Changes to CBC Reference Ranges

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September 28, 2016 July, 2017 Changes to CBC Reference Ranges At Dynacare, our vision is to be Canada s health and wellness solutions leader. As part of our commitment and continuous efforts to enhance testing and support patient care, Dynacare will be modifying reference ranges for the parameter provided for complete blood counts (CBCs) on July 17 th, 2017. Reference ranges represent laboratory test results found in 95% of the healthy population and are meant as a guide as to what is normal in the tested population. In the case of CBCs, reference ranges for hemoglobin, mean red cell volume (CV) and red blood cell counts (RBC) are dependent upon age and gender and are also influenced by the patient s ethnicity. Thalassemia and other mostly-asymptomatic genetic mutations are very common in the increasingly multiethnic population of Ontario. or this reason, what might generally be considered to be normal in Ontario may not be so in other populations. or this reason, CBC reference intervals that have been reported for standardized reference populations (e.g. World Health Organization, WHO) and used to establish clinical diagnoses such as anemia and microcytosis may not be relevant for Ontarians. People of Asian, Southern editerranean and African descent, will on average, have lower CVs and higher RBCs than their Western European counterparts. Additionally, when common thalassemia traits are combined with varying degrees of iron deficiency, average hemoglobin values in many Ontarians will be lower than that found in other populations. Why the change? Our previous reference ranges were derived retrospectively from CBCs performed on Ontario medical patients and using these ranges to define what was normal did have some advantages. However, feedback from our clinicians pointed out that it was very likely that many anemic patients were included in the large cohort of patient data used to calculate our reference

ranges. Clinicians were very clear in their comments to us that despite what the retrospective data might show, a hemoglobin of 89g/L (e.g. in an elderly male) cannot be considered normal and must be further investigated. ailure to flag such a hemoglobin level could result in the anemia being overlooked. or this reason, we have decided to introduce new CBC reference ranges, derived from standardized, confirmed-healthy populations. The age stratification in the reference range for those older than 75 has been eliminated. The new reference ranges correlate more closely with clinical diagnostic entities such as the WHO criteria for anemia and microcytosis and, when used properly, will be useful clinical decision-making tools for our increasingly ethnically-diverse population. What are the implications with the change in reference ranges? Because thalassemia and other, non-disease genetic mutations are so common in Ontario, physicians may notice more of their CBC reports with results flagged as being outside of the new standardized reference range. or example, many Ontarians with thalassemia traits will have small (microcytic) red cells and correspondingly lower CVs these patients CVs might now be flagged so even though a flagged CV may be at times be a normal finding in our diverse population, many of these healthy patients do in fact require additional work-ups (including hemoglobin fractionation and ferritin) to assess for thalassemia status and/or iron deficiency. Questions about the changes? We are committed to providing the highest quality and value to our healthcare system. or further information regarding the new reference ranges please refer to dynacare.ca, under News and edia/partner Updates. If you would like to further discuss, please feel free to contact Customer Care at 800.565.5721 x 5752. Doug Tkachuk D RCPC National Director, Hematology T 800.668.2714 x 5220 tkachukd@dynacare.ca

Table showing current and new reference ranges Test Code CBC Test Information Current Reference Ranges New Reference Ranges 399 WBC 397 RBC Test Component Sex Age Normal Range Sex Age Normal Range 4 1 2-9 >= 10 4 1 2-1 2-14 > 75 > 75 4 1 2-1 8.7-29.0 x 5.0-16.7 x 3.3 16.6 x 3.4-11.3 x 3.9-6.0 x 2.2-5.7 x 3.5-5.4 x 4.0-5.6 x 4.1 5.8 x 3.7-5.2 x 3.1-5.6 x 3.1-5.2 x 0-6 9.0 30.0 x 7-13 14-31 5.0-21.0 x 5.0-20.0 x 1-2 5.0-20.0 x 3-11 5.0-15.0 x 1-4 5.0-12.0 x 5-17 4.0-10.0 x 1 3.2-9.4 x 3.5-6.0 x 1-2 3.5-5.5 x 3-11 3.5-5.0 x 1-4 4.0-5.0 x 5-13 4.5-5.5 x 4.5-5.7 x 4.1-5.1 x 4.2-5.8 x 3.8-5.2 x 136-196 g/l 0-6 150-220 g/l 71-194 g/l 87-138 g/l 7-31 140-200 g/l 1-1 115-180 g/l 2-2 90-135 g/l 3-11 100-140 g/l 418 HGB 2-9 106-143 g/l 1-4 10 g/l 114-153 g/l 5-13 120-160 g/l 126-170 g/l 108-151 g/l > 75 87-166 g/l > 75 89-152 g/l 140-175 g/l 120-153 g/l 129-165 g/l 17 g/l

