HEMATOLOGY COMPLETE BLOOD COUNT (CBC)

OBJECTIVES : 1. Learn to interpret reported values on a CBC report 2. Make a diagnostic plan based on abnormal CBC values 3. Learn to recognize common morphologic abnormalities on a blood smear

The purpose of this laboratory seminar is to discuss the interpretation of the test called CBC. This is one of the most common tests ordered by physicians and can yield valuable information about hematologic and non-hematologic illnesses. There are 2 parts to interpreting this test

1. Interpretation of reported values 2. Review of the blood smear

The reported values are either directly measured or calculated by a machine called Coulter counter. The measured values are:

RBC number Mean Corpuscular Volume (MCV) Hemoglobin (Hg)

The calculated values are:

Hematocrit (HCT) Mean Corpuscular Hemoglobin (MCV) Mean Corpuscular Hemoglobin Concentration (MCHC) Hemoglobin (Hg)

The red cell indices (MCV, MCH, MCHC) can also be calculated by using the following formulae:

MCV = HCT     x 10            RBC number in millions

MCH = Hg in gms     x 10            RBC number in millions

MCHC = Hg     x 100               HCT

In general, MCV is the most useful index and divide the anemias into microcytic, normocytic and macrocytic types. The MCH and MCHC add very little to the information provided by MCV.

Another piece of useful information on the CBC results is Red Cell Distribution Width (RDW). The RDW is an expression of the size distribution spread of the erythrocyte population. It is computed from the RBC histogram and is the co-efficient of variation, expressed in percent, of the red cell size distribution. RDW goes up in 95% of cases with iron deficiency and about two-thirds of the cases with megaloblastic anemia. Significantly, it does not change in anemia of chronic disorder and thalassemias.

Two other terms may be reported in the CBC results: Anisocytosis which means there is marked variation in size of red cells. Poikilocytosis means there is a significant variation in shape of red cells.

The white cells and platelets are counted by the machine. The white cell differential is also done by the machine but is routinely reviewed by a technologist.

The newer machines also give platelet volume (equivalent of MCV for red cells) in the CBC report. Larger platelet volume indicates younger and more active platelets.

RED CELL ABNORMALITIES : The hemoglobin level and red cell number may be increased or decreased from the normal values. An increase is called erythrocytosis and a decrease is called anemia.

ERYTHROCYTOSIS : May be spurious where red cell mass is normal but the plasma volume has decreased. In True Erythrocytosis, there is an absolute increase in the red cell mass in relation to patient's weight. True erythrocytosis can be divided in 2 groups:

1. Low Erythropoietin Group: This group includes only one disorder-Polycythemia Vera. This is a bone marrow stem cell disorder which results in an autonomous increase in all three cell lines i.e. red cells, white cells and platelets. The increase in white cells and platelets is not seen in all cases.

Diagnostic Criteria for Polycythemia Vera are:

Major: -Increase in red cell mass (>32nk/kg I females, >36ml.kg in males           -Arterial O2 saturation of 92% or higher           -Splenomegaly

Minor: -Elevated WBC count >12,000/mm3           -Elevated Platelet Count >400,000/mm3           -Elevated B12 level (>900)           -Elevated Neutrophil Alkaline Phosphatase level (>900)

The diagnosis of Polycythemia Vera is made if the patient has all three major or the first two major plus any two minor criteria. These days, many physicians are obtaining serum erythropoietin level in such patients. It is normal or low in Polycythemia Vera.

2. High Erythropoietin Group: In this group erythropoietin or erythropoietin-like substances are produced which increase the red cell output from the bone marrow.

The overproduction of erythropoietin or similar proteins may be appropriate or inappropriate .

Appropriate : Increased amounts of erythropoietin are produced because of tissue hypoxia. This can result from:

-High altitude-Pulmonary disease -Cyanotic heart disease -Chronic carboxy-hemoglobinemia in smokers -High affinity hemoglobin

Inappropriate : autonomous increase in erythropoietin or erythropoietin-like proteins

-Renal cysts, renal cell carcinoma -Hepatic cell carcinoma -Uterine fibroids -Cerebellar Hemaniopericytoma (Rare)

ANEMIA : Anemia is defined as subnormal hemoglobin level two standard deviations below the normal for the age and sex of the patient. From the CBC report, one can classify anemia as microcytic, normocytic or macrocytic if the MCV is low, normal or high, respectively. Common etiologies of these anemias are as follows:

Microcytic:

Fe deficiency Thalassemias Some patients with anemia of chronic disorder

Normocytic:

Anemia of chronic disorder Anemia of renal failure Anemia due to endocrine disorders

Macrocytic:

B12 deficiency Folate deficiency Preleukmias Some cases of hypothyoidism Hemolytic anemias (because of high reticulocye count)

RDW is a very useful measure in the assessment of anemia. Combined with red cell indices, it can narrow down the diagnostic possibilities. For example, a patient with microcytic

anemia and high RDW is very likely to have iron deficiency. If the RDW is normal thalassemia become much more likely.

