ERYTHROCYTE DISORDERS - indicative of a true decrease

in erythrocytes and
(ANEMIAS: RED BLOOD CELL hemoglobin
MORPHOLOGY AND APPROACH
- mechanisms involved
TO DIAGNOSIS)
include:

o Decreased delivery of red

ANEMIA cells into the circulation

Etiology: “anaimia” = without blood - caused by impaired or

defective production
- decrease in erythrocytes and
hemoglobin resulting to decreased - bone marrow fails to
oxygen delivery to tissues respond; reticulocytopenia
- decrease in the oxygen-carrying
o Increased loss of red cells
capacity of the blood
from the circulation
- can arise if there is insufficient
hemoglobin or the hemoglobin has - acute bleeding
impaired function
- defined operationally as reduction - accelerated destruction
in the hemoglobin content of (hemolytic)
blood that can be caused by a
decrease in RBC’s, hemoglobin, and  MODERATE ANEMIA
hematocrit below the reference
range - Hemoglobin concentration of 7-
10g/dL

HOW ANEMIAS ARE CLASSIFIED? - May cause pallor of conjunctivae

and nail beds
 MORPHOLOGICALLY
 MCV - S/S: dyspnea, vertigo, headache,
 MCH muscle weakness and lethargy
 MCHC
 ETIOLOGY/CAUSE
 SEVERE ANEMIA

- Hemoglobin concentration below

TYPES OF ANEMIA 7g/dL
 RELATIVE (PSEUDO) ANEMIA - S/S: symptoms of moderate
anemia, tachycardia, hypotension
- RBC mass is normal, but plasma
volume is increased

- secondary to an unrelated PATIENT HISTORY AND

condition and can be transient in
CLINICAL FINDINGS
nature
 SKIN (PETECHIAE)
- reticulocyte count is normal;
normocytic/normochromic  EYES (PALLOR, JAUNDICE, AND
anemia HEMORRHAGE)

CAUSES:  MOUTH (MUCOSAL BLEEDING)

 STERNAL TENDERNESS
o Conditions that result in
 LYMPHADENOPATHY
hemodilution (pregnancy
and volume overload)  CARDIAC MURMURS
 SPLENOMEGALY
 ABSOLUTE ANEMIA
 HEPATOMEGALY
- RBC mass is decreased, but
plasma volume is normal
HUMAN BODY ADAPTATIONS TO CAUSES:
ANEMIA
 Deficiency of iron (inadequate
 Anemia Caused by Sudden Loss of intake, malabsorption,
Blood Volume (mins to hours) excessive loss from chronic
bleeding)
 Increased in heart rate,  Deficiency of erythropoietin
respiratory rate, and cardiac (renal disease)
output  Loss of erythroid precursors
 Redistribution of blood flow due to an autoimmune
from skin and viscera to heart, reaction (aplastic anemia,
brain and muscle acquired pure red cell
aplasia)
 Anemia Caused by Slow Loss of  Infection (parvovirus B19)
Blood (days to weeks)  Infiltration of the bone
marrow with granulomas
 Decreased in hemoglobin-oxygen (sarcoidosis) or malignant
affinity by increasing the cells (leukemia)
production of 2,3 DPG/BPG
 Increased in erythropoietin
production by kidneys 2. BLOOD LOSS AND HEMOLYSIS

- anemia can also develop as a

result of acute blood loss
MECHANISMS OF ANEMIA (traumatic injury) or chronic blood
loss (bleeding colonic polyp)
1. INEFFECTIVE AND INSUFFICIENT
ERYTHROPOIESIS - increased hemolysis results in a
shortened RBC lifespan
- normal erythropoiesis occurs in
the bone marrow and is under the
control of erythropoietin
PATHOPHYSIOLOGIC
- ineffective erythropoiesis refers
CLASSIFICATION OF ANEMIA
to the production of erythroid
precursor cells that are defective I. IMPAIRED PRODUCTION

