Membrane cross bonding in red cells in favic crisis: a missing link in the mechanism of extravascular haemolysis.
Red cells of G6PD (D-glucose-6-phosphate:NADP+ 1-oxidoreductase; G6PD) deficient (Mediterranean variant) subjects were studied during a fava bean haemolytic crisis. Two representative cases are described. In Case 1, haemolysis was still going on. In more than 50% of the red cells the Hb was confined to one part of the cell, leaving the other part as transparent as a Hb-free ghost. In this part the membranes appeared tightly bonded because swelling did not peel apart the bonded membrane areas. This feature is defined as membrane cross bonding (MCB). In Case 2, haemolysis had terminated and MCB-cells were less than 1%. MCB was reproduced in vitro by incubating G6PD-deficient whole blood with 1 mM divicine for up to 10 h. Subsequent shrinkage of red cells in hypertonic plasma (400 mOsm) resulted in the rapid formation of MCB. Membrane modifications by divicine, contained in fava beans, followed by osmotic shrinkage in the kidney and/or squeezing in the microcirculation are proposed as the cause of MCB during the favic crisis. MCB reduces the effective surface area of red cells. This is a plausible cause for sequestration by the reticulo-endothelial system. Intravascular haemolysis observed in favic crisis cannot be explained by mechanical forces, but it is possible that the effective surface area is reduced by MCB to such an extent that red cells lyse osmotically.
D002648:Child; D002675:Child, Preschool; D004910:Erythrocyte Membrane / Q000378:metabolism*; D004912:Erythrocytes / Q000187:drug effects / Q000473:pathology; D005236:Favism / Q000097:blood* / Q000201:enzymology; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000097:blood / Q000201:enzymology; D006366:Heinz Bodies / Q000473:pathology; D006461:Hemolysis; D006801:Humans; D008297:Male; D011744:Pyrimidinones / Q000494:pharmacology
D011744:Pyrimidinones; C026511:divicine