Hematological Disorders

  • Blood is a connective tissue in fluid form.
  • Blood contains the blood cells which are called formed elements and the liquid portion known as plasma.

Three types of cells are present in the blood:

  1. Red blood cells or erythrocytes.
  2. White blood cells or leukocytes.
  3. Platelets or thrombocytes.

If blood is collected in a hematocrit tube along with a suitable anticoagulant and centrifuged for 30 minutes at a speed of 3000 revolutions per minute (rpm), the red blood cells settle down at the bottom having clear plasma at the top. Plasma forms 55% and red blood cells form 45% of the total blood. Volume of red blood cells expressed in percentage is called the hematocrit value or packed cell volume (PCV).

Plasma is a straw-colored clear liquid part of blood. It contains 91% to 92% of water and 8% to 9% of solids.

Serum is the clear straw-colored fluid that oozes from blood clot.

Serum = Plasma – Fibrinogen.

  1. Serum albumin.
  2. Serum globulin.
  3. Fibrinogen.
  • Total proteins: 7.3 g/dL (6.4 to 8.3 g/dL)
  • Serum albumin: 4.7 g/dL
  • Serum globulin: 2.3 g/dL.
  • Fibrinogen: 0.3 g/dL.

Red blood cells (RBCs) are the non-nucleated formed elements in the blood. Red blood cells are also known as erythrocytes (erythros = red).

Count ranges between 4 to 5.5 million/cu mm of blood.

  • In adult males – 5 million/cu mm
  • In adult females – 4.5 million/cu mm.

Average lifespan of RBC is about 120 days. The senile (old) RBCs are destroyed in reticuloendothelial system.

The destruction occurs mainly in the capillaries of red pulp of spleen because the diameter of splenic capillaries is very small. So, the spleen is called graveyard of RBCs.

  • Hemoglobin is degraded into iron, globin and porphyrin.
  • Iron combines with the protein called apoferritin to form ferritin, which is stored in the body and reused later.
  • Globin enters the protein depot for later use.
  • Porphyrin is degraded into bilirubin, which is excreted by liver through bile
  1. Pathological Polycythemia

It is the abnormal increase in RBC count. Red cell count increases above 7 million/cu mm of the blood.

Polycythemia is of two types:

    • Primary Polycythemia – Polycythemia Vera
    • Secondary Polycythemia
  1. Anemia

Abnormal decrease in RBC count is called anemia.

Diameter: 7.2 μ (6.9 to 7.4 μ).

Thickness: At the periphery it is thicker with 2.2 μ and at the center it is thinner with 1 μ. This difference in thickness is due to biconcave shape.

Surface area : 120 sq μ.

Volume : 85 to 90 cu μ.

  1. Microcytes (smaller cells).
  2. Macrocytes (larger cells).
  3. Anisocytes (cells with different sizes).

Shape of RBCs is altered in many conditions including different types of anemia.

  1. Crenation: Shrinkage as in hypertonic conditions.
  2. Spherocytosis: Globular form as in hypotonic conditions.
  3. Elliptocytosis: Elliptical shape as in certain types of anemia.
  4. Sickle cell: Crescentic shape as in sickle cell anemia.
  5. Poikilocytosis: Unusual shapes due to deformed cell membrane. The shape will be of flask, hammer or any other unusual shape.

Hemoglobin (Hb) is the iron containing coloring matter of red blood cell (RBC).

AGE

  • At birth: 25 g/dL.
  • After 3rd month: 20 g/dL.
  • After 1 year: 17 g/dL.
  • From puberty onwards: 14 to 16 g/dL.

At the time of birth, hemoglobin content is very high because of increased number of RBCs.

 Sex

  • In adult males : 15 g/dL
  • In adult females : 14.5 g/dL

Hemoglobin is a conjugated protein. It consists of a protein combined with an iron containing pigment. The protein part is globin and iron containing pigment is heme.

Iron

Normally, it is present in ferrous (Fe2+) form. It is in unstable or loose form. In some abnormal conditions, the iron is converted into ferric (Fe3+) state, which is a stable form.

Porphyrin

  • The pigment part of heme is called porphyrin.
  • It is formed by four pyrrole rings (tetrapyrrole) called, I, II, III and IV.
  • Pyrrole rings are attached to one another by methane (CH4) bridges.
  • The iron is attached to ‘N’ of each pyrrole ring and ‘N’ of globin molecule.

