Zinc Protoporphyrin
Note: this site is for informational purposes only. To view test results or book a test, use the NHS app in England or contact your GP.
The zinc protoporphyrin (ZPP) test is a blood test in which a sample is taken from a vein to measure the level of ZPP formed during red blood cell production. It is used to help detect lead exposure and iron deficiency, particularly when these conditions interfere with normal haemoglobin formation.
Why get tested?
To screen for and monitor chronic exposure to lead in industry; as an aid in the diagnosis of iron deficiency in children
When to get tested?
When you have been chronically exposed to lead in your working environment, or when your doctor suspects lead poisoning
Sample required?
An anti-coagulated blood sample taken from a vein in your arm
Test preparation needed?
No test preparation is needed.
What is being tested?
The test measures the concentration of zinc protoporphyrin (ZPP) in the blood. ZPP is present in blood in trace amounts and is formed during the production of haem. Concentrations of ZPP are increased in patients with lead poisoning and iron deficiency. Haem is an essential component of haemoglobin, the protein in red blood cells (RBCs) that carries oxygen from the lungs to the body’s tissues and cells. The formation of haem occurs in a series of reactions that conclude with the insertion of an iron into the centre of a molecule called protoporphyrin. If there is not enough iron available, then zinc is incorporated into protoporphyrin form zinc protoporphyrin (ZPP). ZPP serves no useful purpose in the red blood cells since it cannot transport oxygen around the body.
Lead prevents iron (but not zinc) from attaching to protoporphyrin so zinc protoporphyrin will also be elevated in severe cases of lead poisoning and iron deficiency.
ZPP is measured in two ways. The free erythrocyte protoporphyrin (FEP) test measures both ZPP (which accounts for 90% of protoporphyrin in red blood cells) and free protoporphyrin (not bound to zinc). The ZPP/haem ratio gives the proportion of ZPP compared to haem in red blood cells.
How is the sample collected for testing?
To measure FEP, an anticoagulated blood sample is taken by inserting a needle into a vein in your arm. To determine the ZPP/haem ratio, a drop of blood is placed in an instrument called a haematofluorometer. This instrument measures the fluorescence of ZPP and reports the amount of ZPP per number of haem molecules. Since only a single drop of blood is required, this test is well suited for screening children.
Common questions
Zinc protoporphyrin (ZPP) is primarily requested to detect and monitor chronic exposure to lead in adults and to aid in the diagnosis of iron deficiency in children.
ZPP may be requested in addition to lead, 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, suck or eat paint that contain lead (common in houses built prior to 1960) can have elevated levels of lead and ZPP in their body.
In the UK, the Health Protection Agency (HPA) offers guidance on safety of chemicals both in the environment and the workplace. Currently, only recommendations based on blood lead concentration are given.
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 blood lead concentrations considered safe in children have been set at a very low level 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 requested 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. As more specific tests of iron status are required to confirm iron deficiency, this is seldom used but still has a role in developing countries.
ZPP may be requested alongside lead in 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. ZPP may also rarely be requested as a 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 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 concentrations 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 concentration 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 the blood lead concentration following exposure, and they take longer to drop after exposure to lead has ceased.
An increased ZPP concentration is also seen in erythropoietic porphyrias. In X‑linked dominant protoporphyria (XLDPP) there are increases in both free protoporphyrin and ZPP. However, 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.
ZPP may also be increased in genetic conditions such as Thalassaemia’s where there are surplus globins which are not used in the formation of haemoglobin.
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.
If you are in an occupational setting where you are frequently exposed to lead, your doctor may use the following tests to evaluate your kidneys and red blood cell production: