BC-5300/5380

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2013 深圳迈瑞生物医疗电子股份有限公司版权所有。 是深圳迈瑞生物医疗电子股份有限公司的注册商标 国食药监械（准）字2010第3300644号 深圳市南山区高新技术产业园区科技南十二路迈瑞大厦 产品规格如有变化，恕不另行通知，谨以最新技术资料及检验结果为准。 电话: 755 8188 8998 传真: 755 2658 2680 P/N: ENG-CCS-5300/5380-210145x36-20110804 www.mindray.com 美国纽交所股票代码MR BC-5300/5380 Auto Hematology Analyzer

Full automatic 5-part differentiation of WBC, 27 parameters, 3 histograms and 1 scattergram Laser scatter, Advanced flow cytometry, Chemical dye method Independent Basophil channel Up to 60 samples per hour 2 Sampling modes: Autoloader and Closed tube Large storage capacity: 40,000 results with graphs Preface to Clinical Case Study for spread product portfolio and an established presence in over 165 Mindray Hematology analyzer BC-5300/5380 countries; Mindray takes the task of supporting current healthcare Dr. Vijay Parekh, Scientific Director in Mindray demands seriously.

Microscope and Romanowsky dyes availability have resulted in Clinical case study for BC-5300/5380 hematology analyzer is an accumulation of a vast pool of knowledge about cytological chang- example of that effort. It is a compilation of BC-5300/5380 hemato- es seen in various blood disorders. This is applied prospectively to logy analyzer results obtained on healthy individual and patients not only suspect, but also diagnose or even differentiate haemato- with commonly seen hematological abnormalities. It is designed to logical disorders. It is unthinkable today to practice hematology introduce the BC-5300/5380 user to the benefits of pattern reco- without support from an expert morphologist. At the base of such gnition. We wish to draw user's attention to the 'screening' principle approach lies the process of pattern recognition i.e. first discerning that is fundamental to judicious & proper use of this Clinical case a set of test results (qualitative + quantitative) as not normal (or study book. Currently available hematology analyzers are unable to abnormal) and then establishing its association with a known he- classify all types of morphological abnormalities, primarily due to matological condition. the limitations of technology which cannot match the accuracy of an expert morphologist who observes visual attributes of a well CBC+DIFF or ABC (i.e. Automated Blood Count & differentiation of stained cell and using his past knowledge classifies the cell. How- white cells into 5 common subtypes) is the most ordered blood test ever, the analyzers make up for the lower accuracy by providing far worldwide. While Clinical laboratories world over test millions of greater reproducibility/precision because they count large number blood specimens daily on automated hematology analyzers; Lab of cells and consistency to 'flag' an abnormality. managers also have to grapple with a decreasing pool of expert morphologists. Consequently, the newer entrants to medical pro- Hence, when BC-5300/5380 analyzer 'flags' a result, an expert fession look for solutions that bridge the gap between newer (not morphologist is expected to review patient's blood film from before necessarily well known) technologies and known maladies. Obvi- issuing findings & opinion, of course only after correlating with ously, an interested user is looking for repositories of data produced patient's medical history and clinical condition. by automated devices that establishes link between the data and diseases. It is also our hope that with your feedback, suggestions and newer observations; we will be able to bring out richer editions of Clinical Mindray is a global healthcare manufacturer committed to bring Case Study in future. healthcare within reach of wider section of people. With a wide- 1 2 FS Counting Principles for LEO I lyse breaks down red blood Hematology Analyzer BC-5300/5380 cells and imposes on effect on white blood cells. For RBC/PLT numeration, the classical electrical impedance LEO II lyse densifies the granules of method is used. When cell passing through the aperture by eosinophils. vacuum, it will introduce the change on resistance. In a constant current, the voltage change signal will be recorded and accords with the volume of cell. SS Flow cytometry Cells are injected into a flow cell aperture + - which is located in the optical path vacuum electrode of a light source, usually a laser; Surrounded with sheath flow, the blood cell pass through the center of For WBC 4 parts(lymphocytes, monocytes, neutrophils and flow cell in a single colume at a fast eosinophils) differentiation, chemical dye, flow cytometry speed. and laser scatter are applied.

