The patient was a teenage African American female with a 2-week history of polyuria and polydipsia. There was no weight loss or nausea. She also presented with bilateral pain in her lower extremities and chest pain. During transit by EMS, her capillary glucose measured with a point-of-care device was 368 mg/dL.
These were her labs on admission:
Patient
Result
Reference Interval
Venous pH
7.26
7.3-7.4
Venous pCO2
23 mm Hg
42-53
Venous pO2
73 mm Hg
35-45
Venous HCO3-
10 meq/L
21-27
Venous base deficit
16 meq/L
0-3
Sodium
134 mmol/L
136-145
Potassium
4.1 mmol/L
3.3-5.1
Chloride
111 mmol/L
98-107
Carbon dioxide
8 mmol/L
22-30
Creatinine
0.62 mg/dL
0.40-1.10
BUN
6 mg/dL
6-20
Glucose
181 mg/dL
65-99
Urine glucose
>1000 mg/dL
Negative
Urine ketones
>150 mg/dL
More admission data:
WBC
20.50 K/uL
4.5-13.5K
Hemoglobin
9.9 g/dL
11.5-15.5
Hematocrit
28%
RBC count
3.16 million
4.0-5.2
MCV
87 fL
77-95
Red cell distribution width
16%
11-14
Corrected reticulocyte count
7.4%
0.5-1.8
Neutrophils
70%
40-80
Lymphocytes
18%
20-45
Monocytes
7%
2-10
Eosinophils
2%
0-8
Basophils
1%
0-2
Large unstained cells
3%
0-4
Platelet count
183 K/uL
150-450K
Hemoglobin A1c was requested and was measured at zero (0) percent. Below is the HPLC tracing. Why wasn’t any A1c measured?
Posted by On 1/30/2012
A patient with thse varients have no A0 peak so with ion exchange HPLC A1c can not be detected unless the blood is put on a HPLC with boronate affinity. Boronated affinity is interference free of variants to produce an accurate A1c.
Posted by On 10/6/2011
why elevated Cl and decreased Na levels? This comment was approved by the NACBLOG editorial board. Please remember to add your name and affiliation!
Posted by On 5/13/2011
Fructosomine: for individuals with hemoglobinopathies Hgb A1c is not an accurate method for monitoring diabetic control. For those patients with hemoglobinopathies fructosomine is an alternative , not for the last 12 week Hgb A1c level, but for atleast 2 -3 weeks. Better something than nothing at all. Fructosomine is not utilized by PCP's or endocrinologists because they are not aware of this test availablity. This comment was approved by the NACBLOG editorial board. Please remember to add your name and affiliation!
Posted by On 5/11/2011
Something is causing the A1C to chelate out. Possible Sickle Cell patients. This comment was approved by the NACBLOG editorial board. Please remember to add your name and affiliation!
Posted by On 5/2/2011
Probably Sickle Cell This comment was approved by the NACBLOG editorial board. Please remember to add your name and affiliation!
Several reasons may lead to false low or zero A1c values - especially on HPLC. From the chromatogram, it appears the analysis is done on Bio-Rad D10 HPLC in short mode. The method is based on principle of cation exchange chromatography and formal charge differences between hemoglobin variants. Although, it is highly rare that a whole blood sample would give a false result, but possibilities can not entirely ruled out that the alteration of the HPLC reagents (polarity or ionic nature of the mobile phase) or change in serum polarity cause false lowering of A1c. The inconsistency in polarity simply may have caused A1c to elute either early or late co-elution with other fractions. A clue can be found from the distribution of the overall peak area. Usually a zero A1c value is obtained when the actual A1c is already low in hypoglycemic condition. In this case, the reagents on HPLC should be changed, or calibration should be done. Also, I noticed the CO2 levels are low in the patient sample which may contribute to the blood polarity resulting in discrepancy in the normal chromatographic interaction leading to disappearance of A1c. In this case, immunoassay based analysis should provide proper values. Another possibility is also reported in literature is presence of other abnormal hemoglobin traits such as Hb-D, Hb-E, Hb-C or Hb-S. (Clin Chem, 2008, 130, 136 and Clin Chem, 2008, 54, 1277) Presence of these traits has different effects on the value of A1c (Hb-A1c). Usually modern HPLC based A1c analyzers have a longer mode which allows to detect this traits. If they are present, enzyme assay (not immunoassay) can be performed to obtain correct A1c (www.diazyme.com). Another possibility could be low lifespan of erythrocyte. Patient has slightly lower RBC and Hgb indices. This may contribute to lower A1c than normal. I hope this information will help to get some clue. This comment was approved by the NACBLOG editorial board. Please remember to add your name and affiliation!
