Normal values of various parameters of CBC CBC values vary by age, sex, race and demography. Normal values (reference range) are ultimately determined by the laboratory performing the test in the particular population. As a guide, the normal values for men and women areas follows: RBC Parameters + RBC count-4.2-5.0 x 10"/mm? for women. 4.6-6 x 10*/mm’ for men = Hemoglobin-12.0-15.8 g/dl for women 13.3-16.2 g/dl formen + Hematocrit-35.4-44.4 % for women 38.8-46.4 % for men © Mean corpuscular volume (MGV)-79-98 fL, + Mean corpuscular hemoglobin (MCH)-26.7-31.9 pg ‘+ Mean corpuscular hemoglobin concentration (MCHC)-32-36% «Red cell distribution width (RDW-GV)-11.5-14.5% ‘+ Red cell distribution width (RDW-SD)-35-45 {L. + Reticulocyte count-0.8-2.3% Degen ‘Total WBCs: 4,500-11,000/mm? for women and men ‘+ Neutrophils 50-70% + Lymphocytes 25-35% = Monocytes 4-6% * Eosinophils 1-3% + Basophils 0.4-1% + Bands 0-5% Platelet Parameters: + Platelets: 150000-450000/mm? + Mean platelet volume: 7.4-10.4 fL. + Platelet distribution width: 9-13 fL. + Plateletcrit: 0.108-0.282 VARIOUS INDICES BY AGE GROUP AND CONDITIONS Stunit Hematocrit 0.42-0.68 L/L Hemoglobin 15.4-24.5 g/dL. 9.6-15.3 mmol/L RBC count 4,1-6.2 million/pL 41-62 «10/1, MCV 103-106? 103-106 fL MCH 36-38 pg 2.24-2.37 fmol MCHC 34-36% 21.10-22.34 mmol/L, Platelets 100000-300000/pL. or mm* 100-300 x 10°/L, Scanned with CamScannerReticulocyte production index or corrected reticulocyte count + ‘Thereticulocyte count must be adjusted for the level of anemia to obtain the reticulocyte index, amore accurate reflection of erythropoiesis. + Reticulocyte index = Reticulocyte count x Patient's hematocrit/Normal hematocrit. For example: Reticulocyte count 6%, hematocrit 15, then Reticulocyte index = (6 x 15)/45 = 2% Retina lieu eu anecie Normally reticulocyte survive 3.5 days in marrow and one day in peripheral circulation at normal PCV. In case of anemia and reduced hematocrit the survival time in circulation is increased and this may cause poor correlation of retic count with marrow response. This situation can be dealt with calculation of corrected retic count or reticulo- cyte proliferation index. Reticulocyte proliferation index PCV% Maturation time in Days 45 1 35 15 25 2 15 25 Reticulocyte proliferation index = Corrected retic count/shift correction factor For example, Corrected retic count 7%, PCV—25, RPI = 7/2=3.5 pore Mctetasdig + Hemolytic anemias Response to treatment of iron and Vit B,, and folic acid in anemia Recent hemorrhage ‘Thalassemia Pregnancy + Erythroblastosis fetalis, + HBC disease + Leukemias «Hypoxia An increased count indicates active erythropoiesis GO ass | + Decreased adrenocortical and anterior pituitary activity + Aplastic anemia Cirrhosis Megaloblastic anemia Exposure to radiation Anemia of chronic diseases MDs Scanned with CamScannerHigh hematocrit is due to: Dehydration (such as from severe diarrhea) Kidney disease with high erythropoietin production Low oxygen level in the blood Congenital heart disease Cor pulmonale Pulmonary fibrosis High altitude Polycythemia vera + Smoking Low hematocrit is due to: * Blood loss (hemorrhage) + Bone marrow failure (For example, aplasia or hypoplasia due to radiation, infections, drugs, neoplasia, autoimmune, etc.). Erythropoietin deficiency (usually secondary to kidney disease) Hemolysis (RBC destruction of varied etiology) Leukemia Malnutrition (nutritional deficiencies of iron, folate, vit. B,,, or vit. B,) + Multiple myeloma Autoimmune/collagen-vascular diseases such as lupus erythematosus or rheumatoid arthritis, Scanned with CamScannerNormal|MGV:|(Normocytic Anemia) Following acute hemorrhage Dimorphie anemia Hemoglobinopathies Anemias duc to inadequate blood cell formation = Myelophthisic = Hypoplastic = Aplastic. + Endocrinopathies— (hypopituitarism, hypothyroidism, hypoadrenalism, hypogonadism) «Anemia of chronic disease (chronic infections, neoplasms, uremia). Increased) MCV: (Macrocytic anemia - MCV >98 