Unusually Largevon Willebrand FactorMultimers Increase AdhesionofSickle Erythrocytes toHumanEndothelial CellsunderControlled Flow

Theinteractions ofnormal erythrocytes anderythrocytes from patients having hemoglobin S hemoglobinopathies withnormalhumanendothelial cells (EC) wereinvestigated under flow conditions. WhenECsupernatant, containing 2.8-11.0 U/dlof vonWillebrand factor (vWF)antigen andvWF multimeric forms larger thanthose present innormal plasma, wasthered bloodcell (RBC)-suspending mediuminstead ofserum-free medium(SFM),theadhesion ofsickle RBC,butnotnormal RBC,toendothelial cells wasgreatly increased (range ofenhancement ofsickle RBCadhesion, 2-to27-fold). Adhesion of sickle RBCtoendothelial cells wasreduced tonearserum-free levels whenECsupernatant wasimmunologically depleted of vWF forms. Sickle RBC suspended inSFM containing 200 U/dlofpurified vWF multimers ofthetypefound innormal humanplasmaor300jg/ml humanfibronectin wereonly slightly moreadhesive toendothelial cells thansickle RBC suspended inSFMalone. Thesedataindicate thatunusually large vWF multimers produced byendothelial cells arepotent mediators oftheadhesion ofsickle erythrocytes toendothelial cells. Vaso-occlusive crises insickle cell anemia maybecaused, atleast inpart, byadhesive interactions between theabnormal surfaces of sickle RBCandtheendothelium after therelease ofunusually large vWF multimeric forms fromstimulated ordamaged endothelial cells.