417 HCT 397V 397H CV CH 4-1 2-1 0.42-0.64 l/l 0-6 0.46-0.70 l/l 0.20-0.59 l/l 0.27-0.41 l/l 7-31 0.40-0.65 l/l 1-1 0.35-0.54 l/l 2-2 0.27-0.40 l/l 3-11 0.30-0.42 l/l 2-9 0.33-0.42 l/l 1-4 0.35-0.42 l/l 4-1 2-1 0.35-0.45 l/l 5-13 0.36-0.48 l/l 0.37-0.50 l/l 0.42-0.50 l/l 0.33-0.45 l/l 0.36-0.45 l/l 0.39-0.49 l/l 0.33-0.44 l/l 101-122 fl 0-6 98-118 fl 86-113 fl 58-89 fl 2-9 71-89 fl 7-13 88-126 fl 14-31 86-124 fl 1-1 85-123 fl 2-2 77-115 fl 3-11 74-108 fl 1-5 70-86 fl 6-12 77-96 fl 74-92 fl 13-17 80-100 fl 81-98 fl 80-98 fl 78-98 fl 76-98 fl 0-1 29-39 pg 0-2 24-34 pg 2-1 18-30 pg 2-9 23-30 pg 25-31 pg 3-17 24-31 pg 27-33 pg 24-33 pg 0-17 3265 g/l 417C CHC 317-345 g/l 313-344 g/l 0 1 12.3-23.7 0-1 12.3-23.3 RDW RDW 396 PLT >= 2 12.2 15.7 0-9 > 75 159-537 x 141-406 x 126-367 x 91-420 x 2-17 12.3-17.7 12.5-17.3 0-17 150-400 x 155-372 x

DIERENTIAL WBC'S PV PV 7.5-11.1 fl 4.0-14.0 fl 398 RETIC 372 NEUTROPHILS LYPHOCYTES ONOCYTES EOSINOPHILS BASOPHILS 8-153 x > 4 22-125 x 0-1 2000 x 2-6 15-250 x 7-31 5-50 x 1-1 5-100 x 2-2 5-150 x 3-6 5-250 x > 6 17-142 x 0-1 0.8-7.2 x 0-1 0.6-6.7 x 2-9 1.3-10.7 x 2-9 1.2-8.5 x 1.3-9.0 x 10-17 1.4-7.6 x 1.8-7.7 x >=18 1.4-6.3 x 0-1 2.0-9.5 x 0-1 2.0-9.5 x 2-1 2.4-9.6 x 2-1 2.4-9.6 x 2-9 1.1-6.3 x 2-9 1.3-6.4 x 1.2-4.2 x 10-17 1.2-4.1 x 0.9-3.4 x >=18 1.0-2.9 x 0-1 0.1-2.4 x 0-1 0.1-2.4 x 2-1 >= 2 0.2-1.5 x 2-1 0.2-1.5 x 0.3-1.0 x 2-17 0.3-1.1 x >=18 0.2-0.8 x 0-1 0.0-1.6 x 0-1 0.0-1.6 x 2-1 0.0-1.1 x 2-1 0.0-0.9 x 2-9 0.0-0.9 x 2-9 0.0-0.9 x 0-1 2-1 >= 2 0.0-0.8 x 10-17 0.0-0.7 x 0.0-0.5 x >=18 0.0-0.5 x 0.00-0.24 x 0.00-0.16 x 0.00-0.10 x BANDS 0.00 x 0-1 2-1 2-17 >=18 0.00-0.24 x 0.00-0.15 x 0.00-0.11 x 0.00-0.09 x 0-13 0.00 x >= 14 0.00-1.00 x