COMPLETE

BLOOD PICTURE
Complete blood count in primary
care

Dr Samson EheTeron SpPK

INTRODUCTION

• CBP or hemogram:
One of the most common lab investigations.

• It assesses:

• Red blood cells

(RBC count, hemoglobin, ESR, PCV, MCV, MCH,
MCHC)
• White blood cells (WBC, DC)
• Platelets (platelet count, BT, CT)
• Blood grouping
RBC
NORMAL COUNTS

NORMAL Males Females

VALUES
RBC Count 4.5 – 6 million/cu.mm

Hb% 14 – 18 gm% 11.5 – 16.5 gm%

PCV 42 – 52 % 36 – 48 %

ESR 1 – 7 mm/ 1st hr

MCV 78 – 90 cu.microns

MCH 27 – 32 pico gms

MCHC 30 – 38 %
Anemia- when blood has low O2 carrying
capacity; insufficient RBC or iron deficiency.

-Due to blood loss

-Due to nutritional deficiency
-Due to destruction of RBC
-Due to defects in bone marrow
Polycythemia- abnormal increase in the RBC count.
-8-11 million cells/mm3
-Physiologically seen in people living in high altitudes.
-Pathologically it can be primary or secondary.
-Primary is polycythemia vera, a myeloproliferative
disorder.
-Secondary seen in conditions like
- respiratory disorders like emphysema
- congenital heart disease
- chronic carbon monoxide poisoning
- repeated mild heamorrhages.
Hb %

AGE Hb%
At birth 25 gm%
After 3rd month 20 gm%
After 1 year 17 gm%
Adult male 15 gm%
Adult female 14.5 gm%

Hb often accompanied by PCV can reflect

- Decreased plasma volume (eg: dehydration, alcohol,
cigarette, smoking, diuretics) or
- Increased red cell mass (eg polycythaemia)
HEMATOCRIT (PCV)

% of blood volume consisting of erythrocytes (red blood

cells)
In Males 40 – 45 %
In Female 38 – 42 %
ESR

• Normally, red blood cells remain suspended

uniformly in circulation called suspension stability of
RBC.
• When blood mixed with an anticoagulant is allowed
to stand in a vertical tube, the red cells settle down
due to gravity with a supernatant layer of clear fluid.
• The rate at which the cells settle down is called
erythrocyte sedimentation rate.

• Methods
• 1) westergren’s method :
• 2) wintrobe’s method :
• Factors affecting ESR :
specific gravity of RBC, rouleaux formation, size
of RBC, viscosity of blood, RBC count.
variations in ESR :
- less in infants and children
- more in females
- from 3rd month until parturition increased
upto 35mm per hr.
ESR INCREASED ESR DECREASED
All types of anemia’s except sickle Sickle cell anemia
cell anemia
Tuberculosis Allergic conditions
Malignant tumors Polycythemia
Rheumatoid arthritis Extreme leukocytosis
Rheumatic fever Peptone shock
Liver diseases

It is especially useful in assessing the chronic diseases and

their prognosis during treatement
MCV

• MCV (Mean corpuscular volume)

PCV in 100 ml of blood x 10

• MCV =
RBC count in million per cc

This is the average volume of the RBC

Useful to classify the anaemia

– Microcytic, MCV < 80 cu.microns
– Normocytic, MCV 80 – 100 cu.microns
– Macrocytic, MCV > 100 cu.microns
MCH

• MCH (Mean corpuscular hemoglobin)

Hb% in 100 ml of blood x 10

• MCH =
RBC count in million per cc

This is the quantity of hemoglobin present in one RBC.

Useful to classify the anaemia

– Normochromic, MCH 27 – 33 pg
– Hypochromic, MCH < 27 pg
MCHC

• MCHC (Mean corpuscular hemoglobin concentration)

Hb% in 100 ml of blood x 100

• MCHC =
PCV IN 100 ml of blood

• Indicates the concentration of hemoglobin in one RBC.

• Most important absolute value in diagnosis of anemia.

