OM Lec 2 RED BLOOD CELL DISORDERS part 2

APLASTIC ANEMIA
 Aplastic anemia is a rare bone marrow aplasia causing:

-refractory normocytic normochromic anemia

-leukopenia
pancytopenia
-thrombocytopenia

 Etiology:
1) Primary:
a) Congenital: Fanconi's anemia with features of skeletal, renal and CNS abnormalities.

b) Acquired: immune suppression of bone marrow stem cells by T suppressor cells.

2) Secondary to :
• Drugs : cytotoxic (busulphan) and • Insecticides.
noncytotoxic (chloramphenicol) .
• Viral infection: viral hepatitis and measles .
• Chemical : e.g. benzene.
• Thymoma.
• Ionizing radiation.

 Clinical manifestations:
1) Anemia. 2) Increased susceptibility 3) Bleeding tendency and
to infection. purpura.
 Oral manifestations:
1) Pallor of the oral mucosa.
2) Gingival bleeding.
3) Petechiae and ecchymosis.
4) Ulceration of the oral mucosa having little surrounding erythema.

N.B.: The presence of severe ulcerative stomatitis is a rather constant manifestation of

aplastic anaemia.

 Oral manifestations of advanced cases are similar to acute leukemia.

 Laboratory Findings:
1. Pancytopenia.
2. Absence of reticulocytes.
3. Bone Marrow biopsy: a hypocellular or aplastic bone marrow with increased fat spaces.

 Differential diagnosis:
Aplastic anemia should be differentiated from other causes of pancytopenia.

Causes of pancytopenia:
1) Aplastic anemia 5) Severe sepsis
2) Megaloblastic anemia 6) Bone marrow infiltration by :
3) Hypersplenism • Lymphomas • Acute leukemia
4) Systemic lupus erythematosus • Myeloma • Secondary carcinoma.

 Treatment:
1) Eliminate the cause if possible. 3) Bone marrow transplantation (stem cell
transplant).
2) Supportive treatment :
4) Immunosuppressive drugs:
 RBC and platelets transfusion
 antibiotic therapy  Anti-lymphocyte globulin .
 Steroids
 Cyclosporine

 Dental Aspect of Aplastic Anemia:

1) Oral manifestation and management of aplastic anemia are
similar to acute leukemia:
1) Increased bleeding tendency. 3) Presence of severe anemia.
2) Marked susceptibility to infection.
2) Precaution to the effect of steroid therapy.

3) Graft versus host disease consequent to bone marrow transplant

(Lichenoid lesions & Sjogren syndrome).
 Hemoglobin
 Adult hemoglobin consists of:

-two alpha globin chains (141 amino acid)

-two beta globin chains (146 amino acid)

bound to a single heme moiety.

 Heme contains one ferrous iron atom carried in a porphyrin ring .

 Defects of the globin portion of hemoglobin

induce erythrocytes to carry abnormal hemoglobin hemolytic anemia.

Types of hemoglobin:
Hb Structure
1) Hb A 2 2 92 %
2) Hb A1c 2 2 5%
B-NH It is glycosylated Hb which is increased in patients
A) Adult Glucose with uncontrolled diabetes.
3) Hb A2 2 2 2% Elevated in β thalassemia
 1%
4) Hb F 2 2 Normal Hb of fetus elevated in
β thalassemia, sc. anemia.
 Hb Structure
B) 1) Hb H 4 Found in alpha thalassemia
abnormal Biologically useless
chain
production 2) Hb 4 Comprise 100% of Hb in
Barts homozygous alpha thalassemia
Biologically useless

C) Hb S 2 2 Valine replace glutamic acid in

Abnormal …………………………….. position 6 of β chain
Chain
Hb C 2 2 Lysine replace glutamic acid in position 6 of β
structure
chain

*Adult hemoglobin (Hb A): consist of two alpha and two beta globin chains (α22).

*Fetal hemoglobin (HbF): the beta chains replaced by two gamma chain (α2 γ2).

- In normal person most of the hemoglobin is HbA (92%).

- At birth about 80% of hemoglobin is HbF.

- At six months HbF reduced to 5%.

- Adult life HbF is not more than 1%.

HEMOGLOBINOPATHIES
*Sickle cell disease:
-involves single amino acid abnormality.

-glutamic acid in position 6 in beta globin chain replaced by valine (HbS).

*Thalassemia:
-characterized by diminished synthesis of the alpha or beta globin
chains of hemoglobin.
  SICKLE CELL DISEASE
 Hereditary disorder (autosomal recessive) of hemolytic anemia, characterized by
appearance of numerous sickle shaped red cells in the circulating blood.

