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11-2-2019
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HAEM@CMCVellore 26-27 February 2016 Vellore, India
NEW HEMATOLOGY ANALYZER PARAMETERS AND THEIR CLINICAL SIGNIFICANCE
Pre-analytical and analytical aspects, reference intervals and clinical utility
Hans J. Hoffmann PhD, EuSpLM
H3L Consult, the Netherlands
h3l.consult@gmail.com
HAEM@CMCVellore 26-27 February 2016 Vellore, India
Outline of this presentation
Technological principles of hematology analyzers: how cellular parameters are generated
New RBC, PLT and WBC parameters: pre-analytical and analytical aspects, reference ranges and clinical utility
Limitations and unmet clinical needs
Conclusions
11-2-2019
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HAEM@CMCVellore 26-27 February 2016 Vellore, India
Outline of this presentation
Technological principles of hematology analyzers: how cellular parameters are
generated
HAEM@CMCVellore 26-27 February 2016 Vellore, India
Technological principles applied in hematology analyzers - 1
• All hematology analyzers utilize flow cytometry, for performing measurements on a single cell level
• Flow cytometry requires a small sample volume and enables high throughput
• Some analyzers do a WBC analysis from a single dilution whereas others divide the diluted blood sample over two or more parallel flow channels, each doing their own measurements
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HAEM@CMCVellore 26-27 February 2016 Vellore, India
Technological principles applied in hematology analyzers - 2
• Electric impedance (Coulter principle): single-dimensional volume measurement
• Chemical treatment: cytochemistry or differential lysis. Specific reagents emphasize or eliminate cellular characteristics for distinguishing between different cell types
• Radiofrequency (conductivity): measures intracellular properties like N/C ratio, nuclear density and granularity
• (Laser) light scatter: depends on cellular properties like N/C ratio, granularity, nuclear density, surface etc.
• Fluorescence: uses dedicated fluorescent dyes for staining nuclei and cellular contents like RNA
HAEM@CMCVellore 26-27 February 2016 Vellore, India
How cellular parameters are generated - 1
• In each channel, one or multiple signals are measured of every cell passing the detector(s)
• In multiple-channel analyzers, signals from all channels can be combined for deriving more information. However, detailed information on the single-cell level cannot be achieved
• With multiple measurements in a single channel, all signals belonging to a single blood cell can be combined. This greatly enhances the degree of information on the single-cell level
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HAEM@CMCVellore 26-27 February 2016 Vellore, India
How cellular parameters are generated - 2
• Like in any flow cytometer, signals are displayed in several two-dimensional or even multi-dimensional plots
• Sophisticated software analyses the dots and creates clusters of cells with similar characteristics
• The form, size and spatial location of the clusters are then used for classifying and enumerating the cells
• Intracellular hemoglobin concentration is derived from multi-dimensional light scatter, based on Mie principle
HAEM@CMCVellore 26-27 February 2016 Vellore, India
How cellular parameters are generated - 3
• The cell types in normal blood are directly associated with a cell cluster in the scatterplots
• For other cell types the association is indirect. For example, immature granulocytes are usually derived by correlating cell cluster characteristics with a reference method
• Cell Population Data, recently offered as research parameters, are actually means and SD of the normal cell clusters
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HAEM@CMCVellore 26-27 February 2016 Vellore, India