• Normal range is 30 to 38 %.
RETICULOCYTE COUNT

• Reticulocytes: immature RBCs

• Number helps to determine causes of anemia. Normal

reticulocyte count is 1.0-2.0%

• Low reticulocyte <2.5%= decreased marrow production of

RBCs causing anemia

• Elevated reticulocyte > 2.5% = indicates anemia caused

by RBC loss
RDW
RDW = Red blood cell distribution width

Standard deviation of red cell volume

× 100
mean cell volume

– Normal value is 11-15%

– If elevated, suggests large variability in sizes of RBCs

Definition of Anemia

 Deficiency in the oxygen-carrying capacity

of the blood due to a diminished erythrocyte
mass.
 May be due to:
 Erythrocyte loss (bleeding)
 Decreased Erythrocyte production
low erythropoietin
Decreased marrow response to erythropoietin
 Increased Erythrocyte destruction (hemolysis)
Evaluating the Patient with Anemia

• Check Hemoglobin/Hematocrit
– If female, is Hgb < 12 or Hct < 36?
– If male, is Hgb < 13.5 or Hct < 41?

– If Yes, Patient has ANEMIA!

– If No, they are fine.
Evaluating the Patient with Anemia

• Are the other cell lines also low?

– If WBC and platelets are both low, consider
APLASTIC ANEMIA!
– Check medication list
» NSAIDS (phenylbutazone), Sulfonamides,
Acyclovir, Gancyclovir, chloramphenicol, anti-
epileptics (phenytoin, carbamazepine, valproic
acid), nifedipine
» Check parvovirus B19 IgG, IgM
» Consider hepatitis viruses, HIV
– If Platelets are low consider TTP or HUS!
– Must check smear for schistocytes (for sign of
microangiopathic hemolytic anemia)
– If renal failure, E. Coli O157:H7 exposure → HUS
– If renal failure, neurologic changes, fever → TTP
 ANEMIA

RETICULOCYTE COUNT RETICULOCYTE COUNT

LESS THAN 2.5 MORE THAN 2.5

RED CELL MORPHOLOGY

HEMOLYTIC ANEMIA
NORMOCYTIC OR
NORMOCHROMIC HEAMORRHAGE

MARROW DAMAGE,
DECREASED MICROCYTIC OR
ERYTHROPOITIN MACROCYTIC

NUCLEAR : B12 DEF, FOLATE DEF,

DRUG TOXICITY
CYTOPLASMIC : Fe DEF ANEMIA,
THALASSEMIA, SIDEROBLASTIC ANEMIA
 Evaluating the Patient with Anemia

– If MCV < 80, then it’s a microcytic anemia

 The three most common causes for microcytic
anaemia are:
– Iron deficiency
– Thalassaemia
– Anaemia of Chronic disease

• Check serum iron, ferritin, TIBC

– If iron-deficiency anemia, look for sources of
chronic bleeding – heavy menstrual bleeding,
consider colonoscopy
• Consider lead poisoning, copper deficiency,
thalassemias.
 Differentiating Microcytic Anemias

Type of Ferritin TIBC Iron Other

Anemia Features
IDA ↓ ↑ ↓ Fe/TIBC<18%

Thalassemia Normal Normal Normal Basophilic

Stippling
ACD N or ↑ ↓ ↓ Fe/TIBC>18%

Sideroblastic ↑ Normal ↑ Ringed

Sideroblasts
Iron Deficiency Anemia – Lab
Findings
• Serum Iron
• LOW (< 60 micrograms/dL)
• Total Iron Binding Capacity (TIBC)
• HIGH ( > 360 micrograms/dL)
• Serum Ferritin
• LOW (< 20 nanograms/mL)
• Can be “falsely”normal in inflammatory
states
Thalassemia

• Microcytic anemia
• Smear shows microcytosis with target
cells
Anemia of Chronic Disease

• Usually normocytic, normochromic (but

can become hypochromic, microcytic over
time)
• Occurs in people with inflammatory
conditions such as collage vascular
disease, malignancy or chronic infection.
Evaluating the Patient with Anemia

– If MCV 80-100, then it’s a normocytic anemia

• Any inflammatory conditions that could result
in anemia of chronic disease?
• Consider checking indirect bili, LDH,
haptoglobin, reticulocyte count
Normocytic anaemia

