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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00086476
Other study ID # 040226
Secondary ID 04-HG-0226
Status Completed
Phase N/A
First received July 1, 2004
Last updated June 30, 2017
Start date June 29, 2004
Est. completion date June 13, 2011

Study information

Verified date June 13, 2011
Source National Institutes of Health Clinical Center (CC)
Contact n/a
Is FDA regulated No
Health authority
Study type Observational

Clinical Trial 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, i.e., 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.


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, i.e., 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.


Recruitment information / eligibility

Status Completed
Enrollment 3
Est. completion date June 13, 2011
Est. primary completion date
Accepts healthy volunteers No
Gender All
Age group 2 Years to 80 Years
Eligibility - INCLUSION CRITERIA:

This protocol will include children and adults with a clinical diagnosis of GPS, HPS, isolated delta-SPD, combined alpha delta-SPD, Griscelli disease, Chediak Higashi syndrome, Wiskott Aldrich syndrome or Thrombocytopenia absent radius syndrome. Patients whose platelets exhibit abnormal intracellular vesicle morphology will also be eligible.

EXCLUSION CRITERIA:

Patients younger than 2 years and older than 80 years will be excluded. Patients with severe thrombocytopenia (fewer than 20 times 10(12) platelets/L) will be excluded.

Study Design


Related Conditions & MeSH terms


Locations

Country Name City State
United States National Institutes of Health Clinical Center, 9000 Rockville Pike Bethesda Maryland

Sponsors (1)

Lead Sponsor Collaborator
National Human Genome Research Institute (NHGRI)

Country where clinical trial is conducted

United States, 

References & Publications (3)

McNicol A, Israels SJ. Platelet dense granules: structure, function and implications for haemostasis. Thromb Res. 1999 Jul 1;95(1):1-18. Review. — View Citation

Rendu F, Brohard-Bohn B. The platelet release reaction: granules' constituents, secretion and functions. Platelets. 2001 Aug;12(5):261-73. Review. — View Citation

White JG. Ultrastructural studies of the gray platelet syndrome. Am J Pathol. 1979 May;95(2):445-62. — View Citation

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