What is being tested?

The zinc protoporphyrin (ZPP) test is a blood test that can identify a disruption in the formation of haem. Haem is an essential component of haemoglobin, the protein in red blood cells (RBC) that carries oxygen from the lungs to the body's tissues and cells. The formation of haem occurs in a series of enzymatic steps that conclude with the insertion of an iron atom into the centre of a molecule called protoporphyrin. Lead also inhibits haem synthesis and therefore can cause an increase in RBC ZPP. If there is not enough iron available, then protoporphyrin combines with zinc instead of iron to form zinc protoporphyrin. Since it cannot transport oxygen, ZPP serves no useful purpose in the RBC that contain it.

ZPP is usually measured relative to the amount of haemoglobin.The ZPP/haem ratio gives the proportion of ZPP compared to haem in red blood cells. ZPP itself is measured in two ways. Some methods measures total erthyrocyte protoporphyrin, which includes both ZPP, (more than 90% of protoporphyrin in red blood cells), and free protoporphyrin (FEP), which is not bound to zinc. As ZPP usually makes up most of the total erthyrocyte protoporphyrin, the ability to discriminate between ZPP and FEP is not considered significant. Other methods are able to discriminate between ZPP and FEP measure only ZPP.

How is it used?

Zinc protoporphyrin is primarily ordered to detect and monitor chronic exposure to lead in adults. In screening programmes it can be used to detect iron deficiency in children.

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.

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) in the USA and the National Health and Medical Research Council (NHMRC) in Australia to minimise 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/haem ratio is sometimes ordered as an early indicator of iron deficiency. An increase in the ZPP/haem ratio is one of the first signs of insufficient iron stores and will be elevated in most young people before signs or symptoms of anaemia are present. More specific tests of iron status are required to confirm iron deficiency.

When is it requested?

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 programme, or when someone has a hobby, such as stained glass working, that brings them into frequent contact with lead. The ZPP/haem ratio is ordered as a screening test for iron deficiency in children and adolescents and/or when iron deficiency is suspected.

What does the result mean?

The ZPP concentration in blood is usually very low. An increase in ZPP indicates a disruption of normal haem 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 full blood count (FBC). 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. ZPP remains useful for ongoing monitoring of individuals on treatment with confirmed elevated lead levels.

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

Is there anything else I should know?

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, anaemia 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.

Common questions

  • Besides ZPP and lead levels, what other tests might my physician order to monitor exposure to lead?

If you are in an occupational setting where you are frequently exposed to lead, your physician may order the following tests to evaluate your kidneys and red blood cell production:

  • Urea
  • Creatinine
  • Urinalysis
  • Full Blood Count or haemoglobin and Haematocrit (PCV)
  • Peripheral blood smear

Last Updated: Thursday, 1st June 2023

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