 The causes of normocytic anaemia include:

– Bleeding
– Early nutritional anaemia (iron, B12, folate
deficiencies)
– Anaemia of renal insufficiency
– Anaemia of chronic disease/chronic
inflammation
– Haemolysis
– Primary bone marrow disorder
Evaluating the Patient with Anemia

– If MCV > 100, then it’s a macrocytic anemia

• Check Vit. B 12, folate
• Consider liver disease, alcoholism,
myelodysplastic syndrome
• Check medications: hydoxyurea, AZT,
methotrexate
Macrocytic anaemia

 Common causes:
– Alcohol
– Liver disease
– B12 or folate deficiency
– Thyroid disease
– Some drugs (especially hydroxyurea)
Cobalamin (Vitamin B12)
Deficiency anemia

• Macrocytic anemia
• Lab Values
– Cobalamin level < 200 pg/mL
– Elevated serum methylmalonic acid
– Elevated serum homocysteine
Pernicious anemia:

-ANTIBODIES TO intrinsic factor

- diagnosed by checking antibody levels
-Schilling test

-Smear shows macrocytosis with hypersegmentattion of

-Polymorphonuclear cells, with possible basophilic stipplin
Folate Deficiency

•
– Macrocytic anemia
– Lab Values
– Low folate
– Increased serum homocystine
– NORMAL methylmalonic acid

– Smear shows macrocytosis with hypersegmented neutrophils

Vitamin B12 Deficiency Versus
Folate Deficiency
Vitamin B 12 Folate Deficiency
Deficiency
MCV > 100 > 100
Smear Macrocytosis with Macrocytosis with
hypersegmented hypersegmented
neutrophils neutrophils

Pernicious Yes NO
anemia
Homocystine Elevated Elevated

Methylmalonic Elevated NORMAL

Acid
Evaluating the Patient with Anemia

• Any jaundice, elevated bilirubin, suspicious for

hemolysis?
– Check for increased indirect bilirubin,
increased LDH, decreased haptoglobin,
increased reticulocyte count
– Any sign of infection? Malaria? Babesiosis?
– Is Coombs test positive?
– If yes, may be warm antibody hemolytic
anemia; Consider drug as cause
hemolytiicbs
 LDH: elevated
 Indirect bilirubin: elevated (due to catabolism of
Hgb)
 Haptoglobin: decreased
 Binds to Hgb and taken up by liver
 In a series of reports:
 Elevated LDH, low Haptoglobin was 90% specific
 Normal LDH, Haptoglobin >25 was 92% sensitive for ruling out
hemolysis
 Reticulocyte Count: elevated
 Normal is 0.5-1.5%
 Anemia leads to increase Epo production leading to a
reticulocytosis (4-5% increase above baseline)
 Positive Direct Antiglobulin Test (Coombs)
Anemia due to Destruction of Red
Blood Cells
• Hemoglobinopathies
• Sickle Cell Anemia
• Hemolytic Anemia
• Hereditary spherocytosis
• Glucose-6-phosphate dehydrogenase (G6PD) Deficiency
• Thrombotic Thrombocytopenic Purpura (TTP)
• Hemolytic Uremic Syndrome
• Autoimmune Hemolytic Anemia
– Warm-antibody mediated
– Cold agglutinin Disease
• Infections
– Malaria
– Babesiosis
– Sepsis
• Trauma
– Includes some snake, insect bites
Lab Analysis in Hemolytic Anemia

• Increased indirect bilirubin

• Increased LDH
• Increased reticulocyte count
• Normal reticulocyte count is 0.5 to 1.5%
• > 3% is sign of increased reticulocyte
production, suggestive of hemolysis
• Reduced or absent haptoglobin
• < 25 mg /dL suggests hemolysis
• Haptoglobin binds to free hemoglobin
released after hemolysis
Special Considerations in
Determining Anemia
• Acute Bleed
• Drop in Hgb or Hct may not be shown until 36 to
48 hours after acute bleed (even though patient
may be hypotensive)
• Pregnancy
• In third trimester, RBC and plasma volume are
expanded by 25 and 50%, respectively.
• Labs will show reductions in Hgb, Hct, and RBC
count, often to anemic levels, but according to
RBC mass, they are actually polycythemic
• Volume Depletion
• Patient’s who are severely volume depleted may
not show anemia until after rehydrated
 Red Cell Morphology Possible findings
Significance

