Functional Asplenia in Sickle Cell Anemia—A Reversible Defect

Louis K. DIAMOND (University of California Medical Center, San Francisco): Shortly after hearing of this work of Dr. SCHWARTZ and Dr. PEARSON, we had the opportunity to study two children in one family with severe sickel cell anemia. The younger; a 12-year-old-girl, had a spleen that was easily palpable two to three finger breadths below the costal margin. The older boy, 16 years of age, had an even larger spleen at an age when it is usually fibrosed and not palpable. He had had more than 30 admissions in the first 10 years of his life, several of them with pneumonia, one of them with pneumococcal pneumonia and septicemia. Radiologic studies were done by Dr. DAVID PRICE, of our Nuclear Medicine Division, who has had experience with the use of technetium-99m in more than 800 cases, of both adults and children subjected to this liver and spleen scanning method. The first slide shows the technetium-99m sulfur colloid scintiphotos in this girl. In the upper field on the left are anterior and posterior views of the liver, but there is no splenic uptake visible. In the triangle of three scintiphotos to the right is the uptake in the bone marrow, which shows the unusual finding of active marrow tissue going all the way down into the ankles. The calvarium also clearly shows hypertrophied marrow spaces. The lower group of four shows the scintiphotos after injection of technetium-99m pertechnetate. This is a soluble marker which is quickly demonstrated in the heart and in the abdominal aorta. At succeeding 4-sec intervals, it appears in the kidneys but no spleen is outlined. Finally, at the end of a minute, there is the beginning of spleen visualization in the posterior view, showing a labeled plasma pool within the spleen although perfusion of it was slow and poor. In the second slide, the older boy was injected with autologous heat-treated red cells labeled with chromium. The liver uptake of this longer-lasting tag at 24 h is strikingly heavy but no splenic uptake is seen even though the spleen was quite large at this time. The final slide shows the results of studies before and after transfusion. In September, after technetium-99m sulfur injection, there was no splenic uptake of the colloid, although with a greater intensity of the image, there is a faint splenic trace. He came in at this time for treatment of a hemolytic crisis—was transfused with 2 units of packed red cells, giving him over 60% adult hemoglobin. Within 10 days after transfusion and reinjection of technetium-99m, the spleen became visible, particularly in the posterior view where it was easier to visualize because it is a posterior organ. Some 2 weeks later it was still visible; almost 1.5 months later, at which time his adult hemoglobin was still around 30%, it was faintly yet definitely visible. These studies corroborate the findings reported here by Dr. PEARSON and his associates. They are to be congratulated on adding to our knowledge not only of sickle cell disease but of some of the reasons for frequent infections in these patients and how to combat them. ROLAND B.SCOTT (Howard University College of Medicine, Washington, D.C.): My colleagues and I have been evaluating a group of older children with homozygous sickle cell anemia who exhibit persistent splenomegaly. The children ranged in age from 8 to 15 years. Isotopic scanning was employed as part of our studies. We also observed that the spleens in these children visualized poorly or not at all. In regard to your designation of this finding as ‘functional asplenia’, I would like to point out that our patients with splenomegaly so far have not exhibited greater susceptibility to intercurrent infection particularly of pneumococcal origin than other sicklers without splenomegaly. It is of particular interest to me that your patients with homozygous sickle cell anemia showed functional asplenia but the variant forms (Hgb AS, SC, S-thalassemia) exhibited normal splenic function by isotopic scanning technique. If the most likely mechanism is a mechanical one, I would appreciate further comment about this differential observation since stasis and vasoocclusion appear to be a fairly common finding in the SS, SC, and S-thalassemia types. Dr. SCHWARTZ: I believe that the phenomenon of functional asplenia is related to the degree of in vivo sickling, not simply the presence of sickle hemoglobin. The individual with SC disease or sickle-thalassemia is usually not as severely affected clinically as the homozygous sickler. Of interest is the fact that some patients with sickle-thalassemia have 80–90% hemoglobin S, yet still have splenic function. It is known that these people have less in vivo sickling than the homozygous hemoglobin S patient, although the reason for this is not clear. In fact, the splenic scan may be more accurate in identifying the sickle-thalassemia patient than is the hemoglobin electrophoresis. There is no increased incidence of pneumococcal sepsis in these people. I would like to comment on your observation of the lack of infection in your older patients. The young, splenectomized child is the patient most susceptible to overwhelming infection. Your patients are comparable to older splenectomized children. If an asplenic individual is exposed to an intravenous particulate antigen, he will not form antibodies against it. If he is exposed to the same antigen by the intramuscular, subcutaneous, or intraperitoneal route he can produce antibodies. The older patient probably has had immunologic experience with organisms introduced by routes other than the intravenous one. He, therefore, has antibodies to these organisms and is not usually susceptible to overwhelming infection. J. LAWRENCE NAIMAN (St. Christopher's Hospital for Children, Philadelphia, Penn.): Have you tried to open up the spleen pulp with fresh frozen plasma? PHILIP L.CALCAGNO (Georgetown University Hospital, Washington, D.C.): My question is the same one. Have you tried plasma, saline, or expanders? It would seem to me these might give a good handle to pathogenesis. Dr. SCHWARTZ: We tried to open up the spleen with fresh plasma in several children, but we could not.