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Test ID FRAG Osmotic Fragility, Erythrocytes

Reporting Name

Osmotic Fragility, RBC

Useful For

Evaluating suspected hereditary spherocytosis-associated hemolytic anemia


Confirming or detecting mild spherocytosis

Profile Information

Test ID Reporting Name Available Separately Always Performed
FRAGO Osmotic Fragility No Yes
SCTRL Shipping Control Vial No Yes

Specimen Type

Whole Blood EDTA

Ordering Guidance


Additional Testing Requirements


Shipping Instructions

Specimens must arrive within 72 hours of collection.

Necessary Information

Patient's age is required.

Specimen Required

Both a whole blood EDTA specimen and a shipping control specimen are required. The shipping control specimen is used to evaluate whether a patient result has been compromised by handling conditions such as temperature, motion, or other transportation interferences. Temperature and handling extremes can adversely impact the integrity of the specimen.



Specimen Type: Whole blood

Container/Tube: Lavender top (EDTA)

Specimen Volume: 4 mL

Collection Instructions:

1. Refrigerate specimen immediately after collection.

2. Send whole blood specimen in original tube. Do not aliquot.

3. Rubber band patient specimen and control vial together.


Normal Shipping Control:

Specimen Type: Whole blood

Container/Tube: Lavender top (EDTA)

Specimen Volume: 4 mL

Collection Instructions:

1. Collect a shipping control specimen from a normal (healthy), unrelated, nonsmoking person at the same time as the patient.

2. Clearly hand write “normal control” on the outermost label.

3. Refrigerate specimen immediately after collection.

4. Send control specimen in original tube. Do not aliquot.

5. Rubber band patient specimen and control vial together. The control and patient specimen must be handled in the same manner from specimen collection to receipt in the testing laboratory.

Specimen Minimum Volume

Patient whole blood, shipping control: 2 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Control Refrigerated 72 hours PURPLE OR PINK TOP/EDTA
Whole Blood EDTA Refrigerated 72 hours

Reference Values

≥12 months:

0.50 g/dL NaCl (unincubated): 3-53% hemolysis

0.60 g/dL NaCl (incubated): 14-74% hemolysis

0.65 g/dL NaCl (incubated): 4-40% hemolysis

0.75 g/dL NaCl (incubated): 1-11% hemolysis


NaCl = sodium chloride

Reference values have not been established for patients who are younger than 12 months of age.

Day(s) Performed

Monday through Saturday

Test Classification

This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information


LOINC Code Information

Test ID Test Order Name Order LOINC Value
FRAG Osmotic Fragility, RBC 98904-6


Result ID Test Result Name Result LOINC Value
9064 Osmotic Fragility, RBC 34964-7
SCTRL Shipping Control Vial 40431-9
3306 Osmotic Fragility, 0.50 g/dL NaCl 23915-2
3307 Osmotic Fragility, 0.60 g/dL NaCl 23918-6
3308 Osmotic Fragility, 0.65 g/dL NaCl 23920-2
3309 Osmotic Fragility, 0.75 g/dL NaCl 23921-0
3310 Osmotic Fragility Comment 59466-3

Clinical Information

Spherocytes are osmotically fragile cells that rupture more easily in a hypotonic solution than do normal red blood cells . Because they have a low surface area:volume ratio, they lyse at a higher osmolarity than do normal discocytes (ie, RBC). Cells that have a larger surface area:volume ratio, such as target cells or hypochromic cells, are more resistant to lysing. After incubation, an increase in hemolysis is seen in spherocytes. Hereditary spherocytosis typically has a greater number of spherocytes than other causes of spherocytosis. Therefore, the degree of lysis is usually more pronounced, but this is not always the case. Some rare disorders can also cause marked fragility, and hereditary spherocytosis cases can display moderate fragility.


An interpretive report will be provided.


Spherocytosis of any cause will result in increased osmotic fragility. Infrequently, other congenital hemolytic disorders may also be associated with positive results, as in patients with congenital nonspherocytic hemolytic anemia due to red blood cells (RBC) enzyme deficiencies.


Patients with an immunohemolytic anemia or who have recently received a blood transfusion may also have increased RBC lysis.


Resulting Cautions:

-Osmotic fragility results will be reported if the shipping control is normal.

-If the shipping control is abnormal and the osmotic fragility results on the patient are within normal range, the results will be reported; however, a comment will be added to the report indicating that the shipping control was not entirely satisfactory.

-The test will be canceled if the patient specimen and shipping control are both abnormal.

Clinical Reference

1. Palek J, Jarolin P: Hereditary spherocytosis. In: Williams WJ, Beutler E, Erslev AJ, Lichtman MA, eds. Hematology. 4th ed. McGraw-Hill Book Company; 1990:558-569

2. King MJ, Garcon L, Hoyer JD, et al: International Council for Standardization in Haematology. ICSH guidelines for the laboratory diagnosis of nonimmune hereditary red cell membrane disorders. Int J Lab Hematol. 2015 Jun;37(3):304-325

Method Description

Specimens for erythrocyte osmotic fragility tests are anticoagulated with EDTA. Osmotic lysis is performed using sodium chloride solution, 0.5 g/dL. An incubated fragility test is performed following 24-hour incubation at 37° C at the following sodium chloride concentrations: 0.60, 0.65, and 0.75 g/dL. Results are reported and interpreted.(Larson CJ, Scheidt R, Fairbanks VF: The osmotic fragility test for hereditary spherocytosis: use of EDTA-anticoagulated blood stored at 4° C for up to 96 hours. Am Soc Clin Pathol Meeting Abstract, 1988; Larson CJ, Scheidt R, Fairbanks VF: The osmotic fragility test for hereditary spherocytosis: objective criteria for test interpretation. Am Soc Clin Pathol Meeting Abstract, 1988; King MJ, Zanella A: Hereditary red cell membrane disorders and laboratory diagnostic testing. Int J Lab Hematol. 2013 Jun;35(3):237-243)

Report Available

2 to 5 days

Reject Due To

Gross hemolysis Reject
Clotted blood Reject

Method Name

Osmotic Lysis


If not ordering electronically, complete, print, and send a Benign Hematology Test Request (T755) with the specimen.