Globin

  • Globin contains four polypeptide chains.
  • Two are β-chains and two are α-chains.

Hemoglobin is of two types:

  1. Adult hemoglobin – HbA
  2. Fetal hemoglobin – HbF
  • In adult hemoglobin, the globin contains two α-chains and two β-chains.
  • In fetal hemoglobin, there are two α chains and two γ-chains instead of β-chains.
  • Fetal hemoglobin has more affinity for oxygen than that of adult hemoglobin.

These are formed by carbon monoxide (CO) poisoning or due to some drugs like nitrites, nitrates and sulphanamides.

Abnormal hemoglobin derivatives are:

  1. Carboxyhemoglobin.
  2. Methemoglobin.
  3. Sulfhemoglobin.

Also known as carbon monoxyhemoglobin is the abnormal hemoglobin derivative formed by the combination of carbon monoxide with hemoglobin.

Also known as ferrihemoglobin, an abnormal hemoglobin derivative formed when iron molecule of hemoglobin is oxidized from normal ferrous state to ferric state.

Formed by combination of hemoglobin with hydrogen sulfide. It is caused by drugs such as phenacetin or sulfonamides.

  • Erythrocyte sedimentation rate (ESR) is the rate at which the erythrocytes settle down.
  • Also known as sed rate or Biernacki reaction. 
  1. Westergren method.
  2. Wintrobe method.

By Westergren Method

  • In males : 3 to 7 mm in 1 hour.
  • In females : 5 to 9 mm in 1 hour.
  • Infants : 0 to 2 mm in 1 hour

By Wintrobe Method

  • In males: 0 to 9 mm in 1 hour
  • In females: 0 to 15 mm in 1 hour
  • Infants: 0 to 5 mm in 1 hour.

ESR is helpful in assessing the progress of patients treated for certain chronic inflammatory disorders.

  • Also known as hematocrit value or erythrocyte volume fraction (EVF).
  • Packed cell volume (PCV) is the proportion of blood occupied by RBCs, expressed in percentage.
  1. Diagnosis and treatment of anemia.
  2. Diagnosis and treatment of polycythemia.
  3. Determination of extent of dehydration and recovery from dehydration after treatment.
  4. Decision of blood transfusion.

In males = 40% to 45%

In females = 38% to 42%

Blood indices include:

  1. Mean corpuscular volume (MCV).
  2. Mean corpuscular hemoglobin (MCH).
  3. Mean corpuscular hemoglobin concentration (MCHC).
  4. Color Index (CI).

MCV is average volume of a single RBC and expressed in cubic microns (cu μ).

MCV=    (PCV in mL / 1,000 mL of blood)/(RBC count in million/cu mm of blood)

Normal MCV is 90 cu μ (78 to 90 cu μ).In cases of:

  • Normal MCV, RBC is called- normocyte.
  • Increase MCV,RBC is called – macrocyte
  • Decrease MCV, RBC is called microcyte.
  • MCH is the quantity or amount of hemoglobin present in one RBC.
  • It is expressed in micromicrogram or picogram(pg).

MCH = (Hemoglobin in gram per 1000 ml of blood)/(RBC count in million/cu mm)

Normal value of MCH is 30 pg (27 to 32 pg).

  • MCHC is the concentration of hemoglobin in one RBC.
  • It is the amount of hemoglobin expressed in relation to volume of one RBC.

MCHC = (Hemoglobin in gram/100 mL of blood)/(PCV in 100 mL of blood*100)

  • Normal value of MCHC is 30% (30% to 38%).

In cases of:

  • Normal MCHC, RBC is – Normochromic.
  • Decrease MCHC, RBC- Hypochromic.

Color index is the ratio between the percentage of hemoglobin and the percentage of RBCs in the blood.

Also known as leukocytes, these are the colorless and nucleated formed elements of blood (leuko is derived from Greek word leukos = white).

Leukocytes are classified into two groups:

  1. Granulocytes: which have granules, these are:
  • Neutrophils with granules taking both acidic and basic stains.
  • Eosinophils with granules taking acidic stain.
  • Basophils with granules taking basic stain.
  1. Agranulocytes: which do not have granules, these are:
  • Monocytes.
  • Lymphocytes.