fL) ‘Megaloblastic anemia Pernicious anemia (vitamin B,, oF folate deficiency) Sprue, (e.g. steatorrhea, celiac disease, intestinal resection or fistula) Macrocytic anemia of pregnancy Megaloblastic anemia of infancy Di Guglielmo disease Myelodysplastic syndromes (aplastic anemia, sideroblastic anemia) Myelophthisic anemia Posisplenectomy Infants and newborns Nonmegaloblastic macrocytic anemias Alcoholism Liver disease Anemia of hypothyroidism Drugs: ~ Oral contraceptives - Anticonvulsants, (e.g. phenytoin, primidone, phenobarbital) = Antitumor agents, (eg. methotrexate, hydroxyurea, cyclophosphamide) = Antimicrobials, (e.g. sulfamethoxazole, sulfasalazine, trimethoprim, zidovudine, pyrimethamine). Decreased MCV: |(Microcytic anemia) + Usually hypochromic = Iron deficiency anemia ~ ‘Thalassemia (major or combined with hemoglobinopathy) ~ Lead poisoning = Disorders of porphyrin synthesis + Usually normochromic ~ Anemia of chronic diseases (<1/3rd of patients) ~ Heterozygous thalassemia and hemoglobinopathies Scanned with CamScannerMCHC = (hemoglobin/hematocrit) x 10 MCHC Male and Female normal value 32-36 g/dL. MCHC decreased in: (decrease is defined as = 30:1 g/d! + Hypochromic microcytic anemia. Normal value does not rule out any of these anemias. + Low MCHC may not occur in IDA when performed with automated instruments. MCHC increased in: + Hereditary spherocytosis + Inspherocytosis, the MCHC is increased due to loss of membrane and the consequent spherical shape assumed bythe cell + Infants and newborns + Autoagglutination + _Antifactual (abnormal MCHC may be most valuable clue to artefact) Bete Teas MCHC Decreased + Marked leukocytosis (250,000/4L) MCHC Increased, Hemolysis, (e.g. sickle cell anemia, hereditary spherocytosis, autoimmune hemolytic anemia) with shrinkage of RBCs making them hyperdense + Conditions with cold agglutinins or severe lipemia of serum + Rouleaux or RBC agglutinates + High heparin concentration Scanned with CamScannerRDWis mathematically derived from the RBC histogram with a portion of each of the extreme ends of the histogram curve excluded. ‘This allows for a computation to exclude platelets, platelet clumps, and electrical interference from left side of the curve. ‘The exclusion of the right side of the curve eliminates clumped RBCs (from Rouleaux or agglutination) or overly large RBCs. ‘The MCVis calculated using the entire RBC histogram. ‘The RDW independent of the MCV may be normal when the MCV is normal, low, or high. ‘The six possible combinations classify almost all major possible causes of anemia, + LowMCV = with = NormalRDW == or High RDW + NormalMCV with NormalRDW or High RDW + HighMCV with = NormalRDW or High RDW ena MCV High (Macrocytic) MCV Low (Microcytic) + Anemia of chronic + Aplastic anemia + Anemia of chronic disease + Preleukemia disease NormalRDW | Acute blood loss + Myelodysplastic + ‘Thalassemia (heterozy- (Nonheterogencous) |+ Hemolysis syndrome gous) + Chronic lymphocytic Leukemia (CLL) + Chronic myelogenous leukemia (CML) + Hemoglobinopathy © Normal variant (1) RDW increases before MCV |+ Vitamin B,, deficiency | Iron deficiency becomes abnormal + Folate deficiency Anemia + Earlyiron deficiency} Immune hemolytic © RBC fragmentation anemia anemia © HbH iieraeeou © Early vi = Liver disease «Thalassemia intermedia defficiency © Cold agglutinins «© GGPD deficiency + Earlyfolatedeficiency | Alcoholism (2) Anemic globinopathy like Sickle cell anemia Low RDW is not observed normally but theoretically itis possible only at marrow level when LowRDW RBC produced by marrow have less heterogeneity than the accepted normal. Some observ- ers quote low RDW low MCV in thalassemia minor and low RDW with high MCV in aplastic anemia but the author includes both these under normal RDW ‘The Classification may be grossly summarized as: + Hypoproliferative disorders—Independent of MCV have normal heterogeneity. + Nutritional disorders—Independent of MCV have increased heterogeneity. + Hemolytic