The patient is presenting with diabetic ketoacidosis but also has an underlying issue. The lack of Hemoglobin A suggests a hemoglobinopathy, or hemoglobin variant is present. The patient has symptoms of sickle cell disease. The patient is likely homozygous for Hgb S but should be confirmed with Hemoglobin elecrophoresis. An A1c is measurement is not possible for this patient because she does not make hemoglobin A. This comment was approved by the NACBLOG editorial board. Please remember to add your name and affiliation!
Sickle cell...no Hgb A This comment was approved by the NACBLOG editorial board. Please remember to add your name and affiliation!
Nowhere. If you have no hemoglobin A, you cannot have hemoglobin A1c. Please note that some patients with hemoglobinopathies where there is no hemoglobin A can by some methods, and this can happen with any of the methods, have a "factitious" hemoglobin A1c that is within a range that is believable. This comment was approved by the NACBLOG editorial board. Please remember to add your name and affiliation!
Looks like a diabetic ketoacidosis. The low pH could cause a false negative result for the POCT A1C as acid levels may denature an enzyme test method.
There must be some interefering substance in her blood that masks the A!C from the testing procedure. This comment was approved by the NACBLOG editorial board. Please remember to add your name and affiliation!
Because there is no HbA . The tracing has two large peaks suggesting two Hb variants different from HbA, most likely HbC and HbS. This comment was approved by the NACBLOG editorial board. Please remember to add your name and affiliation!
Patient has got a possible hemoglobinapathy. Sickle cell disease? This comment was approved by the NACBLOG editorial board. Please remember to add your name and affiliation!
The POC device is not detecting the glycosylated hemoglobin variant. This comment was approved by the NACBLOG editorial board. Please remember to add your name and affiliation!
Hemoglobin disorders This comment was approved by the NACBLOG editorial board. Please remember to add your name and affiliation!
no HbA. This comment was approved by the NACBLOG editorial board. Please remember to add your name and affiliation!
Posted by On 5/1/2011
HA1C was ordered but was not obtained or test was not ordered at all. This comment was approved by the NACBLOG editorial board. Please remember to add your name and affiliation!
The patient's hemoglobin was low. The A1C could have been affected by Abnomal RBC's as in Sickle Cell anemia. This comment was approved by the NACBLOG editorial board. Please remember to add your name and affiliation!
The patient doesn´t have Hb A. Probably she has a hemoglobinopahy, p.ex, sickle cell disease or hemoglobinopathy C or SC. This comment was approved by the NACBLOG editorial board. Please remember to add your name and affiliation!
A1C was not measured..it might be due to RBC disorder as looking at eh value of RBC. Bothiraj. Biochemist.
Hemoglobin abnormality This comment was approved by the NACBLOG editorial board. Please remember to add your name and affiliation!
Posted by On 4/30/2011
patient has hemoglobin sc so there is no hgb a available. This comment was approved by the NACBLOG editorial board. Please remember to add your name and affiliation!
The presence of variant hemoglobin structures (hemoglobinoplathies), decreased hemoglobin, and decreased RBC life span can falsely decrease A1c levels. This comment was approved by the NACBLOG editorial board. Please remember to add your name and affiliation!
A1c by HPLC will not show any A1c because the patient only has hemoglobin S. Methods that detect the glycated moeity of the glycated hemoglobin would give an apparent A1c level but it probably wouldn't match the degree of this patient's hyperglycemia because of the different rates of glycation of Hgb S vs. Hgb A ;however, it would not be zero. Fructosamine should be elevated because the patient is diabetic and could be considered for glycemic monitoring but reflects a shorter time interval than glycated hemoglobin. This comment was approved by the NACBLOG editorial board. Please remember to add your name and affiliation!
From the laboratory results, the patient have anemia, maybe she have a hemoglobin variant, such as sickle cell hemoglobin (hemoglobin S), you will have a decreased amount of hemoglobin A. This may limit the usefulness of the A1c test in diagnosing and/or monitoring your diabetes. so the hemolysis lead to your test results may be falsely low. This comment was approved by the NACBLOG editorial board. Please remember to add your name and affiliation!
