RED BLOOD CELL

ABNORMALITIES
(APPROACH TO THE
DIAGNOSIS OF ANEMIA)

Section of Hematology-Oncology
 ANEMIA

Reduction below normal in the

concentration of hemoglobin or
RBC’s in the blood
Anemia is not a diagnosis in
itself, but merely an
objective sign of disease.

First step in its diagnosis is

detection of its presence.
3 FUNCTIONAL CATEGORIES
OF THE ANEMIAS
• Disorders of Proliferation
• Disorders in Erythrocyte Maturation
• Disorders due Primarily to
Erythrocyte Destruction or Red Cell
Loss
 PROBLEM: ANEMIA

Subjective Data
Objective Data
Assessment
Plans:

Diagnostic/Therapeutic
 SUBJECTIVE DATA
Sx of patients w/ anemia depend on the ff:

1. Severity of the anemia

2. Rapidity of onset
3. Patient’s age and CV status
- capacity of the CV & pulmonary system

to compensate for the anemia

6. Associated manifestations of the
underlying disorder
- Endocrine disorder
- Renal disorder
- Hepatic disorder
 SUBJECTIVE DATA
•Onset & Duration of symptoms
insiduous or acute
•Previous prescription for hematinics
& response
•Medication history
•Occupation, household customs &
hobbies
•Symptoms of hemolysis
jaundice, changes in urine color
•Symptoms of blood loss
melena, hematochezia, epigastirc pain
 SUBJECTIVE DATA

•Obstetric & Gynecologic history

# of pads/day
duration
# of pregnancies, abortions - interval
•Concomitant bleeding manifestations
•Dietary history
•Fever, Weight loss
 OBJECTIVE DATA
I. Cardiac Signs
• Hemic murmurs: mid or holosystolic
often in the pulmonic or apical area,
due to increased blood flow and
turbulence
• Gallop rhythms
• Tachycardia/Cardiomegaly
• Strong peripheral pulses with wide
pulse pressure
 II. Integumentary Manifestations
• Pallor: <8 to 10 mg/dL hemoglobin
Affected by:
- state of vasoconstriction/vasodilatation
- degree & nature of pigmentation
- nature & fluid content of the subcutaneous
tissues
Most constantly detected in:
- mucous membranes of the mouth, pharynx,
conjunctivae, lips
- nailbeds

* Areas where vessels are close to the skin surface

Other Integumentary Manifestations
•Dry, Shriveled skin
•Thinning, loss of luster,
premature graying of hair
•Brittle, lackluster nails, spooning
III. Neuromuscular Signs
• Headache • Scotomas
• Vertigo • Lack of mental
• Tinnitus concentration
• Faintness • Drowsiness
• Retinal • Restlessness
hemorrhage
• Paresthesias
IV. GI Manifestations
 Glossitis
 Atrophy of the papillae of the tongue
 Dysphagia
 Oral ulcers
 Gingival hyperplasia
 Hepatosplenomegaly
V. Sternal Tenderness
Lymphadenopathy

VI. Genitourinary Signs

• Slight proteinuria
• Changes in urine color
Always rule out primary disease of the GUT.
 Even the most expert clinical
appraisal does not supplant accurate
measurement of the blood for the
detection, quantification and
characterization of anemia.
 Objective Data
Laboratory tests:

I. Red cell count- hgb, hct, reticulocyte

count, RBC indices
II. White Blood cell count- diff’l, nuclear
segmentation of neutros
III. Platelet count
IV.Peripheral smear morphology
V. Iron Studies
VI. Bone marrow examination
 Changes in Normal Hemoglobin/Hematocrit
Values with Age and Pregnancy
 Age/Sex Hemoglobin g/dl Hematocrit %
At birth 17 52
Childhood 12 36
Adolescence 13 40
Adult man 16(+2) 47(+6)
Adult woman 13(+2) 40(+6)
(menstruating)
Adult woman 14(+2) 42(+6)
(postmenopausal)
During pregnancy 12(+2) 37(+6)
 Red Cell Indices
 Index Normal Value
Mean Cell Volume(MCV):
(hematocrit x 10)/(red cell ct. x 106) 90 + 8 fL

