ZPP

What is being tested?
The zinc protoporphyrin (ZPP) test is a blood test that can identify a disorder of haem formation. 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. Haem is formed through a series of enzyme reactions that end with an iron atom being inserted into the centre of a molecule called protoporphyrin. If not enough iron is available, or if ferrochelatase (the enzyme responsible for inserting the iron) is blocked, protoporphyrin combines with zinc instead of iron to form zinc protoporphyrin. Because it cannot carry oxygen, ZPP is of no use to the red cells that contain it.
The term ZPP is sometimes used interchangeably with free erythrocyte protoporphyrin (FEP). In fact, about 90% of the protoporphyrin in red cells is ZPP, while the rest is present as FEP (not bound to zinc). The method used to measure ZPP measures both substances, and the results may be reported as either ZPP or FEP.

How is the sample collected for testing?
In adults, ZPP is measured directly in a whole blood sample obtained from a vein. In children, the ZPP/haem ratio is often measured, using a drop of blood obtained by fingerprick and an instrument called a haematofluorometer. This instrument measures the fluorescence of ZPP and reports the amount of ZPP per number of haem molecules.

How is it used?
When is it requested?
What does the result mean?
Is there anything else I should know?

How is it used?
Zinc protoporphyrin is requested mainly to help detect iron deficiency in children and to detect and monitor chronic lead exposure in adults. Lead inhibits the action of ferrochelatase, which increases ZPP formation even when there is enough iron. ZPP is considered a better screening test for lead burden (the total amount of lead in the body) than the lead level itself, because blood lead levels tend to vary from day to day and because lead moves from the blood into the organs and bone. While blood samples for lead can be contaminated by lead in the environment at the time of collection, ZPP is not affected by this.
In the general adult population, ZPP may be requested together with lead levels as part of a screening programme for chronic lead exposure. People who work with products containing lead and people who live in old houses are examples of those who may be at increased risk of lead poisoning. This is because lead is usually swallowed or inhaled. People who inhale dust containing lead, handle lead directly or eat it, or – in the case of children – swallow flakes of lead-based paint (common in houses built before 1960), may have high levels of lead and ZPP in their body. In industry, the Occupational Safety & Health Administration recommends the use of ZPP and strongly recommends that ZPP be ordered whenever lead levels are requested to check workers’ exposure to lead. Both are needed because ZPP does not reflect recent or acute lead exposure and does not change quickly when a patient is removed from lead exposure. ZPP is better at showing a person’s average lead exposure over the last 3-4 months.

The maximum lead level considered safe in children has been set very low to minimise the negative impact of lead exposure on their development. ZPP is not sensitive enough to be used as a screening test in children, because values do not rise until lead levels exceed the acceptable limit. In this age group, blood lead must be measured to determine lead exposure.

In children, the ZPP/haem ratio is often ordered as an early indicator of iron deficiency. It is one of the first signs of iron deficiency and will be raised in younger people before the signs and symptoms of anaemia appear. Those with a high ZPP/haem ratio may need further tests to determine the cause. In some cases, a patient may have both lead exposure and iron deficiency.

ZPP is also requested to help diagnose porphyrias. These are a group of rare inherited disorders that cause a deficiency of enzymes needed to produce haem. The lack of an enzyme causes a bottleneck and a build-up of intermediate products that are normally converted into haem. There are two porphyrias in which the levels of ZPP and other porphyrins accumulated in the red cells are very high. The main symptom in these patients is high sensitivity to sunlight.

When is it requested?
ZPP is ordered together with the lead level when chronic lead exposure is suspected, when a worker is part of an occupational lead exposure monitoring programme, or when someone has a hobby, such as glass painting, that brings them into frequent contact with lead. The ZPP/haem ratio is requested as a screening test for iron deficiency in children and adolescents and/or when iron deficiency is suspected. ZPP is sometimes requested when a patient is sensitive to sunlight and the doctor suspects porphyria.

What does the test result mean?
The ZPP concentration in whole blood is usually very low. A rise in ZPP indicates a disturbance of normal haem production but does not show its cause. The main reasons for a rise in ZPP are iron deficiency, lead poisoning and, rarely, porphyria. It is very important for ZPP levels to be assessed in the context of the patient’s history, clinical findings and the results of other tests such as ferritin, whole blood lead and the full blood count. A patient may have both iron deficiency and lead poisoning. In cases of chronic lead exposure, ZPP reflects average lead levels over the previous 3-4 months. However, the amount of lead currently in the blood and the body’s lead burden (the amount in the organs and bone) cannot be determined by ZPP testing. ZPP values rise more slowly than blood lead after exposure, and take much longer to fall after lead exposure has stopped.

A rise in the ZPP/haem ratio in a child is mostly due to iron deficiency. If ZPP or the ZPP/haem ratio is greatly raised and the patient is very sensitive to sunlight, porphyria may be present.

Is there anything else I should know?
ZPP may be raised in inflammatory conditions, infections and severe blood disorders, but it is not generally used to monitor or diagnose these conditions. Depending on the method used to measure ZPP, other fluorescent substances in the blood, such as bilirubin and riboflavin, may produce false-positive results. False-negative results may occur if the samples have not been protected from light.
ZPP is not a test that doctors typically request to screen for iron deficiency; rather, it is used mostly by public health departments for this purpose.

1. Besides ZPP and lead levels, what other tests might the doctor order to monitor lead exposure?

1. Besides ZPP and lead levels, what other tests might the doctor order to monitor lead exposure?
If you work in an occupation where you are frequently exposed to lead, your doctor may order the following tests to check your kidneys and blood cell production:

• Blood urea nitrogen (BUN)
• Creatinine
• Urinalysis
• Full blood count or haemoglobin and haematocrit
• Peripheral blood smear