Normal blood counts

Complete Blood Count (CBC) and Differential Tests

A Complete Blood Count (CBC) that measures the number of white blood cells (WBCs), red blood cells and platelets in the patient's sample of blood should be routinely monitored in CML patients. There are actually five kinds of white blood cells, each with a different function. The five types of white blood cells are monocytes, lymphocytes, basophils , eosinophils and neutrophils . A blood differential that measures the relative numbers of these different kinds of WBCs in the blood and includes information about abnormal cell structure and the presence of blasts or myeloblasts (immature white blood cells) should be done in tandem with the CBC.

The overall White Blood Cell (WBC) count is important to monitor as a significant elevation in WBC may indicate infection, lack of response to treatment, or worsening of leukemia. Conversely, some treatments for leukemia suppress the WBC and it is important to make sure the WBC does not dip below a critical range. The normal range for WBC is generally from 4.0 to 11.0 k/ul.

Neutrophils are a type of white blood cell involved in fighting infection. It is important they remain at adequate levels. As with platelets, neutrophil levels may become depressed in patients on myelosuppressive therapy such as imatinib mesylate (also called IM , Gleevec or Glivec ). The normal range of the percentage of neutrophils is between 45% and 70%.

More important than the percentage of neutrophils is the absolute neutrophil count (ANC) , which should fall between 1.0 to 8.0 k/ul. The reason the ANC represents the true clinical picture better than the percentage of neutrophils is that, in cases where blood counts are suppressed by therapy, the percentage of neutrophils will be higher when the overall counts are low. One may calculate the ANC by multiplying the percentage of neutrophils (in decimal form) plus the percentage of bands (in decimal form) by the total number of white blood cells. The number of bands is usually quite low or even zero, so one may also obtain a fairly accurate ANC by leaving the percent of bands out of the equation

The Basophils should remain within the normal range, generally between 0% and 2%. Some clinicians believe that, as in the case of neutrophils, the absolute basophil count is more important than the percentage of basophils and should fall between 0 to 0.3 k/ul. The absolute basophil count is calculated by multiplying the percentage of basophils (in decimal form) by the total number of white blood cells.

One should monitor blasts in the peripheral blood . Blasts are immature white blood cells and individuals with leukemia have an excessive number of blasts in their peripheral blood and bone marrow. With appropriate treatment, there should not be any blasts in the peripheral blood and fewer than 5% in a bone marrow aspirate .

Platelets also constitute an important component in the hematological picture for a CML patient. An escalated and uncontrolled platelet count may indicate disease progression and is cause for concern. In general, with appropriate treatment, platelet levels should fall within the normal range (150 to 450 k/ul) without platelet-lowering medication. Platelet levels may be depressed in patients on myelosuppressive therapy such as IM and it is important they remain at adequate levels.

Finally, one should keep an eye on hemoglobin and hematocrit counts. If one’s treatment suppresses the counts, it is important not to become too anemic . Normal hemoglobin levels range from 14.0 to 17.0 gm/dL and the hematocrit value should fall between 40.0% and 52.0%.

When are low counts cause for concern?

The answer to that question depends somewhat on the individual patient, the larger clinical picture and the therapy received. In general, for patients on imatinib mesylate therapy ( Gleevec or Glivec ), the following levels may warrant a decrease in dose, an interruption of therapy or the use of growth factors : WBC less than 1.0 k/ul; platelets less than 50 k/ul; hemoglobin less than 10.0 gm/dL; and ANC less than 1.0 k/ul.

It is important to note that the normal or reference range for blood counts will vary slightly between laboratories, but the following table provides a summary of the normal ranges for the counts discussed above.

How often should CBCs and blood differentials be performed?

All patients taking IM should have their blood counts monitored closely. Complete blood counts ( CBCs ) should be monitored weekly in chronic phase patients during the first month of IM treatment. If platelet counts remain over 100,000/mm3 and absolute neutrophil count (ANC) remains over 1,500/mm3 , CBC monitoring can be reduced to every two weeks until 12 weeks of IM therapy has been reached. Thereafter, if counts are stable, monitoring may occur monthly or even longer if appropriate. Patients in accelerated or blast crisis should have CBCs performed more often.

Liver function tests

In addition to monitoring CBCs and blood differentials, it is critical to monitor liver counts through Liver Function Tests (LFTs) , a group of blood tests that can help to show how well a person's liver is working. LFTs include measurements of total protein , albumin , various liver enzymes such as ALT and AST , alkaline phosphatase (ALP) and bilirubin .

Total Protein measures the amount of proteins in the bloodstream. Normal total protein levels in the bloodstream range from 6.5 to 8.2 gm/dL (grams per deciliter). Two of the main proteins found in the bloodstream are albumin and globulin.

Albumin is a protein made in the liver. If the liver is badly damaged, it can no longer produce albumin. Albumin maintains the amount of blood in the veins and arteries. When albumin levels become very low, fluid can leak out from the blood vessels into nearby tissues, causing swelling in the feet and ankles. Very low levels of albumin may indicate liver damage. The normal albumin range is from 3.9 gm/dL to 5.0 gm/dL.