- these defective precursors often A. IMPAIRED STEM CELL

undergo apoptosis in the bone
marrow before they mature into
reticulocyte and be released into the
peripheral circulation
CONDITIONS:
 Megaloblastic anemia (deficient DNA
synthesis due to vitamin B12 or
folate deficiency)
 Thalassemia (deficient globin chain
synthesis)
 Sideroblastic anemia (deficient
protoporphyrin synthesis)
- insufficient erythropoiesis refers
to a decrease in the number of
erythroid precursors in the bone
marrow, resulting in decreased
RBC production and anemia
PROLIFERATION/DIFFERENTIATION
 APLASTIC ANEMIA
 PURE RED CELL APLASIA
 ENDOCRINE DEFICIENCY
 PITUITARY
 THYROID
 ADRENAL
 TESTIS
B. IMPAIRED ERYTHROBLAST
PROLIFERATION/DIFFERENTIATION
 MEGALOBLASTIC ANEMIA
 VIT. B12 DEFICIENCY
 FOLIC ACID DEFICIENCY
 HYPOCHROMIC ANEMIA
 IRON DEFICIENCY ANEMIA
 SIDEROBLASTIC ANEMIA
 THALASSEMIA
  MULTIPLE MECHANISMS  VENOM
 CHRONIC DISEASE  SNAKE
(INFLAMMATORY, INFECTIOUS,  INSECTS
NEOPLASTIC)
 RENAL FAILURE
 MYELOPHTHISIC ANEMIA III. BLOOD LOSS
(BONE MARROW INFILTRATION) A. ACUTE
 REFRACTORY ANEMIA WITH B. CHRONIC
CELLULAR BONE MARROW
 PROTEIN MALNUTRITION

LABORATORY DIAGNOSIS OF
II. INCREASED DESTRUCTION ANEMIA
A. INTRINSIC 1. COMPLETE BLOOD COUNT WITH RBC
INDICES
 HEREDITARY CELL MEMBRANE
DEFECT - to detect the presence of anemia,
 SPHEROCYTOSIS one must determine:
 ELLIPTOCYTOSIS
 STOMATOCYTOSIS  RBC COUNT
 HEMOGLOBIN
 PAROXYSMAL NOCTURNAL CONCENTRATION
HEMOGLOBINURIA (PNH)  HEMATOCRIT
 RBC INDICES
 ENZYMOPATHIES  WBC COUNT
 G-6-P-D DEFICIENCY  PLATELET COUNT
 PYRUVATE KINASE  RDW
DEFICIENCY  RETICULOCYTE COUNT

2. RETICULOCYTE COUNT
 HEMOGLOBINOPATHIES
 HEMOGLOBIN S DISEASE - serves as an important tool to
 HEMOGLOBIN C DISEASE assess the bone marrow’s ability
 HEMOGLOBIN E DISEASE to increase RBC production in
response to anemia
 PORPHYRIAS
 INCREASED
B. EXTRINSIC
- considered as the first sign of
 ANTIBODY-MEDIATED
accelerated erythropoiesis
 AUTOIMMUNE HEMOLYTIC
ANEMIA (IgG) - observed in hemolytic anemias,
 COLD-REACTING ANTIBODIES individuals with iron deficiency
(IgM) anemia, thalassemia, sideroblastic
anemia, acute and chronic blood
 MECHANICAL loss
 PROSTHETIC HEART VALVE
 MICROANGIOPATHIC  DECREASED
HEMOLYTIC ANEMIA - Aplastic Anemia
 BURNS
FORMULAS FOR RETICULOCYTE
 INFECTION
COUNTS
 BACTEREMIA
 PARASITEMIA  ABSOLUTE RETICULOCYTE COUNT
(X 10ꝰ/L)
C. OTHERS
reticulocytes ( % ) x RBC count
 DRUG-INDUCED 100
 HYPERSPLENISM
 OXIDIZING AGENTS
 REFERENCE RANGE: 20-115 ∙  Abnormal cellularity
10ꝰ/L  Lack of iron on iron stains of the
bone marrow (gold standard for
diagnosis of iron deficiency)
 CORRECTED RETICULOCYTE  Presence of granulomata,
COUNT fibrosis, infectious agents, and
tumor cells
- also referred to as
“RETICULOCYTE INDEX” or
“HEMATOCRIT CORRECTION” 5. OTHER LABORATORY TESTS

 ROUTINE URINALYSIS
reticulocytes ( % ) x Hematocrit ∈L/L  STOOL ANALYSIS
0.45 L/L  CHEMISTRY TESTS
 SERUM HAPTOGLOBIN
 LACTATE DEHYDROGENASE
 UNCONJUGATED BILIRUBIN
 RETICULOCYTE PRODUCTION
 RENAL AND HEPATIC FUNCTION
INDEX
TESTS
- also known as “SHIFT  IRON STUDIES
CORRECTION”  SERUM VIT. B12 and FOLATE
ASSAYS
- provides further refinement of the  DIRECT ANTIGLOBULIN TEST
CRC

Corrected Reticulocyte Count

MaturationTime∈the Peripheral B lood IRON

- Most important metal required for

metabolic processes
- Critical to energy production in all
cells
- So critical to the body that there is
no mechanism for active
excretion
- Even recycled to conserve as much
as possible in the body
- Largest percentage (65%) is held
within the hemoglobin of the RBCs
RPI OF >3: ADEQUATE BONE MARROW - 25% is in storage, mostly within
RESPONSE macrophages and hepatocytes
- 10% in muscles, plasma,
RPI OF <2: INADEQUATE BONE MARROW cytochromes of cells, and various
RESPONSE iron-containing enzymes within cells

