True Clinical Variations in Hematology Delta Checks
Delta checks in hematology are critical for identifying true clinical variations versus pre-analytical or analytical errors, with parameter-specific changes reflecting distinct pathophysiological processes.
A. True Clinical Variations by Parameter
Hematocrit (HCT)
1. Decrease in HCT
- Acute blood loss/hemorrhage: Rapid decreases in hematocrit occur with active bleeding, which may initially be masked by normal plasma volume but become evident with serial measurements 1
- Hemodilution from fluid resuscitation or overhydration 2
- Bone marrow suppression (chemotherapy, radiation)
2. Increase in HCT
- Dehydration/hemoconcentration: Plasma volume depletion (severe dehydration, diarrhea, vomiting, diuretic use, burns) causes relative polycythemia 1
- True polycythemia (polycythemia vera, secondary polycythemia from hypoxia) 1
- Smoker's polycythemia (carbon monoxide exposure) 1
White Blood Cell Count (WBC)
3. Decrease in WBC
- Bone marrow suppression: From medications, radiation, or infiltrative disease
- Viral infections (particularly certain viral infections like influenza, HIV)
- Overwhelming sepsis (late stage)
4. Increase in WBC
- Acute infection/inflammation: Bacterial infections typically cause neutrophilia 3
- Leukemia or myeloproliferative disorders
- Physiologic stress response (trauma, surgery, burns)
- Steroid administration
Mean Corpuscular Volume (MCV)
5. Decrease in MCV
- Iron deficiency anemia: Progressive microcytosis develops as iron stores deplete 4
- Thalassemia
- Anemia of chronic disease 4
6. Increase in MCV
- Vitamin B12/folate deficiency: Impaired DNA synthesis leads to macrocytosis 4
- Liver disease
- Medication effect (anticonvulsants, chemotherapy agents) 4
- Myelodysplastic syndrome
B. Delta Flags for Identification Errors
The MCV delta flag is the best indicator of errors due to specimen identification. MCV is a directly measured parameter that remains relatively stable over short time periods in most clinical conditions, making significant rapid changes highly suspicious for specimen mix-ups 5.
Key reasons why MCV is the most reliable parameter for identification errors:
- MCV is directly measured by hematology analyzers using electrical impedance or light scattering technology, not calculated from other parameters 4
- MCV shows less biological variation than WBC counts (which fluctuate with infections) or HCT (which changes with hydration status)
- MCV changes slowly in most pathological conditions, typically taking weeks to months to show significant alterations 4
- MCV measurements are less affected by sample storage conditions than calculated parameters 4
- Sudden large changes in MCV (>5-6 fL) between sequential samples are highly suspicious for specimen mix-ups or analyzer errors 5
Clinical Implications and Best Practices
- Delta check methods should incorporate reference ranges when evaluating changes, as demonstrated by the delta percent change/reference range (DPC/RR) method 5, 6
- Different delta check criteria should be applied to inpatients versus outpatients due to differences in expected physiological changes 5
- Serial measurements of HCT increase sensitivity for detecting blood loss, as initial values in the normal range may mask early-phase bleeding 1
- In critically ill patients, peripheral HCT may overestimate anemia in hypervolemic states due to hemodilution, potentially leading to unnecessary interventions 2
When implementing delta checks in laboratory practice:
- Establish appropriate time intervals between measurements (typically 1 day for inpatients, up to 21 days for outpatients) 5
- Use the 99.5 percentile of observed changes as delta check criteria 5
- Implement a workflow algorithm for identifying test errors that includes retesting and possible resampling when delta check criteria are exceeded 5