• Teardrop cells-Iron deficiency, myelophthisic,

megaloblastic anemias
• Sickle cells -Sickle cell disease
• Target cells-Postsplenectomy thalassemia,
hemoglobinopathy
• Parasites-Malaria, babesiosis
• Basophilic stippling-Thalassemia, lead toxicity
• Bite cells-G6PD deficiency.
• Elliptocyte, ovalocyte-Hereditary, iron deficiency,
megaloblastic anemias
• Burr cells-Uremia, low potassium, artifact, stomach
cancer, peptic ulcer disease
• Spur cells-Liver disease, abetalipoproteinemia
• Stomatocyte-Hereditary condition, alcoholic liver
disease
• Spherocyte-Hereditary condition, immune hemolytic
anemia, water dilution, posttransfusion
• Schistocyte, helmet-Thrombotic thrombocytopenic
purpura, disseminated intravascular coagulation,
vasculitis, myelophthisic glomerulonephritis,
prosthetic heart valve
WBC
NORMAL COUNTS

• Total WBC Count : 4000 – 11000 / cu.mm.

• Differential count

Leukocyte Percentage
Neutrophils 40 – 70 %
Eosinophils 1–4%
Basophils 0–1%
Monocytes 4–8%
Lymphocytes 20 – 40 %
Colorless and nucleated formed element of blood.
WBC differential cells

•
•
 neutrophil eosinophil

basophil

45
small lymphocyte monocyte
WHITE BLOOD CELLS

•Definition:
Blood cells that fight
infection.
•Elevated = leukocytosis
•Decreased = leukopenia.

Leukocytosis Leukopenia
Infections Anaphylactic shock

Common cold Cirrhosis of liver

Disorders of spleen
Tuberculosis
Pernicious anemia
Allergy
Typhoid and paratyphoid fevers
Glandular fever Viral infections
Leukopenia

• Definition: total WBC < 4,300

• Differential dx:
• Infection including bacterial or viral
• Chemotherapy
• Other medications (anti-epileptics, penicillins,
sulfonamides, cephalosporins, thiazides, cimetidine,
ethanol, immunosuppressants)
• Hematologic malignancy
• Aplastic anemia
• Hypersplenism
• Auto-immune disorders
• Low wbc can be normal in certain populations
Leukopenia

• Signs and Symptoms: may be none, symptoms of

infection, fever, lymphadenopathy, weight loss,
night sweats. Check medications

• Physical findings: lymphadenopathy, splenomegaly,

may be asymptomatic

• Management: determine underlying cause

• Blacks can have asymptomatic leukopenia as
baseline
Leukocytosis

• Definition: WBC > 10,800

• Differential dx:

• Infection
• Chronic inflammation
• Medications (steroids)
• Recovery post chemotherapy
• WBC growth factors (neupogen, leukine, neulasta)
used in cancer therapies
• Hematologic malignancy (leukemia) or bone
marrow dysfunction
Leukocytosis

• Signs and Symptoms: may be asymptomatic, fever,

infectious symptoms, cough, SOB, dysuria, skin
infection/abscess, rash, weight loss, fatigue, night
sweats
• Physical findings: may be none. Erythema, edema,
skin rash, lymphadenopathy, cachexia,
hepatosplenomegaly, abnormal heart sounds,
adventitious lung sounds
• Management: determine underlying cause.