Cell cluster analysis
Normal
Left shift
HAEM@CMCVellore 26-27 February 2016 Vellore, India
Outline of this presentation
New RBC parameters: (pre-) analytical aspects, reference ranges and clinical utility
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HAEM@CMCVellore 26-27 February 2016 Vellore, India
New RBC parameters - 1
• RDW (red cell distribution width): calculated from red cell volume histogram, usually expressed in %
• Micro (microcytic red cell %): calculated from red cell volume histogram
• Macro (macrocytic red cell %): calculated from red cell volume histogram
Usual definitions: micro < 60 fL and macro > 120 fL
Note: Methodological differences do exist, but are generally minor
HAEM@CMCVellore 26-27 February 2016 Vellore, India
New RBC parameters - 2
• Hypo (hypochromic red cell %): calculated from red cell Hb concentration histogram
• Hyper (hyperchromic red cell %): calculated from red cell Hb concentration histogram
• HDW (hemoglobin concentration distribution width): calculated from red cell Hb concentration histogram
Usual definitions: hypo < 28 g/dL, hyper > 41 g/dL Sysmex definition: hypo < 17 pg, hyper > 49 pg
Note: Methodological differences do exist, although not of major clinical significance
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HAEM@CMCVellore 26-27 February 2016 Vellore, India
Reticulocyte parameters
• MCVr (reticulocyte MCV): derived from multi-angle light scatter using Mie scatter theory and fluorescence for identifying reticulocytes
• MCHCr (reticulocyte Hb concentration): derived from multi-angle light scatter using Mie scatter theory and fluorescence for identifying reticulocytes
• MCHr or CHr® (reticulocyte Hb content): calculated from MCHCr
• Ret-He (reticulocyte Hb content): derived from single- or multi-angle light scatter, depending on analyzer type
Note: MCHr/CHr ®/Ret-He methods differ between manufacturers.
HAEM@CMCVellore 26-27 February 2016 Vellore, India
MCV and RDW: pre-analytical aspects
MCV increases during sample storage. Stability is up to 6 h
Also RDW increases and is stable up to 12 h
Hoffmann et al. Clin Chem Lab Med 2012; 50: 941-8
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HAEM@CMCVellore 26-27 February 2016 Vellore, India
RDW: analytical aspects
RDW is not standardized: manufacturers use different definitions
Lippi et al. Clin Biochem 2014; 47: 1100-3
HAEM@CMCVellore 26-27 February 2016 Vellore, India
RDW: reporting units
RDW-CV: relative to MCV in %
• Practically all analyzers report RDW-CV
• Division by MCV makes RDW MCV-dependent
RDW-SD: “absolute” RDW in fL
• Few analyzers report RDW-SD
• Independent of MCV
• Theoretically better reflection of RBC heterogeneity
Hoffmann et al. Clin Chem Lab Med 2015; 53: 2015-9
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HAEM@CMCVellore 26-27 February 2016 Vellore, India
RDW: reference intervals
Van den Bossche et al. Clin Chem Lab Med 2002; 40: 69-73Hoffmann. Clin Chim Acta 2012; 413: 824-5
HAEM@CMCVellore 26-27 February 2016 Vellore, India
RDW: reference intervals (Sysmex XE-2100)
RDW increases with age and is higher in females
Lippi et al. Clin Chem Lab Med 2014; 52: e197-9
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HAEM@CMCVellore 26-27 February 2016 Vellore, India
RDW: reference intervals (Abbott Sapphire)
RDW increases with age; no gender effect detectable
11.0
11.5
12.0
12.5
13.0
13.5
age class (y)
RD
W (
%)
<18 18-40 41-55 56-70 71-85 85+
Hoffmann et al. Clin Chem Lab Med 2015; 53: 2015-9
HAEM@CMCVellore 26-27 February 2016 Vellore, India
NHANES III study (Coulter S+ Jr)
MCV increases with age, irrespective of race
Cheng et al. Lab Hematol 2004; 10: 42-53
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HAEM@CMCVellore 26-27 February 2016 Vellore, India
RDW: reference intervals (Abbott Sapphire)
