ANEMIA: A

SYNTHESIS
DDC Medical Laboratory
Science Program
OBJECTIVES
At the end of the lecture, students are expected to articulate the:

• Basic and Fundamentals of anemia

• Different types of anemia
• Pathophysiology of each type of anemia
• Mechanisms involved in each type of anemia
I. ANEMIA CAUSED BY DEFECTS IN
DNA METABOLISM
Impaired DNA production

Megaloblastic anemia - HALLMARK OF THE DISEASE AFFECTING DNA METABOLISM

Increased size of precursors cells due to REDUCED CELL DIVISIONS

I. ANEMIA CAUSED BY DEFECTS IN
DNA METABOLISM
Vitamin B12
Consists of a CORRIN RING
Two Roles:
1st role
METHYLMALONYL COENZYME to SUCCINYL
• Isomeration of COA
• Absence of Vitamin B12 = increased METHYLMALONIC ACID
I. ANEMIA CAUSED BY DEFECTS IN
DNA METABOLISM
I. ANEMIA CAUSED BY DEFECTS IN
DNA METABOLISM
2nd role
o Transfer of a methyl group 5 METHYL THF to HOMOCYSTEINE

o Catalysis by METHIONINE SYNTHASE

o Vitamin B12 acts as coenzyme in the form METHYLOCOBALAMIN

I. ANEMIA CAUSED BY DEFECTS IN
DNA METABOLISM
I. ANEMIA CAUSED BY DEFECTS IN
DNA METABOLISM
Folate
Consists of PTERIDINE RING
Responsible for the transfer of carbon units in the form of methyl groups.
Involved in the metabolism of AMINO ACIDS and NUCLEOTIDES
Circulates as 5 – METHYL THF
Regeneration of THF: DIHYDROFOLATE TO
TETRAHYDROFOLATE
I. ANEMIA CAUSED BY DEFECTS IN
DNA METABOLISM
PLASM
A

Folate
(5 Methyl
(THF) CYTOPLAS
M FOLATE
Folate M homocysteine methionine TRAP
(5 Methyl
(THF) B1 Methionine
synthase
2 B1
Dihydrofolate THF
reductase 2
THF
DHF Thyymidylate Serine
syntthsase serine hydroxymethyl
transferase
M
dITP dTMP dUMP M 5,10 methylene THF B6
glycine
I. ANEMIA CAUSED BY DEFECTS IN
DNA METABOLISM
Pathophysiology:
• Vitamin B12 THYMIDINE NUCLEOTIDE
production
• Folate – Direct effect

• When vitamin B12 is deficient, Folate becomes trapped as 5 METHYL THF FOLATE TRAP
I. ANEMIA CAUSED BY DEFECTS IN
DNA METABOLISM

Thymidine

Uridine

NONFUNCTIO
N DNA
 I. ANEMIA CAUSED BY DEFECTS IN
DNA METABOLISM

RNA production is
not affected
because it uses
URACIL instead of
thymidine.
NUCLEO-CYTOPLASMIC
ASYCHRONY
I. ANEMIA CAUSED BY DEFECTS IN
DNA METABOLISM
MYELODYSPLASTIC SYDROMES (MDS)
✔ Delayed cytoplasmic and nuclear maturation
✔ Vacuoles
✔ Multinucleation

CONGENITAL DYSERYTHROPOIETIC ANEMIA (CDA)

✔ Type I and II
✔ Common in Childhood
✔ CDA I – INTERNUCLEARofBRIDGING
erythroid cells
I. ANEMIA CAUSED BY DEFECTS IN
DNA METABOLISM
✔ CDA III – GIANT MULTINUCLEAR ERYTHROCYTES

FABM6 (Acute Erythroid)

