Zinc protoporphyrin is primarily ordered to help detect iron deficiency in children and to detect and monitor chronic exposure to lead in adults.

ZPP may be ordered, along with a lead level, to test for chronic lead exposure. Hobbyists who work with products containing lead and people who live in older houses may be at an increased risk of developing lead poisoning. This is because lead is usually ingested or inhaled. Those who inhale dust that contains lead, handle lead directly and then eat, or in the case of children, eat paint chips that contain lead (common in houses built prior to 1960) can have elevated levels of lead and ZPP in their body. In an industrial setting, the Occupational Safety & Health Administration (OSHA) mandates the use of the ZPP test and strongly recommends that a ZPP test be ordered every time that a lead level is ordered to monitor an employee’s exposure to lead. Both are necessary because ZPP will not reflect recent or acute lead exposure, and it does not change quickly when a person’s source of lead exposure is removed. ZPP is best at detecting a person’s average exposure to lead over the last 3-4 months.

ZPP is not sensitive enough for use as a screening test in children, as values do not rise until lead concentrations exceed the acceptable range. The maximum lead concentrations considered safe in children have been set at a very low level by the Centers for Disease Control and Prevention (CDC) to minimize the negative impact of lead exposure on their development. In this age group, blood lead measurements should be done to detect exposure to lead.

In children, the ZPP/heme ratio is sometimes ordered as an early indicator of iron deficiency. An increase in the ZPP/heme ratio is one of the first signs of insufficient iron stores and will be elevated in most young people before signs or symptoms of anemia are present. More specific tests of iron status are required to confirm iron deficiency.

ZPP is ordered along with lead for adults when chronic exposure to lead is suspected, when an employee is a participant in an occupational lead monitoring program, or when someone has a hobby, such as stained glass working, that brings them into frequent contact with lead. The ZPP/heme ratio is ordered as a screening test for iron deficiency in children and adolescents and/or when iron deficiency is suspected.

The ZPP concentration in blood is usually very low. An increase in ZPP indicates a disruption of normal heme production but is not specific as to its cause. The main reasons for increases in ZPP are iron deficiency and lead poisoning. It is important that ZPP levels be evaluated in the context of a patient’s history, clinical findings, and the results of other tests such as ferritin, lead, and a complete blood count (CBC). It is possible that the patient may have both iron deficiency and lead poisoning.

In cases of chronic lead exposure, ZPP reflects the average lead level over the previous 3-4 months. However, the amount of lead currently present in the blood and the burden of lead in the body (the amount in the organs and bones) cannot be determined with a ZPP test. Values for ZPP rise more slowly than blood lead concentration following exposure, and they take longer to drop after exposure to lead has ceased.

An increase in the ZPP/heme ratio in a child is most often due to iron deficiency. A decreasing ZPP/heme ratio over time following iron supplementation likely indicates an increase in iron availability.

An increased ZPP level is also seen in erythropoietic porphyrias, but these hereditary diseases are much less common than iron deficiency or lead poisoning.

ZPP may be elevated in inflammatory conditions, anemia of chronic disease, infections, and several blood-related diseases, but it is not generally used to monitor or diagnose these conditions.

Depending on the method used to test ZPP, other substances in the blood that fluoresce, such as bilirubin and riboflavin, can produce false positive results. Falsely low values may occur if the sample is not protected from light before testing.