Serum or Plasma Ferritin
Date of SC final approval
About the Measure
Domain:
Measure:
Definition:
Sickle Cell Disease: Cardiovascular, Pulmonary, and Renal
Serum or Plasma Ferritin
A bioassay to measure the serum concentration of ferritin (i.e., iron).
Purpose:
This measure can be used to evaluate an individual’s iron metabolism, which is
important for determining the presence and severity of anemia, and the assessment of
iron therapy. Additionally this measure is used to assess iron overload (accumulation
of iron in the body), which is associated with hereditary hemochromatosis and with
transfusion therapy for many clinical conditions including sickle cell disease,
thalassemia, other rare anemias, Hodgkin’s disease, acute leukemia,
hemochromatosis, and carcinomas of many tumor types.
About the Protocol
Description of
Protocol:
Selection
Rationale:
Specific
Instructions:
The National Health and Nutrition Examination Survey (NHANES) 2009-2010
Laboratory Procedures Manual for serum/plasma ferritin testing provides
comprehensive instructions for processing and storing blood samples to determine an
individual’s serum ferritin level. Because there are many comparable assays and
instruments for measuring ferritin, the protocol also provides basic guidelines to aid
comparability among different studies.
The Sickle Cell Disease Working Group 1 (Cardiovascular, Pulmonary, and Renal)
selected the National Health and Nutrition Examination Survey (NHANES) 2009-2010
Laboratory Procedures Manual for serum ferritin testing because the method is well
validated and the equipment used is widely available.
 The National Health and Nutrition Examination Survey (NHANES) instructions
for drawing, processing, and storing blood provide a standard methodology
used successfully for many years to ensure comparable results across study
sites. However, the Sickle Cell Disease Working Group 1 (Cardiovascular,
Pulmonary, and Renal) notes that certain aspects (e.g., exclusion criteria) of
the NHANES protocol are study specific and might not be applicable to all
types of studies (e.g., sickle cell disease).

The Working Group acknowledges that the results of serum ferritin testing is
affected by inflammation, liver damage, and ascorbate status.

Collection of blood samples for the measurement of analytes requires a
general determination of whether to use serum or plasma for the assay and
also a determination of the type of collection tube to be obtained. For example,
if serum is to be used, a determination needs to be made as to whether red
top or serum gel separator collection tubes are used. While comparable values
are obtained for many analytes from either serum or plasma, there may be
situations where differences are more pronounced and serum- or plasmaspecific norms will be needed for references. The NHANES protocol presented
here uses red top/serum separator tubes. At times it may be possible to collect
both, but other considerations such as participant burden may be the deciding
factor. It is important to match assay type with sample type. Some automated
devices may preclude the use of serum, for example, while others may be
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Serum or Plasma Ferritin
Date of SC final approval
Protocol Text:
optimized for it. Investigators should choose methods of collection that match
the methods of analysis. This will best be done by communicating with the
laboratory where the proposed assays will be performed. They will become an
important partner with you in ensuring that there is compatibility from collection
to assays to interpretation and reporting of levels and results
The following is a summary version of the full National Health and Nutrition
Examination Survey protocol.
Exclusion Criteria
Persons will be excluded from this component if they:
• Report that they have hemophilia; or
• Report that they have received cancer chemotherapy in the last 4 weeks
SP = Sample Person.
1. Do you have hemophilia?
1[]
2[]
7[]
9[]
Yes
No
Refused
Don’t Know
If the SP answers "Yes," the SP is excluded from the blood draw.
If SP answers "No" or "Don’t Know," blood is drawn from the SP.
2. Have you received cancer chemotherapy in the past four weeks or do you
anticipate such therapy in the next four weeks?
1 [ ] Yes
2 [ ] No
7 [ ] Refused
9 [ ] Don’t Know
If the SP answers "Yes," the SP is excluded from the blood draw.
If SP answers "No" or "Don’t Know," blood is drawn from the SP.