✔ Increased MYELOBLASTS
I. ANEMIA CAUSED BY DEFECTS IN
DNA METABOLISM
Clinical Findings:
MARKED ANEMIA
✔ Fatigue
✔ Exercise intolerance
✔ Progressive cardiac decompensation
NEUROPATHY
✔ Demyelination of the neurons of the CNS
✔ PARESTHESIAS of the hands and feet
✔ Memory loss
✔ Personality changes
✔ FOCAL DORSAL COLUMN and CORTICOSPINAL LESIONS
I. ANEMIA CAUSED BY DEFECTS IN
DNA METABOLISM
Laboratory Diagnosis:
MCV: 100 to 150
Screening Tests fL
✔ Complete Blood Count
✔ Reticulocyte count
✔ WBC count
✔ Serum Bilirubin
✔ Lactate Dehydrogenase
I. ANEMIA CAUSED BY DEFECTS IN
DNA METABOLISM
Peripheral Blood Smear
✔ OVAL MACROCYTES
✔ HYPERSEGMENTATION

Bone marrow
✔ Confirmatory test for diagnosis of MEGALOBLASTIC APPEARANCE
✔ Asynchrony of the POLYCHROMATOPHILIC NORMOBLASTS
I. ANEMIA CAUSED BY DEFECTS IN
DNA METABOLISM
Assays
ANTI-INTRINSIC
ANTI-INTRINSIC
✔ – autoantibodies against parietal cells, IF and
FACTOR
FACTOR IF, important in the diagnosis of PERNICIOUS
cobalamin PERNICIOUS ANEMIA
ANEMIA

✔ SERUM
SERUM GASTRIN
GASTRIN – determines ACHLORHYDRIA
measures the pH, and the
method used is CHEMILUMINISCENSE IMMUNOMETRIC ASSAY

✔ SCHILLINGS TEST – determines the nature of the Vitamin B12

malabsorption defect. Uses RADIOLABELED CYANOCOBALAMIN
. .No longer
used.
I. ANEMIA CAUSED BY DEFECTS IN
DNA METABOLISM
SCHILLINGS TEST Increased RB12
(Diet problem)
First Stage
Ingestion of
Radiolabeled 24 hours
cyanocobalamin

Injection of Decreased RB12

Unlabeled (absorption
cyanocobalamin problem)
Saturate the B12
receptors in the
liver
I. ANEMIA CAUSED BY DEFECTS IN
DNA METABOLISM
SCHILLINGS TEST
Second Stage Increased RB12
(Pernicious
Ingestion of anemia)
24 hours
Radiolabeled
cyanocobalamin
+ instrinsic factor
No dietary and
Intrinsic Factor
Deficiency
I. ANEMIA CAUSED BY DEFECTS IN
DNA METABOLISM
SCHILLINGS TEST
Third Stage Increased RB12
(Bacterial
Ingestion of overgrowth)
24 hours
Radiolabeled
cyanocobalamin
+ antibiotics

No dietary and
Intrinsic Factor
Deficiency
No bacterial
overgrowth
I. ANEMIA CAUSED BY DEFECTS IN
DNA METABOLISM
SCHILLINGS TEST
Fourth Stage
Ingestion of
Increased RB12
Radiolabeled
(Pancreatic
cyanocobalamin
insufficiency)
+ pancreatic
enzymes

Free B12 R
Pepsin Free B12
IF IF
Chief cells protease R
I. ANEMIA CAUSED BY DEFECTS IN
DNA METABOLISM
•Treatment: Oral Vitamin B12 and Folic Acid
II. ANEMIA CAUSED BY BONE
MARROW FAILURE
Cessation or reduction of RBC destruction
PANCYTOPENI
Common manifestation is
A
Reasons:
✔ Hematopoietic stem cell destruction
o Drugs, Injury, Chemicals, Viruses, Radiation
✔ Premature senescence and apoptosis
o Genetic mutations
✔ Ineffective erythropoiesis
o Stem cell mutations
o B12 and Folate deficiency
II. ANEMIA CAUSED BY BONE
MARROW FAILURE
✔ Disruption of bone marrow microenviroment
✔ Decreased growth factors and hormones
✔ Loss of normal hematopoietic tissue due to abnormal cells
II. ANEMIA CAUSED BY BONE
MARROW FAILURE
•Aplastic anemia:
Rare, fatal syndrome
Pancytopenia, reticulocytopenia, and HYPOCELLULAR MARROW
Two types:
✔ ACQUIRED
✔ INHERITED HUMAN PARVOVIRUS
EPSTEIN BARR VIRUS
HIV
II. ANEMIA CAUSED BY BONE
MARROW FAILURE
Acquired
•Pathophysiology:
Quantitative and Qualitative deficiency of hematopoietic stem cells
Decreased CD 34 cells, Increased Fas RECEPTORS
Stromal cells in the bone marrow of patient are normal
II. ANEMIA CAUSED BY BONE
MARROW FAILURE
Related to immune damage (drugs, chemicals, viruses or other agents)
✔ Increased CD8+ , T lymphocytes
✔ Increased cytokines (IFN ɣ and TNF α)
✔ Upregulation of T-bet IFN ɣ
✔ Increased TNF α receptor
✔ Improvement of cytopenias after immunosuppression
II. ANEMIA CAUSED BY BONE
MARROW FAILURE
Shortened TELOMERES

