1. CBC --- Interpretations Dr.Duaa Hiasat

2. objectives In this hour we will review: Definition of anemia
Signs and symptoms
Cause
Possible complication
Utility of the CBC and reticulocyte count
And give you a simple plan to:
Categorize anemias into 3 morphologic groups
Develop a differential diagnosis
Decide on further laboratory evaluation
Quiz questions
objectives

3. CBC- complete blood count
Component of the CBC:
• Red Blood Cells (RBCs) • Hematocrit (Hct) • Hemoglobin (Hgb) • Mean Corpuscular Volume (MCV) • Mean Corpuscular Hemoglobin Concentration (MCHC)
- Red cell distribution width (RDW)
• White Blood Cells (WBCs) • Platelet

4. RBC RBC (varies with altitude): M: 4.7 to 6.1 x10^12 /L
F: 4.2 to 5.4 x10^12 /L
Biconcave disc shape with diameter
of about 8 µm
Function: - transport hemoglobin which carries oxygen from the lung to the tissues
-acid –base buffer.
Life span days.

5. Hemoglobin & Hematocrit
1 week: •1 month: 11-17
6months •1 year:
10years: •15years: 14-18M ; 12-16F
Hematocrit : (packed cell volume)
It is ratio of the volume of red cell to the volume of whole blood.
14-90d:35-49
6m-1yr:30-40
4-10yr: 31-43
Adult:42-52M; F

6. MCV&MCHC MCV = mean corpuscular volume HCT/RBC count= 80-100fL
small = microcytic
normal = normocytic
large = macrocytic
MCHC= mean corpuscular hemoglobin concentration HB/RBC count= 26-34%
decreased = hypochromic
normal = normochromic

7. MCH & RDW MCH (mean corpuscular hemoglobin) HB/HCT = 27-32 pg
RDW (red cell distribution width)
It is correlates with the degree of anisocytosis
_ Normal range from 10-15%

8. The RULE of Three
Applies to normocytic, normochromic erythrocytes only
Useful to detect laboratory error in measuring the Hb, HCT, and RBC count
3 times the RBC count should = Hb
3 times Hb should = Hct

9. The Reticulocyte Count
This important value is needed in the evaluation of any anemia.
Normal range 1-2%
Must correct for degree of anemia
Observed retic count (Actual HCT ÷ Normal HCT) = Corrected retic count
 Retic count goes up with
Hemolytic anemia
Retic goes down with 
Nutritional deficiencies
_ Diseases of the bone marrow itself

10. Definition of Anaemia
Anemia is a level of Red cells, Hemoglobin, or Hematocrit that is below the lower limit of normal for age and sex.
Anemia is not a disease, it is a sign of disease
As such, critical for all practitioners to know how to evaluate / determine its cause / treat
Mechanisms:
Increased loss (external) - hemorrhage
Increased destruction (internal) - hemolysis
Decreased production (trouble in the bone marrow)

11. So What’s the Plan? Hx and examination CBC- define anemia
Look at red cell indices
Categorize the anemia based on RBC size
Reticulocyte count - marrow response
Note any RBC anisopoikilocytosis
Consider the differential diagnosis
Plan your laboratory evaluation

12. Symptoms Can minor or vague Weakness and fatigue Poor concentration
Dyspnea on exertion
Palpitation and angina
Pica
Behavioral disturbances in children
Dizziness
intermittent claudication
Symptoms of heart failure
Impaired infant development
Reduced school performance

13. Clinical Signs to be looked for
Pallor(skin,mucosal lining and nail beds)
Koilonychia in IDA
Jaundice in hemolytic anemia
Bone deformities in thalassemia major
Leg ulcers in sickle cell disease
Signs of hyperdynamic circulation:
Tachycardia
Flow murmure
Cardiac enlargement
glossitis ,smooth red tongue

14. Causes of Anaemia Decreased production of Red Cells
- Hypoproliferative, marrow failure
Increased destruction of Red Cells
- Hemolysis (decreased survival of RBC)
Loss of Red Cells due to bleeding
- Acute / chronic blood loss (hemorrhagic)

15. Anaemia Hypoproliferative Hemolytic Hb% < 12, Hct < 38%
Retics < 2
Retics > 2

16. Workup – Second Test The next step is ‘What is the size of RBC’ ?
MCV indicates the Red cell volume (size)
Both the MCH & MCHC tell Hb content of RBC
If the Retic count is 2 or less we are dealing with either
Hypoproliferative anaemia (lack of raw material)
Maturation defect with less production
Bone marrow suppression (primary/ secondary)