Chemical dye LEO I LEO II Laser scatter Light scattering occurs when a particle EOS deflects laser light. The extent to which this occurs depends on the physical properties of the particle: Other Forward scatter (FS): cell volume WBC Side scatter (SS): cell granularity

RBC

DIFF Channel

3 4 For basophils and WBC total number count, the cells are first LH lyse is also used for HGB quantitative analysis. With the treated by chemical dye, and then numerated by the classical aid of a color reagent, the concentration of HGB is electrical impedance method. determined by the change of absorbance in 525nm using colorimetric method. LH

LH BASO

Other WBC

RBC LH lyse breaks down red blood cells, binds to hemoglobin and converts it to a complex that is measurable at 525nm. WBC/BASO Channel

LH Lyse breaks down red blood cell and shrinks other WBC cells except basophils while keeps the original volume of basophils

5 6 Flags Appendix

Abnormal Suspect

Flag Meaning Flag Meaning

1 Leucocytosis High WBC analysis results WBC numbers of BASO and DIFF channels

2 are inconsistent. The sample may 1 WBC Abn. ? Leucopenia Low WBC analysis results be abnormal, or the analyzer may be 1 abnormal Neutrophilia High neutrophils analysis results Neutropenia1 Low neutrophils analysis results WBC Abn Abnormal WBC scattergram Scattergram? Lymphocytosis1 High lymphocytes analysis results

1 WBC Abn. Lymphopenia Low lymphocytes analysis results Abnormal WBC histogram WBC Histogram? WBC 1 Monocytosis High monocytes analysis results Left Shift? Left shift may exist Eosinophilia1 High eosinophils analysis results

1 Immature cells may exist Basophilia High basophils analysis results Immature Cell? RBC Abn. Distribution Abnormal RBC scattergram Abn./Atypical Abnormal lymphocytes or atypical 1 Lym? lymphocytes may exist Anisocytosis Sizes of RBCs are dissimilar Microcytosis1 Small MCV RBC Lyse Resist? RBC hemolysis may be incomplete

1 Macrocytosis Large MCV RBC/HGB RBC or HGB Abn.?1 Results of RBC or HGB may be inaccurate 1 RBC/HGB Erythrocytosis Increased RBCs 1 PLT PLT Clump? PLT clump may exist Anemia Anemia Hypochromia1 Hypochromia

Diamorphologic RBC dimorphic distribution 1 The criterions which trigger the flag information can be edited from the Thrombocytosis1 PLTs increase software version of V01.19. 2 For this flag, if the analyzer determines that it is resulted from fragile WBCs, or PLT Thrombocytopenia1 PLTs decrease the WBC result in the predilute mode is between 0.5x109/L and 2.0x109/L, the analysis result will be displayed; otherwise, the analysis result shows ”***”. PLT Abn Distribution PLT histogram distribution abnormal

7 8 Normal Sample

Normal scattergram appearance; the WBC sub-populations are well differentiated from each other and aggregate with- Microscopic Differential in expected areas; no flag message for abnormal cells. The WBC DIFF (n=200) WBC/BASO, RBC and PLT histograms are normal. Neutrophilic band granulocyte 1% Neutrophilic segmented Lym granulocyte 54% Lymphocyte 37% Monocyte 4% Neu Eosinophil 3 .5% Basophil 0.5%

RBC morph Normal PLT morph Normal

Under microscope, the morphology of erythrocytes, platelets and all sub-populations of leukocytes were normal, and no atypical or imma- ture cells were observed.

Screen Interpretation: Upper part: results, reference ranges and flag information areas Lower part: histograms and scattergram ( lymphocytes monocytes neutrophils eosinophils) Male, 27-year-old healthy volunteer.