• If unable to determine cause or if leukocytosis

persists or is rising after treating for infection,
consult for bone marrow biopsy
Leukemia

• Definition: hematologic malignancy of the bone

marrow whereby abnormal immature cells crowd
out normal cells. WBC can be elevated or
decreased in leukemia. RBC and platelets can be
normal or decreased

• Types of leukemia:

• Acute Myelogenous Leukemia

• Acute Lymphocytic Leukemia
• Chronic Myelogenous Leukemia
• Chronic Lymphocytic Leukemia
 Neutrophils

• 60% of all WBCs

• Nuclei of 2-6 lobes
• Other names:
– Polymorphonuclear cells (PMNs, polys, segs)
– Granules have enzymes
– Can damage tissue if severe or prolonged
– Pus

52
Neutrophils – Low

 Significant levels
< 0.5 x 109/L (high risk infection)
 Most common causes
– viral (overt or occult)
– autoimmune/idiopathic
– Drugs
Neutrophils – High

 Most common causes

– infection/inflammation
– Necrosis/malignancy
– any stress/heavy exercise
– drugs
– pregnancy
– CML
 Eosinophils

• 1-4 % of leukocytes
• Bilobed nucleus
• Granules have digestive enzymes
• Role in ending allergic reactions and in fighting
parasitic infections
Eosinophils

 Eosinophils – Low
– no real cause for concern

 Eosinophils – High
Most common causes:
– allergy/atopy: asthma/hayfever
– parasites (less common in developed countries)
Rarer causes:
– Hodgkins
– myeloproliferative disorders
Basophils

• Rarest WBC
• Bilobed nucleus
• Dark purple granules
• Later stages of reaction to allergies and parasitic
infections

57
Basophils

 Basophils – Low
– difficult to demonstrate

 Basophils – High
Associated with
– myeloproliferative disorders
– other rare causes
Lymphocytes

• Most important WBC

• 20-45%
• Most are enmeshed in lymphoid connective tissue,
e.g. lymph nodes, tonsils, spleen
• Response to antigens (foreign proteins or parts of
cells) is specific
• Two main types attack antigens in different ways
• T cells
• B cells
• plus “natural killer cells”
nucleus occupies most of the cell volume
Lymphocytes

 Lymphocyte – Low
– not usually clinically significant

 Lymphocyte – High
– isolated elevated count not usually significant
Causes
• acute infection (viral, bacterial)
• smoking
• hyposplenism
• acute stress response
• autoimmune thyroiditis
• CLL
Monocytes

• 4-8% of WBCs
• Largest leukocytes.
• In connective tissue they transform into
macrophages (phagocytic cells with
pseudopods)

61
Monocytes

 Monocytes – Low
– not clinically significant
– acute stress reaction
– pt on steroids
– chemo and immunosuppressant therapies

 Monocytes – High
– usually not significant
– watch levels > 1.5 x109/L more closely
– Infection
– granulomatous disease (sarcoid)
– collagen vascular disease.
Total WBC may be misleading

 The absolute count of each of the cell types is more

useful than the total.
 The total count may be misleading, eg: low
neutrophils with an elevated lymphocyte count may
produce a total white count that falls within the
reference range.
PLATELETS
Thrombocytosis

• Definition: elevated platelet count > 500,000

• Diff Dx includes: bone marrow myeloproliferative

disorder as in essential thrombocythemia (ET) or
secondary to iron deficiency, splenectomy,
infection, malignancy or inflammatory disease
• Lab findings: CBC showing elevated platelet count.
Iron studies may show iron deficiency.
• Signs and Symptoms: often asymptomatic and
found on routine CBC. ET patient may experience
headaches, TIAs
Thrombocytosis

 Most likely causes

– reactive conditions eg infection, inflammation
– pregnancy
– iron deficiency
– post splenectomy
– essential thrombocythaemia
Thrombocytopenia
• Definition: platelet count < 100,000.
• Differential Dx: bone marrow dysfunction,
malignancy, auto-immune response, medication,
chemotherapy, acute bleeding, acute thrombosis,
DIC, HIT, lab error
• Incidence: ITP: 100 cases per million people per
year with children accounting for half of those.
Females more likely to be affected.
 Most common causes
– viral infection
– idiopathic thrombocytopenic purpura
– liver disease
– hypersplenism
– autoimmune disease
– pregnancy
Thrombocytopenia

• Lab/diagnostic studies:

• check CBC for other cytopenias,

• platelet aggregation studies,
• anti-platelet antibodies,
• bleeding time,
• bone marrow biopsy would show elevated
megakaryocytes (platelet precursors) in destruction
problem however low megakaryocytes in bone
marrow production disorder.
• Splenic ultrasound to evaluate for sequestration
Thrombocytopenia

