Hematopoiesis and Red Blood Cell Disorder

Dr. Md. Nazrul Islam

Dr. Niaz Mahmud
Resident- Phase -B
Pediatric Hematology and Oncology dept.
 Regulation of Haemopoiesis

Controlled cell
Controlled cell production
death

• There should be a balance between cell production

and cell death except at the times of requirement
.
Erythropoiesis
.
Red Blood Cell Disorders
 Red Blood Cell Disorder
 Erythrocytosis/Polycythemia
.
 Polycythemia Vera

 Classification of anemia

 Iron deficiency anemia

 Anemia owing to hemolysis

 Sickle cell anemia

 Thalassemia

 Megaloblastic anemia

 Aplastic anemia
 Erythrocytosis/Polycythemia
A conditions with an increase in circulating red blood cells (RBCs),
characterized by a increased hemoglobin level.

2 types- relative and absolute

Relative polycythemia: Occur as a result of loss of fluid with

hemoconcentration of cells.

Seen in: vomiting, diarrhea or loss of electrolytes with accompanying loss of

water.

-Increase in number of RBC is only relative to the total blood volume.

Absolute erythrocytosis
.
Primary polycythemia: True idiopathic increase in the number
of circulating RBC and of the hemoglobin level.
Bone marrow with an inherited increased proliferative activity.

Secondary polycythemia: known etiology

Absolute increase in RBC mass resultant to enhanced

stimulation of RBC production.

Bone marrow anoxia — pulmonary dysfunction, high altitude, CO

poisoning.

Production of an erythropoietic stimulating factor- drugs and

chemicals such as coal-tar, mercury, iron, bismuth.
 Polycythemia Vera

.
 Chronic stem cell disorder with an insidious onset characterized as a
pan-hyperplastic, malignant and neoplastic marrow disorder.

 Absolute increase in the number of circulating RBC and in

the total blood volume because of uncontrolled RBC production.

 Accompanied by increase in WBC and platelet production.

 Clinical Manifestation
. Asymptomatic

 Pruritis

 Vertigo

 Gastrointestinal pain

 Headache

 Paresthesias, fatigue, weakness

 Visual disturbances, tinnitus‘

Oral Manifestations
Erythema of mucosa
Glossitis
Erythematous & oedematous gingiva
Spontaneous gingival bleeding

Laboratory Fingdings
RBC- Normochromic, normocytic
Hb- >20gm/dl
Hematocrit- more than 65%
Platelets- 400000-800000 /dl
Bone Marrow- hypercellular, megakaryocytes are increased
Treatment
 Phlebotomy
 Chemotherapy
 Radioactive phosphorus

Oral Health Consideration

 Clinically significant bleeding may paradoxically require platelet transfusion

 Tranexamic acid can be used
Anaemia

Anemia refers to reduction in

 Red blood cell
 Hemoglobin content
 Packed cell volume
Etiologic classification of anemia
1 Loss of blood
Acute post hemorrhagic anemia
Chronic post hemorrhagic anemia
2 Excessive destruction of RBC
a. Extra corpuscular cause: Antibodies, infection (malaria)
Splenic sequestration & destruction
Drugs, chemical & physical agents
b. Intracorpuscular cause :
1.Hereditary
Red cell enzyme defects, abnormalities of RBC membrane
abnormalities in synthesis of globin
2. Acquired- lead poisoning
3.Impaired blood production resulting from deficiency of substances
essential for erythropoiesis
a Iron deficiency
b Deficiency of vit B12, folic acid & protein
4. Inadequete production of mature erythrocytes
a Pure red cell aplasia
b Infiltration of bone marrow: leukemia, lymphoma
c chronic renal disease
d chronic inflammatory disease
Morphologic classification
Normocytic
Acute blood loss
Anemia of chronic disease

Microcytic
IDA, Thalassemia

Macrocytic
Vit B 12, folic acid deficiency
Iron Deficiency Anemia
Iron deficiency anemia defined as reduction in total body iron to an extent that
iron stores are fully exhausted and some degree of tissue iron deficiency is
present
Females are mostly affected

Etiology
Chronic blood loss
Inadequate dietary intake
Faulty iron absorption
Increased requirements of iron
infancy, childhood, pregnancy
Anemia owing to hemolysis
Hemolytic disease result in anemia if bone marrow is not able to replenish
adequetely the prematurely destroyed RBCs

Either inherited or acquired

Mechanism accelerated destruction of RBCs

 Molecular defect inside the red cells
 Abnormality in membrane structure & function
 Environmental factor- mechanical trauma
Clinical manifestation
 Signs & symptoms depend on mechanism that lead to red cell destruction
 Acute back pain
 Fatigue
 Breathlessness
 Tachycardia
 Hemoglobinuria
 Renal failure
 Physical findings- Yellow color of skin & mucosa, splenomegaly
Sickle cell disease/ Sickle cell anemia
 Hereditary type of chronic hemolytic anemia transmitted as a mendelian
dominant character.
 Exclusively in black and in whites of Mediterranean origin.
 A concordance exists between the prevalence of malaria and HBS.

HbA is genetically altered to produce HbS.

Substitution of valine for glutamine at sixth position of the globin

chain.
.