  Feature

WBCs

RBCs

  Color

Colorless

Red

  Number

Less: 4,000 to 11,000/cu mm

More: 4.5 to 5.5 million/cu mm

  Size

Maximum diameter = 18 μ

Maximum diameter =7.4 μ

  Shape

Irregular

Disk-shaped and biconcave

  Nucleus

Present

Absent

  Granules

Present in some types

Absent

  Types

Many types

Only one type

  Lifespan

Shorter: ½ to 15 days

Longer:120 days

Depending upon the size:

  1. Large lymphocytes: Younger cells with a diameter of 10 to 12 μ.
  2. Small lymphocytes: Older cells with a diameter of 7 to 10 μ.

Depending upon the function:

  1. T lymphocytes: Cells concerned with cellular immunity.
  2. B lymphocytes: Cells concerned with humoral immunity.

Total WBC count (TC): 4,000 to 11,000/cu mm of blood.

  WBC

Percentage

Absolute value

per cu mm

  Neutrophils

50 to 70

3,000 to 6,000

  Eosinophils

2 to 4

150 to 450

  Basophils

0 to 1

0 to 100

  Monocytes

2 to 6

200 to 600

  Lymphocytes

20 to 30

1,500 to 2,700

  WBC

Substance secreted

Action

  Neutrophil

Proteases

Myeloperoxidases

Elastases

Metalloproteinases

Destruction of microorganisms

Defensins

Antimicrobial action

Anti-inflammatory action

Wound healing

Chemotaxis

Cathelicidins

Antimicrobial action

NADPH oxidase

Bactericidal action

Platelet-activating factor

Aggregation of platelets

  Eosinophil

Eosinophil peroxidase

Destruction of worms, bacteria and tumor cells

Major basic protein

Destruction of worms

Eosinophil cationic protein

Destruction of worms

Neurotoxic action

Eosinophil-derived neurotoxin

Neurotoxic action

Interleukin-4 and 5

Acceleration of inflammatory response

Destruction of invading organisms

  Basophil

Heparin

Prevention of intravascular blood clotting

Histamine

Production of acute hypersensitivity reactions

Bradykinin

Serotonin

Proteases

Destruction of microorganisms

Myeloperoxidases

Interleukin-4

 

