2. Hematology
Key components of
hematologic system are:
⚫ Blood
⚫ Blood forming tissues
Bone marrow
Spleen
Lymph system
2
Transportation
⚫ Oxygen
⚫ Nutrients
⚫ Hormones
⚫ Waste Products
Regulation
⚫ Fluid, electrolyte
⚫ Acid-Base balance
Protection
⚫ Coagulation
⚫ Fight Infections
What Does Blood Do?
3. 3
Red blood cell disorders
Erythrocytes/Red Blood Cells
Composed of hemoglobin
Erythropoiesis
⚫ = RBC production
Stimulated by hypoxia
Controlled by erythropoietin
⚫ Hormone synthesized in kidney
Normal lifespan of RBC = 120 days
5. Anemia
Reduction of the oxygen carrying capacity of blood
usually related to decrease in the number of circulating RBCS
as well as reduction in hemoglobin quantity .
• Causes:
• 1-Blood loss, as in common iron deficiency anemia.
• 2-Increased destruction of red blood cells, as in the hemolytic anemias.
• 3-Decreased production of red cells, as in pernicious and folic acid
deficiency anemias.
• 4-Combinations of these three.
6. • Anemias may be classified according to the size of the red cells
• Microcytic
• Normocytic
• Macrocytic
• Or according to the hemoglobin concentration
• Hypochromic
• Normochromic
Classification
7. Symptoms
Pallor or lack of color
Fatigue, dizziness,
headaches
Decreased exercise
tolerance
Rapid heartbeat, and
shortness of breath
Untreated anemia
may progress to death
from heart failure
8. IRON DEFICIENCY ANEMIA
Iron deficiency anemia (blood loss anemia, hypochromic
microcytic anemia) is the most common of all anemias.
Etiology
1- Chronic blood loss, such as that occurs in menstrual or
menopausal bleeding, and bleeding hemorrhoids.
Bleeding malignant lesion or ulcer in the gastrointestinal tract.
2- Iron malabsorption from GIT.
3- Increased iron requirements.
4- Decreased iron intake.
9. Oral Manifestations.
1-Pallor of the mucosa.
2-The oral epithelial cells become
atrophic, with loss of normal
keratinization.
3-The tongue may become smooth
due to atrophy of the filiform and
fungiform papillae, and
glossodynia can be a presenting or
associated symptom.
4-In long-standing cases,
esophageal strictures or webs can
develop, resulting in dysphagia.
10. Lab findings
1-Hemoglobin is less than 11 g/dL.
2- Low serum iron concentrations and high serum iron-
binding capacity
3-Immature RBCs irregular in size (anisocytosis)or in
shape (poikilocytosis)
4-Serum ferritin levels are markedly reduced.
5-RBCs are low in number (3000000-4000000/mm3)
11. Treatment
A- Cause should be identified
B- Iron tablets are to be applied (refer to patient’s physician)
Dental implications.
1- CBC should be evaluated before treating anemic patients
2-Elective oral surgical or periodontal procedures should not be
performed on patients with marked anemia because of the potential
for increased bleeding and impaired wound healing.
3- Avoid general surgery when hemoglobin levels fall below 10 g/ld.,
because the low oxygen tension affects the interactions between the
cellular components of blood, mainly platelets and endothelium,
decreasing their ability to clot effectively.
12. Plummer-Vinson Syndrome.
-Dysphagia: as a result of muscular
degeneration in the esophagus.
-Microcytic hypochromic anemia
-Relative degrees of achlorohyria
Plummer-Vinson syndrome is potentially serious because
pharyngeal and intraoral carcinomas are more common in these
patients.
One manifestation of iron deficiency anemia
13. Megaloblastic Anemias
Vitamin B12 (Cobalamine) Deficiency/Pernicious Anemia.
Conditions that can lead to cobalamine
deficiency include a) pernicious anemia,
b) gastrectomy, c) small bowel bacterial
overgrowth, d) medications such as neomycin
and colchicine.
-anemia,
-gastrointestinal disorders
-neurologic complications.
Intrinsic factor acts by binding to the vitamin B12 molecule, forming a
complex that crosses the ileal mucosa and protects the vitamin from
proteolysis. The disease can be the result of an autoimmune reaction to
either the gastric parietal cells or intrinsic factor.
