In vitro can be produced by treating blood with potassium ferricyanide.

In vivo, it is produced by certain oxidant drugs or exposure to poisons like chlorates, acetanilid, nitrites, nitrobenzene, antipyrin, and sulfonamide drugs.

Familial methemoglobinemia is an inherited disorder due to lack or absence of methemoglobin reductase.

At 10-20% saturation, patient exhibits mild cyanosis.

At 20-40% saturation, patient exhibits visible cyanosis and fatigue.

At 40-60% saturation, patient exhibits severe cyanosis, tachycardia, and depression.

At greater than 60%, patient exhibits ataxia, severe cyanosis, loss of consciousness, and death.

In HbM, His F8 has been replaced by tyrosine. Fe(III) forms a tight ionic complex with the phenolate anion of tyrosine that stabilizes the Fe(III) form.

Alpha-chain HbM: T state is favored, O2 affinity is reduced, and the Bohr Effect is absent.

Beta-chain HbM: R-T switching, Bohr Effect is present.