Venipuncture Procedures
Editor’s Note: Please review chapter 4 of the Laboratory Procedures Manual from the
2009-2010 National Health and Nutrition Examination Survey (NHANES) for a full
description of phlebotomy procedures. This manual is posted here, and is also
available at the NHANES website:
http://www.cdc.gov/nchs/data/nhanes/nhanes_09_10/lab.pdf
Venipuncture should generally be performed using the median cubital, cephalic, or
basilic veins in the left arm unless this arm is unsuitable. If the veins in the left arm are
unsuitable, look for suitable veins on the right arm. If the veins in the antecubital
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Serum or Plasma Ferritin
Date of SC final approval
space on both arms are not suitable, then look for veins in the forearm or dorsal side
of the hand on the left arm/hand and then the right arm/hand.
Fill a 3 or 4 ml K3 EDTA tube with blood.
Recording the Results of the Venipuncture Procedure
Immediately after completing the venipuncture, record the results of the blood draw,
the reasons for a tube not being drawn according to the protocol, and any comments
about the venipuncture. Collection tube should be standardized across the study
duration.
Laboratory Assay for Ferritin
The Sickle Cell Disease Working Group 1 (Cardiovascular, Pulmonary, and Renal)
notes that there are a number of different assays and instruments that are appropriate
to measure ferritin. Once an assay is chosen for a particular study, the Working Group
recommends that no changes in the protocol be made over the course of the study.
To aid comparability, the Working Group recommends that the investigator record the
make and manufacturer of equipment used and the repeatability and coefficients of
variation for the assay.
Reference Ranges (Normal Values) for Ferritin
Ferritin reference ranges are assay-specific. The Roche Diagnostics kit used by
NHANES specifies expected values of 30-400 ng/mL for men and 13-150 ng/mL for
women.
Participant:
Source:
Language of
Source:
Note: A full description of the National Health and Nutrition Examination Survey
procedure for serum ferritin testing can be found in the 2009-2010 Laboratory
Procedure Manual posted here, and is also available at the NHANES website:
http://www.cdc.gov/nchs/data/nhanes/nhanes_09_10/FERTIN_F_met_ferritin.pdf
All ages
Centers for Disease Control and Prevention (CDC). (2009). National Health and
Nutrition Examination Survey Questionnaire. Laboratory Procedures Manual.
Hyattsville, MD: U.S. Department of Health and Human Services, Centers for Disease
Control and Prevention.
English
Personnel and
Training Required:
Equipment Needs:
Phlebotomist
Protocol Type:
Bioassay
Laboratory that can perform the serum ferritin test.
Requirements:
Requirements Category
Major equipment
Required (Yes/No):
No
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Serum or Plasma Ferritin
Date of SC final approval
Common Data
Elements:
General
References:
Specialized training
No
Specialized requirements for biospecimen
collection
Average time of greater than 15 minutes in an
unaffected individual
TBD by PhenX Team
No
No
Adamkiewicz, T. V., Abboud, M. R., Paley, C., Olivieri, N., Kirby-Allen, M., Vichinsky,
E., Casella, J. F., Alvarez, O. A., Barredo, J. C., Lee, M. T., Iyer, R. V., Kutlar, A.,
McKie, K. M., McKie, V., Odo, N., Gee, B., Kwiatkowski, J. L., Woods, G. M., Coates,
T., Wang, W., & Adams, R. J. (2009). Serum ferritin level changes in children with
sickle cell disease on chronic blood transfusion are nonlinear and are associated with
iron load and liver injury. Blood, 114(21), 4632-4638.
Drasar, E., Vasavda, N., Igbineweka, N., Awogbade, M., Allman, M., & Thein, S.L.
(2012). Serum ferritin and total units transfused for assessing iron overload in adults
with sickle cell disease. British Journal of Haematology, 157(5), 645-647.
Additional Information About the Measure
Essential Data:
Gender, Current age, Race, Ethnicity
Related PhenX
Measures:
Derived Variables:
Keywords/Related
Concepts:
None
None
Serum ferritin, plasma ferritin, iron, anemia, sickle cell disease, SCD, thalassemia,
iron overload, hereditary hemochromatosis, iron deficiency, cancer, lung, colon,
liver, prostate, acute leukemia, Hodgkin’s disease, hemochromatosis, carcinoma,
NHANES
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