The most common form of vitamin B12
deficiency is pernicious anemia, which is due
to atrophy of the gastric mucosa resulting in a
lack of intrinsic factor secretion.
14. ORAL MANIFESTATIONS.
1- Glossitis and glossodynia
2-The tongue is “beefy red” and inflamed, there is
a loss of filiform papillae, and, in advanced disease,
the papillary atrophy involves the entire tongue
surface together with a loss of the normal muscle
tone.
3-Patients may complain of dysphagia and taste
aberrations.
4- Pallor of oral mucosa, APHTHUS STOMATITIS,
AND XEROSTOMIA
Following treatment with vitamin B12, the tongue
undergoes complete healing with cessation of the
symptoms and reversal of the morphologic
alterations.
15. To diagnose pernicious anemia, the Schilling test is
used.
TREATMENT
Injection of hydrocobalamine over long time ( for life time)
In the Schilling test, the patient is given a measured
small amount of radioactive vitamin B12 by mouth,
followed shortly by a large flushing dose of parenteral
non-radioactive vitamin B12. The normal patient
excretes in urine 15 to 30% of the radioactive B12 in 24
hours, whereas the patient with pernicious anemia
excretes no more than 3%. If the test is repeated with
giving intrinsic factor, excretion will return back to
normal if there is no ileal disease.
16. Folate deficiency
Diagnosis is made by detection of
hematologic changes (the same as
those in pernicious anemia) with:
- Normal Schilling test and serum
vitamin B12 assays,
- Low serum assays of folic acid.
Treatment of folic acid deficiency
consists of oral folic acid tablets
( Folic acid 5 mg daily orally).
17. Aplastic Anemia
Rare bone marrow aplasia leading to decrease of all blood elements.
Etiology
1- Primary, could be congenital or acquired
(bone marrow immune suppression)
2-Secondary to drugs, chemicals
radiation and viral infection
Clinical features?
Diagnosis
- Aplastic bone marrow
- Pancytopenia
- Absence of reticulocytes
- Treatment:
- Cause elimination
- Supportive treatment
- Bone marrow transplantation
- Immunosuppressive drugs
18. Hemoglobinopathies
Defects in the globin portion of the
hemoglobin molecule cause
hemoglobinopathies. These defects render
the erythrocyte more susceptible to
hemolysis.
Normal hemoglobin:
Normal hemoglobin molecule consists of two
pairs of amino acid chains, α and β chains.
Types:
Hemoglobin A may be represented by the formula α2
A β2
A, indicating that there
are two α and two β chains.
Hemoglobin F (Fetal hemoglobin), normal in the fetus but abnormal in adult.
Hemoglobin F is represented by the formula α2
A У 2
F, indicating thatthe two
β chains are replaced by two У chains.
20. Sickle Cell Disease
•A disorder characterized by abnormality in the β
chain of hemoglobin in which the normal glutamic
acid is replaced by valine on position 6. The
formula for hemoglobin S (HbS) is α2A β2A 6
valine.
This relatively minor biochemical change results
in profound undesirable physical characteristics
in the hemoglobin. In the presence of either a
lowered blood oxygen tension or an increased
blood pH, the hemoglobin forms a sickle-shaped
crystal (a tactoid) within the erythrocyte. This
sickling of the erythrocyte leads to stasis and
hemolysis of the red cells, especially in end-
capillary circulation. The stasis then results in
an even lower oxygen tension, an increased pH,
21. The disease is hereditary and may
manifest itself as the sickle cell trait
or as sickle cell anemia.
In sickle cell anemia ( disease), both
β chains are abnormal and 80 to 90%
of the hemoglobin is hemoglobin S,
and the remainder is hemoglobin F
.(Hb SS)
In sickle cell trait, one of the β chains
is thought to be abnormal and 20 to
45% of the hemoglobin is
hemoglobin S, and the rest is normal
hemoglobin A. (Hb AS)
22. Sickle cell anemia
Patients with sickle cell anemia show marked underdevelopment
and often die before 40 years of age.