Hoffmann et al. Clin Chem Lab Med 2015; 53: 2015-9
9.0
10.0
11.0
12.0
13.0
age class (y)
RD
W-S
D (
fL)
<18 18-40 41-55 56-70 71-85 85+
11.0
11.5
12.0
12.5
13.0
13.5
age class (y)
RD
W (
%)
<18 18-40 41-55 56-70 71-85 85+
80
85
90
95
100
age class (y)
MC
V (
fL)
<18 18-40 41-55 56-70 71-85 85+
“Absolute” RDW also increases with age, independent of MCV
HAEM@CMCVellore 26-27 February 2016 Vellore, India
RDW: clinical utility
Traditionally, RDW is used as a diagnostic tool in anemia (as an objective measure of anisocytosis):
• Increased RDW correlates with reticulocytosis
• Patients with pernicious anemia may have increased RDW
• Screening of thalassemia carriers
• RDW differentiates between sickle cell anemia and other types of anemia
• Part of algorithms for differentiating between iron deficiency anemia and thalassemia
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HAEM@CMCVellore 26-27 February 2016 Vellore, India
RDW: clinical utility
0
50
100
150
200
250
300
350
400
1975 1980 1985 1990 1995 2000 2005 2010 2015
publications on RDW per year
HAEM@CMCVellore 26-27 February 2016 Vellore, India
RDW: clinical utility
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HAEM@CMCVellore 26-27 February 2016 Vellore, India
RDW: clinical utility
RDW has been proven to be a prognostic marker of:
• Mortality risk in acute coronary syndromes
• Survival in atherothrombotic diseases
• Long-term risk in heart failure
• Mortality risk in chronic kidney disease
• Life expectancy in cancer patientsAbrahan et al. Cardiol Res 2018; 9: 144-52
Ahmad et al. Int J Rheumatol 2018; 2018: 2476239Lippi et al. World J Cardiol 2018; 10: 6-14Lippi et al. Acta Biomed. 2017; 87: 323-8
Zhang et al. Arch Med Res 2017; 48: 378-85Montagnana & Danese. Ann Transl Med 2016; 4: 399
HAEM@CMCVellore 26-27 February 2016 Vellore, India
RDW: clinical utility
RDW has been suggested to be a prognostic marker in:
• Pulmonary arterial hypertension
• Peripheral artery disease
• Recurrence of atrial fibrillation
• Progression of atherosclerosis
• Incidence of venous thromboembolic events in middle-aged persons
• Inflammatory bowel disease
• Esophageal carcinoma
• Mortality of community-acquired pneumonia
• Disease activity in Behçet’s disease
• Uncontrolled glycaemia in type 2 diabetes
• Mortality in the general population
• Mortality following hip fracture
• Survival after venous thromboembolic events
• Attacks in migraine patients
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HAEM@CMCVellore 26-27 February 2016 Vellore, India
RDW: mechanism of disease association
RDW reflects RBC dynamics, including erythropoietic activity, lifespan and clearance in response to anemia and/or inflammatory processes
Higgins. Clin Lab Med 2015; 35: 43-57Patel et al. Amer J Hematol 2015; 90: 422-8
HAEM@CMCVellore 26-27 February 2016 Vellore, India
Micro and hypo RBC: pre-analytical aspects
Due to RBC swelling, microcytic RBC slightly decrease and hypochromic RBC substantially increase during sample storage. Stability < 6 h
Ermens et al. Int J Lab Hematol 2012; 34: 274-82
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HAEM@CMCVellore 26-27 February 2016 Vellore, India
Micro and hypo RBC: reference intervals (Sapphire)
Hoffmann et al. Clin Chem Lab Med 2012; 50: 941-8
HAEM@CMCVellore 26-27 February 2016 Vellore, India
Micro and hypo RBC: clinical utility
Differentiating iron deficiency anemia (IDA) from other forms of anemia such as anemia of chronic disease (ACD)
Rehu et al. Clin Chim Acta 2011; 412: 1809-13
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HAEM@CMCVellore 26-27 February 2016 Vellore, India
Micro and hypo RBC: clinical utility
• M/H ratio distinguishes thalassemia trait from iron deficiency anemia (IDA) in patients with microcytic anemia
• Population screening for thalassemia trait in endemic areas