9 10 Diamorphic RBC

The dimorphic RBC population in this case indicates aniso- Microscopic Differential cytosis and evidenced by presence of two red cell popula- tions with different cell size distributions. Dimorphic RBC is WBC DIFF (n=200) Neutrophilic band commonly seen in patients with sideroblastic anemia. It can granulocyte 1% Large RBC also be seen in patients recovering from iron deficiency Neutrophilic segmented granulocyte 55% anemia upon receiving iron therapy or patients who have Small RBC Lymphocyte 35% received massive blood transfusion. Monocyte 4% Eosinophil 4.5% Basophil 0.5%

RBC mor p h Vary in size, the pale area in the center of some RBC expanded PLT morph Normal

Under microscope, the erythrocytes varied in size; All WBC sub- populations were within normal limits.

Report Analysis: Inaccurate RDW-CV and RDW-D results displayed as “**.*”; MCV results might be affected; related parameters including HCT, MCV and MCHC were flagged with ”?” where microscopic examination was suggested RBC flag messages: “Dimorphologic” and “Anisocytosis” Male, 50-year-old, outpatient. Histogram: dimorphic RBC histogram indicated anisocytosis; in the Diagnosis: Rectal cancer PLT histogram, the right part was raised from the X axis, indicating an abnormal PLT distribution which might be interfered by microcytic red cells

11 12 Microcytosis

Microcytosis is a condition where red blood cells are reveal- ed to be unusually small when their mean corpuscular Microscopic Differential volume is measured. A large number of hypochromic micro- WBC DIFF (n=200) erythrocytes appear in blood smear, indicating reduction in Neutrophilic band granulocyte 1% hemoglobin synthesis. It is seen in case of iron deficiency Neutrophilic segmented anemia and thalassemia. However the microerythrocyte in granulocyte 51% Lymphocyte hereditary spherocytosis is well filled with hemoglobin and 42.5% Monocyte 4% Neu the hypochromic area in its physiological center disappears. Eosinophil 1% Basophil 0.5%

RBC morph Decrease in size, microcytic PLT morph Normal

Under microscope, the erythrocytes decreased in size, but were in similar sizes.

Report Analysis: RBC and PLT counts increased; MCV decreased significantly RBC flag messages: “Microcytosis” and “Erythrocytosis” Male, 34-year-old, outpatient. Histogram: the RBC dominant peak moved to left, indicating that there were microcytes; in the PLT histogram, the right part was raised from the X axis, indicating an abnormal PLT distribution due to interference by microcytes

13 14 Aplastic Anemia

Aplastic anemia (AA) is a hematopoietic depletion syndrome WBC Differential which may be caused by exposure to chemical toxins, physi- cal trauma, biological factors or may be idiopathic in origin. WBC DIFF (n=200) Promyelocyte 1% The hematopoietic stem cell dysfunction is prominent, Myelocyte 1% which leads to the replacement of hematopoietic red pulp by Metamyelocyte 2% Neutrophilic band fat, resulting in decrease of healthy blood cells causing pro- granulocyte 12% gressive anemia, hemorrhage or infection. AA is usually seen Neutrophilic segmented granulocyte 71.5% in adults. Neu Lymphocyte 12% Monocyte 1% Eosinophil 0.5%

RBC morph Normal PLT morph Normal

Under microscope, the erythrocytes and leukocytes appeared fewer than normal. The leukocyte in the field view on this page, was a neutrophilic segmented granulocyte.