17. Mean Cell Volume (MCV) Microcytic < 80 fl Normocytic Macrocytic
RBC volume is measured by
The Mean Cell Volume and RDW
Microcytic
< 80 fl
MCV
Normocytic
Macrocytic fl
> 100 fl
< 6.5 µ µ
> 9 µ

18. Anaemia Workup - MCV Microcytic Normocytic Macrocytic MCV
Iron Deficiency IDA
Chronic Infections
Thalassemias
Hemoglobinopathies
Sideroblastic Anemia
Chronic disease
Early IDA
Primary marrow disorders
Combined deficiencies
Increased destruction
Megaloblastic anemias
Liver disease/alcohol
Metabolic disorders
Marrow disorders

19. Red cell Distribution Width - RDW
Normal
High
Population Uniform
Population Double

20. Anaemia Workup - 4th Test Peripheral Smear Study
Are all RBC of the same size ?
Are all RBC of the same normal discoid shape ?
How is the colour (Hb content) saturation ?
Are all the RBC of same colour/ multi coloured ?
Are there any RBC inclusions ?
Are leucocytes normal in number ?
Is platelet distribution adequate ?

21. Causes of IDA Inc. need : pregnancy. normal growth.
Dec. intake or absorption:
nutrition
gastric surgery
celiac sprue
Inc. blood loss:
GERD,PUD, gastritis
IBD
malignancy
menstruation

22. IDA -CBC

23. Microcytic Hypochromic - IDA

24. IDA – Special Tests Iron related tests Normal IDA
Serum Ferritin (pmo/L)
33-270
< 33
TIBC (µg/dL)
> 400
Serum Iron (µg/dL)
50-150
< 30
Saturation %
30-50
< 10
Bone marrow Iron ++
Absent

25. IDA Summary Microcytic MCV < 80 fl, RBC < 6 µ
RDW Widened with low MCV
Hypochromic MCH < 27 pg, MCHC < 30%
RI < 2
Serum ferritin Very low < 30 (p mols/L)
TIBC Increased > 400 (µg/dL)
Serum Iron Very low < 30 (µg/dL)
BM Fe Stain Absent Fe
Response to Fe Rx. Excellent

26. Treatment Explore the cause and treat it Medical : Iron supplement.
Nutrition such as:
Chicken and turkey
peas, and beans
Eggs (yolk)
Fish
Meats (liver is the highest source)
Peanut butter
Soybeans
Whole-grain bread
apricots ,Spinach
Medical :
Iron supplement.
Take iron tablets on an empty stomach.
Take iron tablets with vitamin C.
Vitamin C improves the absorption of iron

27. IDA- Some Nuggets Look for occult blood loss
Pica and Pagophagia – Ice sucking
Food, Ca, Phosphate, antacids ↓absorption
Ascorbic acid ↑absorption
Oral iron Rx. always is the best,
FeSO4 is the best. Reserve parenteral Rx.
Packed cell transfusion in emergency
Continue Fe Rx at least 2 months after normal Hb
1 gram ↑in Hb every week can be expected
Always supplement protein for the Globin component

28. Microcytic Anaemias ↓↓ ↑↑ N MCV < 80 fl Serum Iron TIBC RDW
Iron Def. Anemia ↓↓ ↑↑
Increased
Chronic Infection
Normal
Thalassemia N
Hemoglobinopathy
Lead poisoning
Sideroblastic

29. Thalassemia
It is forms of inherited autosomal recessive blood disorders that originated in the Mediterranean region
patients with thalassemia traits do not require medical or follow-up care after the initial diagnosis is made.
Patients with β-thalassemia trait should be warned that their condition can be misdiagnosed for the common Iron deficiency anemia.
Counseling is indicated
Screening by CBC
Hb MCV RBC 5.9
Mentzer index:MCV/RBC
> IDA
< Thalassemia

30. Therapy for beta thalassemia primarily involves chelation or removal of excessive iron deposits in the blood
Curative methods Bone Marrow Transplant
Beta-thalassemia major requires lifelong blood transfusions.
Alpha-thalassemia major is also referred to as hydrops fetalis
Diagnosed by blood electrophoresis
Hb A2 >3.5
Hb A <95 Hb F >1

32. Complication Iron overload
Infection: This is especially true if the spleen has been removed.
Bone deformities: Thalassemia can make the bone marrow expand, which causes bones to widen especially in the face and skull.
Enlarged spleen
Slowed growth rates:Puberty also may be delayed in children with thalassemia.
Heart problems: such as congestive heart failure and abnormal heart rhythms (arrhythmias), may be associated with severe thalassemia.