Urrechaga et al. Int J Lab Hematol 2015; 37: 334-40Hoffmann et al. Clin Chem Lab Med 2015; 53: 1883-94
Urrechaga & Hoffmann. Clin Chem Lab Med 2017; 55: 1582-91
HAEM@CMCVellore 26-27 February 2016 Vellore, India
Hyperchromic RBC: pre-analytical aspects
Due to RBC swelling, hyperchromic RBC decrease during sample storage. Stability up to 6 h maximum
Rooney et al. Int J Lab Hematol 2015; 37: 98-104
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HAEM@CMCVellore 26-27 February 2016 Vellore, India
Hyper RBC: reference intervals (Abbott Sapphire)
Hoffmann et al. Clin Chem Lab Med 2012; 50: 941-8
HAEM@CMCVellore 26-27 February 2016 Vellore, India
Hyperchromic RBC: clinical utility
Screening of (hereditary) spherocytosis
Rooney et al. Int J Lab Hematol 2015; 37: 98-104
0.972 (0.957-0.983) 4.9 96.4 99.1 95.5
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HAEM@CMCVellore 26-27 February 2016 Vellore, India
Reticulocyte parameters: pre-analytical aspects
MCVr and MCHCr have limited stability due to EDTA-induced RBC swelling
MCHr is essentially stable over time
Ermens et al. Int J Lab Hematol 2012; 34: 274-82
HAEM@CMCVellore 26-27 February 2016 Vellore, India
MCHr and CHr®: clinical utility
• Diagnosing iron restriction in anemic and non-anemic subjects
• Diagnosing functional iron deficiency (inability to release iron fromadequately filled stores)
• Monitoring early response to intravenous iron therapy
• Monitoring erythropoietin therapy in patients with anemia due to renalfailure
Thomas & Thomas. Clin Chem 2002; 48: 1066-76Brugnara & Mohandas. Curr Opin Hematol 2013; 20: 222-30
Thomas & Thomas. Eur J Haematol 2017; 99: 262-8
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HAEM@CMCVellore 26-27 February 2016 Vellore, India
MCVr: clinical utility
Diagnosing clinical and sub-clinical cobalamin deficiency
Ceylan et al. Int J Lab Hematol 2007; 29: 327-34.Khan & Agha. Int J Lab Hematol 2019; 41: e1-e4
HAEM@CMCVellore 26-27 February 2016 Vellore, India
Outline of this presentation
New PLT parameters: (pre-) analytical aspects, reference ranges and clinical utility
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HAEM@CMCVellore 26-27 February 2016 Vellore, India
New PLT parameters - 1
• MPV (impedance): platelet volume is directly measured and MPV calculated
• MPV (optical): volume of individual platelets is derived from multi-angle light scatter and MPV calculated
• PCT (plateletcrit): calculated from MPV and PLT count
• PDW (platelet distribution width): calculated from platelet volume
histogram
•Note: MPV and PDW methods differ strongly between manufacturers
HAEM@CMCVellore 26-27 February 2016 Vellore, India
New PLT parameters - 2
• IPF (immature platelet fraction): derived from RNA fluorescence signals of platelets in reticulocyte analysis of Sysmex analyzers
• retPLT (reticulated platelets): measured from RNA fluorescence signals of platelets in reticulocyte analysis of Abbott analyzers
Note: IPF and retPLT methods differ between manufacturers and IPF differs between Sysmex XE-and XN-series analyzers
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HAEM@CMCVellore 26-27 February 2016 Vellore, India
MPV: pre-analytical aspects
MPV increases rapidly during sample storage, due to EDTA-induced platelet swelling
Beckman Coulter LH750
Lancé et al. Lab Hematol 2010; 16: 28-31
Technicon H*1
Wynn et al. Clin Lab Hematol 1995; 17: 173-6
HAEM@CMCVellore 26-27 February 2016 Vellore, India
MPV: analytical aspects
Lippi et al. Blood Coag Fibrinol 2015; 26: 235-7
MPV is not standardized and thus depends on the hematology analyzer
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HAEM@CMCVellore 26-27 February 2016 Vellore, India
MPV: reference intervals
Hoffmann. Thromb Res 2012; 129: 534-5
MPV standardization is still an unresolved issue
HAEM@CMCVellore 26-27 February 2016 Vellore, India
Does MPV change with age?