TELOMERASE
II. ANEMIA CAUSED BY BONE
MARROW FAILURE
•Clinical Findings:
Insidious onset anemia
Pallor, fatigue, weakness
•Laboratory Findings:
.PANCYTOPENIA
Hemoglobin <10 g/dL
Decreased Reticulocyte count
Can be Macrocytic or normocytic
II. ANEMIA CAUSED BY BONE
MARROW FAILURE
Increased liver enzymes
Paroxysmal Nocturnal Hemoglobinuria

•Bone marrow
Fat cells predominate
.PATCHY MARROW CELLULARITY
Decreased progenitor cells
II. ANEMIA CAUSED BY BONE
MARROW FAILURE
•Treatment:
Identify the causative agent
Blood product replacement
.HSCT (Hematopoietic Stem Cell Transplant) <40 years old px

>40 years old px Cyclosporine and antithymocyte globulin

II. ANEMIA CAUSED BY BONE
MARROW FAILURE
•Inherited
•Fanconi’s anemia
Chromosome instability disorder
Skin pigmentation, short stature, and hypogonadism
•Clinical Findings:
Skeletal abnormalities
Kidneys and eye abnormalities
Low birth weight, delayed development
Increased cancer risk
II. ANEMIA CAUSED BY BONE
MARROW FAILURE
•Pathophysiology: X LINKED RECESSIVE
15 genes: FANCA, FANCB, FANCE, FANCD1, FANCD2, FANCE, FANCF,
FANCG, FANCI, FANCL, FANCL, FANCM, FANCN, FANCO, FANCP.
Increased TELOMERE SHORTENING AUTSOMAL RECESSIVE
Late S phase cycle defects
Hypersensitivity to oxidants
II. ANEMIA CAUSED BY BONE
MARROW FAILURE
•Laboratory Findings
FA = increased
Similar with the acquired type chromosome breaks and
Pancytopenia rings

Macrocytes DNA cross-linking agents

Thrombocytopenia diepoxybutane
CHROMOSOMAL BREAKAGE (DEB) or mitomycin C
.
ANALYSIS (MMC).

Fibroblast cells
II. ANEMIA CAUSED BY BONE
MARROW FAILURE
Prognosis:
40% develop bone marrow failure
1/3 develop MDS and AML
Squamous cell carcinoma

Treatment:
Transfusion
HSCT
II. ANEMIA CAUSED BY BONE
MARROW FAILURE
Dyskeratosis congenita
Rare inherited bone marrow failure and pancytopenia
•Clinical Findings:
Triad
✔ Abnormal skin pigmentation
✔ Dystrophic nails
✔ Oral leukoplakia
Pulmonary Fibrosis
Liver disease
Short stature
II. ANEMIA CAUSED BY BONE
MARROW FAILURE
•Pathophysiology:
very short telomeres
inherited defect telomere complex
Genetic:
✔ X linked autosomal dominant
✔ Autosomal dominant
✔ Autosomal recessive
Mutations in the long arm of the X CHROMOSOME on the DKC1 GENE DYSKERIN
TERC
Elongation of
Premature apoptosis telomeres
II. ANEMIA CAUSED BY BONE
MARROW FAILURE
•Laboratory Findings
Pancytopenia, macrocytic RBCs
Increased Fetal Hemoglobin
FISH – to identify short telomeres has been proposed