33. Macrocytic Anaemias Megaloblastic Macrocytic – B12 and Folate↓
(hypersegmented neutrophil)
B. Non Megaloblastic Macrocytic Anaemias
Liver disease/alcohol
Hemoglobinopathies
Metabolic disorders, Hypothyroidism
Myelodystrophy, BM infiltration
Accelerated Erythropoesis - ↑destruction
Drugs (cytotoxics, immunosuppressants, anticonvulsants)

34. Anemia - Macrocytic (MCV > 100)
Macrocytic anemias may be asymptomatic until
the Hb is as low as 6 grams
MCV fl
must look for other causes of macrocytosis
almost always folate or B12 deficiency

35. MBA

36. Symptoms of MBA memory loss, depression,
personality changes, and psychosis
peripheral neuropathy.
ataxia,
become weak,
lose proprioceptive and vibratory senses.
If not treated, mental and neurological changes can become permanent.
in pregnant woman folate deficiency causes neural tube defect in the infant
numbness or tingling in hands and feet
smooth and tender tongue

37. Causes
digestive diseases celiac disease, chronic infectious enteritis, and enteroenteric fistula. lack of intrinsic factor in gastric (stomach) secretions.
malabsorption Inherited congenital folate malabsorption, without detection cause mental retardation.
Medication-induced folic acid deficiencY that prevent seizures, such as phenytoin, primidone, and phenobarbital,
Foods that are rich in folic acid include the following: Oranges,Spinach, Liver, Rice, soy beans, green, leafy vegetables, Bean, peanuts
Foods that are rich in folic acid and vitamin B12 include the following: Eggs, Meat, Poultry, Milk, Shellfish
Fortified cereals

38. TREATMENT Must be tailoret to cause Replacement : Folic acid : 1 mg /d
Vit B12 : 1000 micr gr/d I.M for 5 days ,then q week until Hct normal, then q month for life .

39. Macrocytosis -MBA

40. HSN - MBA

41. Basophilic Stippling - MBA
BS occurs in Lead poisoning also

42. MBA - BM

43. Pernicious Anaemia - Tongue
Bald, smooth, lemon yellowish red tongue

44. Normocytic Anaemias Chronic disease Early IDA Hemoglobinopathies
Primary marrow disorders
Combined deficiencies
Increased destruction
Frequent sampling -ICU

45. Anaemia of Chronic Disease
Thyroid diseases
Malignancy
Collagen Vascular Disease
Rheumatoid Arthritis
SLE
Polymyositis
Polyarteritis Nodosa
IBD
– Ulcerative Colitis
– Crohn’s Disease
Chronic Infections
– HIV, Osteomyelitis
– Tuberculosis
Renal Failure

46. CBC in ACD
Anemia of chronic disease is often a mild normocytic anemia, show a low reticulocyte production index, suggesting that reticulocyte production is impaired and not enough to compensate for the decreased red blood cell count.
While no single test is always reliable to distinguish the two causes of disease, there are sometimes some suggestive data:
ferritin levels should be normal or high, reflecting the fact that iron is stored within cells, and ferritin is being produced as an acute phase reactant
TIBC should be low or normal in anemia of chronic disease

47. ‘Dimorphic’ Anaemia RDW is increased very much
Folate & Fe deficiency (pregnancy, alcoholism)
B12 & Fe deficiency (PA with atrophic gastritis)
Thalassemia minor & B12 or folate deficiency
Fe deficiency & hemolysis (prosthetic valve)
Folate deficiency & hemolysis (Hb SS disease)
Peripheral smear exam is critical to assess these
RDW is increased very much

48. RBC Size – Anisocytosis Different sizes of RBC

49. Poikilocytosis Different Shapes of RBC

50. Polychromasia - Spherocytosis

51. Target Cells
Liver Disease
Thalassemia
Hb D Disease
Post splenectomy

52. High RBCs count
. Increased RBC count = Polycythemia A. Primary B. Secondary living at altitude chronic lung/heart disease tobacco use/carbon monoxide C. Relative Polycythemia dehydration