Mean Cell Hemoglobin (MCH):

(hemoglobin x 10)/ (red cell ct. x 106) 30 + 3 pg

Mean Cell Hemoglobin Concentration:

(hemoglobin x 10)/ hematocrit, 33 + 2%
or MCH/MCV
 RETICULOCYTE COUNT

 Normal Value: 0.5 – 1.5% (old)

5 – 15 x 10-3 (SI)
Correction:
Patient’s Hct x Reticulocyte count % = corrected
45 reticulocyte

Corrected Reticulocyte = RPI

2
 WHITE BLOOD CELL COUNT

 Normal Value: 4.5 – 10.0 x 10 9/L

Percentage Absolute No.
Bands 0-0.05 0-0.7
Segmenters 0.50-0.70 1.8-7.0
Lymphocytes 0.20-0.40 1.0-4.8
Monocytes 0-0.07 0-0.80
Eosinophils 0-0.05 0-0.45
Basophils 0-0.01 0-0.20
Normal Peripheral Smear
Normal bone marrow (LPO)
Normal bone marrow (HPO)
 ASSESSMENT
(Possible Cause of Anemia)
 CLASSIFICATION OF ANEMIAS
BASED ON ETIOLOGY
I. Increased Blood Loss
Acute and Chronic Hemorrhage
III. Excessive Blood Destruction ((Hemolysis)
A. Congenital
1. Red Cell Morphologic Defects
(e.g. Congenital Spherocytosis)
2. Hemoglobinopathies
(e.g. Thalassemias)
3. Enzyme Defects
(e.g. G6PD Deficiency)
B. Acquired
1. Immune Disorders
(e.g. LE)
2. Non-Immune Disorders
(e.g. Infections, Allergy, etc.)
I. Marrow production defects
a. Hematinic deficiencies – iron, Vit.
B12, Folic Acid
b. Infiltrative Diseases – Leukemias,
lymphomas, Cancer
c. Aplasia
d. Miscellaneous – Endocrine, Renal,
Infections
 CASE STUDIES
 Case 1
Mr. Santos, 48 years old farmer
consulted because of progressive weakness
and pallor.
No jaundice nor hepatosplenomegaly on

P.E.
Petechiae noted on both L.E.’s
CBC Result:
Hb: 7 gm/dl
Hct: 21
WBC: 4,000
lymph: 48%
segs: 52%
Platelet count: 80,000
Reticulocyte Count:5 x 10-3
Bone Marrow: FATTY MARROW
 APLASTIC ANEMIA
 A type of hypoproliferative anemia
characterized by pancytopenia with
marrow hypocellularity
 Etiology:

1. Primary
a. Congenital
Fanconi’s Anemia
b. Idiopathic
2. Secondary
a. Radiation
b. Drugs and Chemical
Regular effects
Idiosyncratic effects
c. Viruses
d. Immune diseases
e. PNH
f. Pregnancy
Pathogenesis:
1. Depletion of hematopoietic cells by an
agent or event that kills stem cells
2. Suppression of proliferation and
maturation of stem cells by an
immunologic or lymphocyte mediated
mechanism
Clinical Features:
- symptoms related to decrease RBC,
WBC, platelets
- Physical exam: lymphadenopathy and

splenomegaly not typical

- Laboratories: Pancytopenia, decrease

reticulocyte count
Bone marrow: fatty marrow
Management Options:
1. Transfusion support
2. Bone marrow transplantation
3. Immunosuppression with anti-
thymocyte globulin, with or without
steroids
4. Androgen stimulation
 Case 2
J.K., 35 year old housewife complains of
progressive easy fatigability of about 3
months duration.
Review of System: (-) epigastric pain
(-) hematochezia nor
melena
menses – 28 days cycle, 7 days duration,
3 days profuse flow consuming
5-6 fully soaked pads/day
 (-) bruises/ecchymoses