  Monocyte

Interleukin-1

Acceleration of inflammatory response

Destruction of invading organisms

Colony stimulation factor

Formation of colony forming blastocytes

Platelet-activating factor

Aggregation of platelets

Chemokines

Chemotaxis

  T lymphocytes

Interleukin-2, 4 and 5

Acceleration of inflammatory response

Destruction of invading organisms

Activation of T cells

Gamma interferon

Stimulation of phagocytic actions of cytotoxic cells, macrophages

and natural killer cells

Lysosomal enzymes

Destruction of invading organisms

Tumor necrosis factor

Necrosis of tumor

Activation of immune system

Promotion of inflammation

Chemokines

Chemotaxis

  B lymphocytes

Immunoglobulins

Destruction of invading organisms

Tumor necrosis factor

Necrosis of tumor

Activation of immune system

Acceleration of inflammatory response

Chemokines

Chemotaxis

  1. Neutrophilia or neutrophilic leukocytosis (Increase in neutrophil count):
    • Acute infections
    • Metabolic disorders
    • Injection of foreign proteins
    • Injection of vaccines
    • Poisoning by chemicals & drugs like lead, mercury,benzene derivatives, etc.
    • Poisoning by insect venom
    • After acute hemorrhage.
  2. Neutropenia(Decrease in neutrophil count)
    • Bone marrow disorders.
    • Tuberculosis.
    • Typhoid.
    • Autoimmune diseases.
  3. Eosinophilia(Increase in eosinophil count)
    • Allergic conditions like asthma.
    • Blood parasitism (malaria, filariasis).
    • Intestinal parasitism.
    • Scarlet fever.
  4. Eosinopenia(Decrease in eosinophil count)
    • Cushing’s syndrome
    • Bacterial infections
    • Stress
    • Prolonged administration of drugs like steroids, ACTH and
    • Epinephrine
  5. Basophilia( Increase in basophil count)
    • Smallpox
    • Chickenpox
    • Polycythemia vera
  6. Basopenia (Decrease in basophil count)
    • Urticaria (skin disorder)
    • Stress
    • Prolonged exposure to chemotherapy or radiation therapy.
  7. Monocytosis( Increase in monocyte count)
    • Tuberculosis
    • Syphilis
    • Malaria
    • Kala-azar
  8. Monocytopenia (Decrease in monocyte count)
    • Prolonged use of prednisone (immunosuppressant steroid)
  9. Lymphocytosis (Increase in lymphocyte count).
    • Diphtheria
    • Infectious hepatitis
    • Mumps
    • Malnutrition
    • Rickets
    • Syphilis
    • Thyrotoxicosis
    • Tuberculosis
  10. Lymphocytopenia (Decrease in lymphocyte count)
    • AIDS.
    • Hodgkin’s disease (cancer of lymphatic system).
    • Malnutrition.
    • Radiation therapy.
    • Steroid administration.

It was first described by Vaquez in 1892. So, called Vaquez’s disease and other name includes polycythemia rubra vera, Osler’s disease, and erythema.

  • Primary proliferative polycythemia (polycythemia rubra vera).
  • Secondary polycythemia.
  • Apparent polycythemia.
  • Myeloproliferative disorder characterized by excessive proliferation of erythroid elements along with granulocytic and megakaryocytic cells
  • The red blood cell (RBC) volume increases to an erythrocyte count of 6 to 12 million/mm3 with a hemoglobin concentration of 18 to 24 g/dL, leading to increased blood viscosity and thrombosis.

Acquired genetic changes in the stem cell leading to disturbances of normal cellular growth.

  • Ruddy cyanosis on face and extremities.
  • Headache.
  • Dizziness.
  • Tinnitus.
  • Fullness of head and face.
  • Pruritus.
  • Splenomegaly
  • Coronary thrombosis
  • Erythromelalgia may manifest as paresthesias involving the cranial nerves
  • Purplish red discoloration of tongue, cheeks, and lips.
  • Gingivae is red and may bleed spontaneously.
  • Petechiae and ecchymoses (platelet abnormalities).
  • Varicosities in ventral tongue.
  • A mildly elevated white cell count, especially the neutrophil (a type of white blood cell) count which doesn’t progress.
  • An elevated platelet count, which occurs in at least 50 percent of patients which may progress.
  • An elevated red cell mass.
  • Normal or near-normal arterial oxygen saturation.
  • A low erythropoietin (EPO) assay in the blood. 
  • Phlebotomy.
  • Alkylating agents and radioactive phosphorus (32P)
  • Chemotheraputic agents such as busulfan, chlorambucil, cyclophosphamide, and melphalan
  • Hydroxyurea
  • High-risk patients (60 years of age or older or those who have had a thrombosis or hemorrhagic event at any age) treated with cytoreductive drugs (e.g. hydroxyurea).
  • Intermediate-risk patients (> 60 years who have not had thromboses, but platelet counts >1,500 × 109 /l or have significant cardiovascular risk factors) treated with low-dose aspirin (40-325 mg).
  • Low-risk patients (<60 years old who have not had thrombosis, no cardiovascular risk factors, and platelet counts are <1,500 × 109 /l) placed on low dose aspirin along with phlebotomy.
  • Risk of bleeding or thrombosis.
  • Advise complete blood count prior to treatment.
  • Hemoglobin should be reduced below 16 g/dL and the hematocrit to below 47% as these are the thresholds at which medical management is instituted.
  • Require special attention to local hemostasis.
  • Preoperative myelosuppressive treatment should be considered prior to dental treatment when blood counts are not controlled with phlebotomy alone.

Secondary polycythemia is due to an increase in erythropoietin production to compensate for hypoxia in conditions such as:

  1. Respiratory disorders like emphysema.
  2. Congenital heart disease.
  3. Ayerza’s disease (condition associated with hypertrophy of right ventricle and   obstruction of blood flow to lungs).
  4. Chronic carbon monoxide poisoning.
  5. Poisoning by chemicals like phosphorus and arsenic.
  6. Repeated mild hemorrhages.

