Taking The Fear Out of Abnormal CBC’s

Problems of Production, Destruction or loss

Joanne Eddington, MN, FNP, AOCN

Providence Oncology and Hematology Care Clinic - Eastside

Blood Cell Abnormalities

Abnormalities of production

Parts? Factory?

Abnormalities related to loss

Bleeding? Sequestration?

Abnormalities related to destruction

Autoimmune/Idiopathic?

Variables to focus on

Hgb and Hct

MCV

RBC distribution width (RDW)

Platelets

WBC with differential

Patients baseline, differences based on sex and race.

If abnormality exists out of context, repeat the test.

Coulter counter

Counts circulating blood cells by electrical pulse

The height of the pulse indicates cell volume

Newer counters give multimodal assessment of cell size and content which is the differential.

5 part differential includes neutrophils, lymphocytes, monocytes, eosinophils and basophils

Stick The Tube In The Machine- And Let IT Do Magic

Automated Hematology Analyzer

2 CHAMBERS In one chamber, the red cells are counted. The detecter is set to count merely the cells the size limits of Red Blood Cells. In the other chamber, the blood is put into a solution that lyses the red blood cell leaving merely WBC and platelets intact.

Approaches to evaluation

History

Physical exam

Review of differential and peripheral smear as appropriate

Additional tests as appropriate

Depending on results, Hematology referral.

Platelet Abnormalities

Thrombocytopenia

Definition: Platelet count < 150,00

Asymptomatic Thrombocytopenia Found on routine CBC

Symptomatic Thrombocytopenia Bleeding, bruising or petechiae

Thrombocytopenia

Decreased platelet production Viral infection, HIV, Hep C, Parvovirus Leukemia, Vitamin deficiency

Increased Platelet Destruction Drugs: Heparin, Valproic acid Autoimmune destruction ( TTP, ITP, Lupus) DIC

Platelet loss / Psuedothrombocytopenia Platelet clumping (EDTA induced), Pregnancy Splenic sequestration

Critical Values

Surgeons will generally consider platelet number to be adequate if >50,000

Spontaneous bleeding does not occur unless platelet count is < 20,000

Transfuse platelets if <10,000 or spontaneous bleeding

Laboratory evaluation for Thrombocytopenia

CBC with manual differential, PT/PTT and review of Peripheral smear

Evaluate for drug induced thrombocytopenia and hypersplenism Abdominal ultrasound

Rule out HIV infection, lymphoproliferative disorder and autoimmune disease. HIV testing, ANA and SPEP

Points to remember…….

TTP/hemolytic uremic syndrome need urgent therapy.

Idiopathic thrombocytopenic purpura is a diagnosis of exclusion.

ITP: less likely to bleed spontaneously as platelets are often young and vigorous!

Bone Marrow biopsy or platelet antibody tests are not indicated in most work-ups of ITP.

It is appropriate to initiate work-up but most situations should be referred to Hematology.

Thrombocytosis

Marrow over production

Myeloproliferative disorder

Can be a result of something else going on (Reactive Thrombocytosis)

Seen in iron deficiency

Seen in post surgical patients

Seen in infection

Seen in trauma

Thrombocytosis

Defined as >450,000 but evaluation is not necessarily indicated unless near 600,000 Primary Thrombocytosis versus Reactive Thrombocytosis

Elevated platelet count can be due to a myeloid malignancy or myeloproliferative process

Elevated platelet count can be due to a secondary process such as:

Iron Deficiency Anemia Infection/Inflammation/Tissue Damage Hemolysis Nonmyeloid malignancy Splenectomy

Thrombocytosis continued

The difference between primary thrombocytosis and reactive thrombocytosis is clinically relevant because primary thrombocytosis is associated with increased risk of thrombohemorragic complications and reactive thrombocytosis is not.

Clinical evaluation of Thrombocytosis

Patient History

Old medical record will determine if a new or longstanding problem

Splenectomy? Chronic thrombocytosis in patients with a spleen is highly suggestive of primary thrombocytosis.

Chronic thrombocytosis in patient without a spleen is a benign condition.

Laboratory evaluation

CBC

Increased HGB, MCV or WBC or immature WBC, suggests Primary Thrombocytosis/Myeloproliferative disorder

Serum Ferritin

Rule out iron deficiency

C-Reactive Protein

Elevation indicates an inflammatory cause

Normal levels are seen in a marrow disorder

If no cause can be found for a reactive process, refer……….