disorders—Independent of MCV have heterogeneity that is increased in direct proportion to the degree of anemia caused by the disorder. Scanned with CamScannerMICROCYTIC, HYPOCHROMIC RED CELLS ‘The RBCs are smaller than the nucleus of the small lymphocyte and have markedly increased central pallor, which exceeds Vrd the diameter of the RBC. Such RBCs, are microcytic (< 7.0 pum in diameter) and hypochromic. Both features, i.e. microcytosis, and hypochromia usually coexist, and indicate abnormal hemoglobin synthesis. ‘The major causes are: + Iron deficiency anemia * Thalassemia minor + Sideroblastic anemia + Anemia of chronic disease + Hemoglobinopathies. — Scanned with CamScannerMACROCYTIC RED CELLS Most of the red cells are larger than the nucleus of the small lymphocyte (Size > 8.5 im indiameter). ‘The major causes of macrocytic red cells are: + Vitamin B,, or folate deficiency + Alcoholism + Liverdisease + Myelodysplastic syndrome(MDS) + Hypothyroidism, + Drugs that impair DNA synthesis. Oval macrocyte Round hypochromic macrocyte Seon in: + Aeoholism + Neonates + Hypothyroidism + Response to anemic + Liver disease stress: + Postsplenenctomy Scanned with CamScannerCauses of high white blood cell counts: Acute and chronic bacterial infections Viral infections Polycythemia vera Rheumatoid arthritis Drugs Allergy, especially severe allergic reactions Acute lymphocytic leukemia Acute myeloid leukemia (AML) + Smoking + Stress, such as severe emotional or physical stress + Tissue damage, such as from burns + Chronic lymphocytic leukemia + Chronic myelogenous leukemia + Hairy cell leukemia + Lymphoma spillage + Measles * Myelofibrosis. Causes of low white cell counts: * Chemotherapy and radiation therapy + Sepsis © Typhoid + Malaria + Tuberculosis + Dengue + Enlargement of the spleen + Leukemia (as malignant cells overwhelm the bone marrow) Folate deficiencies Psittacosis Drugs like various antipsychotic + Myelofibrosis + Aplastic anemia (failure of bone marrow production) + HIVand AIDS + Influenza + Systemic lupus erythematosus Scanned with CamScannersee oecrsiO rane peu ees yuu (A) Physiologic increase | (C) Tissue injury and inflammation | (F) Miscellaneous causes (Demargination) © Hemolyticanemia © Release of cells in «Myocardial infarction . foaehemernee : marginal pool + Bum injury * Splenectomy leukocytosis + Mediated by stress + Collagen vascular disease may persist months). (stress leukocytosis) © Hypersensitivity reaction + Exercise seizures (G) Neoplasms + Anxiety + Metastatic cancer. «Epinephrine. (B) Acute bacterial infection (D) Metabolic condition (H) Medications (and other infections) (E) © Acute renal failure + Eclampsia + Ketoacidosis. Mycloproliferative disorder + Myelacytic leukemia + Myeloid metaplasia + Polycythemia vera + Corticosteroids + Lithium + Beta agonist. Scanned with CamScannerCauses of Neutropenia Decreased or ineffective production Increased removal from circulation + Aplasticanemia «Immunological - SLE, drugs + Drugs + Hypersplenism + Disorders-vitamin deficiencies (B,,, folate) + Tutilization - Infections (mainly bacterial) + Myelodysplastic syndromes <5000/jiL. * Inherited disorder - Kostmann syndrome (defective <150000/p1L. genes of granulocyte differentiation Hematological Scoring System (HSS) and Early Diagnosis of Neonatal Sepsis Neonatal Sepsis + Neonatal sepsis or sepsis neonatorum or neonatal septicemia is the systemic response to infection in newborn infants + [Link] be useful test to distinguish the infected from the noninfected infants + Higher score is indicative of sepsis. thas high sensitivity and specificity 4 Animmature to total neutronphil ratio (1:T) along with degenerative changes followed by an immature to mature neutrophil ratio (1: M) is the most sensitive indicator in identifying infants with sepsis + Immature neutrophils include promyelocyte, myelocyte, metamyelocytes and band cells + Degenerative changes in neutrophils include vacuolization, toxic granules and Dahle bodies. + ‘The diagnosis