Report Analysis: WBC, RBC, HGB and PLT counts decreased significantly; lymphocyte and neutrophil numbers decreased, especially the neutrophil number, which was consistent with the features of aplastic anemia histogram Female, 30-year-old. WBC flag message: “WBC Abn. scattergram” Diagnosis: aplastic anemia confirmed half a year ago. RBC flag message: “Anemia” PLT flag messages: “PLT Abn. Distribution” and “Thrombopenia”

15 16 M o n o c

Monocytes and phagocytes in tissues form a defense mecha- y t

Microscopic Differential o nism by phagocytizing or killing damaged cells and antigens s i s . Monocytosis is an increase in the number of circulating WBC DIFF ( n=200) Neutrophilic segmented monocytes in blood. Physiological monocytosis is commonly granulocyte 49% found among children and infants, while pathological Lymphocyte 32.5% Monocyte 16% monocytosis is usually seen in patients with subacute infec- Eosinophil 2.5% tious endocarditis, malaria, kala-azar, active tuberculosis. It Mon RBC morph Normal may also present during the convalescence of an acute infec- Mon PLT morph Normal tion or hematological diseases such as malignant histocyto- sis, lymphomatosis and agranulocytosis.

Under microscope, the monocyte proportion increased, in the micro- scopic field shown here, two monocytes could be observed.

Report Analysis: WBC count increased and monocyte number increased significantly RBC and HGB results were within normal range; PLT count increased Male, 20-year-old, outpatient. WBC flag message: "Monocytosis" Diagnosis: ankylosing spondylitis. Scattergram: in the DIFF scattergram, the monocyte area was brighter than normal, indicating an intense aggregation of spots and increase of monocyte proportion 17 18 Eosinophil is capable of inhibiting allergic responses, Microscopic Differential phagocytizing and is involved in immunological reactions to WBC DIFF (n=200)

parasites. Eosinophilia, elevated eosinophil count, is E

Neutrophilic segmented o

granulocyte s commonly seen in patients with parasitic diseases, allergic 42.5% i n

Lymphocyte 28% o reactions and dermatological diseases. Increased eosino- p Monocyte 4.5% h i l phil count is not unusual in chronic granulocytic leukemia, Eosinophil 24.5% i a polycythemia vera, multiple myeloma. Eosinophilia may Basophil 0.5% Eos also be seen in patients with malignant tumors, infectious RBC morph Normal diseases, rheumatic diseases, pituitary gland anterior lobe PLT morph Normal deterioration, adrenal cortex deterioration and allergic Eos interstitial nephritis.

Under microscope, the eosinophils population appeared increased. In the microscopic field shown here, two eosinophil granulocytes could be observed.

Report Analysis: Female, 25-year-old, outpatient. Eosinophil number increased significantly; MCV decreased Diagnosis: edema of unknown cause. WBC flag message: "Eosinophilia" Scattergram: in the DIFF scattergram, there were a significant increase of eosinophil spots and increase of eosinophil proportion 19 20 Large Immature Cell (LIC) refers to the increase of stab cells Microscopic Differential and/or the presence of metamyelocytes, myelocytes and promyelocytes in the peripheral blood. It can be divided into WBC DIFF (n=200) Myelocyte 1% reproductive left shift and degenerative left shift. The form- Metamyelocyte 2.5% er is a kind of left shift accompanied by elevated WBC count. Neutrophilic band granulocyte 2% Left shift has its significance in evaluating the seriousness of Neutrophilic segmented granulocyte illness and the patients’ ability to respond. Myelocyte 66.5% L Lymphocyte a 22.5% r g

Monocyte 3.5% e I

Eosinophil 1% m Basophil 1% m Metamyelocyte a t u r

RBC morph Normal e C PLT morph

Normal e l l

Under microscope, a trend of left shift, for neutrophils & promyelocytes, was observed. The cell in the left of the microscope field shot shown on this page were a myelocyte and a metamyelocyte .

Report Analysis: WBC count increased, RBC and HGB decreased There was no clear distinction to differentiate neutrophil spots and monocyte spots. The abnormal cells might affect the Baso histogram; Neu#/%, Mon#/% and Bas#/% were flagged with “?”, indicating these results might have been affected by presence of abnormal cells and a Male, 34-year-old, outpatient. microscopic examination was indicated Diagnosis: Adult Still’s disease. WBC flag message: ”Immature cell”? Scattergram: in the DIFF scattergram, there was an cluster of spots in the LIC area