Hematology evaluation will likely include:

JAK 2 testing

Bone Marrow biopsy

Bcr/Abl

Primary Thrombocytosis

Myeloproliferative disorders

Essential Thrombocytosis

Polycythemia Vera

Primary Myelofibrosis

Myeloid Malignancies

MDS

CML

White Blood Cell Abnormalities

Leukopenia/Neutropenia

Leukopenia refers to a low total WBC

Granulocytopenia refers to a decrease in circulating neutrophils, eosinophils and basophils

Neutropenia refers to a decrease in circulating neutrophils

ANC or absolute neutrophil count =

Total WBC x percent (polys + bands) / 100

Points to remember

Patients with moderate to severe neutropenia will not demonstrate classic signs of infection other than fever.

Ethnic variations: African Americans, Yemenite Jews, Ethiopians and certain Arabs normally have a slightly lower WBC and ANC. Benign Ethnic Neutropenia (ANC not <500)

Acquired vs congenital Neutropenia

Congenital neutropenias are rare

Acquired causes: Drugs or infections (virus, sepsis) are more common

Immune disorders: HIV, Chronic Idiopathic Neutropenia

Leukemia or other hematologic malignancies rarely present with isolated neutropenia

Lymphopenia

Often caused by immune suppressive drugs including steroids and anti-lymphocyte monoclonal antibodies

HIV

Critical illness

Connective tissue diseases

Lymphopenia seen in elderly patients, where it is usually of no clinical significance. No further investigation is advised in an elderly patient with a lymphocyte count >0.5×109/L in the absence of any concerning symptoms

Persistent lymphopenia that remains stable over a six month period and in the absence of symptoms, clinical findings, or abnormal results from investigations does not require further investigation

Diagnostic Approach

If leukopenia, neutropenia or granulocytopenia is identified along with other blood abnormalities such as normocytic anemia and/or thrombocytopenia, a peripheral smear and an immediate referral to a hematologist for a bone marrow biopsy should be done.

Mild neutropenia without recurrent infections or protracted infection can be observed.

Diagnostic Approach cont’

If observation is appropriate ANC should be checked at least 2-3 times per week for 6-8 weeks.

If neutropenia persists, refer to Hematologist for a bone marrow biopsy and further evaluation.

Moderate to severe neutropenia with infection should be referred directly to Hematologist for bone marrow biopsy and further evaluation.

Leukocytosis

First step in evaluation is to determine which WBC type is increased.

The increase maybe secondary to immature precursors (blasts) or an expansion of mature leukocytes such as granulocytes, lymphocytes, monocytes.

Manual differential and review of peripheral smear will help classify and rule out acute leukemia.

Leukocytosis

Total WBC > 11,000

Leukocytosis commonly is due to an increase in the number of circulating neutrophils

Leukocytosis can also be due to an increase in other white blood cell such as lymphocytes, eosinophils, monocytes or rarely basophils.

Causes to consider:

Normal variation

By definition 2.5% of the population will be greater than 2 SD above the mean

Blood sampling problem

Platelet clumping

Infection or inflammation

Total WBC + CRP + Neutrophils

Drugs

Bone Marrow disorder

Specific differential abnormalities

Neutrophilic leukocytosis: infection, stress, smoking, pregnancy, PV and CML

Lymphocytic leukocytosis: Infections such as mono, ALL, CLL, NHL

Monocytic leukocytosis: Acute bacterial infections, TB, AML and CML/MDS

Eosinophilic or basophilic leukocytosis: paracytic infections, allergic reactions, solid tumors, forms of chronic and acute leukemia's (HES)

Red Blood Cell Abnormalities

Anemia's

Various definitions (hemoglobin and hematocrit levels)

< 12 in women and < 14 in men

Production problems, destruction problems or loss

Classification:

Normocytic, Macrocytic, Microcytic

Anemia Parameters

Print out from out from machine RBC counted (coulter) HB measured (light abs) MCV – from size distribution

Initial questions to ask:

Is the patient bleeding?

Is there evidence for RBC destruction/hemolysis?

Is the bone marrow suppressed?

Is there iron deficiency? If so why?

Is there B12 or folate deficiency? If so why?

Initial test to order

Complete Blood Count with differential

Iron studies with ferritin

B 12 and Folate

Reticulocyte count

CMP (creatinine, total protein, LFT’s)

TSH

Additional studies depending on these results.