of sepsis is confirmed by positive results of blood culture. Hematological scoring system (HSS) Criteria Abnormality Score + Total WBC count < 5000 /jL. 1 >25000 at birth 1 >30000-(12 to 24 hr) 1 >21000 day2 onwards 1 + Total PMN count No mature PMN seen 2 Increased/destruction 1 + Immature PMN count Increased 1 + Immature: Total PMN ratio Increased 1 + Immature: Mature PMN ratio >03 1 + Degenerative changes in PMN Toxic granules/cytoplasmic vacuoles 1 + Platelet count <150000/iL. 1 Minimum score is 0 and maximum score is 8 Interpretation of hematological scoring system Score Interpretation <2 Sepsis is unlikely ord Sepsis is possible 25 Sepsis or infection is very likely Scanned with CamScannereS Oris eey Mild (700-1500 per microliter) + Allergic rhinitis, extrinsic asthma, mild drug reaction, long-term dialysis, immunodeficiency Moderate (1500-5000 per microliter) + Parasitic disease, intrinsic asthma, pulmonary eosinophilia syndrome Marked (> 5000 per microliter) Trichinella, hookworm, Toxocara canis, eosinophilic leukemia, severe drug reaction. OTHER CAUSES Drug induced eosinophilia Severe, long-standing rheumatotd arthritis Psoriasis Crohn's disease, ulcerative colitis Systemic lupus erythematosus Malignant disease Implies metastatic disease—Poor prognosis ee : No identifiable causes— Hypereosinophilic syndromes. eS Wea ey Usually related to increased circulating steroids Cushing's syndrome Drugs ACTH, epinephrine, thyroxine, exogenous steroids Acute bacterial infection Normal diurnal pattern. Scanned with CamScannerBASOPHILIA —- CAUSES Hypothyroidism, myxedema Chronic myeloid leukemia Ulcerative colitis Polycythemia vera Urticaria Hodgkin's lymphoma/disease Chickenpox Splenectomy Scanned with CamScannerMONOCYTOSIS Monocyte levels > than 700 /mel or > than 12% of WBCs. ‘Usual causes: © Viral infe © Tuberculosis = Subacute bacterial endocarditis * Collagen diseases Chronic inflammation © Stress response jons Hyperacrenocorticism Infectious mononucleosis Sarcoidosis Concomitant with neutrophilia + Autoimmune conditions * Crohn's disease + Rheumatoid disease + Systemic lupus erythematosus * Ulcerative colitis. MONOCYTOPENIA Very uncommon by itself, Usual causes: © Hairy cell leukemia * Aplastic anemia Scanned with CamScannerLymphocytosis—Causes Infectious mononucleosis Mycobacterium tuberculosis Acute lymphoblastic leukemia Brucellosis Burkiu's lymphoma Chronic lymphocytic leukemia Cytomegalovirus Epstein-Barr virus Hairy cell leukemia Hepatitis A Hepatitis B Myeloma Non-Hodgkin's lymphoma Phenytoin Rubella Secondary syphilis Serum sickness Syphilis, congenital ‘Toxoplasma Waldenstrdim maeroglobulinemia Whooping cough X-linked lymphoproliferative disease, Lymphopenia— Viral infection HV SARS Drugs like vinblastine, chloramphenicol, doxorubicin ‘Marrow suppression Pancytopenia ses Scanned with CamScannerCAUSES OF THROMBOCYTOPENIA, We ee eames “Thrombocytopenia wih absent ea (TAR) syndeome Amegakaryeeytic thrombocytopenia Aplasile anemia Myelodysplastic syndrome (MDS) Bone marrow bypopasia de to— = Chemotherapy = Radiation = Toxins = mune. + Bone marrow inftration by— = Fibrosis = Malignancy’ = Granlomas + Selective matro suppression of platelet preduction dae to— = Drugs = Infections = tuhanal + Ineffective teombopotesis due to— = Folate or, deficeney. + Herediary disorders + May-Hegglin anomaly © Wiskot-Aldrch syndrome. imac ‘Immune mediated Systemic lupus erythematosus {ymphoproliferaive disorders ‘Drugs including hepacin induced Infections ineluding HIV related Postransfusion purpura [diopathi/immune thrombocytopenia (ITP). Scanned with CamScannerCAUSES OF INCREASED PLATELET COUNT—THROMBOCYTOSIS Myeloproliferative Disorders + Essential (primary) thrombocythemia—clonal overproduction + Idiopathic myelofibrosis + Polycythemia vera + Chronic granulocytic leukemia, ‘Transfer from extravascular pools into elreulation + Splenectomy (Over 70% of platelets stored in spleen) + Exercise + Epinephrine + Parturition, ‘Thrombocytosis