3. PERIPHERAL BLOOD FILM LAB ASSESSMENT OF BODY IRON

EXAMINATION STATUS

 RBC DIAMETER 1. SERUM IRON

 SHAPE
 COLOR - can be measured colorimetrically
 RBC INCLUSIONS using reagent such as FERROZINE
- iron is first released from transferrin
by acid, then the reagent is allowed
4. BONE MARROW EXAMINATION to react with the iron, forming a
colored complex that can be
- important findings in the bone detected spectrophotometrically
marrow that could point to
underlying cause of anemia:
 - has limited utility on its own of erythropoiesis in the prior 24-
because of its high within day and hour period
between-day variability - amount of hemoglobin in
- increased after recent ingestion of reticulocytes provide a near real-
iron-containing foods and time assessment of iron available for
supplements hemoglobin production
- specimen: fasting and early in the
morning (when levels are expected 7. ZINC PROTOPORPHYRIN (ZPP)
to be higher)
- accumulates in RBCs when iron is
not incorporated into heme and zinc
2. TOTAL IRON BINDING CAPACITY (TIBC) binds instead to protoporphyrin
IX
- amount of iron in plasma/serum - easily detected with fluorescence
that will be limited by the amount
of transferrin that is available to
carry it
- transferrin is maximally saturated MORPHOLOGIC CLASSIFICATION OF
by addition of excess ferric iron to ANEMIA BASED ON MEAN CELL
the specimen VOLUME (MCV)
- any unbound iron is removed by
precipitation with magnesium 1. MICROCYTIC ANEMIA
carbonate powder - characterized by an MCV of
- the amount of iron detected <80fL with small RBCs (<6um)
represents all the binding sites - often associated with
available on transferrin hypochromia
- indirect measure of transferrin - RBCs with increased central
pallor
- MCHC: <32g/dL
3. % TRANSFERRIN SATURATION - DEFECTIVE HEME SYNTHESIS
 IRON DEFICIENCY
- Serum Iron/ TIBC X 100% = %  CHRONIC INFLAMMATORY
Transferrin Saturation STATES
- About 1/3 of transferrin is  DEFECTIVE
typically saturated with iron PROTOPORPHYRIN
SYNTHESIS
4. PRUSSIAN BLUE STAINING o SIDEROBLASTIC
- Reagent: PRUSSIAN BLUE ANEMIA
- ferric iron in the tissue reacts with o LEAD POISONING
the reagent forming the Prussian  DEFECTIVE GLOBIN CHAIN
Blue compound that is readily seen SYNTHESIS
microscopically dark blue dots o THALASSEMIA
- considered as gold standard for o HEMOGLOBIN E
assessment of body iron DISEASE

5. FERRITIN 2. MACROCYTIC ANEMIA

- characterized by an MCV of
- convenient assessment of body
>100fL with large RBCs (>8um)
iron stores
- arise from conditions that result
- the level of serum ferritin has been
in megaloblastic or non-
shown to correlate highly with
megaloblastic red cell
stored iron
development in the bone marrow
- an acute phase reactant
A. MEGALOBLASTIC ANEMIA
6. HEMOGLOBIN CONTENT OF
 caused by conditions that
RETICULOCYTES
impair the synthesis of DNA
- number of circulating o VIT. B12 DEFICIENCY
reticulocytes represent the status o FOLATE DEFICIENCY
 o THIAMINE NON-IMMUNE RBC

DEFICIENCY INJURY
o MYELODYSPLASIA  MCV between 80-100fL
o ERYTHROLEUKEMIA  If RETIC Ct is
o SOME DRUGS NORMAL/DECREASED:
o APLASTIC ANEMIA
 CHARACTERISTICS: o ANEMIA OF RENAL
o Oval macrocytes DISEASE
o Hypersegmented o MYELOPHTHISIC
neutrophils in the ANEMIA
peripheral blood o INFECTION
o Megaloblasts or large (PARVOVIRUS B19)
nucleated RBC o ANEMIA OF CHRONIC
precursors in the bone INFLAMMATION
marrow
o MCV can be markedly
increased up to 150Fl GENERAL CONCEPTS IN ANEMIA