The clinical manifestations are the results of:
-Anemia and hemolytic process (jaundice, pallor, and cardiac
failure)
-Necrosis following stasis of blood and vaso-occlusion that
manifested by splenic infarction, chronic leg ulcers, priapism,
cerebral vascular thromboses (“strokes”), and painful attacks of
abdominal and bone pain (pain crises).
23. Acute crises may occur spontaneously or precipitated by
Infection Dehydration Hypoxia Sedatives and local anaesthetics
Cold
Hemolytic
Anemia
Weakness
Splenomegaly
Heart failure
Increased
viscosity and
clumping of
RBCs
Thrombosis
Ischemia
Infarction
24. Dental Aspects
Oral Manifestations
-Pale and yellow oral mucosa -Maxillary overgrowth
Delayed eruption -Enamel hypoplasia-
Radiographic
findings
- Ladder like effect
- Dense lamia dura
-Osteosclerosis and osteoporosis (salt and pepper
like appearance)
-Hair on eng appearance oskull.
- Frontal bossing.
26. Dental considerations and
management
Never
❑Anesthetize or operate on patients during
crisis (except for the relief of pain and
treatment of infection).
❑Use tourniquet
❑Use GA in the clinic (GA must be carried out
in a hospital with full anesthesia facilities and
in close cooperation with a hematologist)
❑Prescribe drugs that can cause respiratory
depression and hypoxia such as sedatives
(Nitrous oxide can be used safely as long as
oxygen conc. is >50%).
27. Expect
❖Cerebral or cardiac
hypoxia my result in
these patients with minor
procedure
❖Poor wound healing
after minor surgery or
extraction
❖Pulpal symptoms are
common without obvious
dental disease
❖Infarction of bone may
result in osteomyelitis
esp. in the mandible
28. Remember
-Patient’s physician should be consulted about the
patients myocardial status.
-Preventive dental care is important.
-Dental infections should be treated vigorously, if facial
cellulitis develops patient should be admitted to the
hospital.
-Pain medications for patients with sickle cell disease
include paracetamol, paracetamol with Codeine, NSAID’s
and narcotics especially morphine. However, the use of
Meperidine (Demerol) should be avoided as much as
possible since one of its toxic metabolites
(normeperidine) has a long plasma half-life and can cause
seizures.
29. -Due to high risk of infection in such patients, prophylactic
antibiotic regimen for prevention of endocarditis should be
followed before any dental procedures that can cause transient
bacteremia.
-After surgical procedures, antibiotics ( 500 mg penicillin VK 4
times/day or erythromycin, 250 mg 4 times/day, for penicillin-
allergic patients) should be continued for 7-10 days
postoperatively.
-Use of vasoconstrictor in local anesthesia is controversial,
however, for short routine procedures lacking discomfort , the
vasoconstrictor should not be used. If the procedure requires
long profound anesthesia, 2% lidocaine with 1/100,000
adrenaline is the anesthetic of choice.
30. If general anesthesia is required, it is
advisable to carry out comprehensive dental
treatment, including any extraction or
restoration that may be required, so as to
avoid a second procedure.
31. Trait
-60% of hemoglobin is HbS
-Patient is asymptomatic and lives normal life
-Sickle cell crisis can be precipitated by reduced oxygen
tension
-Few problems in management
*General anesthesia better be performed in hospital with full
oxygen supply
*Acute infections should be treated immediately
*Prophylactic antibiotic cover before surgery
32. Thalassemia
Group of congenital disorders characterized by
deficient synthesis of either α or β chains of
hemoglobin .
Alpha thalssemia Beta thalassemia
Imbalance in globin chain precipitation of these
chains in RBCs ineffective erythropoiesis
+ hemolysis
33. Beta thalassemia
1-Homozygous thalassemia (Cooly’s
anemia) no or few normal beta chains
2-Heterozygus thalassemia
Cooley’s anemia
Oral manifestations
Pale oral mucosa
Painful swelling of salivary glands
Painful tongue
Teeth discoloration
Hyperplasia of bone marrow
Large head and mongoloid
characters
Enlargement of premaxilla
Spacing of upper ant.
teeth
Delayed sinuses’
pneumatization
34. Dental implications
1- Expect poor wound healing
2- Antibiotic is required to control infection without delay
3- Avoid GA in dental clinic .