P.E. Pale, no jaundice

(-) hepatosplenomegaly
Laboratory results:
CBC: Hb: 60g/L WBC: 6 x 109/L
Hct: .21 seg: 70%
MCV: 80fL lymph: 25%
MCH: 25 pg eos: 3%
MCHC: 28% mono: 2%
platelets: adequate
Reticulocyte count: 1.5 x 10-3
Peripheral smear: HYPOCHROMIC
Iron studies:
Ferritin: 8ug/L
Iron: 10 (N.V.9 - 27 umol/L)
TIBC: 60 (N.V. 54 – 64 umol/L)
Percent Saturation: 17%
 IRON DEFICIENCY ANEMIA

 Most common cause of anemia worldwide

 Iron is absorbed primarily in the duodenum

and upper jejunum

 Picture : causes of iron anemia
 Case 3
Mrs. Cruz, 75 year old female consulted
because of progressive weakness and loss of
balance. She also complains of numbness
and tingling sensation in all extremities. She
has no gastrointestinal complaints.
- not a diabetic but is hypertensive
- prefers to eat vegetables and fish
because of poor dentition
P.E.
Patient is pale with smooth, red
tongue.
No organomegaly noted
Laboratory Results

CBC: Hb: 80 g/L WBC: 9 x 109/L

Hct: .26 seg: 74%
MCV: 102fL lymph: 20%
MCH: 36 pg eos: 2%
MCHC: 38% mono: 4%
platelets: adequate
Peripheral Smear: Macrocytes
MEGALOBLASTIC ANEMIA
- disorder caused by impaired DNA
synthesis
- Cell primarily affected: blood cells
GI epithelial cells
- slowed nuclear cell division with normal
progression of cytoplasmic maturation
Megaloblastosis
 Folate sources: mainly fruits and
vegetables
Cobalamin sources: meat & dairy foods

Cause: B12 or/& Folate Deficiency

Clinical Manifestations:
2. Anemia with slight icteresia
3. GI manifestations – glossitis, smooth,
beefy red tongue, malabsorption
3. Neurologic manifestations (Cobalamin) - subacute
combined degeneration of CNS
peripheral neuropathy – numbness,
weakness, ataxia, paresthesia,
disturbances of mentation
 Management:
1. Treatment of underlying problem
2. Replacement therapy
oral folic acid
parenteral B12
 Case 4
Mrs. Santos, 50 year old male was
referred for evaluation of anemia. She
begun to experience easy fatigability
about 5 weeks PTC. She also noticed
passage of highly colored urine.
(+) weight loss of about 5 lbs in the last 2
months
(+) febrile episodes
 P.E. icteric sclerae
(+) cervical lymphadenopathy
(-) hepatomegaly
(+) splenomegaly
CBC: Hb: 70 g/L WBC: 13x 109/L
Hct: .21 seg: 80%
MCV: 98fL lymph: 20%
MCH: 35pg
MCHC: 36%
platelets: adequate
Reticulocyte count: 80 x 10-3/L
Peripheral smear: spherocytes
Other tests:
Direct Coombs: +++
Peripheral Smear: SPHEROCYTES
 IMMUNE HEMOLYSIS
Warm-antibody Immunohemolytic Anemia
- induced by IgG or IgM Abs reacting
specifically on antigens on RBC
membrane
Diagnosis: (+) Coomb’s test
Management:
Steroids
Splenectomy
Immunosuppresants
 Case 5
JA, 18 year old male consulted
because of recurrent jaundice and pallor.
Jaundice was first noted when he was 4
years old.
No history of blood transfusions.
Family history is positive for another
sibling with similar problem.
P.E. Icteric sclerae
moderate splenomegaly
CBC: Hb: 81 g/L
Hct: .30
WBC: 11.5 x 109/L
seg: 75%
lymph: 24%
eos: 1%
platelets: adequate
Reticulocyte count: 60 x 10-3/L
Peripheral smear: (+) spherocytes
 HEREDITARY SPHEROCYTOSIS

- inherited RBC membrane abnormality –

autosomal dominant pattern of
inheritance
- Characterized by spherical RBC due to a
molecular defect in one of the proteins of
the cytoskeleton of the RBC membrane
ankrin
Protein 3
Spectrin
Clinical Manifestations:
anemia
jaundice
cholelithiasis