 Normochromic normocytic anemia.

 It is genetically determined hemolytic anemia caused by……………….

mutation in Hb polypeptide chain gene.

 Pathogenesis:
1) In the beta globin chains:
glutamic acid is replaced by valine in position 6
physical changes in the hemoglobin (HbS).
2) deoxygenated state or decreased PH acidosis

HbS molecules become insoluble and polymerize

Flexibility of RBCs decreases (rigid)

sickle shaped
3)This process is reversible initially.
-With repeated sickling, cells lose their membrane flexibility and remain deformed.

 Sickling is precipitated by:

• Infection •Dehydration • Hypoxia (high altitude, general anesthesia).

• Cold •Acidosis • In many cases the etiology is unknown.

1) Hb S releases its oxygen contents to the tissues more easily than Hb A.

2) Patients therefore feel well despite being anemic except during crisis or
complication.
Sickling can lead to:
1) Destruction of sickle cells (hemolysis within 30 days) with features of anemia.

2) Increased viscosity & clumping of cells in the microcirculation:

thrombosis ischemia pain, & infarction

Sickle cell disease is classified into:

1) Homozygous state " sickle cell anemia”
-The patient receives two abnormal alleles- one from

each parent abnormalities of all  chains of his hemoglobin (HbSS)

2) Heterozygous state "sickle cell trait”

-The patient receives ………an abnormal allele from one parent and ……………………………
a normal one from the other (HbSA)

-The sickle cell trait is less severe due to presence of some normal  chain (HbA).

o The disease occur mainly in Africans (25% carry the gene).

o It is also found in middle east, India and southern Europe.
 1) SICKLE CELL ANEMIA (HbSS)
 It is a serious disease since 80-90% of Hb is HbS and the remainder is HbF.

 Clinical feature:
Signs and symptoms appear around 5 months of age. They vary from person to person and
change over time.

1) -Chronic anemia which may be mild asymptomatic to severe hemolytic anemia.

-The affected patient shows underdevelopment with pallor and icteric tinge in the sclera.

-The patient is weak, short of breath and easily fatigued.

2) Painful or infarctive crisis: (major symptom)

-Periodic obstruction of small blood vessels by ……..……………………………
rigid non deformable sickled RBC hypoxia and microinfarction.

 -Precipitating factors:
fever …………… pregnancy……….. cold ………. dehydration ………..psychic stress
hypoxia………………acidosis ……………..surgery
 Periodic episodes of pain called pain crises, are major symptom of sickle cell anemia.
 The pain varies in intensity and can last from few hours to a few weeks.
 Some people have only a few crises a year.
Others have a dozen or more pain crises a year.
 A severe pain crises requires a hospital stay.
 Some adolescents and adults have also chronic pain which
result from bone and joint damage, ulcers or other causes.

 Clinical features :
1) Bone and joint pain is the commonest 4) Retinal damage, vision problems.
feature.
5) Dactylitis (severe inflammation and
2) Pain: abdomen, chest, spleen, liver. swelling of fingers and toes) and leg ulcers.
3) Cerebral damage: hemiparesis, fits. 6) Kidney infarcts causing hematuria.

-The attack lasts from few hours to few days and associated with low grade fever .
-During infarctive crises the degree of anemia is usually stable and Hb does not fall
unless there is hematological crisis.
3) Hematological crisis:
a) Hemolytic crisis: The rate of RBC hemolysis increases due to:
 -drugs
 -acute infection
 -glucose 6 phosphate dehydrogenase deficiency (G6PDD)

b) Aplastic crisis:

1) Acute, self-limiting erythroid aplasia, lasting 5-10 days, due to

……………………parvovirus B-19 (bone marrow arrest).

2) Life threatening anemia requires immediate transfusion therapy.

3) Occurs once because immunity develops after first infection.

4) Key for diagnosis is the marked fall of hematocrite and reticulocyte count.

c) Hypoplastic crisis:
- Infection suppresses bone marrow with drop of hematocrite and reticulocyte count.

- Rarely life threatening.

- Transfusion indicated only on the basis of other symptoms.

d) Splenic Sequestration crisis:

Sequestration of the sickled RBCs occur in all patients with HbS.

 In early childhood:

Spleen enlarged with entrapment of sickle cells (acute condition) infant death < 1 year.

 In adults:

-Splenomegaly is rare repeated infarction

fibrosis and functional aplasia in early childhood.

-Splenic function is lost and the patients are susceptible to infection.

-Patients are regarded as moderately immuno- compromised and at great risk for
infectious disease.

-Main cause of death is infection and thrombosis (patients die before 40 years age)!!!
 Oral Manifestations:
• The oral mucosa especially the soft palate is pale and has yellowish tinge.