The hemoglobin may be too low. There may have been mostly serum/plasma if this was a fingerstick. This comment was approved by the NACBLOG editorial board. Please remember to add your name and affiliation!
Low RBC count, low hematocrit, low hemoglobin, high reticulocytes suggest very high RBC turnover, and therefore much lower HbA1c than expected. I cannot see clearly what the symbols are on the HPLC tracing. It looks like HbS is present. Is any peak overwhelming the HbA1c ? This comment was approved by the NACBLOG editorial board. Please remember to add your name and affiliation!
The patient is homozygous for HbS. The HPLC chromatogram would verify the presence of HbS. An immunochemical method will likely quantitate a result that is erroneous, if at all. This comment was approved by the NACBLOG editorial board. Please remember to add your name and affiliation!
Patient has fetal HB without LA1c/CHb-1. This comment was approved by the NACBLOG editorial board. Please remember to add your name and affiliation!
firstly, as CBC reflect the patient has anisocytosis along with a normocytic normochromic anemia and, according to HPLC curve of hemoglobin separation yields at least one (possibly a secondary between Hba1c and HbA and adjacent to HbA) pathological fraction which may be HbE. Thus the patient seems to be a heterozygous for a hemoglobin variant. (as the resolution of the diagram is not well, I could have not ben able to discriminate in a clear cut manner) So if the patient have such a variant that is I assume it to be leading to a hemolytic pattern (due to normocytic normochromic picture -chronic hemolytic case-as well as high RDW and reticulocytosis) the aminoacid moieties of Hb molecule may have not get the chance of long life for interacting with glucose in order to form glycosidic bonds of Hba1c; additionally any glycosylated Hb molecule may have been destroyed during their short life duration. Then expected high quantity of Hb A1c is not seen. Moreover, as the POCT devices utilize an immunoassay based methods (or boronate chromatography) for identification of Hba1c molecule (I mean valin aminoacid of beta chain of Hb), glycosylated moity of variant hemoglobin may have been missed, as well.
I think the patient has Hb variant and has no beta chain. This comment was approved by the NACBLOG editorial board. Please remember to add your name and affiliation!
Patient must be case of another Hemoglobinopathy which is thus masking the HbA1c and giving a zero reading. We recently encountered such a patient. This comment was approved by the NACBLOG editorial board. Please remember to add your name and affiliation!
Posted by On 4/29/2011
Probably due to a sampling error, A1C was tested in plasma rather than whole blood!!! Dr Aamir Ijaz, Karachi Pakistan
Hemolytic anemia like G6PD deficiency reduces RBC lifespan and could induces falsely low values of HbA1c. Maybe it's a case of diabetic acidosis which cause hemolytic crisis. However, this effect lowering HbA1c, but I don't know if it may cause a result of zero percent? Philippe Desmeules clinical chemist Hôpital St-Eustache Québec, Canada
looks like a hemoglobinopathy with a double heterozygote, possibly S-C This comment was approved by the NACBLOG editorial board. Please remember to add your name and affiliation!
It looks like there is a variant present. Perhaps she is a double heterozygote. She could be an S/C or a S/D because their are two peaks where te A0 peak usually is. There is no A1c because she does not have hemoglobin A. Her Hgb S or C would get glycated but we do not know the percentage. My question would be wy did they do a venous gas instead of an arterial gas?? Between her diabetes and her anemia due to a variant hemoglobinopathy - I certainly hope she feels better after proper treatment. This comment was approved by the NACBLOG editorial board. Please remember to add your name and affiliation!
This teenager has a hemoglobinopathy of some sort (possibly sickle cell?). Most variant hemoglobins (especially S and E )interfere with several of the A1c tests. This comment was approved by the NACBLOG editorial board. Please remember to add your name and affiliation!
Patient has hemoglobinopathy, possibly SS or SC disease. Depending on assay value will be falsely lowered. Patient in obvious ketoacidosis. This comment was approved by the NACBLOG editorial board. Please remember to add your name and affiliation!
The patient's red cells hemolyzed therefore the absence of glycated hemoglobin. This comment was approved by the NACBLOG editorial board. Please remember to add your name and affiliation!
ADA Endorses HbA1c for Diabetes Diagnosis. CLN February 2010
Expert Committee Endorses HbA1c Test for Diagnosing Diabetes. CLN August 2009