Samir K. Ballas

The spectrum of epilepsy in sickle cell anemia

In a study population of 152 patients seen at Thomas Jefferson University Hospitals sickle cell center between 1981 and 1992, 21 patients with seizures were identified. Clinical charts, electroencephalograms and neuroradiological studies were reviewed retrospectively. Seventeen patients with epilepsy were identified. Eleven had generalized tonic-clonic, 2 had partial, and 4 had poorly characterized seizures. CT/MRI evaluation was focally abnormal in 6 patients, 4 of whom had cortical lesions. Atrophy was noted in 3 patients, while imaging studies were normal in 6 patients. The EEGs demonstrated focal epileptiform discharges in 9 patients, generalized slowing in 5 patients, and was normal in 3 patients. Four patients had generalized seizures only with meperidine administration, all of whom had nonfocal EEG and radiological studies. We concluded that (1) epilepsy is more common in sickle cell patients than in the general population; (2) the majority of our epileptic sickle cell patients have nonfocal CT or MRI studies but demonstrate focal EEG abnormalities; and (3) meperidine administration is associated with generalized seizures in sickle cell patients.

Marrow infarction in sickle cell anemia: Correlation with marrow type and distribution by MRI☆

Ischemic necrosis of bone is believed to occur exclusively in areas of predominantly fatty marrow. Sickle cell disease is unusual in that marrow infarction occurs in areas of active hematopoiesis. MR images of long bone obtained in ten patients with sickle cell anemia (SCA) were analyzed to correlate the distribution and appearance of marrow infarction with the type of marrow. While the hematopoietic marrow predominated in metaphyseal and diaphyseal regions of femurs and tibias, the fatty or mixed marrow was the most common pattern in epiphyses. Infarcts occurred in fatty as well as hematopoietic marrow. Marrow infarcts were isointense or minimally hyperintense on T1 weighted images with the hematopoietic marrow and therefore difficult to detect. On T2 weighted images, the infarcts showed very high signal. T2 weighted images are essential for detection of marrow infarction. Soft tissue changes seen as low signal on T1 and high signal on T2, may be secondary to intramuscular injections of analgesics or muscle ischemia occurring during sickle crisis.

Femoral head avascular necrosis in sickle cell anemia: MR characteristics

Since considerable expansion of hematopoietic marrow occurs in patients with sickle cell anemia (SCA), magnetic resonance images of 20 hips in 10 patients with known homozygous SCA were reviewed to determine a) if low signal hematopoietic marrow extended into the femoral capital epiphysis and b) if the MR characteristics of avascular necrosis (AVN) differed depending on the type of epiphyseal marrow. Our results revealed variable epiphyseal marrow type; mixed (fatty and hematopoietic) marrow (42%), fatty marrow (32%), hematopoietic marrow (16%) and hemosiderotic marrow (10%). AVN occurred irrespective of the underlying marrow. Segmental areas of low signal intensity in variable shapes (ring, band, crescent or large homogeneous area) was the most consistent MR manifestation of AVN in SCA. A low signal intensity peripheral rim surrounding a central zone, isointense with epiphyseal marrow on T1 and T2 weighted images, was most frequently observed similar to that described in patients without hemoglobinopathy. The notable difference, however, was of segmental areas within the same femoral head that demonstrated variable central zone signal on T2 weighted images. Further, while an increase in hip joint fluid is commonly seen with both early and advanced AVN in patients without hemoglobinopathy; it was increased in only one hip in patients with SCA. The observed differences in MR characteristics may be due to different pathophysiology of AVN in patients with SCA.

Red Cell Membrane Protein Changes Caused by Freezing and the Mechanism of Cryoprotection by Glycerol

Membranes isolated from frozen‐thawed erythrocytes and analyzed by polyacrylamide gel electrophoresis in sodium dodecyl sulfate have significantly decreased band six, which is the glycolytic enzyme, glyceraldehyde 3‐phosphate dehydrogenase. The total membrane protein and sialic acid contents of these membranes are also significantly decreased. The red blood cell membrane protein abnormality is reproduced by suspending membranes in NaCl solutions of increasing molarity. Glycerol prevents the elution of band six in NaCl solutions less than 0.2 M and ameliorates it in solutions of higher ionic strength. When intact cells are suspended in hypertonic salt solution, there is no elution of band six, indicating that exposure of the inner surface of the membrane to toxic concentrations of solutes results in this elution. The data indicate that freezing with its associated hypertonicity induces a specific membrane change which is ameliorated by the addition of glycerol.

Urinary retention in sickle cell syndromes

Four patients with sickle cell disease noted the development of urinary retention during an acute painful crisis. The acute urinary retention resolved with improvement in the painful sickle cell crisis. No evidence of anatomic urologic defect, systemic neurologic abnormality, or infection was documented in these patients. Patients with sickle cell disease in painful crisis should be observed for signs of acute urinary retention.

