Fetal hemoglobin in sickle cell disease: relationship to erythrocyte phosphatidylserine exposure and coagulation activation

In sickle cell disease (SCD), loss of erythrocyte membrane phospholipid asy mmetry occurs with the exposure of phosphatidylserine (PS), which provides a docking site for coagulation proteins. In vivo sickling/desickling, with resulting red cell membrane changes and microvesicle formation, appears to be one of the factors responsible for PS exposure. We evaluated children wi th SCD homozygous for sickle hemoglobin (SS disease) and controls (n = 65) and demonstrate that high levels of fetal hemoglobin (assessed as F cells) are associated with decreased microvesicle formation, PS exposure, and thro mbin generation. F cells correlated inversely with both microvesicles and P S positivity (P < .000001) in SS disease, Multiple regression analyses usin g various hematologic parameters as independent variables, and either micro vesicles or PS positivity as the dependent variable, showed a strong relati onship only with F cells. Additionally, plasma prothrombin fragment F1.2 le vels (a marker for thrombin generation) correlated with both PS positivity (P < .001) and F cells (P < .01). An F-cell level of approximately 70% was associated with normal levels of prothrombin fragment F1.2 and with microve sicle formation indistinguishable from control values. We suggest that the use of such surrogate biologic markers in conjunction with F-cell numbers m ay provide valuable insights into the biology and consequences of in vivo s ickling. (C) 2000 by The American Society of Hematology.