Patient Test Information

Zinc Protoporphyrin

Also known as:

ZPP; ZP; Free Erythrocyte Protoporphyrin; FEP; ZPP/Heme Ratio

Formal name:

Zinc Protoporphyrin

Related tests:

Serum Iron; Iron Tests; Lead; Complete Blood Count; Hemoglobin; Hematocrit; Porphyrin Tests

Why Get Tested?

To screen for and monitor chronic exposure to lead in adults; to detect iron deficiency in children

When to Get Tested?

When you have been chronically exposed to lead, as part of a program to monitor lead exposure, and/or when your healthcare provider suspects lead poisoning; as part of a screening program for iron deficiency in children and adolescents

Sample Required?

A blood sample drawn from a vein in your arm or from a fingerstick

Test Preparation Needed?

None

How is it used?

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

ZPP is a substance that is normally found in small amounts in red blood cells. Most of the protoporphyrin in red blood cells combines with iron to form heme, the molecule in hemoglobin that carries oxygen. Zinc combines with protoporphyrin instead of iron when there is insufficient iron available to form heme, as in iron deficiency, or when lead is present and blocks the formation of heme, as in lead poisoning. The level of ZPP in the blood will rise with these conditions.

Two types of test are available to measure ZPP:

  • The free erythrocyte protoporphyrin (FEP) test measures both ZPP, which accounts for 90% of protoporphyrin in red blood cells, and free protoporphyrin, which is not bound to zinc.
  • The ZPP/heme ratio gives the proportion of ZPP compared to the normal iron-containing heme in red blood cells.

Lead exposure

ZPP testing 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. Those who inhale dust that contains lead or handle lead directly and contaminate their hands and then eat may have elevated lead levels. Children who 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 lead screening test in children, as values do not rise until lead concentrations exceed the acceptable range. The maximum lead concentration considered safe in children has been set at a very low level by the Centers for Disease Control and Prevention (CDC). In this age group, tests that measure the blood lead concentration are done to detect exposure to lead.

Iron deficiency anemia

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.

When is it ordered?

ZPP may be ordered along with a lead test when chronic exposure to lead is known or suspected. Signs and symptoms of lead poisoning include:

  • High blood pressure
  • Numbness and/or tingling in the hands and feet
  • Memory loss, mood disorders
  • Weakness
  • Abdominal pain
  • Headache

The test may be ordered when an employee is a participant in an occupational lead monitoring program or when someone has a hobby, such as working with stained glass, that brings the person into frequent contact with lead.

The ZPP/heme ratio may be ordered as a screening test for iron deficiency in children and adolescents or when iron deficiency is suspected. Some symptoms of iron deficiency include:

  • Chronic fatigue, tiredness
  • Dizziness
  • Weakness
  • Headaches

If the iron-deficiency anemia is severe, shortness of breath, dizziness, chest pain, headaches, and leg pains may occur. Children may develop learning (cognitive) disabilities. Besides the general symptoms of anemia, there are certain symptoms that are characteristic of iron deficiency. These include pica (cravings for specific substances, such as licorice, chalk, dirt, or clay), a burning sensation in the tongue or a smooth tongue, sores at the corners of the mouth, and spoon-shaped fingernails and toenails.

What does the test result mean?

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 person'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 person 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 amount in the organs and bones cannot be determined with a ZPP test. Values for ZPP rise more slowly than blood lead concentrations 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 successful treatment.

Is there anything else I should know?

ZPP may be elevated in inflammatory conditions, infections, and in people with anemia of chronic disease, but it is not generally used to monitor or diagnose these conditions. A very high ZPP level may be seen in two hereditary diseases: protoporphyria and congenital erythropoietic porphyria (see Porphyria). Both of these disorders are very rare and present with symptoms related to the skin (extreme sensitivity to sunlight). 

Depending on the method used to test ZPP, high levels of other substances in the blood, 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.

What is being tested?

Zinc protoporphyrin (ZPP) is normally present in red blood cells in small amounts, but the level may increase in people with lead poisoning and iron deficiency. This test measures the level of ZPP in the blood.

To understand how lead poisoning and iron deficiency affect the ZPP level, it is first necessary to know about heme. Heme is an essential component of hemoglobin, the protein in red blood cells that carries oxygen from the lungs to the body's tissues and cells.

The formation of heme occurs in a series of steps that conclude with the insertion of an iron atom into the center of a molecule called protoporphyrin. When there is not enough iron available, as in iron deficiency, or when the insertion of iron is inhibited, as in lead poisoning, then protoporphyrin combines with zinc instead of iron to form zinc protoporphyrin. ZPP serves no useful purpose in red blood cells since it cannot bind to oxygen.

ZPP may be measured in one of two ways:

  • The free erythrocyte protoporphyrin (FEP) test measures both ZPP, which accounts for 90% of protoporphyrin in red blood cells, and free protoporphyrin, which is not bound to zinc.
  • The ZPP/heme ratio gives the proportion of ZPP compared to the normal iron-containing heme in red blood cells.

How is the sample collected for testing?

To measure FEP, a blood sample is taken by inserting a needle into a vein in the arm. To determine the ZPP/heme ratio, a drop of blood from a fingerstick is placed in an instrument called a hematofluorometer. This instrument measures the fluorescence of ZPP and reports the amount of ZPP per number of heme molecules. Since only a single drop of blood is required, this test is well suited for screening children.

NOTE: If undergoing medical tests makes you or someone you care for anxious, embarrassed, or even difficult to manage, you might consider reading one or more of the following articles: Coping with Test Pain, Discomfort, and Anxiety, Tips on Blood Testing, Tips to Help Children through Their Medical Tests, and Tips to Help the Elderly through Their Medical Tests.

Another article, Follow That Sample, provides a glimpse at the collection and processing of a blood sample and throat culture.

Is any test preparation needed to ensure the quality of the sample?

No test preparation is needed.

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

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

  2. Should everyone have a ZPP test?

    No. This test will only be done for adults with suspected chronic exposure to lead, as a screening test to detect iron deficiency in children, or occasionally to test for a porphyria that affects the skin. 

  3. If I have a hobby such as stained glass working but no symptoms, do I need to have a ZPP test done?

    Talk to your healthcare provider about this. If the hobby is a frequent activity, then it may be recommended that you have a ZPP test and a lead test to evaluate your lead exposure. You can have an increased ZPP level with few to no symptoms or you may have symptoms that have not yet been linked to lead exposure.