B. NONMEGALOBLASTIC ANEMIA - Anemia may result whenever:

 due to disruption of the  RBC PRODUCTION IS
cholesterol-to-phospholipid IMPAIRED,
ratio  RBC LIFESPAN IS
o APLASTIC ANEMIA/ SHORTENED, or
BONE MARROW  there is FRANK LOSS OF
FAILURE CELLS
o CHRONIC LIVER
DISEASE
IMPAIRED OR DEFECTIVE
o ALCOHOL
ABUSE/ALCOHOLISM PRODUCTION ANEMIAS
o OBSTRUCTIVE A. IRON DEFICIENCY ANEMIA
JAUNDICE - Most common form of anemia
o POST-SPLENECTOMY in the United States
o RETICULOCYTOSIS - Develops when the intake of iron
o HYPOTHYROIDISM is inadequate to meet a standard
o MYELOPROLIFERATIV level of demand, when the need
E DISEASE for iron expands without
o DRUGS compensated intake, when there
is impaired absorption, or when
 CHARACTERISTICS: there is chronic loss of
o round macrocytes hemoglobin from the body.
o MCV: greater than
115Fl  CAUSES:
o Inadequate intake
C. NORMOCYTIC ANEMIA o Increased need
 MCV between 80-100fL o Impaired absorption
 If RETIC Ct is INCREASED o Chronic Blood Loss
(HEMOLYTIC ANEMIA):
o INTRINSIC - Prevalent in infants and
 MEMBRANE children, pregnancy, excessive
DEFECTS menstrual flow, elderly with poor
 HEMOGLOBINOPA diets, malabsorption syndromes,
THIES and chronic blood loss (GI blood
 ENZYME loss, hookworm infection)
DEFICIENCIES
o EXTRINSIC  TREATMENT
 IMMUNE o Treat any underlying
MEDIATED contributing cause
 o STANDARD PRESCRIPTION: o Without reticulocytosis
oral supplements of ferrous o Cells are usually
sulfate (3 tablets/day NORMOCYTIC/NORMOCHR
containing 65mg of elemental OMIC or MICROCYTIC
iron) HYPOCHROMIC
o In cases of impaired o With leukocytosis,
intestinal absorption: thrombocytosis or both
parenteral administration of
iron dextrans can be used  TREATMENT
o Red Blood Cell transfusion: o ADMINISTRATION OF
rarely used unless patients ERYTHROPOIETIN, WITH
hemoglobin levels become CONCURRENT
dangerously low ADMINISTRATION OF IRON

 LABORATORY DIAGNOSIS OF C. SIDEROBLASTIC ANEMIA

IDA - Caused by blocks in the
protoporphyrin pathway
resulting in defective hemoglobin
synthesis and iron overload
- Excess iron accumulates in the
mitochondrial region of the
immature erythrocyte in the
bone marrow and encircles the
nucleus and these are called
ringed sideroblasts
- Excess iron accumulates in the
mitochondrial region of the
mature erythrocyte in
circulation and these cells are
called as siderocytes; inclusions
B. ANEMIA OF CHRONIC
are called siderotic granules/
INFLAMMATION
Pappenheimer bodies
- Due to inability to use available
iron for hemoglobin TYPES OF SIDEROBLASTIC
production ANEMIA (ACQUIRED)
- Impaired release of storage iron
associated with increased o PRIMARY
hepcidin levels
- IRREVERSIBLE; cause of
- Associated with persistent
the blocks are unknown
infections, chronic inflammatory
disorders (SLE, rheumatoid - 2 RBC populations
arthritis, Hodgkin’s (dimorphic) is seen
lymphoma, cancer)
- 2nd most common cause of o SECONDARY
anemia
- REVERSIBLE
 LABORATORY DIAGNOSIS -causes: ALCOHOL, ANTI-TB
DRUGS,
CHLORAMPHENICOL,
ISONIAZID, LEAD,
CHEMOTHERAPEUTIC
AGENTS, COPPER
DEFICIENCY and ZINC
EXCESS
o Mild anemia
o Hemoglobin concentration
usually 8-10g/dL
  LABORATORY DIAGNOSIS
 TREATMENT
o SALTS OF EDTA: used to
chelate the lead present in
the body so it can be excreted
in the urine

