In people with sickle-cell disease, red blood cells break down, clump, and clog the blood vessels. the blood vessels and the broken cells accumulate in the spleen. among other things this leads to physical weakness, heart failure, joint pain, and brain damage. such a suite of symptoms can be explained by

a) a bacterial infection interacting with the sickle-cell allele
b) the pleiotropic effects of the sickle-cell allele
c) the polygenic nature of sickle-cell disease
d) an epistatic interaction between the sickle-cell allele and a proteolytic enzyme gene
e) side effects of the drugs used to cure sickle-cell disease