PubMed · 7677964
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H F Bunn. 1993-01-14. Reversing ontogeny.. https://doi.org/10.1056/nejm199301143280210
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Sickle red blood cells (RBC) become dehydrated as a consequence of potassium loss. This process depends at least partly on deoxygenation and may be influenced by the presence of oxygenation/deoxygenation cycles and the frequency of cycling. In this study, sickle RBC were subjected to approximately 180 oxygenation/deoxygenation cycles during 4 hours to evaluate RBC dehydration with cycle periods more similar to in vivo cycles than those in previous studies. A continuous-flow, steady-state apparatus circulated a dilute RBC suspension through gas-permeable silicone tubing with segments that were exposed to either nitrogen or ambient oxygen. The percentage of sickling and partial pressure of oxygen were measured by means of sampling ports in the deoxygenation and oxygenation regions. The density increase (dehydration) of young (transferrin receptor-positive) and mature (transferrin receptor-negative) RBC and the requirements for calcium and chloride were evaluated. Density increase correlated with the percentage of sickled cells at the deoxygenation sampling port and was observed only in the presence of calcium, thereby implicating the calcium-dependent potassium channel (Gardos pathway). Density increase was not dependent on the presence of chloride, making it unlikely that KCl cotransport was an important pathway under these conditions. (Blood. 2000;95:2164-2168)
A low cation conductance and a high anion conductance are characteristic of normal erythrocytes. In sickle cell anemia, the polymerization of hemoglobin S (HbS) under conditions of low oxygen tension is preceded by an increase in cation conductance. This increase in conductance is mediated in part through Ca(++)-activated K(+) channels. A net efflux of potassium chloride (KCl) leads to a decrease in intracellular volume, which in turn increases the rate of HbS polymerization. Treatments minimizing the passive transport of ions and solvent to prevent such volume depletion might include inhibitors targeting either the Ca(++)-activated K(+) channel or the anion conductance. NS1652 is an anion conductance inhibitor that has recently been developed. In vitro application of this compound lowers the net KCl loss from deoxygenated sickle cells from about 12 mmol/L cells/h to about 4 mmol/L cells/h, a value similar to that observed in oxygenated cells. Experiments performed in mice demonstrate that NS1652 is well tolerated and decreases red cell anion conductance in vivo. (Blood. 2000;95:1842-1848)
BACKGROUND: Sickle cell intrahepatic cholestasis is a potentially catastrophic complication of sickle cell anemia Once acute liver failure develops, transplantation is the only option. We describe a patient with sickle cell intrahepatic cholestasis who underwent liver transplantation. METHODS: Data were obtained from the chart. Serial hemoglobin S levels were monitored, and measures were taken to maintain hemoglobin S <20% to prevent sickle cell crisis. RESULTS: Although the allograft functioned well initially, the patient developed veno-occlusive disease and required repeat transplantation at 5 months after transplant. Histologic examination of the explant revealed occlusion of the terminal hepatic venules due to fibrosis and packed red cells. Repeat transplant was complicated by thrombosis of the intrahepatic portion of the hepatic artery, and sepsis. The patient died of sepsis after a third transplant. CONCLUSION: Liver transplantation for sickle cell disease involving the liver may carry a high risk of graft loss due to vascular problems. Repeat transplantation may not be feasible if disease recurs.