E. PORPHYRIAS
- Group of inherited disorders
characterized by a block in the
protoporphyrin pathway of heme
 TREATMENT synthesis; heme precursors
o PYRIDOXINE: cofactor in before the block accumulate in
the first step of porphyrin the tissues and large amounts
synthesis are excreted in urine and feces
- Derived from Greek word
D. LEAD POISONING “porphyra”=purple
- Lead interferes with porphyrin - Clinical symptoms:
synthesis at several steps Photosensitivity, Abdominal
including: pain, CNS disorders
o Conversion of ALA to PBG by TYPES OF PORPHYRIA
ALA DEHYDRATASE/PBG
SYNTHASE leading to o ACQUIRED PORPHYRIAS
accumulation of ALA  LEAD
o Incorporation of iron into POISONING/PLUMBIS
protoporphyrin IX by M
ferrochelatase/heme
- Lead inhibits
synthase leading to
pyrimidine 5’
accumulation of iron and
nucleotidase and
protoporphyrin
ferrochelatase
- Seen mostly in children exposed
to lead-based paints - LAB PROFILE:
- Clinical symptoms: Abdominal hypochromic RBCs
pain, muscle weakness, and a with basophilic
gum lead line that forms stipplings; toxic
blue/black deposits of lead granulation in
sulfate neutrophils
- Most often
NORMOCYTIC/NORMOCHROM  PORPHYRIA CUTANEA
IC but with chronic exposure, it TARDA
can lead to
MICROCYTIC/HYPOCHROMIC - maybe acquired or
blood picture inherited
- Expected inclusion: - CLINICAL
BASOPHILIC STIPPLINGS FEATURE:
PHOTOSENSITIVIT
 LABORATORY DIAGNOSIS Y

o HEREDITARY PORPHYRIAS
 ACUTE
INTERMITTENT
PORPHYRIA
 CONGENITAL
ERYTHROPOIETIC
PORPHYRIA (CEP)
  HEREDITARY
COPROPORPHYRIA
 VARIEGATE o STAGE 2
PORPHYRIA  characterized by
 ERYTHROPOIETIC exhaustion of the
PROTOPORPHYRIA storage pool of iron
(EPP)  hemoglobin content of
 POPHYRIA CUTANEA reticulocytes begins to
TARDA decrease, but overall
 X-LINKED hemoglobin measurement
ERYTHROPOIETIC is still normal
PROTOPORPHYRIA  RDW may begin to
(XLEPP) increase
 serum iron and ferritin
levels are DECREASED
 TIBC is INCREASED

o STAGE 3
 “FRANK ANEMIA”
 hemoglobin and
hematocrit are relatively
LOW
 levels of STORAGE and
TRANSPORT IRON are
DIMINISHED
 RBCs become microcytic
and hypochromic
 serum ferritin levels are
REVIEW! EXCEEDINGLY LOW
 FEP and transferrin
 STORAGE COMPARTMENT: receptors continue to
principally as FERRITIN in the INCREASED
bone marrow macrophages and  patient experiences non-
liver cells specific symptoms of
 TRANSPORT COMPARTMENT: anemia (fatigue,
as serum TRANSFERRIN weakness, shortness of
 FUNCTIONAL COMPARTMENT: breath, pallor, glossitis,
as HEMOGLOBIN, MYOGLOBIN, stomatitis/cheilosis,
and CYTOCHROMES koilonychias and pica)

F. STAGES OF IRON DEPLETION G. IRON OVERLOAD

o STAGE 1 - Body’s rate of iron acquisition
 progressive loss of exceeds the rate of loss, which is
storage iron usually about 1mg/day
 there is no evidence of
 CAUSES:
iron deficiency in the
o Repeated transfusions
peripheral blood
 patient does not (transfusion-related
experience any symptoms hemosiderosis)
of anemia o Sickle cell anemia
 serum ferritin levels are o B-thalassemia major
decreased o Hereditary Hemochromatosis:
 also called as the mutations to genes for the
“LATENT/SUBCLINICAL proteins of iron metabolism;
IRON DEFICIENCY most common form of iron
STAGE” overload disease
  COMPETITION FOR THE
 LABORATORY DIAGNOSIS VITAMIN
o SCREENING TEST  LATUM INFECTION
 SERUM FERRITIN:  BLIND LOOP SYNDROME
INCREASED
 TRANSFERRIN SATURATION: o FOLATE DEFICIENCY
INCREASED  INADEQUATE INTAKE
 TREATMENT  INCREASED NEED
o AVOIDING FOODS THAT  IMPAIRED ABSORPTION
CONTAIN IRON  IMPAIRED USE DUE TO
o PHLEBOTOMY DRUGS
o DESFERRIOXAMINE/DESFERA  EXCESSIVE LOSS WITH
L RENAL DIALYSIS

o OTHER CAUSES OF
MEGALOBLASTOSIS
ANEMIAS CAUSED BY DEFECTS OF
 MYELODYSPLASTIC
DNA METABOLISM SYNDROMES
A. MEGALOBLASTIC ANEMIA  ACUTE ERYTHROID
LEUKEMIA
- Hallmark of the diseases  CONGENITAL
affecting DNA metabolism DYSERYTHROPOIETIC
ANEMIA
- Root cause is impaired DNA  REVERSE TRANSCRIPTASE
synthesis INHIBITORS
- Characterized by very large cells
of the bone marrow that develops o CLINICAL SYMPTOMS OF
distinctive morphology VIT. B12 DEFICIENCY
 JAUNDICE
- Defective DNA synthesis causes  WEAKNESS
abnormal nuclear maturation;  GLOSSITIS
RNA synthesis is normal, so the  GASTROINTESTINAL
cytoplasm is not affected. The DISORDER
nucleus matures slower than the  NUMBNESS
cytoplasm (asynchronism)  OTHER CNS PROBLEMS