• Delayed eruption and enamel hypoplasia may be seen.

• Maxillary overgrowth.

 Radiographic changes:
1) The jaw bone shows both:
-osteoporosis. ….. radiolucent….because… hyperplastic bone marrow

-areas of osteosclerosis. ….radiopaque ….

o Bone changes results from two opposing mechanisms:

 RBCs have short life span (30 days) -1/4 of the normal red cell life span

hyperplastic bone marrow evident by osteoporosis.

 Thrombosis in capillaries of bone marrow by sickled cells

act as a nidus for calcification resulting in osteosclerosis.

o Osteoporosis and osteosclerosis affect:

-mandible and maxilla
-skull
-vertebrae and long bones

2) The trabecular pattern of alveolar bone appears as

Ladder like effect (runs horizontally between roots of teeth)

-Lamina dura appears dense and distinct.

3) In skull films:
-The diploe is thickened (due to bone marrow erythroid hyperplasia)

-The trabeculae are coarse and run perpendicular to

the inner and outer table giving Hair on end appearance

-The frontal bossing is very prominent.

 Laboratory Findings:
1) Normochromic normocytic anemia.

2) Sealing fresh blood in a small chamber of microscopic slide with

a reducing agent (sodium metabisulphite) for 1 hour Sickling

3) Sickling solubility test: a mixture of Hb S in reducing solution (sodium dithionite)

turbid appearance due to precipitation of Hb S
(Hb A: gives clear solution).

4) Hemoglobin electrophoresis is
more accurate methods for the diagnosis
(different electrophoretic pattern)
80% - 90% is Hb S, the remainder is Hb F.

 Management: (symptomatic)
1) Precipitating factors for crises avoided.
2) No treatment required for steady state of anemia.
3) Acute attack: supportive therapy (IV fluid, oxygen, antibiotic & narcotic analgesic).
4) Folic acid given during pregnancy and those with severe hemolysis.
5) Blood transfusion during aplastic crisis where Hb level is extremely low.

Repeated blood transfusion should be avoided because:

a. Its effect is transitory. c. Risk of transmission of viral hepatitis.
b. Patient may develop antibodies to donors d. Risk of iron overload (hemosiderosis).
RBC.

6) Bone marrow transplant in severe cases.

 Dental Implication
1) Never anesthetize or operate on patient during sickle cell crisis.

2) General anesthesia is hazardous in sickle cell anemia (crisis may develop):

- If general anesthesia is required Hb should be at least 10 g/dl.

- Select a phase when hemolysis is minimal.

-Partial exchange transfusion with packed red cells and oral administration of folic acid
are valuable in correcting the anemia.

-Avoid episodes of hypoxia because cerebral or myocardial thrombosis can result.

3) Dental treatment should be carried out under local anesthesia.

-Vasoconstrictor content of anesthetic solution can precipitate the crisis.

4) Tourniquet should not be used.

-May precipitate a crisis or even may lead to loss of the limb.

5) Antibiotic: given as a prophylactic cover in any operation in sickle cell anemia (and
sickle cell trait). … prophylactic cover Why !!! patients are susceptible to infection !!!
……...immunocompromised ,,,splenomegaly,, bone marrow arrest so low white blood cells,,,,,, Splenic
Sequestration crisis which leads to Loss of spleen function

-Acute infection should be treated immediately.

6) Avoid drugs which may cause respiratory depression (sedatives) as it may lead to
hypoxia.

7) Always expect poor wound healing!! after extraction or surgery in any patient with
hemolytic anemia.

8) Cerebral or cardiac hypoxia may result in these patients with minor procedures.

9) Infarction in the bone may predispose to osteomyelitis especially in the mandible.

10) Pain is usually of local dental origin but it may be caused by infarction or osteomyelitis.

Pulpal symptoms are common in the absence of any obvious dental disease.
 2) SICKLE CELL TRAIT (HbAS)
 Heterozygous cases in whom 60% of hemoglobin is HbS, ,,
remainder is normal hemoglobin.

• Patient is asymptomatic and lives normal life unaffected by his abnormal

hemoglobin.

• Sickle cell crises can be caused by reduced oxygen tension (general anesthesia, high
altitude or unpressurized aircraft).

• Patients may have renal complications causing hematuria or splenic infarcts.

• If general anesthesia is necessary full oxygen must be maintained.

• Respiratory infection should be treated vigorously.

• Sickle cell trait protects against Plasmodium falciparum malaria.

 Diagnosis is made by :
1) Positive sickling test.

2) Hb electrophoresis.

3) Blood count and film are normal.