•Prognosis:
Mean survival : 42 years
Deaths due to bone marrow failure

•Treatment:
Androgen therapy
II. ANEMIA CAUSED BY BONE
MARROW FAILURE
•Shwachman-Bodian-Diamond Syndrome
Inherited multisystem disorder characterized
, PANCREATIC INSUFFICIENCY
cytopenia, skeletal abnormalities and genetic
predisposition to hematologic malignancies

•Clinical Findings:
Delayed bone maturation, failure thrive and short stature.
II. ANEMIA CAUSED BY BONE
MARROW FAILURE
II. ANEMIA CAUSED BY BONE
MARROW FAILURE
•Laboratory Findings:
Peripheral blood cytopenia, decreased pancreatic enzyme secretion
Nearly all have neutropenia
•Pathophysiology:
Autosomal recessive disorder
Biallelic mutations in the SBDS genes
Quantitative and Qualitative Deficiencies in CD34+ cells
Dysfunctional bone marrow cells
Increased apoptosis
MITOTIC SPINDLE destabilization in hematopoietic cells
II. ANEMIA CAUSED BY BONE
MARROW FAILURE
II. ANEMIA CAUSED BY BONE
MARROW FAILURE
short telomeres
FECAL FAT
Increased
SECRETION
Decreased TRYPSINOGENand ISOMYLASE
NORMAL SWEAT CHLORIDE
Similar with CYSTIC FIBROSIS except for the
RESULT
II. ANEMIA CAUSED BY BONE
MARROW FAILURE
•Treatment:
Some cases requires no treatment
Enzyme replacement and G CSF administration is recommended for some
cases.
ALLOGENEIC BONE MARROW
.
TRANSPLANTATION
II. ANEMIA CAUSED BY BONE
MARROW FAILURE
•Other forms of Bone marrow Failure:
Pure Red Cell aplasia: selective and severe decrease in erythrocyte
precursors in an otherwise normal bone marrow.
✔ Acquired Pure Red Cell Aplasia:
o Children or Adults
o Acquired or Chronic
o Idiopathic or autoimmune
o Secondary PRCA – associated with, THYMOMA hematologic malignancies, solid
tumors and infection
II. ANEMIA CAUSED BY BONE
MARROW FAILURE
Auto-antibodies, natural killer
(NK) cell-mediated or T
lymphocyte-mediated
II. ANEMIA CAUSED BY BONE
MARROW FAILURE
o TRANSIENT ERYTHROBLASTOPENIA OF CHILDHOOD : immune
mechanism that targets red cell production following a history of viral
infection
II. ANEMIA CAUSED BY BONE
MARROW FAILURE
✔ Diamond-Blackfan (Congenital)
o Congenital erythroid hypoplastic disorder of early infancy
o RPS7, RPS10, RPS17, RPS19, RPS24, and RPS26 in the 40S subunit and RPL5,
RPL11, RPL35A in the 60S subunit.

25 % of the mutations occur

Ribosomal genes
II. ANEMIA CAUSED BY BONE
MARROW FAILURE
o DISTINGUISHED FROM APLASTIC ANEMIA THROUGH BONE MARROW
EXAMINATION.
o Increased hemoglobin F and. ERYTHROCYTE DEAMINASE
III. ANEMIA CAUSED BY INCREASED
DESTRUCTION OF ERYTHROCYTES
Classification:
✔ ACUTE VS. CHRONIC, INHERITED VS. ACQUIRED, INTRINSIC VS EXTRINSIC,
INTRAVASCULAR VS EXTRAVASCULAR, FRAGEMENTATION VS
MACROPHAGE MEDIATED

Extravascular hemolysis: increased turnover of senescent RBCs to

reticuloendothelial system. Leads to the change from a normal red blood
cell to a spherocyte SPHEROCYTOSIS
III. ANEMIA CAUSED BY
INCREASED DESTRUCTION OF
ERYTHROCYTES