- Main cause: Vit. B12 deficiency o CLINICAL SYMPTOMS OF

and Folate deficiency
FOLATE DEFICIENCY
 CAUSES:  MEGALOBLASTIC ANEMIA
o VIT. B12 DEFICIENCY WITH BLOOD PICTURE AND
 INADEQUATE INTAKE SYMPTOMS SIMILAR TO VIT.
 INCREASED NEED B12 DEFICIENCY EXCEPT
 IMPAIRED ABSORPTION THERE IS NO CNS
 FAILURE TO SPLIT FROM INVOLVEMENT
FOOD  ASSOCIATED WITH:
 FAILURE TO SPLIT FROM  POOR DIET
HAPTOCORRIN  PREGNANCY
 LACK OF INTRINSIC  CHEMOTHERAPEUTIC
FACTOR ANTI-FOLIC ACID DRUGS
 GENERAL MALABSORPTION (METHOTREXATE)
 INHERITED ERRORS IN
ABSORPTION OR  LABORATORY DIAGNOSIS OF
TRANSPORT MEGALOBLASTIC ANEMIA
 IMERSLUND-GRASBECK o SCREENING TESTS
SYNDROME  CBC: slight macrocytosis is
 TRANSCOBALAMIN the earliest sign of
DEFICIENCY megaloblastic anemia
 (+) oval macrocytes
  (+) hypersegmented BONE MARROW FAILURE
neutrophils (6 or more
lobes) - Reduction or cessation of blood
 RETICULOCYTE COUNT: low production affecting one or more
absolute reticulocyte count cell lines
 WBC DIFFERENTIAL COUNT:
- PANCYTOPENIA: decreased
hypersegmentation of
numbers of circulating
neutrophils is
RBCs/WBCs/Platelets
pathognomonic for
megaloblastic anemia
 SERUM BILIRUBIN: elevated  PATHOPHYSIOLOGY
total and indirect bilirubin o Destruction of hematopoietic
 LACTATE stem cells due to injury by
DEHYDROGENASE: elevated drugs, chemicals, radiation,
values viruses, or autoimmune
mechanisms
 SEQUENCE OF DEVELOPMENT OF o Premature senescence and
MEGALOBLASTIC ANEMIAS apoptosis of hematopoietic stem
1. Decrease in vitamin levels cells due to genetic mutations
2. Hypersegmentation of o Ineffective hematopoiesis due
neutrophils in peripheral blood to stem cell mutations or Vit.
3. Oval macrocytes in peripheral B12 or folate deficiency
blood o Disruption of the bone marrow
4. Megaloblastosis in bone marrow microenvironment
5. Anemia o Decreased production of
hematopoietic growth factors or
 TREATMENT related hormones
o BETTER NUTRITION o Loss of normal hematopoietic
o TREATMENT FOR D. LATUM tissue due to infiltration of the
o HIGH DOSE ORAL VIT. marrow space with abnormal
B12/FOLIC ACID cells
o IRON SUPPLEMENTS
A. APLASTIC ANEMIA
B. NON-MEGALOBLASTIC
MACROCYTIC ANEMIA - Rare, but potentially fatal bone
 CAUSES: marrow failure syndrome
o Alcoholism - Disease was given name by
o Liver disease Vaquez and Aubertin in 1904
o Bone Marrow Disorder/Failure
- Can occur at any age with peak
incidence at 15-25 years and 2nd
highest frequency at greater than
60 years

 Characteristic features:
o PANCYTOPENIA
o RETICULOCYTOPENIA
o BM HYPOCELLULARITY
o DEPLETION OF HSC’S
 2 TYPES
o ACQUIRED (80-85% of cases)
o INHERITED (15-20% of cases)