21 22 Atypical lymphocytes (ALY), also known as reactive lympho- Microscopic Differential cytes, are enlarged and elongated white cells with an ellip- tical nucleus. They are usually associated with viral illnesses WBC DIFF (n=200) Neutrophilic band when normal lymphocytes are stimulated by the viral anti- granulocyte 1% gens. These are commonly seen in infectious mononucleosis, Neutrophilic segmented ALY granulocyte 14% infectious hepatitis, measles, viral pneumonia, pertussis- Lymphocyte 75.5% like syndrome, influenza, epidemic hemorrhagic fever and Atypical lymphocyte 5% Monocyte even common cold. 3% Eosinophil 0.5% Basophil 1%

ALY RBC morph Normal PLT morph Normal A t y

Under microscope, the ALY proportion appeared increased. The micro- p i c scope field shot here showed two mononuclear atypical lymphocytes. a l Ly m p h o c y t e

Report Analysis: There was no clear demarcation to differentiate clusters of lympho- cyte and monocyte. The abnormal cells might affect the Baso histogram; Lym#/%, Mon#/%, Eos#/% and Bas#/% are flagged with “?” , indicating that these results might be affected by presence of Female, 2-year-old, inpatient; Virus test results: adenovirus: abnormal cells and a microscopic examination was indicated weak positive; respiratory syncytial virus: positive; Coxsackie virus: positive. WBC flag messages: ”Abn./Atypical Lym ? “, ” Lymphocytosis” and Diagnosis: bronchopneumonia; virus infection confirmed. “Neutropenia” Scattergram: there was a cluster of spots in the ALY area 23 24 Acute promyelocytic leukemia (FAB M3) is a type of acute Microscopic Differential myeloblastic leukemia. In FAB M3, there is an abnormal WBC DIFF (n=200) accumulation of promyelocytes. The disease presents a chro- Blast 6% mosomal translocation involving the retinoic acid receptor Promyelocyte 81% alpha (RARα or RARA) gene and is unique from other forms of Myelocyte 2% Metamyelocyte 1% AML in its responsiveness to all-trans retinoic acid (ATRA) Lymphocyte 10% therapy. Promyelocyte RBC morph Normal Promyelocyte PLT morph Normal

Most of the cells observed under microscope were promyelocytes with increased number of abnormal grains, and there were a few myeloblasts and other granulocytes.

Report Analysis: WBC count increased, RBC and PLT counts decreased A

WBC flag message: ”WBC Abn scattergram” P M

RBC flag message: “Anemia” L PLT flag message: “Thrombopenia” Scattergram: there was a cluster of spots in the immature cell area; the monocyte spots mixed with the granulocyte spots, while the Female, 33-year-old. Chief complaints: increased menstrual lymphocyte spots were clearly differentiated, indicating an abnormal blood loss and ecchymosis. Physical examination results: anemic look; petechiae all over granulocyte morphology. Therefore, microscopic examination was her body; no superficial lymphadenodes could be detected recommended during physical exam.

25 26 Acute myelo-monocytic leukemia (FAB M4) is a form of acute Microscopic Differential myeloid leukemia that involves a unwanted proliferation of CFU-GM myeloblasts and monoblasts. It is a common type of WBC DIFF (n=200) Blast 20% pediatric AML. The symptoms may be non-specific: weakness Promyelocyte 15% Promonocyte , pallor, fever, dizziness and respiratory symptoms. More Myelocyte 4% Metamyelocyte 4% specific symptoms include bruises and/or bleeding, DIC, Promonocyte 14% neurological disorders and gingival hyperplasia. Neutrophilic band granulocyte 3% Monoblast Neutrophilic segmented granulocyte 14% Lymphocyte 14% Monocyte 12% Promyelocyte NRBC 5/100

RBC morph Normal PLT morph Normal

Under microscope, a large number of promyelocytes and premonocytes were observed, as well as active phagocytes. In the microscope field shot, there were three leukocytes: promonocyte, promyelocyte and Report Analysis: blast. WBC count increased and RBC and PLT counts decreased WBC flag message: “WBC Abn scattergram” RBC flag message: “Anemia” PLT flag messages: ”PLT Abn. Distribution” and “Thrombopenia” A