Short Life span

III. ANEMIA CAUSED BY INCREASED
DESTRUCTION OF ERYTHROCYTES
Intravascular hemolysis: minor cause of RBC destruction. Results to
decreased. HAPTOGLOBIN and HEMOPEXIN Patients have HEMOGLOBINURIA

✔ Trauma
✔ Prosthetic hear valves
✔ Parasites
III. ANEMIA CAUSED BY
INCREASED DESTRUCTION OF
ERYTHROCYTES
B1

HG
CD163 receptor

HEMOPEXIN B2
Urobilinogen
III. ANEMIA CAUSED BY
INCREASED DESTRUCTION OF
ERYTHROCYTES
•Clinical Findings:

Fatigue, dyspnea, and dizziness

, JAUNDICE AND ICTERUS (increased indirect bilirubin)

Cholelithiasis
Kernicterus in newborns
Splenomegaly (chronic macrophage mediated hemolysis)
III. ANEMIA CAUSED BY
INCREASED DESTRUCTION OF
ERYTHROCYTES
•Laboratory Findings:
Fragmentation hemolysis:
✔ Macroscopic analysis: COFFEE BROWN COLOR
of plasma. ROOT BEER urine.
ROOT BEER COLOR

✔ Complete Blood Count: presence of and . Presence of inclusions

SPHEROCYTES
such as malaria and anomalies. Increase polychromatophiic cellsSCHISTOCYTES
III. ANEMIA CAUSED BY
INCREASED DESTRUCTION OF
ERYTHROCYTES
✔ . UNCONJUGATED BILIRUBIN
✔ Decreased haptoglobin and increased lactate dehydrogenase
(intravascular hemolysis)
GLYCATED
✔ Measurement of
HEMOGLOBIN
✔ Increased reticulocyte count
IV. ANEMIA CAUSED BY DISORDERS
OF IRON KINETICS AND HEME
METABOLISM
Causes:
✔ Inadequate intake: iron starvation, 1mg of iron is lost in the body through
the mitochondria of the desquamated skin, and the sloughing of the
intestinal epithelium.
✔ Increase need: rapid growth, childhood, pregnancy and adolescence.
✔ Impaired absorption: malabsorption sydromes (celiac disease), mutation
in the MATRIPTASEprotein,
2 decreased HCl production.
✔ Chronic blood loss: gastrointestinal bleeding, gastritis, parasitosis, or
hemorrhoids.
IV. ANEMIA CAUSED BY DISORDERS
OF IRON KINETICS AND HEME
METABOLISM

MATRIPTASE 2
Iron will not be
absorbed
HEPCIDIN
IV. ANEMIA CAUSED BY DISORDERS
OF IRON KINETICS AND HEME
METABOLISM
•Pathophysiology:
•Three stages:
Stage 1 (STORAGE IRON DEPLETION)
✔ No evidence of iron deficiency
✔ Low serum ferritin
✔ Patient appears healthy without any signs and symptoms
IV. ANEMIA CAUSED BY DISORDERS
OF IRON KINETICS AND HEME
METABOLISM
Stage 2 (TRANSPORT IRON DEPLETION)
✔ Exhaustion of stored iron
✔ Anemia is still not evident
✔ Hemoglobin begins to drop
✔ RDW starts to increase
✔ Decreased Serum Ferritin and Iron
✔ Increased TIBC and % transferrin
✔ FEP starts to accumulate
IV. ANEMIA CAUSED BY DISORDERS
OF IRON KINETICS AND HEME
METABOLISM
Stage 3 (Frank anemia)
✔ Low hemoglobin and hematocrit
✔ RBC precursors are affected
✔ .MICROCYTIC AND HYPOCHROMIC CELLS
✔ .INCREASED ERYTHROPOIETIN AND DECREASED HEPCIDIN
✔ Increased TIBC and % transferrin
✔ Decreased Serum Ferritin and Iron
✔ Manifestation of signs and symptoms
IV. ANEMIA CAUSED BY DISORDERS
OF IRON KINETICS AND HEME
METABOLISM
•Laboratory Findings:
Complete Blood Count:
✔ Anisocytosis, poikilocytosis, microcytosis and hypochromia
✔ Decreased RBC indices (MCV, MCH, MCHC)
✔ . DECREASED RBC COUNT
✔ .LOW RETICULOCYTE COUNT
✔ .THROMBOCYTOSIS
IV. ANEMIA CAUSED BY DISORDERS
OF IRON KINETICS AND HEME
METABOLISM
Iron studies:
✔ Low Ferritin, Serum Iron
✔ High TIBC, FEP, % Transferrin