Balanced globin synthesis in idiopathic myelofibrosis.

Four patients with idiopathic myelofibrosis were found to have microcytic and/or hypochromic red cell indexes. The alpha/beta globin synthetic ratio determined by incubating peripheral blood with [14C]leucine was within normal limits in all patients studied. This is unlike a recent report of acquired hemoglobin H disease with decreased alpha/beta synthetic ratio in primary myelofibrosis. This indicates that mechanisms other than alpha-thalassemia-like defects may also be involved in the production of microcytic and hypochromic red cells in myelofibrosis.

Effect of temperature on the red cell membrane protein and its antigenic reactivity

The red blood cell membrane protein pattern of erythrocytes exposed to 50 C for 10 to 15 minutes was found to be abnormal by polyacrylamide gel electrophoresis in sodium dodecyl sulfate. Membranes of heated red blood cells consistently had significant elevation of band 7 and 8. The total membrane protein content (mg/109 cells) of heated erythrocytes was increased, but the sialic acid content was normal. Heated erythrocytes showed a consistent decrease in the reactivity of Fya and Jka antigens. Other blood group antigens were variably affected by temperature elevation. These observations may explain the mechanism of antibody elution by heat.

Pre‐transfusion testing problems caused by anti‐lymphocyte globulin and their solution

Anti‐lymphocyte globulin (ALG) is an antibody to human lymphocytes used to decrease T‐cells in renal transplant patients. We recently encountered serologic problems in testing blood from patients treated with ALG. Thirty‐nine patients undergoing acute kidney rejection developed positive direct and indirect antiglobulin tests following the administration of equine ALG. Sera from these patients reacted with all red cells (RBCs) tested using both polyspecific and monospecific anti‐ IgG anti‐human sera. Eluates prepared from the patients RBCs showed similar reactivity. The ALG panagglutinin did not react by manual hexadimethrine bromide (Polybrene) technique. The ALG panagglutinin could be neutralized by anti‐human globulin. In our hands, these techniques were useful in distinguishing ALG panagglutinin from co‐ existing alloantibodies.

Survival of Kn(a+) McC(a+) red cells in a patient with anti- "Kna/McCa".

The in vivo survival of Kn(a+)McC(a+) red cells in a patient with anti‐ “Kna/McCa” was studied using 51Cr‐labeled incompatible cells. The antibody was IgG4, demonstrable at 37 degrees C in the antiglobulin test, and did not bind complement. Survival of tagged cells was 82.2 percent after 24 hours. The patient was transfused with a total of 29 units of incompatible blood with no evidence of ill effects. The direct antiglobulin test became positive after transfusion and remained positive for 2 1/2 months of observation. The findings suggest that individuals with anti‐ “Kna/McCa” may be transfused with Kn(a+)McC(a+) red cells.

Photopheresis: a therapy or an eclipse?

To the Editor: Recently, a new treatment for cutaneous T-cell lymphoma has come into use.’ This procedure involves giving the patient an oral dose of a photoactive drug, methoxsalen, which is followed by an apheresis procedure in which the patient’s blood is removed and the white cells (WBCs) are separated and exposed to ultraviolet (W) light. Methoxsalen intercalates in the DNA of the WBCs, and with exposure to UV light, causes covalent crosslinking. The WBCs are then returned to the patient, along with the unexposed plasma and red cells. Irradiated lymphocytes die over several days, thus destroying many cells of the expanded malignant clone. Furthermore, i t is thought that the exposure of these defunct lymphocytes to the reticuloendothelial system leads to a specific immunologic reaction against the clone, having a beneficial anti-tumor effect. This therapeutic process has been variously termed extracorporeal photochemotherapy’ or photopheresis.2 The term apheresis comes from two Greek words apo and haireinY3 which taken together mean the taking away or removal of something. Brevity is commendable but should be accompanied by accuracy, so calling this procedure photopheresis is a misnomer, as that would, in fact, mean the removal or obscuration of light, that is, an eclipse, whereas in reality, UV light is transmitted to WBCs during the procedure. Because speaking of “extracorporeal photochemotherapy” every time we wish to refer to this procedure is tiresome and time-consuming, we believe that the use of an acronym is desirable, but this term should reflect the reality of the procedure. As extracorporeal membrane oxygenation is known as “ECMO,” we propose calling extracorporeal photochemotherapy “ECPHO.” Thus, those of us who use acronyms can be brief but accurate, showing that we understand what semantics is about. CAROL A. TALACW SAMIR K. BALLAS, MD Cardeza Foundation for Hematologic Research Department of Medicine Thomas Jefferson University Hospital Blood Bank Philadelphia, PA 19107 Letters to the Editor