 Erythrocyte have their normal biconcave discoid shape distorted, generally

presenting a sickle like shape.
 Reduce both their plasticity and lifetime from the normal 120 days average
down to 14 days.
 This results in the underlying anemia and hypertrophic bone marrow.
 In heterozygote- 40% Hb is HbS.
 In homozygote – nearly Hb is HbS.
 Deoxygenation of the heme moiety of HbS

Hydrophobic interaction between adjacent Hb molecule.

Aggregate into larger polymer

Distorting the RBC into

Classic sickle shape

Obstructs microcirculation

Hypoxia-promotes sickling
CLINICAL MANIFESTATIONS
 Common in female,before the age of 30 years.
 Cerebrovascular accidents.
 Aplastic crisis leading to severe anaemia.
 Chronic leg ulcer.
 Aseptic osteonecrosis.
 Retinitis
 Splenic sequestration.
 Renal failure.
 Acute chest syndrome
fever, cough, sputum production, dyspnea.
Oral manifestations
 Significant bone change in dental radiograph.
 Mild to severe generilized osteoporosis.
 Loss of trabeculation of the jaw bone.
 Enamel hypomineralization
 Pallor of oral mucosa.
 Delayed eruption of teeth.
 Pulpal necrosis.
Lab findings
 RBC may reach to a level of 1000000 cells/cumm.
 Decrease Hb level.
 High reticulocyte count.
 Increased marrow response.
 Elevated LDH and decrease level of haptoglobin – confirm hemolysis.

 PBF
Typical sickle shaped RBCs seen.
Treatment
 Management of vaso-occlussive crisis.
 Management of chronic pain syndrome.
 Management of chronic hemolytic anaemia.
 Treatment of infection.

 Oral health consideration

Good oral hygiene.
Aggressive treatment of oral infection.
Avoid long , stressful dental visit.
Thalassemia
 Thalassemia ia group of genetic disorders of hemoglobin synthesis
characterized by a disturbance of either alpha or beta chain production.
 First discovered by Thomas Cooley in 1925.
Pathogenesis
 Alpha thalassemia – Deficient synthesis of alpha chain.
 Beta thalassemia- Deficient synthesis of beta chain.
An excess of alpha chain producing unstable hemoglobin
and thus damage to erythrocytes and vulnerable to destruction.
Megaloblastic anemia
 The Megaloblastic anemia is characterized by distinctive cytological and
functional abnormalities in peripheral blood and bone marrow cells due to
impaired DNA synthesis that results from a deficiency of one of the B group
vitamin either vit B12 or Folate.

 Megaloblastic anemia is so named because it is characterized by the

appearance in the bone marrow of morphologically abnormal nucleated red
cell precursors, which Ehrlich in 1880 called megaloblast.

 Megaloblasts are abnormal in function as well as in appearance,with the result

that the mature red cells formed from them are abnormal in size and shape , the
most prominent abnormality being macrocytosis.
Clinical manifestations
 Hematologic : Pallor, fever, occasional bleeding manifestation.
 Neurologic : Paresthesia, tingling and numbness of hands and feet.

Peripheral neuropathy.
Muscle weakness.
Syncope.
 Psychiatric : Fatigue, irritability,

Personality changes, memory impairment

Depression.
 Myocardial infarction and storke.
Oral manifestations
 Burning sensation in the tongue, lips, buccal mucosa.
 The tongue is generally inflammed described as “beefy red” in color.
 Characteristically with the glossitis, glossodynia and glosspyrosis.
 There is gradual atrophy of the papillae, tongue that eventuates in a smooth or
bald tongue – “ Hunter’s glossitis or Moeller’s glossitis”
 Fiery red appearance of the tongue may undergo periods of remission,
recurrent attacks are common.
Laboratory finding
 Red cell changes:
Hb markedly reduced.
Red cell indices: MCV increased.
Blood smear: Macrocytosis, macro-ovulocytes, marked
anisopoikilocytosis with tear drop cells, presence of Cabot ring, Howell-Jolly
bodies.

 WBC changes:
Counts reduced to 1500-4000/cumm.
Hyper segmented neutrophil present.
.

 Platelet count:
Reduced to 50000/cumm.

 Bone marrow :
Hyperplastic marrow.
Large RBC with open lacy nuclei. Frequent mitosis , nuclear remnants,
Howell-Jolly bodies, bi or tri nucleated cell, dying cells present.
Larger metamylocytes, hypersegmented neutrophils present.
Megakaryocytes shows increase in nuclear lobes.
.

 S. vitamin B12 level: Less than 80pg/ml always indicative of vitamin B12
deficiency.
 S. Folate level: Less than 3 ng/ml is indicative of folate deficiency.
 RBC Folate level: Less than 160 ng/ml is considered low.

If vitamin B12 is suspected then Schilling test is done.

Treatment
 Vit B12 deficiency:
Several daily doses of 25-100mg intramuscular cyanocobalamin.
Maintainance monthly doses between 200-1000mg depending upon
causes.

 Folic acid deficiency:

100-200 mg/day.
Aplastic anaemia
 Aplastic anaemia is a blood dyscrasia in which peripheral blood pancytopenia
results from reduced or absent blood cell production in the bone marrow and
normal hematopoietic tissue in the bone marrow has been replaced by fatty
tissue.
 Paul Ehrlich introduced the concept of aplastic anaemia in 1888.
 In 1904 it was termed as aplastic anaemia by Chauffard.
 Environmental exposures such as drugs, viruses, toxins are thought to trigger
the aberrant immune response in some patients, but most cases are classified as
idiopathic.