Study of Megakaryocytes From Patients With Abnormal Platelet Vesicles

This study has been completed.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00086476
First received: July 1, 2004
Last updated: June 14, 2011
Last verified: June 2011
  Purpose

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.


Condition
Blood Coagulation Disorders

Study Type: Observational
Official Title: Investigations of Megakaryocytes From Patients With Abnormal Platelet Vesicles

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Enrollment: 3
Study Start Date: June 2004
Estimated Study Completion Date: June 2011
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, 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.

  Eligibility

Ages Eligible for Study:   2 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • 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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00086476

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00086476     History of Changes
Other Study ID Numbers: 040226, 04-HG-0226
Study First Received: July 1, 2004
Last Updated: June 14, 2011
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Chediak Higashi Syndrome
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
Wiskott Aldrich Syndrome
Platelet
Congenital Bleeding Disorders
SAC
Vesicle

Additional relevant MeSH terms:
Blood Coagulation Disorders
Hemostatic Disorders
Hematologic Diseases
Vascular Diseases
Cardiovascular Diseases
Hemorrhagic Disorders

ClinicalTrials.gov processed this record on September 30, 2014