Characterized by an increased hemoglobin concentration and packed-cell volume but normal RBC mass due to reduction in plasma volume.

  • Affects middle-aged obese men with hypertension.
  • Smoking.
  • High alcohol consumption.
  • Diuretic therapy.

Treatment is usually geared toward the underlying disorder.

Anemia ( ἀναιμία anaimia, meaning “lack of blood”, from ἀν- an-, “not” and αἷμα haima, “blood”.) is defined by a decrease in the total amount of hemoglobin or the number of red blood cells.

CLASSIFICATION OF ANEMIA

1 – BLOOD LOSS

  • Acute: Trauma
  • Chronic: Lesions of GI tract, gynaecologic disturbance.

2 – INCREASED RATE OF DESTRUCTION (HEMOLYTIC ANEMIA)

A – Intrinsic (intracorpuscular) abnormalities of red cells:

HEREDITARY

1 – Red cell membrane disorders

  • Disorders of membrane cytoskeleton spherocytosis elliptocytosis.
  • Disorders of lipid synthesis: Selective increase in membrane lecithin

2 – Red cell enzyme deficiencies

  • Glycolytic enzyme: Pyruvate kinease deficiency, hexokinase deficiency.
  • Enzymes of hexose mono phosphate shunt: G6PD,glutathione synthetase.

3 – Disorders of hemoglobin synthesis

  • Deficient globin synthesis: Thalassemia syndromes.
  • Structurally abnormal globin synthesis (hemoglobinopathies): Sickle cell anemia, unstable hemoglobins.

ACQUIRED

1 – Membrane defect; Paroxysmal nocturnal hemoglobinuria.

B – Extrinsic (Extracorpuscular) abnormalities:

  1. Antibody mediated:
    • Isohemagglutinins: Transfusion reactions, erythroblastosis fetalis
    • Autoantibodies: Idiopathic (primary), drugs associated, SLE, malignancies, mycoplasma infections.
  2. Mechanical trauma to red cells.
    • Microangiopathic haemolytic anemias: Thrombotic thrombocytopenic purpura, DIC
    • Cardiac traumatic haemolytic anemia.
  3. Infections: Malaria
  4. Chemical injury: Lead poisoning
  5. Sequestration in mononuclear phagocyte system hypersplenism.

 C – IMPAIRED RED CELL PRODUCTIONS

  1. Disturbance of proliferation and differentiation of stem cells: aplastic anemia, pure red cell aplasia, anemia of renal failure, anemia of endocrine disorders.
  2. Disturbance of proliferation and maturation of erythroblasts:
    1. Defective DNA synthesis: Deficiency or impared utilization of vitamin B12 and Folic Acid (megaloblastic anemia)
    2. Deficient hemoglobin synthesis
      1. Deficient heme synthesis: Iron deficiency
      2. Deficient globin synthesis: Thalassemias
    3. Unknown or multiple mechanisms: Sideroblastic anemia, anemia of chronic infections, myelophthisic anemias due to marrow infiltrations.
  • Normocytic Normochromic Anemia: Size (MCV) and color (MCHC) of RBCs are normal. But the number of RBC is less.
  • Macrocytic Normochromic Anemia: RBCs are larger in size with normal color. RBC count is
  • Macrocytic Hypochromic Anemia: RBCs are larger in size. MCHC is less, so the cells are pale (less colored).
  • Microcytic Hypochromic Anemia: RBCs are smaller in size with less color

Iron deficiency (ID) is defined as the decrease of the total content of iron in the body.

    1. Digestive disorders
      1. Increased loss of iron:
        • Cancer/polyp: colon, stomach, esophagus, small bowel
        • Peptic ulcer, esophagitis
        • Inflammatory bowel disease: ulcerative colitis, Crohn’s disease
      2. Reduced iron absorption
        • Celiac disease
        • Gastrectomy (partial and total) and gastric atrophy
    2. Urological and gynecological disorders.
    3. Intravascular hemolysis: Paroxysmal nocturnal hemoglobinuria, multiple blood donations
    4. Deficient iron intake.
  • Pallor of skin, palpebral conjunctiva and nail beds.
  • Tendency of the nails to crack and split.
  • General weakness.
  • Fatigue.
  • Irritability.
  • Poor concentration.
  • Headache.
  • Intolerance to exercise.
  • Pica.