Diagnosis: spherocytes on smear

reticulocytosis
(-) Coomb’s test
(+) Osmotic fragility test
Management:
Splenectormy – for moderate to
severe hemolysis
Folic Acid supplementation
TH ANK Y OU
APPROACH TO THE
BLEEDING PATIENT
 SCREENING HISTORY
• A history taken to evaluate hemostasis
should answer these questions:
• Has the patient experienced abnormal
bleeding or bruising? If so, are symptoms
recently acquired or do they date back to
childhood?
• Is there a history of an acquired disorder
that would impair hemostasis? E.g.,
chronic liver disease, SLE, uremia or a
hematologic malignancy.
• Is the patient taking a drug that could
interfere with hemostasis?
• Have other members of the family bled
abnormally?
 In questioning a parent about significant
bleeding in a small child, one should ask
specifically about:
• Bleeding from umbilical stump
• Bleeding after circumcision
• Bleeding from cuts in mouth
• Frequency & size of hematomas of scalp
• Extent of bruising from minor trauma, eg.
Falls from swings or bicycles or down
steps
• Nosebleeds that stop w/in mins, even if
frequent, suggest that hemostasis is N.
Prolonged nosebleeds requiring medical
intervention arouse suspicion of impaired
hemostasis.
 In assessing bleeding history of an adult
patient, one evaluates:

• Abnormal bruising, ask specific questions:

• How often do you notice a new bruise on your body?
• Do you develop bruises larger than a 1in dm without
remembering how you got the bruise? If so, how big
was the largest of these bruises?
• Do you notice bruises after injections?

• Excessive bleeding from small cuts

• Bleeding after previous surgery
• Bleeding after dental extractions. Bleeding that
lasts >24h after extraction of a permanent tooth
or that starts again after 3-4 days is suggestive
of a hemostatic abnormality.
 DRUGS THAT INTERFERE
WITH HEMOSTASIS
• Aspirin, clopidogrel, dipyridamole
• Drugs that interfere with blood
coagulation: heparin, oral
anticoagulants, (?) herbal medications
 PHYSICAL EXAMINATION
• Bleeding into skin and soft tissues
• Petechiae: characteristic of vessel & platelet
problem. Usually pinhead size but maybe
bigger. Characteristically develops 7 regress
in crops. Most conspicuous in areas of
increased venous pressure.
Must be distinguised from small telangiectsias
& angiomas
• Ecchymoses, hematomas: large superficial
hematomas maybe seen in coagulation
disorders.
• Palpable purpuras may be seen in vasculitis
• Hemarthorses – bleeding into synovial
joints and virtually diagnostic of a severe
hereditary coagulation disorder. May
develop without discoloration or other
external evidence of bleeding.

• Traumatic bleeding
Response to trauma is an excellent
“screening test” for the presence of
hereditary hemorrhagic disorder. A
history of surgical procedures or
significant injury w/o abnormal bleeding is
equally good evidence against presence of
such disorder.
• Miscellaneous bleeding manifestations

spontaneous bleeding from body orifices

menorrhagia melena
metrorrhagia epistaxis
hematuria gingival bleeding
hematemesis hemoptysis
Bleeding into serous cavities & internal
fascial spaces
retroperitoneal space
psoas sheath
CNS
retina
 CLINICAL DISTINCTION BETWEEN DISORDERS OF
VESSELS & PLATELETS & DISORDERS OF BLOOD
COAGULATION
FINDINGS COAG D/O PLT OR VESSEL D/O

Petechiae Rare Characteristic

Deep dissecting Characteristic Rare
hematomas
Superficial ecchymoses Common, usually Characteristic, usually
large & solitary small & multiple
Hemarthrosis Characteristic Rare
Delayed bleeding common Rare
Bleeding from sup. cuts minimal Persistent, often
& scratches profuse
Sex of patient 80-90% of Relatively more
hereditary forms M common in F
(+) family hx common rare
THANK YOU