Secondary to + Iron deficiency anemia + Malignancy + Infections + Noninfectious inflammation + Acute blood loss « Hemolysis + Recovery from thrombocytopenia Scanned with CamScannerNonimmune mechanisms + Severe bleeding «Disseminated intravascular coagulation (DIC) + Abnormalities in small vessels + Vasculitis + von Willebrand disease (vWD) + ‘Thrombotic thrombocytopenic purpura + Hemolytic uremic syndrome. (3) ABNORMAL DISTRIBUTION + Dilutional, from massive transfusion + Hypersplenism (4) ARTIFACTUAL (PSEUDOTHROMBOCYTOPENIA) ‘Thrombocytopenia in asymptomatic patient alarms the possibility of artifactual or “pscudothrombocytopenia” as the etiology. ‘This is caused by in vitro clumping of platelets due to various causes which include: (A) EDTA-induced Platelet Agglutination (EIPA) «This in vitro phenomenon is due to the presence of naturally occurring autoantibody against a crypt antigen on the GPIb/IIa platelet receptor. When calcium is chelated by EDTA, the GPIIb protein undergoes a change that exposes the crypt antigen. The autoantibody then binds to the exposed site and crosslink to other platelets causing agglutination + The condition occurs in aprox. 1% of hospitalized patients + This condition may persist for decades without any evidence of abnormal hemostasis + EDTA-platelet clumping needs to be recognized and documented in the patient's history to prevent unneces- sary treatment for thrombacytopenia + Confirmed by evaluating a repeat blood specimen drawn into Sodium Citrate (NaCitrate), revealing normal platelet count. let Satellitism: + In this phenomenon platelets rosette are formed around neutrophils or rarely around other cells. The satellite platelets are not counted by auto- ‘mated cell counters, resulting in spurious thrombocytopenia + Platelet satellitism fs caused by EDTA-dependent antiplatelet and anti- neutrophil IgG antibodies in the patient's plasma. ‘The diagnosis is made by making a blood smear and looking platelet rosettes. The phenomenon has not been associated with any disease state or drug and Is thought to be benign. (C) Cold Agglutinins «This phenomenon is temperature-dependent. Agglutination occurs in cit rate and heparin as well as EDTA anticoagulants + The specimen should be maintained at 37°C or warmed to 37°C to obtain an accurate platelet count. Scanned with CamScannerEe 4. C. EOSINOPHILS + "Eosin—Rose color’, *-phil—love”—Exhibit a rose color when stained + Eosinophils can appear at the myelocytic stage and move through the maturation sequence * Size: 10to 16 pm + Cytoplasm: Large, distinctive red-orange specific granules with orange-pink cytoplasm, granules are highly metabolic and contain histamine and other substances + Granules are uniformly round, large, and individualized + Nucleus: Blue dense chromatin, 2 lobes like a pair of glasses + Lives 6 to 12 hours in circulation migrate into tissues. Normal range: * Percentage of total WBC 1 - 4% of total white blood cells * Absolute count 12-500 cells per microliter, Diurnal variation (related to cortisol levels) * Eosinophils lowest in the morning © Eosinophils highest in the evening. eS Oe Mild (700-1500 per microliter) + Allergic rhinitis, extrinsic asthma, mild drug reaction, long-term dialysis, immunodeficiency Moderate (1500-5000 per microliter) ‘+ Parasitic disease, intrinsic asthma, pulmonary eosinophilia syndrome Marked (> 5000 per microliter) Trichinella, hookworm, Taxocara canis, eosinophilic leukemia, severe drug reaction. OTHER CAUSES * Druginduced eosinophilia ‘+ Severe, long-standing rheumatoid arthritis Psoriasis Crohn's disease, ulcerative colitis Systemic lupus erythematosus Malignant disease Implies metastatic disease—Poor prognosis Hypopituitarism (decreased steroids) No identifiable causes— Hypereosinophilic syndromes. _ Besa ey Usually related to increased circulating steroids Cushing's syndrome Drugs ACTH, epinephrine, thyroxine, exogenous steroids Acute bacterial infection Normal diurnal pattern. Scanned with CamScanner