An eating disorder in which there is an irresistible desire to lick or eat non-nutritive and unusual substances, such as soil, chalk, gypsum, ice (pagophagia) or paper.

  • Pallor of the mucosa.

Mild cases

  • Discomfort and redness of tongue.
  • Flattening of papillae round the margin of the tongue. 

Severe Cases

  • Redness and atrophy of filiform and fungiform papillae.
  • Reduce number of prickle cells.
  • Thinning of epithelium
  • Absence of papillae in lamina propia.

Buccal mucosa:

  • Thinning of epithelium.
  • Decrease in the melanin pigmentation
  • Increase in number of prickle cells
  • Abnormal keratinization.

Diagnosis is based on:

  • Low hemoglobin.
  • Peripheral smear- cells are microcytic and hypochromic.
  • MCH,MCHC & MCV values get decreased.
  • Low serum iron concentrations.
  • High serum iron-binding capacity.
  • Reduced serum ferritin levels.
  • Patient with significant low hemoglobin should be referred to physician.
  • Elective oral surgical or periodontal procedures should not be performed (increased bleeding and impaired wound healing).
  • Low hemoglobin levels affect the rheologic interactions between blood cellular components due to low oxygen tension, mainly platelets and endothelium, decreasing their ability to clot effectively.
  • General anesthesia should not be administered unless the hemoglobin is at least 10 g/dL.
  • Never treat the patient with iron until the cause of the microcytic hypochromic anemia is found.
  • Plummer-Vinson syndrome is defined by the classic triad of dysphagia, iron-deficiency anemia and esophageal webs.
  • Plummer-Vinson syndrome, named after Henry Stanley Plummer (1874–1936) and Porter Paisley Vinson (1890–1959).
  • Another term is Paterson-Kelly syndrome, named after Donald Ross Paterson (1863–1939) and Adam Brown-Kelly (1865–1941), both British laryngologists, who published their findings independently in 1919.
  • Postcricoid dysphagia, upper esophageal webs and iron deficiency anemia.
  • Affects white middle-aged women, in the 4th to 7th decade of life.
  • The dysphagia is usually painless and intermittent or progressive over years limited to solids and sometimes associated with weight loss.
  • Weakness, pallor, fatigue and tachycardia.
  • Characterized by glossitis, angular cheilitis and koilonychia (spoon-shaped finger nails).
  • Enlargement of the spleen and thyroid.
  • This syndrome has been identified as a risk factor for developing squamous cell carcinoma of the upper gastrointestinal tract.
  • Based on the evidence of iron-deficiency anemia and one or more esophageal webs with postcricoid dysphagia.
  • Esophageal webs can be detected by barium swallow X-ray, upper G.I.T endoscopy that appear smooth, thin, and gray with eccentric or central lumen.
  • The webs typically occur in the proximal part of the esophagus and may be missed and accidentally ruptured unless the endoscope is introduced under direct visualization.
  • Clarify the cause of iron deficiency in order to exclude active hemorrhage, malignancy or celiac disease.
  • Plummer-Vinson syndrome can be treated easily and effectively with iron supplementation and mechanical dilation.
  • After endoscopic placement of a guide wire, dilators with a diameter of up to 17 mm can be used.
  • Hemolytic anemia is a condition in which red blood cells are destroyed and removed from the bloodstream before their normal lifespan is over.
  • Recognized by clinical jaundice and other evidence of increase bile pigment.
  • Yellowish brown discoloration of teeth (persistent icterus during dental development).
  • Expansion of bone marrow (due to compensatory hyperplasia of marrow)
  • Remodeling of maxilla especially premaxilla leads to mongoloid features.
  • Splayed anterior teeth.
  • Anterior open bite.
  • Osteoporosis. 
  • Decreased Hb levels.
  • Decreased hepatoglobulins.
  • Increased reticulocyte count.
  • Increased serum bilirubin.(unconjugated form)
  • Peripheral blood smear shows normocytic normochromic cells, but in hereditary spherocytosis & elliptocytosis exhibit abnormal spheric or elliptic shape.
  • By measuring red cell survival time.
  • Coomb’s test: Demonstrate antibodies to erythrocytes.
  • Direct Coombs test: Demonstrates incomplete antibodies attached to the erythrocytes, which require antihuman globulin to produce hemolysis.
  • Indirect Coombs test: Detects antibodies to the red cells, which are present in the patient’s serum, usually immunoglobulin IgG1 and IgG3.