WHITE CELL ABNORMALITIES : Since the white cell population includes different types of cells (neutrophils, lymphocytes, monocytes, eosinophils, etc), it is important to identify the affected cell type. To do that, absolute numbers of each cell type need to be calculated. These days, absolute numbers are given in the report.

Example: Total WBC count is 26,000. The differential count shows 1% neutrophils and 99% lymphocytes

Absolute neutrophil count is 26000 x 1 = 260/mm3                                          100

Absolute lymphocyte count is 25,740/mm3

Thus, this patient has leukocytosis, lymphocytosis and neutropenia.

Increased numbers of various cell types are associated with the following conditions:

Neutrophilia:

-Acute infections -Inflammation -Acute hemorrhage -Acute hemolysis -Chronic granulocytic leukemia -Malignancy -Medications (steroids, lithium) -Vigorous exercise

Lymphocytosis:

-Viral infections -Toxoplasmosis -Pertussis -Chronic lymphocytic leukemia

Monocytosis:

-Infections like TB, Subacute bacterial endocarditis -Malignancy -Inflammatory bowel disease

Eosinophilia:

-Allergic disorders

-Parasitic infestations -Malignancy (Hodgkin's disease) -Myeloproliferative disorders

Decrease in various cell types can be associated with the following disorders:

Neutropenia:

-Certain bacterial infections like Brucellosis, Typhoid -Viral infections -Medications like chemotherapy, anti-arthritis medications -Aplastic anemia -B12 and Folic acid deficiency -Sequestration due to splenomegaly

Lymphopenia:

-Viral infections (HIV) -Steroids -Radiation, chemotherapy

MANY AFRICAN-AMERICANS NORMALLY HAVE LOW WBC AND LOW NEUTROPHIL COUNT. THIS IS NOT A TRUE DECREASE BUT RESULTS FROM INCREASED MARGINATION BY NEUTROPHILS.

PLATELET ABNORMALITIES : Platelet count may be elevated (Thrombocytosis) or decreased (Thrombocytopenia). These may result from a variety of disorders.

Thrombocytosis:

Reactive:

-Vigorous exercise -Acute hemorrhage -Infections -Malignancy

Autonomous:

-Chronic myeloproliferative disorders (polycthemia vera, chronic granulocytic leukemia, early phase myelofibrosis, essential thrombocythemia)

Thrombocytopenia:

Decreased Marrow Production:

-Aplastic anemia

-Chemotherapy, radiation -B12, folate deficiency -Leukemia, Preleukemia

Increased Destruction/Sequestration

-Immune thrombocytopenia -Disseminated intravascular coagulation -Splenomegaly

The following terms are occasionally used in reporting CBC results:

Pancytopenia : When all three cell-lines are decreased. This can result from aplastic anemia, infilterative processes of the bone marrow like leukemia or myeloma, preleukemia, and B12 or folate deficiency

Leukemoid Reaction : The CBC report resembles that seen in leukemia (acute or chronic). This can be seen in severe infections, malignancies and severe hemolysis.

Leukoerythroblastic Reaction : The blood report shows presence of immature erythroid as well as granulocytic cells. This is seen in infilterative processes in the marrow which may be a malignancy, hemolytic anemia, infections, fractures of marrow containing bones

REVIEW OF BLOOD SMEAR: Common abnormalities seen on blood smear and their significance:

 

ABNORMALITY DIAGNOSTIC SIGNIFICANCE

Polychromatophilia High reticulocyte count(acute bleeding, hemolysis)

Mirocytes, hypochromia Iron deficiency, ThalassemiaMacro-ovalocytes B12 or Folate deficiency

Spherocytes Immune hemolytic sanemia Hereditary spherocytosis

Scgusticttes Fragmented RBCs Valvular heart diseqae, DICSickled CBCs Sickle cell anemia

Target cellsChronic liver disease Hemoglobin C disease Asplenia

Burr cells (echinocytes) Chronic renal or liver disease