ANXA5 and sickle cell disease: This hypothesis is supported by the evidence in the most extreme example of PS-dependent simultaneous multiple microvascular occlusions, namely in patients with sickle cell disease, where an imbalance between available Annexin A5 and PS expression in erythrocytes is linked to the severity of the vaso-occlusive crisis and vascular injury [30,76], with this imbalance proposed to be the driving force behind extensive vascular injury during a vaso-occlusive crisis in sickle cell disease [29,77].