What Test Tells Production v Destruction? Reticulocytes

Reticulocytes are immature red blood cells, typically composing about 1% of the red cells

Reticulocytes mature in bone marrow and then circulate for about a day in the blood stream

They are called reticulocytes because of a reticular (mesh-like) network of ribosomal RNA that becomes visible under a microscope with certain stains such as new methylene blue

This test must be ordered separately Modern instruments can automate

the process

Microcytic Anemia

Definition: MCV < 80

Caused by:

Iron deficiency

Thalassemia

Chronic disease

Serum ferritin should be the first test to check as part of initial work-up.

Iron deficiency is unlikely in the presence of persistently normal or elevated serum ferritin.

What do you see? Microcytosis and increase in RDW

MCV= 72 Classic Iron deficiency anemia

Iron Deficiency Anemia (IDA)

Most common form of anemia

Should be ruled out initially in every anemia workup.

Can see iron deficiency combined with other types of anemia

# 1 cause of iron deficiency is bleeding

The cause of bleeding should be sought in every case.

IDA continued

Always trial oral iron unless patient has documented absorption problem

Parenteral iron can replenish iron stores in 1 dose. But not risk free.

Standard of care is to replace iron stores. Don’t transfuse.

Note- it will take 1-2 mos for HB to rise, be patient

If patient is bleeding, stop the bleeding first as they will not retain the iron you give them!

Thalassemia

This should be considered if patient is microcytic but not iron deficient.

Patient can have Thalassemia and IDA. Iron deficiency must be corrected before testing for

Thalassemia. History is very important in identifying Thalassemia Don’t give iron unless iron deficient. Use Hematologist to interpret Hgb electrophoresis

Microcytic anemia of chronic disease

Otherwise known as anemia of inflammation

These are anemias of Chronic Inflammatory diseases, like RA. THIS IS NOT CHF, HTN, DM which are chronic diseases, not characterized by inflammation

Usually iron studies demonstrate:

Low serum iron, low total iron binding capacity and increased serum ferritin.

However, ferritin could be elevated by inflammatory process itself.

Bone marrow biopsy maybe necessary to rule out iron deficiency.

Macrocytic Anemia

Definition: MCV > 100

Caused by:

B12 or folate deficiency (consider MMA levels)

Hypothyroidism

Hemolysis (consider LDH and Direct Coombs)

Myelodysplastic syndrome

Alcoholism, liver disease

Medications

Macrocytic anemia continued

Once the cause is determined, appropriate treatment can then be administered as indicated.

Hematology evaluation is indicated if MDS or hemolytic anemia is suspected.

Normocytic Anemia

MCV 80 -100

Caused by:

Bleeding

Renal insufficiency

Hemolysis (valve, TTP/HUS, DIC, autoimmune, etc.)

Nutritional deficiency (yes…iron, B12 and folate)

Bone marrow disorders

Anemia of Chronic Inflammation (here too- both micro and normo cytic )

Normocytic anemia

If the work-up excludes bleeding, nutritional deficits, renal insufficiency, hemolysis, then the anemia is related to chronic disease or a primary bone marrow disorder.

Evaluation for hemolysis:

Schistocytes or spherocytes on smear

Haptoglobin, Lactate dehydrogenase (LDH), Direct coombs, indirect bilirubin, and reticulocyte count. Consider drug-induced.

Polycythemia

Suspected when Hgb and Hct are elevated.

Primary Polycythemia (Polycythemia rubra vera; PV)

Is a myeloproliferative disorder of the bone marrow.

Secondary Polycythemia

Caused by increased EPO levels due to hypoxia or an EPO producing tumor.

Relative Polycythemia

Caused by a decreased plasma volume increasing Hgb, Hct and RBC count.

Laboratory evaluation of Polycythemia

Carboxyhemoglobin levels

Elevated in smokers

Erythropoietin levels

Elevated Suggests erythropoietin producing tumor

Low is characteristic of Polycythemia Vera

JAK 2 testing

Diagnostic for Myeloproliferative Disorder and Polycythemia Rubra Vera.

In summary

If the patient feels sick and has abnormal blood counts…..be worried and refer.

If the patient has more than 1cell line abnormal even if they don’t feel bad….be worried and refer.

If the laboratory result does not fit with the clinical situation, recheck. Consider running CBC in heparin instead of EDTA.

In Summary continued

If the patient has mildly low abnormalities and feels fine…..consider watching and waiting.

Pay attention to the work-ups that your friendly hematologist does on your patients. This will improve your initial work-up overtime.