Verdoia et al. Exp Gerontol 2015; 62: 32-6
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HAEM@CMCVellore 26-27 February 2016 Vellore, India
Does MPV change with age?
Hoffmann et al. Exp Gerontol 2015; 62: 41-2
No indications for age- or gender-dependent MPV reference intervals
HAEM@CMCVellore 26-27 February 2016 Vellore, India
MPV: reference intervals
Hoffmann et al. Arch Pathol Lab Med 2013; 137: 1635-40
MPV correlates inversely with PLT count
Should MPV reference intervals be stratified for PLT count?
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HAEM@CMCVellore 26-27 February 2016 Vellore, India
MPV: clinical utility
MPV is traditionally used as a diagnostic tool in patients with thrombocytopenia:
• MPV may identify patients with congenital platelet disorders that are associated with platelet volume
Wiskott-Aldrich syndrome (micro platelets)Bernard-Soulier syndrome (giant platelets)
• MPV can discriminate between bone marrow aplasia and peripheral destruction
• MPV helps to predict bone marrow recovery after chemotherapy and transplantation
HAEM@CMCVellore 26-27 February 2016 Vellore, India
MPV: clinical utility
0
50
100
150
200
250
300
350
400
450
500
1975 1980 1985 1990 1995 2000 2005 2010 2015
publications on MPV per year
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HAEM@CMCVellore 26-27 February 2016 Vellore, India
MPV: clinical utility
MPV has been suggested to be a biomarker for:
• Outcome following acute myocardial infarction
• Restenosis after coronary angioplasty
• Development and outcome of pre-eclampsia
• Thrombotic risk in peripheral artery disease
• Development of deep vein thrombosis and pulmonary embolism
• Pulmonary arterial hypertension
• Risk of stroke in atrial fibrillation
• Risk of atherosclerotic renal artery stenosis
• Prognosis of sepsis
• Prognosis in advanced pancreatic cancer
• Predicting survival in metastatic colorectal cancer
• Mortality prediction in infants of preeclamptic mothers
• Bleeding severity and prognosis in gastrointestinal bleeding
• Mortality indicator in patients on peritoneal dialysis
• Diagnosis of pemphigus vulgaris
HAEM@CMCVellore 26-27 February 2016 Vellore, India
MPV: clinical utility
But, there is very serious concern about the validity of most, if not all, MPV risk studies published:
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HAEM@CMCVellore 26-27 February 2016 Vellore, India
Flow cytometry (retPLT)
Considered the preferred research method, but all published methods are cumbersome and lack standardization. Key issues are fluorescent staining details and gating strategy (Matic correction)
Immature platelet fraction (IPF)
Automated methods available on Sysmex XE- and XN-series analyzers
Reticulated platelets (retPLT)
Automated method available on Abbott CELL-DYN Sapphire and Abbott Alinity hq analyzers
Note: IPF and rPLT methods differ between manufacturers and IPF differs between Sysmex XE- and XN-series analyzers
Reticulated or immature platelets: analytical aspects
HAEM@CMCVellore 26-27 February 2016 Vellore, India
Reticulated or immature platelets: analytical aspects
Principles of determinations in Sysmex XE (A), Sysmex XN (B) and Abbott CELL-DYN Sapphire (C)
Hoffmann. Clin Chem Lab Med 2014; 52: 1107-17
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HAEM@CMCVellore 26-27 February 2016 Vellore, India
Reticulated or immature platelets: analytical aspects
The two hematology analyzer methods show poor analytical correlation
