantities for experimental purposes Recent advances have made it possible to culture megakaryocytes using serum-free media supplemented with recombinant human thrombopoietin TPO Such cultured human megakaryocytes amplified from bone marrow-derived CD34 stem cells synthesize and store organellar proteins and produce functional platelets In this protocol we plan to obtain bone marrow aspirates from 40 children and adults ages 2 to 80 years with GPS HPS and related disorders Patients admitted to the NIH Clinical Center on specific disease-related protocols will be enrolled in this protocol during their routine 3-5 day visits We will culture megakaryocytes from CD34 stem cells isolated from bone marrow aspirates Studies of cultured megakaryocytes will include evaluation of granule membrane and soluble proteins using fluorescent antibodies and immunoelectron microscopy and comparison of RNA and protein expression patterns between normal and patient cells Precautions will be taken to prevent the primary risk of the bone marrow aspiration ie prolonged bleeding at the aspiration site Standard diagnostic studies on the bone marrow sample may reveal information that may directly benefit patients However the broader benefit of this study is the acquisition of a better understanding of the characteristics of functional platelet disorders and the process of intracellular vesicle formation
Detailed Description:
Congenital bleeding disorders characterized by abnormal platelet granules include Gray Platelet syndrome GPS defective alpha-granules Hermansky-Pudlak syndrome HPS defective delta-granules and combined alpha delta-storage pool deficiency alpha delta-SPD Other diseases associated with variable defects in platelet gamma-granules include Chediak-Higashi Griscelli Wiskott-Aldrich and Thrombocytopenia Absent Radius syndromes These disorders are models for the study of organelle formation in megakaryocytes and platelets Characteristics of megakaryocytopoiesis in these disorders have not been investigated because megakaryocytes could not be cultured from patients in sufficient quantities for experimental purposes Recent advances have made it possible to culture megakaryocytes using serum-free media supplemented with recombinant human thrombopoietin TPO Such cultured human megakaryocytes amplified from bone marrow-derived CD34 stem cells synthesize and store organellar proteins and produce functional platelets In this protocol we plan to obtain bone marrow aspirates from 40 children and adults ages 2 to 80 years with GPS HPS and related disorders Patients admitted to the NIH Clinical Center on specific disease-related protocols will be enrolled in this protocol during their routine 3-5 day visits We will culture megakaryocytes from CD34 stem cells isolated from bone marrow aspirates Studies of cultured megakaryocytes will include evaluation of granule membrane and soluble proteins using fluorescent antibodies and immunoelectron microscopy and comparison of RNA and protein expression patterns between normal and patient cells Precautions will be taken to prevent the primary risk of the bone marrow aspiration ie prolonged bleeding at the aspiration site Standard diagnostic studies on the bone marrow sample may reveal information that may directly benefit patients However the broader benefit of this study is the acquisition of a better understanding of the characteristics of functional platelet disorders and the process of intracellular vesicle formation
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 04-HG-0226 | None | None | None |