Study of Megakaryocytes From Patients With Abnormal Platelet Vesicles

NCT00086476 | Completed

• 2 other identifiers: 04022604-HG-0226
• Study Type: observational
• Target: 3
• Locations: 1 country
• Sites: 1

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, 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.

Conditions

Blood Coagulation Disorders

Keywords

Gray Platelet Syndrome; Hermansky-Pudlak Syndrome; Storage Pool Deficiency; Organelle Formation; Megakaryocyte Development; Megakaryocytes; Platelets; Dense Granules; Alpha Granules; Lysosome-related Organelles; GPS; HPS; Griscelli Disease; Chediak Higashi Syndrome; Wiskott Aldrich Syndrome; Platelet; Congenital Bleeding Disorders; SAC; Vesicle

Eligibility Criteria

• Age: 2 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Human Genome Research Institute (NHGRI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Rendu F, Brohard-Bohn B. The platelet release reaction: granules' constituents, secretion and functions. Platelets. 2001 Aug;12(5):261-73. doi: 10.1080/09537100120068170.

  PMID: 11487378 BACKGROUND

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

  PMID: 453324 BACKGROUND

• McNicol A, Israels SJ. Platelet dense granules: structure, function and implications for haemostasis. Thromb Res. 1999 Jul 1;95(1):1-18. doi: 10.1016/s0049-3848(99)00015-8.

  PMID: 10403682 BACKGROUND

MeSH Terms

Conditions

Blood Coagulation Disorders; Gray Platelet Syndrome; Hermanski-Pudlak Syndrome; Platelet Storage Pool Deficiency; Chediak-Higashi Syndrome; Wiskott-Aldrich Syndrome; Blister

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases; Blood Platelet Disorders; Blood Coagulation Disorders, Inherited; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Albinism, Oculocutaneous; Albinism; Eye Diseases, Hereditary; Eye Diseases; Hemorrhagic Disorders; Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Skin Diseases, Genetic; Hypopigmentation; Pigmentation Disorders; Skin Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Phagocyte Bactericidal Dysfunction; Leukocyte Disorders; Primary Immunodeficiency Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Lymphopenia; Leukopenia; Cytopenia; Genetic Diseases, X-Linked; Skin Diseases, Vesiculobullous; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: observational
• Sponsor Type: NIH

Study Record Dates

• First Submitted: July 1, 2004
• First Posted: July 2, 2004
• Study Start: June 29, 2004
• Study Completion: June 13, 2011
• Last Updated: July 2, 2017

Record last verified: 2011-06-13

Locations

US (1)