Histogram: PLT number was very low and indices not reported M M

Scattergram: there was an cluster of spots in the immature cell area; o

Male, 30-year-old. Chief complaints: hypodynamia and L the monocyte spots mixed with the granulocyte spots while the pyrexia for 1 month; pain in left hip for 1 day. lymphocyte spots were clearly differentiated, which indicated that the granulocyte and monocyte morphs were abnormal, so microscopic examination was suggested

27 28 Acute Megakaryocytic Leukemia (AMKL) is a rare kind of Microscopic Differential leukemia. Its clinical symptoms are similar to other types of acute leukemias. Micromegakaryocytes that look like lym- WBC DIFF (n=200) Blast 10% phocytes can be observed in blood smear; in marrow smear, Myelocyte 1% the abnormal proliferation of megakaryocytes can be found Metamyelocyte 2% Immature cell 30% with the count of megakaryocytes over 1000, among which Neutrophilic band megakaryoblasts and promegakaryocytes are prominant. granulocyte 4% Neutrophilic segmented granulocyte 25% Megakayocyte Lymphocyte 24% Monocyte 3% Basophil 1%

RBC morph Normal PLT morph Normal

A large number of immature cells which resembled lymphocytes (could be megakaryoblasts or promegkaryocytes) were observed under microscope. In the microscope field shot on this page, there were two megakaryocytes. Report Analysis: WBC count increased and RBC and PLT count decreased WBC flag message: ” WBC Abn scattergram” RBC flag messages: ”RBC Distribution Abn.” and “Anemia” PLT flag messages: “PLT Abn. Distribution” and “ Thrombopenia” Female, 71-year-old. Chief complaints: hypodynamia and Histogram: PLT number was low and indices reported with low dazziness for half a year. reliability Physical examination results: anemic appearance; with scattered petechiae on skin; bleeding observed on the left of Scattergram: there was an cluster of spots in the immature cell area, A

oral mucosa, no superficial lymphnodes discovered by M

and the abnormal spots were on the top right; the monocyte spots K

physical exam. L mixed with the granulocyte spots while the lymphocyte spots were clearly differentiated 29 30 Chronic myelocytic leukemia (CML) is a clonal proliferative Microscopic Differential disease which originates from the hematopoietic stem cells WBC DIFF (n=200) with primary changes in myelocyte proliferation. The disea- Myelocyte 1% se is typically diagnosed in individuals aged between 20 and Metamyelocyte 1% 50. One of the most distinctive features is enlarged or swoll- Neutrophilic band granulocyte 2% en spleen. From the cytogenetic perspective, a positive CML Neu Neutrophilic segmented diagnosis is confirmed when the test for Philadelphia chro- granulocyte 46% Lymphocyte 37% mosome is positive and the BCR/ABL fusion gene is detected. Atypical lymphocyte 1%

Band Monocyte 8% Basophil 4%

RBC morph Macrocytes present PLT morph Normal

Promyelocytes were seen under microscope. Basophil number increa- sed significantly. In the microscope field shot on this page, there were one neutrophilic segmented granulocyte and one neutrophilic band granulocyte.

Report Analysis: The number of basophil increased, and immature cells were observed, which indicated a possibility of chronic myelocytic leukemia WBC flag messages: ” Immature Cell?”, “Abnormal/Atypical Lym?” and “ Basophilia” Male, 32-year-old. Chief complaint: leucocytosis for 2 years. RBC flag messages: ”Anisocytosis” and “Macrocytosis” Physical examination result: Normal. Bone marrow examina- Scattergram: there were a few spots scattered in the immature cell tion result showed a possibility of chronic myelocytic leuke- area and the abnormal/atypical lymphocyte area which indicated an mia. C

abnormal WBC morph, so microscopic examination was suggested M L 31 32