Scrambling of cell membranes exposing phosphatidyl serine is a general non-self signal that operates in platelet activation, apoptosis, necroptosis, hematological disorder, neuron synaptic pruning etc (46–48) and may reflect the activation mechanism of C3 that is available already in evolutionary old species e.g. tunicate (500-million-year-old) in which other complement factors, such as FB and FD, are absent and where C3 is part of extracellular phagocytic and intracellular processes (49). The gene discussed is C3; the disease is hematologic disorder.