Meintker et al. Clin Chem Lab Med 2013; 51: 2125-32
HAEM@CMCVellore 26-27 February 2016 Vellore, India
IPF: pre-analytical aspects (Sysmex)
Sinclair. Aust J Med Sci 2012; 33: 10-7
The stability of IPF is controversial
Osei-Bimpong. Hematology 2009;14:118-21
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HAEM@CMCVellore 26-27 February 2016 Vellore, India
retPLT: pre-analytical aspects (Sapphire)
retPLT are stable for at least 6 hours at ambient temperature
Hoffmann et al. Arch Pathol Lab Med 2013; 137: 1635-40
HAEM@CMCVellore 26-27 February 2016 Vellore, India
IPF: reference intervals (Sysmex)
Authors (year) Mean Range n Analyzer
Briggs et al (2004) 3.4 1.1 – 6.1 50 XE-2100
Abe et al (2006) 3.3 1.0 – 10.3 129 XE-2100
Cho et al (2007) 1.7 0.4 – 5.4 142 XE-2100
Kim et al (2007) 2.2 1.7 – 5.2 30 XE-2100
Cremer et al (2009) 4.3 0.7 – 7.9 456 XE-2100
Di Mario et al (2009) 2.4 0.8 – 5.1 53 XE-2100
Meintker et al (2013) 2.5 0.8 – 7.9 110 XE-5000
Joergensen et al (2016) 3.7 1.3 – 9.0 1674 XE-5000
Ko et al. (2015) 2.6 0.5 – 9.7 2104 XN-1000
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HAEM@CMCVellore 26-27 February 2016 Vellore, India
retPLT: reference intervals (Sapphire)
Authors (year) Mean Range n Analyzer
De Wit et al (2009) 2.2 0.4 – 6.4 53 Sapphire
Gordillo et al (2011) 1.7 0.1 – 11.3 196 Sapphire
Costa et al (2012) 1.4 0.4 – 2.8 151 Sapphire
Getaldic et al (2013) - 0.5 – 4.6 174 Sapphire
Hoffmann et al (2013) 1.6 0.4 – 6.0 8089 Sapphire
Lang et al (2013) 2.5 0.6 – 5.9 90 Sapphire
Meintker et al (2013) 2.2 1.0 – 3.8 110 Sapphire
HAEM@CMCVellore 26-27 February 2016 Vellore, India
retPLT: reference intervals (Sapphire)
In adults, retPLT increase with age
retPLT are inversely related to MPV
Hoffmann et al. Arch Pathol Lab Med 2013; 137: 1635-40
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HAEM@CMCVellore 26-27 February 2016 Vellore, India
Reticulated or immature platelets: clinical utility
Diagnostic utility has been confirmed for:
• Distinguishing decreased production from accelerated destruction as the cause of thrombocytopenia
• Predicting thrombopoietic recovery after chemotherapy, bone marrow and peripheral stem cell transplantation
Meintker et al. Clin Chem Lab Med 2013; 51: 2125-32Strauss et al. Pediatr Blood Cancer. 2011;57:641-7
Sakuragi et al. Int J Hematol 2018; 107: 320-6
HAEM@CMCVellore 26-27 February 2016 Vellore, India
Outline of this presentation
New WBC parameters: (pre-) analytical aspects, reference ranges and clinical utility
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HAEM@CMCVellore 26-27 February 2016 Vellore, India
WBC parameters: analytical aspects
• CPD (Cell Population Data) represent the raw measurement data from a WBC cluster
• CPD cannot be calibrated
• CPD depend on the “optical signature” of an individual hematology analyzer
Seghezzi et al. J Med Biochem 2018; 37: 1-13
HAEM@CMCVellore 26-27 February 2016 Vellore, India
WBC parameters: clinical utility
CPD have been suggested to be a biomarker for:
• Early diagnosis of sepsis
• Exclusion of acute promyelocytic leukemia
• Screening for viral infection
• Timing and efficiency of stem cell transplantation
• Screening of myelodysplastic syndrome
• Screening of paroxysmal nocturnal hemoglobinuria
• Distinction of reactive versus clonal lymphocytosis
• Postprandial leukocyte activation
• Screening of malaria infectionPark et al. Int J Lab Hematol 2015; 37: 190-8
Urrechaga et al. J Clin Pathol 2018; 71: 259-66Buoro et al. Ann Transl Med 2016.10.73