It is intracorpuscular defect is an acquired clonal stem cell disorder that results in abnormal sensitivity of the RBC membrane to lysis by complement.

  • Anemia.
  • Mild granulocytopenia.
  • Thrombocytopenia.
  • Back pain.
  • Abdominal pain, and headaches(due to ischemia).

Complications: Venous thromboses, hemoglobinuria, and hemosiderinuria.

Sucrose hemolysis test: Demonstrate increased sensitivity of the erythrocytes to complement.

  • Corticosteroids or androgens are the line of treatment.
  • Blood transfusions are necessary prior to the surgical intervention.
  • Survival rate is less than 10 years due to thrombosis or renal failure.
  • It is x-linked hereditary defect due to deficiency of hereditary enzyme Glucose-6-Phosphate Dehydrogenase.
  • Hemolysis due to reduced capacity of RBCs to deal with oxidative stresses.
  • Deficiency of enzyme RBC do not maintain the required level of reduced glutathione
  • As a result, sulfhydryl groups of Hb and the cell membrane get oxidized, leaving Hb to precipitate in the cell and eventual cell lysis.
  • G6PD deficient RBC, the denatured Hb with stromal proteins forms Heinz bodies due to oxidation and removed from circulation resulting in hemolytic anemia.
  • No treatment is necessary
  • Severity and correction of anemia should be evaluated before major dental interventions because Hb level may come to 3 to 4 g/dL.
  • Drugs which induce hemolysis better to be avoided like dapsone, sulfasalazine, and phenacetin.
  • It is a genetic disease caused by replacement of glutamic acid by valine in position 6 at the N-terminus of the beta-chain of globin, thus resulting in hemoglobin S.
  • Under conditions of hypoxia, erythrocytes that predominantly contain hemoglobin S take on a shape resembling a sickle.

Microvascular occlusions are responsible for clinical manifestations.

  • Jaundice.
  • Pallor.
  • Cardiac failure
  • Splenic infarction.
  • Chronic leg ulcers.
  • Priapism.
  • Cerebral vascular thromboses.
  • Painful attacks of abdominal and bone pain (pain crises).
  • It consists of an episode of severe pain of 1 to 2 weeks duration, often accompanied by a low-grade fever and leukocytosis.
  • Crisis may be precipitated by infection, dehydration or acidosis or may be associated with any identified etiology.
  • Jaundice and pallor of oral mucosa.
  • Delayed eruption.
  • Disorders of enamel and dentin mineralization.
  • Malocclusion.
  • Hypercementosis.
  • Decreased number of trabeculae on dental radiographs.
  • Trabeculae may appear as horizontal rows (ladderlike effect )
  • Lamina dura appears dense and distinct.

In skull films:

  • Diploë is thickened.
  • Coarse trabeculae run perpendicular to the inner and outer tables (“hair on end” appearance).
  • Areas of increased radiopacity represent past thrombosis with subsequent bony infarction.
  • Peripheral smear shows normochromic normocytic cells.
  • Hemoglobin electrophoresis: It detects hemoglobin S.
  • Hemoglobin values of 5 to 9 g/dl.
  • RBC survival time is markedly decreased.
  • Seal fresh blood in a small chamber of a microscopic slide with sodium metabisulfite (a reducing agent) for 1 hour and then observed for sickling.
  • No treatment other than symptomatic treatment.
  • Antibiotics (in infection).
  • Transfusions are avoided unless the patient has an aplastic crisis
  • Cytotoxic agents: Hydroxyurea (increase hemoglobin F and reduce the frequency of painful episodes).
  • Allogeneic stem cell transplantation.
  • Elective dental procedures involving the soft tissues should not be performed in poorly controlled. (Complications secondary to chronic anemia and delayed wound healing).
  • Elimination of oral sources of infection.
  • General anesthesia should be used with caution; when used, avoid episodes of hypoxia, cerebral or myocardial thrombosis can result.

This hemoglobinopathy is a group of hereditary disorder characterized by lack or decreased synthesis of globin chains.