3- Avoid excessive bleeding during surgery.
35. Glucose 6 Phosphate Dehydrogenase
Deficiency (G6PDD)
Erythrocyte metabolic defect characterized by hemolysis
due to denaturing of hemoglobin in presence of oxidant
compounds.
Life span of RBCs is 2/3 the normal and this is
compensated by liver and bone marrow
Diabetes
Infection
Oxidants compounds
General anesthesia
Dental management
1- Avoid oxidant drugs eg asprin, phenacetin,
sulphonamides, chloramphenicol, and vit .K
2-Infection should be treated without delay
Hemolysis
36. Polycythemia
• Characterized by an increase in the
number of circulating red blood cells
– May be absolute or relative
• The three forms of polycythemia are
– Polycythemia Vera (primary)
– Secondary Polycythemia
– Relative Polycythemia
37. Relative Polycythemia
• Caused by a decrease in plasma
volume
– Causes may include diuretics,
vomiting, diarrhea, or excessive
sweating.
– Most patients are middle-aged
white men under physiologic
stress, mildly overweight,
hypertensive, and heavy
smokers.
Secondary Polycythemia
• Caused by a physiologic response
to decreased oxygen.
– A decrease in blood oxygen causes
an increase in erythropoietin by the
kidneys.
– May be due to pulmonary disease,
heart disease, living at high altitude,
or elevation in carbon monoxide
38. Polycythemia Vera (Primary Polycythemia)
– Unknown cause
– More common in men than in women
– Age of onset usually between 40 and
60 years of age
Clinical features
– Headache, dizziness, and itching
(pruritus)
– Thrombi may form.
– Hypertension, extended veins of neck.
A neoplastic proliferation of bone marrow stem cells causes an
abnormally high number of circulating red blood cells.
39. Oral Manifestations of
Polycythemia
The oral mucosa may appear deep red to purple;
the gingiva may be edematous and bleeds easily.
⚫ Submucosal petechiae, ecchymosis, and hematoma
formation may be present.
Diagnosis and treatment
Laboratory testing and measurement of
hemoglobin and hematocrit
RBCS 18 million/mm3
Hb 20 mg/dl
⚫ Treatment may include removal of causative
factors, chemotherapy, and phlebotomy
Dentally:
-Avoid bleeding
and thrombosis
-Strict oral
hygiene
-Blood count
evaluation before
dental treatment.
41. Types and Functions of Leukocytes
Granulocytes
Neutrophil
Eosinophil
Basophil
Phagocytosis, early phase of inflammation
Phagocytosis, parasitic infections
Inflammatory response, allergic response
Agranulocytes
Lymphocyte
Monocyte
Cellular, humoral immune response
Phagocytosis; cellular immune response
TYPE CELL FUNCTION
41
42. LEUKEMIA
▪Neoplastic proliferation of the white
blood cells and characterizd by
presence of immature cells in
peripheral blood and bone marrow.
▪Leukemic cells look different than
normal cells and do not function
properly.
43. LEUKEMIAS
Classifications:
1- Speed of evolution:
a- Acute b- Chronic
2- Individual cells : a- Myeloid b-lymphocytic
c-Monoblatic
3- Number of circulating cells
A-Aleukemic: Normal number of WBCs and no immature WBCs in peripheral
circulation, but bone marrow is crowdwd with immature WBCs
B-Subleukemic: Normal number of WBCs but immature cells are present in
peripheral circulation.
C-Leukemic: Increased number of WBCs and immature WBCs are present in
peripheral circulation.
44. TYPES OF LEUKEMIA
Lymphocytic and myelogenous leukemia
▪ Cancer can occur in either the lymphoid or
myeloid white blood cells.
▪ When the cancer develops in the lymphocytes
(lymphoid cells), it is called lymphocytic
leukemia.
▪ Cancer develops in the granulocytes or
monocytes (myeloid cells) – myelogenous
leukemia.
45. Acute and chronic leukemia
▪ Acute leukemia - The immature cells, called blasts, remain very
immature and cannot perform their functions. The blasts increase in
number rapidly, and the disease progresses quickly. Affect young age
groups mainly.
