Unified hypothesis for the origin of aplastic anemia and periodic hematopoiesis

Abstract

The clinical and laboratory data related to periodic hematopoiesis (PH) are briefly reviewed, and it is concluded that the dynamics of PH probably originate in the hematopoietic pluripotential stem cell (PPSC) population. A model for the PPSC population is developed and analyzed. Based on the model, the simplest hypothesis for the origin of aplastic anemia (AA) and PH is that they are both due to the irreversible loss of proliferative stem cells. In addition to offering estimates for normal PPSC parameters in man and dogs, the model offers an explanation for the rarity of PH and its observed dynamics. The hypothesis predicts that for subjects without proliferative PPSC loss and with a normal differentiation flux M* out of the PPSc, the effect of cell loss from proliferation will be hypocellularity and pancytopenia. However, in both man and dogs withanM* significantly less than normal, loss of proliferating PPSC at a low rate gives mild pancytopenia, loss at a higher rate gives PH, and at an even higher rate severe pancytopenia appears. The thresh