a. ACQUIRED APLASTIC ANEMIA

o IDIOPATHIC (70% of cases)
o SECONDARY (10-15% of
cases)
 CYTOTOXIC DRUGS
  BENZENE globulin and cyclosporine is used
 HERBICIDE/INSECTICID for patients older than 40 years
E of age and for patients without
 CUTTING/LUBRICATING an HLA-identical sibling
OILS
 ANTIBIOTICS:  DIAGNOSTIC CRITERIA FOR
CHLORAMPHENICOL and APLASTIC ANEMIA
SULFONAMIDES
 RADIATION/
CHEMOTHERAPY
 VIRUSES: PARVOVIRUS
B19, HEPATITIS VIRUS,
MEASLES, CMV, EBV,
HIV
 MISCELLANEOUS
CONDITIONS:
AUTOIMMUNE
DISEASES, PREGNANCY
 MYELODYSPLASTIC
SYNDROMES:
LEUKEMIA, SOLID
TUMORS, PNH B. INHERITED APLASTIC ANEMIA
 FANCONI ANEMIA
 CLINICAL FINDINGS IN  DYSKERATOSIS CONGENITA
ACQUIRED APLASTIC ANEMIA  SCHWACHMAN-BODIAN-DIAMOND
o Insidious-onset anemia SYNDROME
o Pallor
o Fatigue a. FANCONI ANEMIA
o Weakness o Chromosomal instability
o Serious cardiovascular disorder characterized by
complications (tachycardia, aplastic anemia, physical
hypotension, cardiac failure, abnormalities, and cancer
death) susceptibility
o Thrombocytopenia (bruising, o With 3-fold higher prevalence
epistaxis, mucosal bleeding, in the Ashkenazi Jews and
menorrhagia, retinal South Africans
hemorrhages, intestinal bleeding, o Most common of the inherited
intracranial hemorrhage) aplastic anemias

 LABORATORY FINDINGS  CLINICAL FINDINGS IN FANCONI

o PANCYTOPENIA ANEMIA
o Hemoglobin: <10g/dL o Physical malformations
o MCV: INCREASED/NORMAL o Skeletal abnormalities
o RBCs are MACROCYTIC or  Thumb malformations
NORMOCYTIC  Radial hypoplasia
o TOXIC GRANULATION may be  Microcephaly
observed in neutrophils  Hip dislocation
o (-) CD55 and CD59  Scoliosis
o Skin pigmentation
 TREATMENT  Hyperpigmentation
o HSCT: treatment of choice for  Hypopigmentation
patients with severe aplastic  Café-au-lait lesions
anemia who are younger than 40 o Short stature
years of age and have an HLA- o Abnormalities of the eyes,
identical sibling kidneys, and genitals
o Imunosuppressive therapy o Pancytopenia
consisting of anti-thymocyte o Increased cancer risk
 o ELEVATED HEMOGLOBIN F
o HYPOCELLULAR BONE
 LABORATORY FINDINGS IN MARROW (usually)
FANCONI ANEMIA  TREATMENT
o PANCYTOPENIA o G-CSF
o RETICULOCYTOPENIA o TRANSFUSION
o HYPOCELLULAR BONE o ENZYME REPLACEMENT
MARROW o BM TRANSPLANT
o STRIKINGLY ELEVATED
HEMOGLOBIN F
o INCREASED AFP
OTHER FORMS OF BONE MARROW
 TREATMENT
FAILURE
o ADMINISTRATION OF
CYTOKINES A. PURE RED CELL APLASIA
o HSCT: only curative treatment
- Rare disorder of erythropoiesis
characterized by selective and severe
decrease in erythrocyte precursors
b. DYSKERATOSIS CONGENITA
in an otherwise normal bone
o Rare inherited bone marrow
marrow.
failure syndrome with fewer
than 600 cases known cases  CLINICAL FINDINGS
worldwide. o Severe anemia (usually
normocytic)
 CLINICAL FINDINGS o Reticulocytopenia
o Mucocutaneous abnormalities o Normal WBC and Platelet
o Bone marrow failure count
o Pancytopenia
o Abnormal skin pigmentation a. ACQUIRED PURE RED CELL
o Dystrophic nails APLASIA
o Oral leukoplakia o May occur in children or adults
o Multisystem abnormalities  PRIMARY PRCA
 IDIOPATHIC
c. SHWACHMAN-BODIAN-DIAMOND  AUTOIMMUNE-RELATED
SYNDROME  SECONDARY PRCA
o Is an inherited multisystem  UNDERLYING THYMOMA
disorder characterized by  HEMATOLOGIC
pancreatic insufficiency, MALIGNANCY
cytopenia, skeletal  SOLID TUMOR
abnormalities, and a  INFECTION
predisposition for hematologic  CHRONIC HEMOLYTIC
malignancies ANEMIA
 COLLAGEN VASCULAR
 CLINICAL FINDINGS DISEASE
o Peripheral blood cytopenia  EXPOSURE TO DRUGS
o Decreased pancreatic enzyme OR CHEMICALS
secretion
o Neutropenia  TREATMENT
o Immune dysfunction o IMMUNOSUPPRESSIVE
o Increased risk of severe THERAPY
infections  CYCLOSPORINE
o Sepsis  CORTICOSTEROIDS
o RED CELL TRANSFUSION
 LABORATORY FINDINGS
o NEUTROPENIA b. CONGENITAL PURE RED CELL
APLASIA: DIAMOND-BLACKFAN
o ANEMIA
ANEMIA
o THROMBOCYTOPENIA
 o A congenital erythroid o Caused by mutations in the
hypoplastic disorder of early SEC23B gene on chromosome
infancy with an estimated 20
incidence of 7-10 cases/ million o RBCs are normocytic with
live births anisocytosis, poikilocytosis, and
basophilic stippling
 CLINICAL FINDINGS o Occasional pseudo-Gaucher
o PHYSICAL ANOMALIES cells are also evident
 CRANIOFACIAL o Circulating RBCs hemolyzed
DYSMOPHISMS with Ham’s acidified serum
 SHORT STATURE test but not with sucrose
 NECK AND THUMB hemolysis test
MALFORMATIONS o Also known as: HEMPAS
o SEVERE MACROCYTIC ANEMIA
WITH RETICULOCYTOPENIA c. CDA III
o Least common of the subtypes
B. CONGENITAL  Familial autosomal
DYSERYTHROPOIETIC ANEMIA dominant form is caused by
mutations in the KIF23
- Heterogeneous group of rare
gene
disorders characterized by
 Non-familial form is also
refractory anemia, reticulocytopenia,
known as sporadic form
hypercellular bone marrow with
o Characteristic feature:
markedly ineffective erythropoiesis,
 RBCs are macrocytic;
and distinctive dysplastic changes
poikilocytosis and basophilic
in bone marrow erythroblast
stippling are evident
 CLINICAL FINDINGS  BM has megaloblastic
o JAUNDICE changes, and giant
o CHOLELITHIASIS erythroblasts with up to 12
o SPLENOMEGALY nuclei are present