Treatment:
✔ Treat the cause of deficiency
✔ Oral supplements (ferrous sulfate)
IV. ANEMIA CAUSED BY DISORDERS
OF IRON KINETICS AND HEME
METABOLISM
•Anemia of Chronic Inflammation
Commonly associated with systemic diseases:
✔ rheumatoid arthritis, chronic infections and malignancies
Role of acute phase reactants:
✔ HEPCIDIN – APR that is produced by the liver. It causes the
FERROPORTIN
degradation of .

✔ LACTOFERRIN – iron binding protein in the granulocyte. Used in the

prevention of phagocytized to utilize. INTRACELLULAR IRON
IV. ANEMIA CAUSED BY DISORDERS
OF IRON KINETICS AND HEME
METABOLISM
✔ FERRITIN – RBCs does not have receptors for ferritin-iron complex.

✔ Production of inflammatory cytokines TNF ALPHA AND INTERFERON GAMMA

IV. ANEMIA CAUSED BY DISORDERS
OF IRON KINETICS AND HEME
METABOLISM
IV. ANEMIA CAUSED BY DISORDERS
OF IRON KINETICS AND HEME
METABOLISM
•Laboratory findings:
Complete Blood Count: <8 to 10 g/dL
Normocytic and normochromic
Leukocytosis, thrombocytosis, or both
Low serum Iron and TIBC
Increased serum ferritin
Increased FEP
IV. ANEMIA CAUSED BY DISORDERS
OF IRON KINETICS AND HEME
METABOLISM
•Treatment:
Erythropoietin
Control and treat underlying condition
IV. ANEMIA CAUSED BY DISORDERS
OF IRON KINETICS AND HEME
METABOLISM
•Sideroblastic anemia

Interference in the production of adequate PROTOPORPHYRIN.

RING SIDEROLASTS – HALLMARK OF SIDEROBLASTIC

.
ANEMIA

Hereditary or acquired
IV. ANEMIA CAUSED BY DISORDERS
OF IRON KINETICS AND HEME
METABOLISM
Acquired:
✔ Lead poisoning: Lead affects the central nervous system and the
hematologic system. Interferes with. PORPHYRIN SYNTHESIS.
o Normocytic, normochromic (microcytic hypochromic in chronic exposure)
o . BASOPHILIC STIPPLING
IV. ANEMIA CAUSED BY DISORDERS
OF IRON KINETICS AND HEME
METABOLISM LEAD
POISONING
PORPHYRIA.
IV. ANEMIA CAUSED BY DISORDERS
OF IRON KINETICS AND HEME
METABOLISM
✔ Porphyrias: impaired production of the porphyrin component of heme.
Psychosis is a prominent clinical feature.

PORPHYRIN: is harmful to
the skin and brain .
V. ACQUIRED NON-IMMUNE
ANEMIAS OF INCREASED RBC
DESTRUCTION
•Microangiopathic Hemolytic Anemia
Fragmentation and thrombocytopenia
Decreased hemoglobin, increased reticulocyte count increased lactate
dehydrogenase, increased serum indirect bilirubin, urine urobilinogen.
.INTRAVASCULAR HEMOLYSIS
Thrombocytopenia
V. ACQUIRED NON-IMMUNE
ANEMIAS OF INCREASED RBC
DESTRUCTION
•Thrombotic Thrombocytopenic Purpura (TTP)
Low Von Willebrand Factor cleaving factor ADAMTS 13
. IDIOPATHIC, SECONDARY OR INHERITED