▪ Chronic leukemia - There are some blast cells present, but they are
more mature and are able to perform some of their functions. The cells
grow more slowly, and the number increases less quickly, so the
disease progresses gradually. Affect older age groups
46. LEUKEMIA IS CLASSIFIED INTO ONE OF
THE FOUR MAIN TYPES OF LEUKEMIAS
▪Acute myelogenous leukemia (AML)
▪Chronic myelogenous leukemia (CML)
▪Acute lymphocytic leukemia (ALL)
▪Chronic lymphocytic leukemia (CLL)
47. SIGNS AND SYMPTOMS
▪ More frequent infections and fevers
▪ Anemia and its symptoms: pale skin, fatigue,
weakness, bleeding, bruising, fever, chills, loss
of appetite, loss of weight, swollen or tender
lymph nodes, liver, or spleen, petechiae (tiny
red spots under the skin), swollen or bleeding
gums, sweating, bone or joint pain.
▪ Acute leukemia: headaches, vomiting,
confusion, loss of muscle control, swollen
testicles, sores in the eyes or on the skin.
48. ▪ Chronic leukemia may affect the skin, central
nervous system, digestive tract, kidneys, and
testicles.
▪ The symptoms of acute and chronic leukemias
may resemble other blood disorders or medical
problems
49. DIAGNOSIS
▪ Physician examination for swelling in the: liver,
spleen, lymph nodes under the arms, in the
groin, and in the neck
▪ Blood tests and laboratory tests
▪ Blood tests to examine the blast (immature)
blood cells
▪ Bone marrow aspiration and biopsy
▪ Lymph node biopsy
▪ Imaging procedures, such as x-ray, ultrasound,
and computed tomography (CT)
50. Oral Manifestations
• 80% in acute monblastic leukemia
• 40% in acute myeloid leukemia
• 20% in acute lymphoblastic leukemia
• 12% in chronic leukemias
54. Dental considerations
• 1-Conservative dental treatment
• 2-Imrove patients oral hygiene
• 3-Paliative treatment for acute symptoms
• 4-Patients with chronic leukemia have less infection can be
dentally managed in remission phase , assess bleeding time,
keep aseptic conditions, avoid prescribing asprin.
55. TREATMENT
▪ Chemotherapy
▪ Radiation therapy
▪ Bone marrow stem cell transplantation
▪ Biological therapy
▪ Platelet transfusion
▪ Red blood cell transfusion
▪ Medications to prevent or treat damage to other
systems of the body caused by leukemia
treatment
56.
57. Leukopenia, neutropenia and
agranulocytosis
• Leukopenia: Of the number of WBCs
below 4000 cell/mm3
• Neutropenia is defined as a total circulating
neutrophil count lower than 2000 cell /mm3.
• Agranulocytosis is absence of neutrophils
in peripheral blood smear.
• Aetiology
• General manifestations?
• Oral manifestations? Ulcers
58. Leukopenia: Neutropenia
• Clinical features:
– Infections, oral ulcers with white thick pus (pseudo membrane) of
bacteria or fungus (candida common)
59. • Cyclic neutropenia is characterized by a
very severe neutropenia (<200 cell /mm3(
lasting from 3 to 6 days every 21 days,
although in some cases the hematopoiesis
cycles can vary from 2 to 5 weeks It can be
asymptomatic except in the neutropenic
stage when fever, aphthous stomatitis,
gingivitis, stomatitis and cellulitis appear.
• Periodontitis?
60. Leukocytosis: Neutrophilia
▪ Increased granulocytes:
• Trauma, Acute Infections, inflammation, Bacterial*
▪ When severe with immature forms – Leukemoid reaction.
▪ Clinical features:
• Fever, Fatigue, Inflammation.
61. Lymphocytosis: Infectious Mononucleosis
(Glandular Fever , Kissing Disease )
▪ Epstien Bar Virus
infection ( found in saliva
during infection)
▪ Clinical features: fever,
headache , malaise ,
cervical
lymphadenopathy,
spleenomgally.
