Redefining the Reference Interval and Cut-Off Values of the Hematological and Biochemical Parameters and Deriving a Sensitive Predictive Marker for Crisis Events in Sickle Cell Disease

The heterogeneity in clinical presentations in sickle cell disease (SCD) alters between crisis and steady state phases. Considering the pathophysiology, it is crucial to establish a disease-specific reference interval for hematological and biochemical parameters and identify the sensitive predictive markers for crisis. The case-control study included fifty-four healthy control, forty SCD cases in crisis state, and forty-six steady state cases. Blood samples were evaluated for complete blood count (CBC) and biochemical parameters. Red cell indices were calculated. 2.5th and 97.5th percentile values were delineated in the steady state cases as new reference interval. The new cut-off values were evaluated for sensitivity and specificity. The steady state cases reported a significant decrease in urea, sodium, Hb, Hct, and RBC count compared to the control group, whereas potassium, and red cell indices were higher. Compared to the steady state, the crisis state depicted a significant increase in urea, liver enzymes, leucocytes, inflammatory indices, and all red cell indices, whereas sodium, albumin, iron, Hb, Hct, and LMR were decreased. The revised 95 percentile ranges were sodium-132.35-143.65 mmol/L, potassium-3.75-6.09 mmol/L, albumin-2.9-5.0 g/dL, Hb-7.51-12.17 g/dL, RBC count-2.2-5.49 x 106/mu L, and Hct-22.54-36.1%. Red cell indices like Ricerca, Green and King, and Huber-Heklotz could be good screening tools for crisis events with more than 70% sensitivity. Thus, the laboratory must derive a new reference interval and cut-off values at the steady state in the SCD population it is catering samples rather than comparing it with normal healthy individuals.

Automated summary

The study emphasizes the importance of establishing disease-specific reference intervals for hematological and biochemical parameters in sickle cell disease (SCD). It provides evidence that the steady state and crisis state have distinct differences in blood parameters. Red cell indices show potential as screening tools for crisis events.