Schematic map of the different shapes of the haptoglobin polymers as determined by phenotype.

These shapes have been confirmed by electron microscopic analysis of haptoglobin purified from patients with haptoglobin 1-1, 2-1, or 2-2.20 Critical disulfide linkages necessary for covalent cross-linking of haptoglobin monomers (circles) to form polymers are found on exons 3 and 4 (α-chain of haptoglobin). The haptoglobin 2 allele has a duplication of exons 3 and 4. The haptoglobin 1 monomer is monovalent (note single arrow) and thus can only associate with one other haptoglobin molecule to create dimers. The haptoglobin 2 monomer is bivalent (note 2 arrows) and can associate with 2 different haptoglobin monomers. Consequently, the haptoglobin in persons homozygous for the 2 allele will be cyclic polymers.