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Lab Test Significant Change

How Much Can A Laboratory Test Change And Still Be The Same?

Monitoring an individual’s health often requires assessment of serial laboratory results. Repeat results are seldom identical. Changes in laboratory values may be due to biological variation, analytical imprecision, or a change in the individual’s condition. Sometimes it is difficult to decide if a change in a laboratory result really reflects a change in health status. The magnitude of change that must occur before the difference is considered medically significant has been calculated for the most common chemistry, hematology and lipid tests.

Chemistry Tests

The column labeled, “Significant Change %” lists the percent that each test must change before different results are considered medically significant. These values were calculated at the 95% confidence level. The third column gives a hypothetical test result for a healthy person and the fourth column illustrates how much a subsequent result would have to change to be considered medically significant. For example, if a patient’s initial hemoglobin was15 g/dL a subsequent level would have to change more than 1.1 g/dL to be considered medically significant.

Hematology Tests

The degree of variability observed in hematology tests over time is inversely correlated with the lifespan of the three hematopoietic cell lines. Red blood cells circulate for 120 days and have the smallest variability, while white blood cells survive only a few days and have the highest variability. Platelets have an intermediate lifespan of 7 days and have slightly lower variability than white blood cells.

Studies on the biological variability of hematology and chemistry tests are performed on healthy ambulatory patients. Hospitalized patients may experience even greater shifts in laboratory tests due to changes in posture, activity levels, diet, fluid balance, and medications.

Lipids

Lipid and lipoprotein concentrations vary during the normal course of daily activity. Studies have demonstrated that within person variability is sufficient to make an individual move in and out of the predefined risk categories defined by the National Cholesterol Education Program (NCEP). As many as 11% of patients would be mistreated if risk assessment were made on the basis of a single lipid panel. NCEP guidelines acknowledge this variation by stressing that patient management decisions should be based on an average of at least two results.

Cholesterol concentration must change at least 18%, HDL cholesterol 27% and triglycerides 84% before one can be assured that the difference is not simply due to intra-individual and analytical changes.

Prothrombin Time

Use of the international normalized ratio (INR) has greatly standardized and improved the monitoring of oral anticoagulant therapy. However 25-30% of INR values fall outside the therapeutic range, raising the issue of warfarin dose adjustment. Random variation of INR values may occur in a patient, despite stable intensity of oral anticoagulant therapy, as a result of both biological variation (such as minor changes in diet or intestinal vitamin K absorption) and analytic variation (such as minor changes in blood drawing or processing). A recent study addressed the important issue of how to evaluate whether a change in INR represents random variation, not requiring a warfarin dose change, or whether it represents a significant clinically relevant change, requiring an adjustment of the warfarin dose (Clinical Chemistry 1995; 41:1171-76).

The authors determined that combined analytical and biological variation within a subject on a stable dose of warfarin amounts to approximately 10%. Taking this random variation into account, they calculated that a significant change in INR in a patient on fixed dose and steady state warfarin therapy can be expressed as a change (increase or decrease) of greater than 0.28 times the previous INR (for a 95% level of significance). For example, if the previous INR was 2.5, a significant change in the INR value necessitating a change in warfarin dose would be greater than +/- 0.7 (0.28 x 2.5). The table shows the values for significant changes in INR and ranges of acceptable INR variation at various previous INR values, using this formula. Please note that these values apply only to patients who are on a fixed dose of warfarin, having achieved a steady state of anticoagulation. The authors do caution that if the INR value is unacceptably high, indicating an increased risk for hemorrhage, reduction of dose must be considered solely on the basis of clinical judgment.

The authors claim that use of these guidelines is likely to avoid the “ping-pong” effect on the INR of inappropriately changing the warfarin dose up and down in response to minor random variations in that value, which may result in under- or over-anticoagulation. In summary, using this approach in patients stably anticoagulated with warfarin may provide some guidance in determining whether a change in warfarin dose is warranted, thus improving oral anticoagulant control.