• Lab Error: can have platelet clumping due to EDTA

tube this may cause platelet count to appear falsely
low – peripheral smear examination can confirm
normal platelet count. Blood can be collected in NA
citrate tube and re-run to confirm normal count

• For TTP (thrombotic thrombocytopenic purpura) this

rare disorder of the anticoagulation system will
cause patient to require plasmapheresis to remove
inhibitors of VW factor. Give pt FFP (fresh frozen
plasma) to replace normal VW factor. This is a rare
but serious disease that requires care under
hematologist.
Bleeding Disorders

• Hemophilia
• Definition: genetic disorder characterized by lack of
blood clotting factors.
• Hemophilia A: lack of factor VIII (most common).
Sex linked occurring in 1:10,000 males
• Hemophilia B: lack of factor IX (Christmas factor)
occurring in 1:100,000 males
• Labs/diagnostic testing: diagnosed by checking
factor activity levels, CBC, PT/PTT, bleeding time.
• Signs and symptoms: easy bruising, prolonged
bleeding, painful joints due to hemarthrosis. Older
hemophiliacs likely to be infected with HIV due to
receiving contaminated factor products
HEMOPHILIA

• Physical findings: Ecchymoses, bleeding,

edematous painful joints

• Management:
• Patients with hemophilia require replacement of
factor when bleeding occurs or sometimes daily
based on severity of disease.
Bleeding Disorders

• Von Willebrand disease (VWD)

• Definition: bleeding disorder caused by lack of Von

Willebrand factor which interferes with platelet
function thereby increasing risk for bleeding. Most
forms of VWD are mild
• Incidence: most common blood clotting disorder
occurring in 1 in 800-1000 people
• Labs: normal CBC, bleeding time (prolonged), Von
Willebrand factor assay (reduced), platelet
aggregation study (reduced).
Von Willebrand Disease

• Signs and symptoms: easy bruising, prolonged

bleeding after surgery, dental procedure,
menorrhagia, epistaxis

• Physical findings: may be normal or may see

ecchymoses, petechiae, bleeding

• Management:
• Desmopressin (DDAVP) nasal spray – helps to
increase factor VIII and VW factor in the blood
• Fresh frozen plasma/cryoprecipitate in acute
bleeding or surgery
BLOOD TYPING

ABO blood groups: A, B, AB, and O

74
 ABO blood group types
The blood types are “codominant” – i.e. if genotype is AB,
then you have both A and B antigens on your RBCs
Bloodtype Antigen on Antibodies in Can receive blood from: Can donate blood to Frequenc
RBC blood (usually RBCs only): y
in US
A A anti-B A A 40%
O AB
not B (you have anti-B) *
not AB (you have anti-B) *
B B anti-A B B 10%
O (no Ags so you won’t AB
reject)
not A (you have anti-A) *
not AB (you have anti-A) *
AB A and B none to AB AB is universal AB 4%
A or B recipient
A
B
O
O not A nor Anti-A and anti- not A (have anti-A)* A 46%
B B not B (have anti-B)* B
not AB (have both AB
antibodies)* O O is universal
O donor
Ag = antigen on red blood cell. *=transfusion reaction (hemolysis of new cells)
If a blood transfusion is given to a person who has
antibodies to that type of blood, then the transfused
blood will be attacked and destroyed (transfusion
reaction)
76
 Rh FACTOR

• The “Rh factor” is another major antigen on the RBC,

called D Antigen.(autosomal recessive)
– DD: Rh+, Dd: Rh+, dd: Rh-

• Rh Incompatibility(Erythroblastosis Fetalis).

• If mom is Rh- then give “Rhogam” during pregnancy

[(is anti- Rh(D): Rh(D) Ig (immunoglobin)], an antibody
which will destroy any of the baby’s RBCs which leak
into mom’s blood during the pregnancy so she will not
mount an immune response to the D antigen

77
INTERPRET RESULTS IN CLINICAL
CONTEXT
• All haematology results need to be interpreted
in the context of a thorough history and
physical examination, as well as previous
results.