Furundarena et al. Int J Lab Hematol 2018; 40: 41-8
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HAEM@CMCVellore 26-27 February 2016 Vellore, India
Outline of this presentation
Limitations and unmet clinical needs
HAEM@CMCVellore 26-27 February 2016 Vellore, India
Limitations of RBC parameters
• Pre-analytical changes due to EDTA (nearly all parameters)
• Incomparability of RDW between different methods
• Lack of international standardization (RDW and newer RBC parameters)
• Different reference intervals (RDW and newer RBC parameters)
• Gender- and age-dependency not adequately explored in risk assessment studies (RDW)
• Expression of RDW (% or fL)
Goossens et al. Clin Lab Haematol 1991; 13: 291-5Mehmood et al. J Clin Lab Anal 2018; 32: e22188
Hoffmann. Clin Chim Acta 2012; 413: 824-5Hoffmann et al. Clin Chem Lab Med 2015; 53: 2015-9
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HAEM@CMCVellore 26-27 February 2016 Vellore, India
Limitations of reticulocyte parameters
• Pre-analytical changes due to EDTA (nearly all parameters)
• Incomparability between different methods
• Lack of harmonization and standardization (MCHr, most importantly)
• Different reference intervals (all parameters)
HAEM@CMCVellore 26-27 February 2016 Vellore, India
Limitations of PLT parameters
• Pre-analytical changes due to EDTA, storage time and temperature (MPV, PDW)
• Incomparability due to different methods (MPV, PDW, retPLT, IPF)
• Lack of harmonization and standardization (MPV, PDW, retPLT, IPF)
• MPV is not normally distributed, so what is ‘mean’?
• Gender- and age-dependency (all parameters)
• PLT count dependency not properly investigated in risk assessment studies (MPV)
Hoffmann et al. Clin Chem Lab Med 2015; 53: 2015-9Beyan & Beyan. Blood Coag Fibrinol 2017; 28: 234-6
Dima et al. Diagnosis 2016; 3: 91-3Mehmood et al. J Clin Lab Anal 2018; 32: e22188
Buttarello et al. Clin Chem Lab Med 2018; 56: 830-7
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HAEM@CMCVellore 26-27 February 2016 Vellore, India
Limitations of WBC parameters
• Pre-analytical aspects not yet thoroughly investigated
• Incomparability between different analyzer types
• Variation between individual analyzers of the same type and harmonization require further studies
• International standardization impossible
Seghezzi et al. J Med Biochem 2018; 37: 1-13
HAEM@CMCVellore 26-27 February 2016 Vellore, India
Blood cell parameters – unmet clinical needs
• Clinically validated parameter for immature granulocytes
• MPV standardization, analytical and pre-analytical
• MCHr/CHr analytical standardization
• retPLT/IPF standardization, analytical and pre-analytical
• RDW expressed in fL
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HAEM@CMCVellore 26-27 February 2016 Vellore, India
Outline of this presentation
Conclusions
HAEM@CMCVellore 26-27 February 2016 Vellore, India
Conclusions
These new hematology analyzer parameters
• Are all sensitive for pre-analytical influences, requiring strict procedures of sample handling and processing
• Suffer from lack of analytical standardization
• Some have been proven to be diagnostically useful in certain hematological patients
• Their role as prognostic risk indicators looks promising, but requires studies with appropriate pre-analytical and analytical standardization
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HAEM@CMCVellore 26-27 February 2016 Vellore, India
Thank you for your attention
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