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
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
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.
Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal bone marrow disorder, resulting from
an acquired, somatic X-linked mutation of the PIG-A gene in an hematopoietic stem cell.
Absence of PIG-A function in a cell prevents synthesis of the glycosylphosphatidylinositol
(GPI) moiety, which anchors many different types of proteins to the cell membrane.
Intravascular red cell destruction, the hallmark of the disorder, is caused by
susceptibility of the abnormal erythrocyte to complement-mediated lysis; this sensitivity is
due to lack of CD59, a potent inhibitor of the late components of complement and reactive
lysis. In vitro studies from this laboratory have demonstrated transfer of GPI-linked
proteins, CD55 and CD59, from normal to deficient cells and transfer is associated with
resistance to hemolysis. Patients with PNH frequently require transfusion as their standard
care. In addition, patients with all blood groups requiring transfusion will often receive
compatible group O blood. Group O blood is prevalent in blood bank inventories; and red
cell survival after transfusion is equal to that after transfusion of "in group" blood. The
purpose of this study is to examine protein transfer of GPI-linked proteins from transfused
cells to deficient cells obtained from patients with PNH. Patients with group A(1) blood
will receive compatible group O blood so that donor and recipient blood cells can be
discriminated. Flow cytometric studies will be performed subsequently to determine if
transfer of GPI-linked protein to patients' cells has occurred.
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.
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
Psychiatric, addictive or any disorder that compromises ability to give truly informed
Patients who are moribund or who have concurrent hepatic, renal, cardiac disease.