PENTAD (FATRN)
✔ Fever, Anemia, thrombocytopenia, renal disease, neurologic symptoms
V. ACQUIRED NON-IMMUNE
ANEMIAS OF INCREASED RBC
DESTRUCTION
Platelet Plug

Increased
Thrombi
V. ACQUIRED NON-IMMUNE
ANEMIAS OF INCREASED RBC
DESTRUCTION
•Hemolytic Uremic Syndrome
Acute renal failure
Atypical and typical
: SHIGA TOXIN
E.coli O157:H7, Shigella

•Disseminated Intravascular Coagulation

Widespread activation of the hemostatic system
Massive consumption of platelets
APTT and PT prolonged
Decreased Fibrinogen and INCREASED D DIMER
VI. ACQUIRED IMMUNE ANEMIAS
OF INCREASED RBC
DESTRUCTION
.ANTIBODY MEDIATED IMMUNE MECHANISM
Amount of hemolysis exceeds the ability of the bone marrow to
compensate
•Paroxysmal Cold Hemoglobinuria
Acute form of cold-reactive hemolytic anemia
.DONATH LANDSTEINER ANTIBODY
Children present acute fever, malaise and back, leg abdominal pain C1 to C4
Severe but self-limiting
P

C3 to C9
VII. INTRINSIC DEFECTS LEADING TO
HEMOLYSIS
•Paroxysmal Nocturnal Hemoglobinuria
rare, chronic intravascular disorder
LACKS
. GPI (CD55 AND CD59)
.
PHENOTYPIC MOSAICISM

CD55,5
GP1 9

CD55,5
GP1 9
VI. ACQUIRED IMMUNE ANEMIAS
OF INCREASED RBC
DESTRUCTION
Hemolytic anemia, thrombosis, and bone marrow failure
Hemoglobinemia, hemoglobinuria
DAT negative
Bone marrow: normocellular and hypocellular
FLOW CYTOMETRY, SUGAR WATER TEST, HAM
Tests:
TEST
Treatment: ECULIZUMAB
 VI. ACQUIRED IMMUNE ANEMIAS
OF INCREASED RBC
DESTRUCTION
SUGAR WATER TEST

PX CONTROL
SICKLE CELL ANEMIA
Inherited a sickle (S) gene from one parent and S,C, or Ɓ-thalassemia from
the other.
Homozygous SS = severe manifestations
α2 Ɓ2 6Glu->Val
Eight genotypes that cause disease: Hb SS, Hb S-Ɓºthal, severe Hb S- Ɓ+thal,
Hb SD- Punjab, Hb SO-Arab, Hb SC-Harlem, Hb CS-Antilles, Hb
S-Quebec-CHORL
SICKLE CELL ANEMIA
•Clinical Findings:
no symptoms to a potentially lethal state
Hallmark: VASOOCCLUSIVE CRISIS
Acidosis, hypoxia, dehydration, infection, and fever
Related with G6PD deficiency
SICKLE CELL ANEMIA

Rigid and
Sticky

Hgb SA
SICKLE CELL ANEMIA
•Laboratory Diagnosis:
Associated with chronic hemolytic anemia
Normocytic, normochromic
Marked poikilocytosis
Increased RDW, MCV
Increased thrombocytes
Increased Immunoglobulin A
HPLC, Hemoglobin electrophoresis, capillary electrophoresis, Isoelectric
focusing
SICKLE CELL ANEMIA
•Treatment:

.SUPPORTIVE THERAPY
REFERENCES
• Lotspeich-Steininger, C. A., Stiene-Martin, E. A., & Koepke, J. A. (1992). Clinical
hematology: Principles, procedures, correlations. Philadelphia: Lippincott.
– Rodak, B. F., Fritsma, G. A., & Keohane, E. M. (2012). Hematology: clinical
principles and applications. 4th ed. St. Louis, Mo.: Elsevier Saunders.
– Turgeon, M. L. (2012). Clinical hematology: Theory and procedures (5th ed.).
Philadelphia, PA: Wolters Kluwer Health/Lippincott Williams & Wilkins.
END