Transfer of GPI-Linked Proteins to Transfused Patients With Paroxysmal Nocturnal Hemoglobinuria

NCT00039923 | Completed

• 2 other identifiers: 02022702-H-0227
• Study Type: observational
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

This study will examine blood cells of patients with paroxysmal nocturnal hemoglobinuria (PNH) after they receive a blood transfusion to determine if certain proteins (GPI-linked proteins) in the transfused blood transfer to the patient's blood cells. GPI-linked proteins, which are normally present on red cells and regulate red cell survival, are absent in patients with PNH. Their lack is believed to account for the premature destruction of red blood cells in these patients, resulting in a low hemoglobin and hematocrit. Patients may experience fatigue, flank pain and other symptoms, requiring treatment with blood transfusion. Patients with PNH 18 years of age or older with group A1 blood who require at least three units of red cells and who have not been transfused with group O blood within the last 3 months may be eligible for this study. Participants will come to the NIH Clinical Center for the following procedures:

• Interview about the severity of their anemia-related symptoms
• Blood test
• Blood transfusion, if required. Patients will be transfused with compatible group O blood. The donor blood will be washed (rinsed with a salt solution) until it is 99% free of donor plasma. Group O blood is given instead of group A1 in order to be able to distinguish the patient's cells from the transfused cells. Blood samples of 3 teaspoons each will be drawn 1 day, 1 week, and 3 weeks after the transfusion. These samples may be collected by the patient's doctor locally and sent to NIH by mail. If it is found that GPI-linked proteins transfer to the patient's cells, the study will also examine how long the proteins remain attached and will assess whether the proteins are functional and prevent cell destruction.

Conditions

Paroxysmal Hemoglobinuria

Keywords

Hemolysis; CD55; CD59; Transfusion; Paroxysmal Nocturnal Hemoglobinuria; PNH

Eligibility Criteria

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

You may qualify if:

• The following must be met before the subject may be enrolled:
• PNH patients with group A(1) blood who require at least three units of red cells as judged by their primary care physician; criteria for transfusion would include hemoglobin below 7.5 g/dl or symptoms related to anemia (impaired exercise tolerance, angina, shortness of breath) that warrant therapy.
• A PNH clone of greater than 40% and not have been transfused with group O blood for at least three months previously.
• Eighteen years of age or older.
• Karnofsky performance status of 60% or better.
• Adequate organ function as defined by serum creatinine less than 2.0 mg/dl.
• Able to comprehend and willing to sign an informed consent.

You may not qualify if:

• Any one of the following eliminates a subject from participating:
• Evidence of uncontrolled infection.
• Known alloimmunization to red cell antigens.
• Treatment with investigational agent or hematopoietic growth factors within 4 weeks of study entry.
• Psychiatric, addictive or any disorder that compromises ability to give truly informed consent.
• Patients who are moribund or who have concurrent hepatic, renal, cardiac disease.

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (1)

National Heart, Lung and Blood Institute (NHLBI)

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Sloand EM, Maciejewski JP, Dunn D, Moss J, Brewer B, Kirby M, Young NS. Correction of the PNH defect by GPI-anchored protein transfer. Blood. 1998 Dec 1;92(11):4439-45.

  PMID: 9834251 BACKGROUND

• Rosse WF. Phosphatidylinositol-linked proteins and paroxysmal nocturnal hemoglobinuria. Blood. 1990 Apr 15;75(8):1595-601. No abstract available.

  PMID: 2183885 BACKGROUND

• Luzzatto L, Bessler M, Rotoli B. Somatic mutations in paroxysmal nocturnal hemoglobinuria: a blessing in disguise? Cell. 1997 Jan 10;88(1):1-4. doi: 10.1016/s0092-8674(00)81850-4. No abstract available.

  PMID: 9019395 BACKGROUND

MeSH Terms

Conditions

Hemoglobinuria, Paroxysmal; Hemolysis

Condition Hierarchy (Ancestors)

Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Myelodysplastic Syndromes; Bone Marrow Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: observational
• Sponsor Type: NIH

Study Record Dates

• First Submitted: June 14, 2002
• First Posted: June 17, 2002
• Study Start: June 1, 2002
• Study Completion: June 1, 2005
• Last Updated: March 4, 2008

Record last verified: 2005-06

Locations

US (1)