▪ Orally , sore throat,
petichiae, pharyngeal
edema , mucosal and
gingival ulceration.
nodes
62. Lymphocytosis: Infectious Mononucleosis
(glandular Fever)
▪ Diagnosis
1-Increased Lymphocytes: (Activated)
2-Large lymphocytes, more cytoplasm, also known as atypical
lymphocyte or virocyte
3-Heterrophil antibodies
- Paul Bunnel test; agglutination of sheep erythrocytes.
- Monospot test: agglutination to
- Horse erythrocytes . The titre of
antibodies develop,1-2 weeks of
Disease and disappear 3-6 months
Later.
4- Epstien bar antibodies against
viral capsid antigen
63. Lymphoma
▪ Definition: Solid cancer of lymphoid tissue
▪ Two Major Types: & many subtypes.
▪ Hodgkins lymphoma (HL) – Reed-Sternberg cells.
▪ Non-Hodgkins lymphoma (NHL) – no RS cells.
▪ Hodgkin's disease causes the cells in the
lymphatic system to abnormally reproduce,
eventually making the body less able to fight
infection.
64. HODGKIN'S LYMPHOMA NON-HODGKIN'S LYMPHOMA
-type of lymphocyte affected is
B and T cells
-Rc are not present.
-more common than Hodgkin
lymphoma.
-The majority of non-Hodgkin
patients are over the age of 55
when first diagnosed
- may arise in lymph nodes
anywhere in the body,
-type of lymphocyte
affected is B cells
-presence of Reed-
Sternberg cells
- Age ;15 and 34 median
age 39
-begins in the upper
body, such as the neck
(70%), chest or arm pits.
65. SIGNS AND SYMPTOMS
▪ Painless swelling of lymph nodes in neck,
underarm, and groin
▪ Fever
▪ Night sweats
▪ Fatigue
▪ Weight loss
▪ Itching of the skin
▪ It may resemble other blood disorders or
medical problems, such as influenza or other
infections. / Recurring infection NHL
66. DIAGNOSIS
▪ Additional blood tests
▪ X-rays of the chest, bones, liver, and spleen
▪ Biopsy of the lymph nodes
▪ Radiation therapy
▪ Chemotherapy
TREATMENT
67. Burkitt’s lymphoma: large B cell NHL
▪ Endemic in Africa
▪ Epstein Barr Virus (EBV)
▪ B Cell Lymphoma.
▪ Dark large B lymphocytes
(malignant) with plenty of
pale macrophages. (Starry
sky pattern).
68. Oral considerations of lymphomas
▪ Early diagnosis
▪ Complications of radiotherapy
▪ Suspected swellings of the palate, gingiva,and
tongue should be biopsied.
69. Multiple Myeloma:
▪ Malignancy of Plasma cells
(Mature B lymph, Ab) - Old age,
males.
▪ Marrow, LN, Blood.
▪ Multiple, punched out Lytic
bone lesions (Osteolysis)
▪ Hyper gammaglobulinemia
▪ Monoclonal antibody peak –
serum protein
electrophoresis.
▪ Immunodeficiency →
infections.
70. MULTIPLE MYELOMA
• Monoclonal paraprotein
❑ Intact immunoglobulin in serum
❑ Light chains in serum or urine (Bence Johnes protein)
• Marrow plasmacytosis (> 20% - may be patchy)
• Lytic bone lesions
DIAGNOSIS
71. MULTIPLE MYELOMA
• Anemia progressing to pancytopenia
• Bone pain/destruction
• Hypercalcemia
• Humoral immune defect
• Local effects of plasmacytomas
• Systemic effects of paraprotein
CLINICAL MANIFESTATIONS
72. MONOCLONAL GAMMOPATHY
• Hyperviscosity (IgM >> IgA > IgG)
• Renal dysfunction (light chains)
❑ Glomerular
❑ Tubular
• Neuropathy
• Other organ damage (rare)
• Amyloidosis
COMPLICATIONS
73. Oral manifestations & dental consideration
• The oral manifestations of MM are the
first sign of the disease in about 14% of
the patients.
• The patient may experience pain, swelling,
numbness of the jaws, epulis formation, or
unexplained mobility of the teeth.
• Amyloidosis of the tongue , bleeding and
susceptibility to infection should be
considered before treating the patient.