53. A six year old black child with abdominal and joint pains.
CBC:
Hb/Hct= 5.6/17.9
MCV= 90
Retic = 10%

54. Sickle cells are seen on the blood smear
Anemia is present
Sickle cells are seen on the blood smear
This patient has Sickle Cell Anemia
How do I confirm it?
Hemoglobin Fractionation - demonstration of Hemoglobin S (and no Hemoglobin A)

55. A 9 year old Hispanic girl with fatigue, mild jaundice; palpable spleen
CBC: H/H = 8.1/25.6, MCV = 80, RDW = 16
Retic = 10%
Peripheral smear
Anisocytosis
Cells with no central pallor

56. osmotic fragility – confirm the spherocytes
It is normochromic, normocytic Reticulocytes are increased Spherocytes are present on the smear The findings are consistent with Hereditary Spherocytosis
osmotic fragility – confirm the spherocytes
Anemia +  reticulocyte count
Must rule out a source of bleeding
Extravascular (in the spleen)
 indirect bilirubin, urobilinogen,  LDH, haptoglobin
Spherocytes on the peripheral smear
Intravascular
indirect bilirubin, urobilinogen, LDH, haptoglobin, + free plasma hemoglobin, hemoglobinuria, + hemosiderinuria
Schistocytes on the peripheral smear

57. 5 year old boy with fatigue, URI, petechial rash, hepatosplenomegaly
CBC: H/H=7.8/24, MCV=81, WBC=24 with “abnormal cells”, platelets=56
Reticulocyte count = 1.2%
Peripheral smear:

58. Infiltrative processes in the bone marrow may cause normochromic, normocytic anemia (and often pancytopenia)
Bone marrow
smear
90% blasts
Patient has ALL

59. 9 year old seen for “sports” physical examination. Has some pallor.
CBC: RBC=4.7x106, H/H=10.5/30.2, MCV=64, MCH=22, MCHC=34, RDW=13, WBC= 8, platelets=340, diff=WNL
Reticulocyte count = 2%

60. What category of anemia? What further tests?
Is anemia present?
RBC count is normal, but H/H are low
What category of anemia?
MCV and MCH are low --> Hypo/micro
What further tests?
Iron studies
Hemoglobin fractionation

61. Iron studies: Serum iron = 100 g/dl, transferrin = 300 mg/dl, Saturation = 33% ferritin = 200 ng/ml
Hemoglobin fractionation: A=89%, A2=6.7%, F=4.3%
Diagnosis: beta thalassemia trait

62. An 18-month-old previously healthy girl is brought to your clinic for pallor. She eats a regular diet. She is alert and interactive but very pale. The remainder of the physical examination is normal.
CBC reveals a normal WBC and platelet counts. The Hgb = 4.5 g/dL and MCV = 74 fL
What is the most likely diagnosis?
Acute lymphoblastic leukemia
Diamond-Blackfan anemia
Glucose-6-phosphate dehydrogenase deficiency
Iron deficiency anemia
Transient erythroblastopenia of childhood

63. TEC results in transient failure of the erythroid cell line
Previously healthy child presents with severe, normocytic anemia and otherwise normal findings
TEC results in transient failure of the erythroid cell line
Cause is unknown; may have history of viral illness
Average age = 2 years (rare in the first year of life)
Normal physical exam, except for signs of anemia
Labs: normocytic anemia and reticulocytopenia
Treatment: erythrocyte transfusion for children who have Hgb < 5 g/dL
Prognosis is excellent

64. WBC WBCs are involved in the immune response.
The normal range: 4 – 11x10^9 /L
Two types of WBC:
1) Granulocytes consist of:
Neutrophils: %
Eosinophils: 1 - 5%
Basophils: up to 1%
2) Agranulocytes consist of:
- Lymphocytes: %
Monocytes: 1 - 6%

65. WBC The type of cell affected depends upon its primary function:
In bacterial infections, neutrophils are most commonly affected
In viral infections, lymphocytes are most commonly affected
In parasitic infections, eosinophils are most commonly affected.

66. Neutrophil Neutrophil disorders
Neutrophilia – an increase in neutrophils
Conditions associated with neutrophilia are:
1-Bacterial infections (most common cause)
2-Tissue destruction
e.g. tissue infarctions, burns.
3- leukemoid reaction
4-Leukemia

67. Neutrophil Neutropenia – this may result from
1-Decreased bone marrow production
e.g. BM hypoplasia.
2-Ineffective bone marrow production
E.g. megaloblastic anemias and myelodysplastic syndromes.
3- post acute infection
_ e.g. typhoid fever, brucellosis.