a. CDA I C. MYELOPHTHISIC ANEMIA

o Inherited autosomal recessive
o Characterized by mild to severe
chronic anemia
o Caused by mutations in the CDAN-
1 gene on chromosome 15
o Malformations of fingers and toes,
brown skin pigmentation, and
neurologic defects are found more
frequently in CDA I
o RBCs are macrocytic and may
exhibit marked poikilocytosis,
basophilic stippling, and Cabot
rings
o Erythroblasts are megaloblastoid
and have internuclear chromatin  CLINICAL FINDINGS
bridges or nuclear stranding
o Characteristic feature of CDA I
erythroblast: spongy
heterochromatin with “Swiss
cheese” appearance
- Hypoproliferative anemia due to
infiltration of abnormal cells into the
bone marrow and subsequent
destruction and replacement of
normal hematopoietic cells
- Associated with cancers with
bone metastasis
- Disruption of normal bone
marrow architecture by the
infiltrating cells, the marrow
releases immature hematopoietic
cells
o Mild to moderate anemia
o Normocytic RBCs
o Reticulocytopenia
o Teardrop cells and nucleated
RBC’s

b. CDA II D. ANEMIA OF CHRONIC KIDNEY

o Most common subtype DISEASE
o Inherited autosomal recessive
 o Anemia is a common
complication of chronic kidney
disease
o Primary cause of anemia in CKD
is inadequate renal production
of erythropoietin
o Another contributor is UREMIA,
which inhibits erythropoiesis and
increases RBC fragility
o Patients experience chronic
blood loss and iron deficiency
from hemodialysis and frequent
blood draws
o NORMOCYTIC/NORMOCHROM
IC with reticulocytopenia
o BURR CELLS are common
findings in cases complicated
with uremia

BLOOD LOSS ANEMIA

A. ACUTE BLOOD LOSS ANEMIA

- Characterized by sudden loss of

blood resulting from trauma or
other severe forms of injury

- Clinical symptoms: Hypovolemia,

rapid pulse, low blood pressure,
pallor

 LABORATORY FINDINGS:
o NORMOCYTIC/NORMOCHROMI
C ANEMIA
o Normal RETICULOCYTE COUNT
and H/H (initially)
o Increased in PLATELET COUNT
and LEUKOCYTOSIS (after a few
hours)
o Shift to the left, drop in H/H and
RBC COUNT
o RETICULOCYTOSIS in 3-5 days

B. CHRONIC BLOOD LOSS ANEMIA

- Characterized by gradual, long-

term loss of blood; often caused by
gastrointestinal bleeding

 LABORATORY FINDINGS
o NORMOCYTIC/NORMOCHROMI
C ANEMIA (initially)
o Decreased in H/H
o Gradual loss of iron
(MICRO/HYPO)