ALT and AST are enzymes made in the liver. They are also called transaminases . ALT is sometimes called SGPT and AST is sometimes called SGOT . The normal range of ALT levels is between 5 IU/L (International Units per Liter) and 60 IU/L. The normal range of AST levels is between 5 IU/L and 43 IU/L. Elevated liver enzymes may be a sign of hepatotoxicity (liver toxicity).

Alkaline phosphatase (ALP) is another enzyme found in the liver. Abnormally high ALP levels may indicate liver problems. The normal range of ALP is between 30 IU/L and 115 IU/L.

Bilirubin is a yellow fluid produced in the liver. When bilirubin levels are too high, it can cause a condition called jaundice in which the eyes and skin appear yellow, urine becomes very dark and feces are light. There are two measures of bilirubin: Total Bilirubin, which measures the amount of bilirubin in the bloodstream and Direct Bilirubin, which measures the amount of bilirubin made in the liver. Normal total bilirubin levels range from .20 mg/dL (milligrams per decileter) to 1.50 mg/dL. Normal direct bilirubin levels range from .00 mg/dL to .03 mg/dL.

When are abnormal liver function tests (LFTs) cause for concern?

Any abnormalities in LFTs should be addressed and monitored closely. Current guidelines suggest stopping IM treatment when transaminases (liver enzymes) are more than five times the upper limit of normal. If liver function begins to return to normal, IM may be resumed at a lower dose, then increased to the prior dose in appropriate cases.

The consumption of alcohol may affect liver function, so it is important to eliminate or moderate one’s alcohol intake while taking IM. Also, acetaminophen (brand name Tylenol) may not be safe to take during treatment with IM since it, also, is metabolized through the liver. One should not take Tylenol or take it only under the guidance of a physician while taking IM.

How often should liver function tests (LFTs) be performed?

Because of concerns regarding hepatotoxity with IM treatment, LFTs should be obtained before IM treatment is started, every other week during the first month of IM treatment, and at least monthly thereafter. Of course, if any indications of liver problems arise, closer monitoring of LFTs is critical.

Low Counts: Many patients (<1% to 46%) experience low blood counts while taking IM due to myelosuppression , the inability of the bone marrow to produce an adequate number of cells. All patients taking IM should have their blood counts monitored closely. Complete blood counts (CBCs) should be monitored weekly in chronic phase patients during the first month of IM treatment. If platelet counts remain over 100,000/mm3 and absolute neutrophil count (ANC) remains over 1,500/mm3, CBC monitoring can be reduced to every two weeks until 12 weeks of IM therapy has been reached. Thereafter, if counts are stable, monitoring may occur monthly or even longer if appropriate. Patients in accelerated or blast crisis should have CBCs performed more often.

Myelosuppression due to IM therapy is more common in patients with CML in the accelerated or blast crisis stages, but can also occur in chronic phase patients. Myelosuppression and low counts are evident by low platelet counts (thrombocytopenia), low absolute neutrophil counts (neutropenia) and/or low red blood cell counts ( anemia ), usually measured by a decrease in hemoglobin . A mild or moderate reduction in counts may require no intervention at all and the counts often recover with continued therapy. In more extreme cases, depending on the type and severity of the myelosuppresion and the phase of CML, a physician may recommend the use of growth factors such as Neupogen (for neutropenia), Neumega (for thrombocytopenia) and Procrit or Aranesp (for anemia); interruption of treatment with IM; or, in some cases, a transfusion. The article referenced below, “Practical Management of Patients with Chronic Myeloid Leukemia Receiving Imatinib,” discusses these options in further detail.

Normal Ranges

The normal range describes the range where 95% of the normal healthy population will lie. This also means that there is 5% of the normal healthy population will fall outside the "normal range", however they too are normal. Normal ranges are a guide. There are many instances where the FBC will fall outside the "normal range" and yet these could be described as totally normal for the given clinical situation, for example, it is normal for patients who have had a splenectomy to have a moderately raised lymphocyte count or a patient on haemofiltration to have a raised eosinophil count. These variations would show as outside the normal range, however they are normal for the situation. It is very useful therefore for biomedical scientists and haematology clinicians to have appropriate clinical details added to the request so that interpretation and best clinical advice can be given on the report where appropriate.

Each report from the laboratory will give the appropriate normal range for the age and sex of the patient. Children have various normal ranges depending on age and sex. Ethnicity can affect the WBC and platelet normal ranges. If the patient is Black Afro-Caribbean or Black African, the WBC and neutrophils count normal ranges are much lower. In these instances, the normal adult range must be interpreted depending on the patients ethnic background. If further information is required, contact your local laboratory.

Interpretation of a Full Blood Count

A full blood count must be interpreted with reference to the clinical picture and other pathology results. Caution must be given to certain abnormal results such as low platelets that may be artefact and repeats should be considered. The laboratory will usually investigate abnormalities that may be haematological in nature by assessing the blood film (by microscopy) and referring this to haematology clinicians where appropriate. In the event of serious abnormalities that require urgent attention, such as; acute leukaemia or severe haemolysis, the laboratory staff will allert the On-Call haematology doctors.

Further information on interpretation of blood count results can be found on the NHS Leeds Teaching Hospital's website.