68. Eosinophil Eosinophilia may be found in Parasitic infections
Allergic conditions and hypersensitivity reaction

69. Lymphocyte No specific granules 20-40% of WBC =1.55-3.5x10^9/ L
Diameter 8-10 µm
T cells: cellular
(for viral infections)
B cells: humoral (antibody)
Natural Killer Cells

70. Lymphocyte Lymphocytosis – may indicate _ Viral infection
e.g. Infectious mononucleosis, CMV
_ Bacterial infection
e.g. TB or pertussis.
Lymphopenia – caused by
_Stress.
_Steroid therapy
_ Irradiation

71. Manifestation of leukopenia
Infection of the mouth and throat.
Painful skin ulceration.
Recurrent infection.
Septicemia.

72. Platelets Small granular non-nucleated discs. Diameter about 2-4 µm
Normal range; x10^9 /L
Destroyed by macrophage cells in the spleen.
Function; involved in coagulation and blood haemostasis.
Life span 7-10 days

73. Platelets Numbers of platelets
Numbers of platelets
Increased (Thrombocythemia)
Pregnancy.
Exercise.
High attitudes.
splenectomy
Decreased (Thrombocytopenia)
Menstruation.
Haemorrhage.
Bone marrow destruction or suppression e.g. leukemia  
The values have to fit the clinical situation.

74. Manifestation of thrombocytopenia
Petechial hemorhage.
Easy bruising.
Mucosal bleeding
e.g. _ epistaxes.
_ gum bleeding

75. ITP
condition of having an abnormally low platelet count, As most incidents of ITP appear to be related to the production of antibodies against platelets
the spontaneous formation of purpura and petechiae , especially on the extremities, bleeding from the nostrils, gums, and menorrhagia ,A very low count may result in the spontaneous formation of hematomas (blood masses) in the mouth or on other mucous membranes. Bleeding time from minor lacerations or abrasions is usually prolonged.
Serious and possibly fatal complications due to an extremely low count may include subarachnoid or intracerebral hemorrhage , lower gastrointestinal bleeding or other internal bleeding.

76. The diagnosis of ITP is a process of exclusion
The diagnosis of ITP is a process of exclusion.  First, the clinician has to determine that there are no blood abnormalities other than low platelet count, and no physical signs except for signs of bleeding.  Then, the secondary causes (usually 5–10 percent of suspected ITP cases) should be excluded.  Secondary causes could be leukemia, medications (e.g., quinine, heparin), lupus erythematosus, cirrhosis, HIV, hepatitis C, congenital causes, antiphospholipid syndrome, von Willebrand factor deficiency
. Treatment may not be necessary in mild cases, but very low counts or significant bleeding might prompt treatment with steroids, intravenous immunoglobulin, anti-D immunoglobulin, or stronger immunosuppressive drugs. ITP not responsive to conventional treatment may require splenectomy. Platelet transfusions may be used in severe bleeding together with a very low count.

77. TTP is a rare disorder of the blood-coagulation system,
Classically, the following five features are indicative of TTP;
Thrombocytopenia leading to bruising or purpura
Microangiopathic hemolytic anemia (anemia, jaundice and a blood film featuring evidence of mechanical fragmentation of red blood cells)
Neurologic symptoms (fluctuating), such as hallucinations, bizarre behavior, altered mental status, stroke or headaches
Kidney failure
Fever

78. Secondary TTP
Cancer
Bone marrow transplantation
Pregnancy
Medication use:
Quinine
Platelet aggregation inhibitors (ticlopidine, clopidogrel, and prasugrel)
Immunosuppressants (cyclosporine, mitomycin, tacrolimus/FK506, interferon-α)
HIV-1 infection

79. Treatment
, plasmapheresis has become the treatment of choice for TTP; the procedure has to be repeated daily to eliminate the inhibitor and abate the symptoms.
Lactate dehydrogenase levels are generally used to monitor disease activity.
Plasmapheresis may need to be continued for 1–8 weeks

80. References Essentials of family medicine sixth edition
Nelson Essentials of pediatrics fourth edition
Kumar and clarck clinical medicine
The american family physician (web site)november
Family practice review course:anemia Dx and Rx Reid Blackwelder, East Tennessee State University
Medicinenet.com,definition of anemia (http//
Emedicine-anemia,chronic:article by Fredrick M Abrahamian,DO,FACEP (