  1. α thalassemia (reduce or deficient α chain)
  2. β thalassemia:
  • β+ thalassemia (reduced amounts of β chains are produced)
  • βo thalassemia (no normal β chains are produced )

β Thalassemia

Thalassemia major

(Cooley’s anemia)

Homozygous

βo/ βo or  β+/ β+

Severe, requires blood transfusions regularly.

Thalassemia minor

Heterozygous

βo/ β or β+/ β

Asymptomatic with mild or no anemia

RBC abnormalities seen

α Thalassemia

Silent carrier

– α/ αα

Asymptomatic, no RBC abnormality

α Thalassemia trait

– α/- α

Asymptomatic with mild or no anemia

RBC abnormalities seen

  • Often remain undetected.
  • Mild insignificant microcytic anemia.
  • No treatment is required.
  • Genetic counselling for risk couples.
  • Clinical manifestation starts with 4 to 6 months of life as fetal Hb starts transforming into adult chains.
  • Hb level drops to 2 to 3 g/dL.
  • Hemolysis and iron overload is maximum.
  • Decreased growth and development in children.
  • Delay in secondary sex characteristics.
  • The skin becomes ashen-gray (combination of pallor, jaundice, and hemosiderosis).
  • Cardiomegaly, hepatomegaly and splenomegaly.
 

Features

Cause

Facial features

Class II malocclusion

Maxillary protrusion, mandibular atrophy

 

Maxillary protrusion

Early fusion of occipital sutures,

hyperplasia of anterior maxillofacial

structures

 

Lateral displacement of orbits

Marrow overgrowth in maxillary bone

 

Chipmunk facies

Malar prominence, saddle nose, frontal

bossing

 

Brodie syndrome

Mandibular arch is telescoped within the maxillary arch

 

Pneumatisation of paranasal sinuses

Hyperplasia of marrow in frontal, temporal and facial bones

Oral manifestations

Malocclusion

Maxillary protrusion, increased overjet, anterior open bite

 

High caries index

Poor oral hygiene, less phosphorous and IgA in saliva

 

Mucosal pallor, atrophic glossitis

Decreased haemoglobin levels

 

Severe gingivitis

If splenectomy done

 

Inflammation of salivary glands

Iron deposits

 

Dark coloured gingiva

High ferritin levels in blood

 

Thin mandibular cortex

Marrow proliferation, expansion of medulla

 

Multiple diastemas

 
 

Roots- short and spike shaped, taurodontism

 
  • Generalized rarefaction of the alveolar bone.
  • Thinning of cortical bone.
  • Enlarged marrow spaces.
  • Coarse trabeculae.
  • In the parietal bones, the thin cortex covering the coarse vertical trabeculae and the enlarged diploë produce a “hair on end” picture.
  • Peripheral blood smear shows microcytic hypochromic cells.
  • Hb electrophoresis shows increased HbF and variable HbA.
  • Absence of HbA (in homozygous βo patients).
  • Prenatal diagnosis can be done by DNA analysis of amniotic fluid.
  • Any invasive procedure should be done under antibiotic cover and immediately after transfusion.
  • Liver function and coagulation tests should be done before dental procedures.
  • Orofacial defects and malocclusions in less severe types can be treated surgically followed by orthodontic treatment.
  • Less severe malocclusions can be corrected by orthodontic treatment at an early age.
  • Tetracycline, metronidazole and erythromycin estolate should be avoided.
  • Paracetamol is a safe alternative to NSAIDS and aspirin.
  • Caution should be exercised in thalassemia due to complications related to compromised immunity, liver function, splenectomy and cardiovascular issues.
  • Multidisciplinary approach involving dental surgeon, haematologist and orthodontist should be practiced.

This category includes the anemias caused by an in-adequate supply of certain substances to the bone marrow that are necessary for hematopoiesis.

The most common deficiencies are:

  • Iron: iron deficiency anemia
  • Folic acid & Vitamin B12: Megaloblastic anemia.

Other causes of diminished erythropoiesis:

  • Suppression of marrow stem cells(aplastic anemia)
  • Infiltration of bone marrow.
  • This group of disorders characterized by a distinct morphologic pattern in hematopoietic cells that have small immature nuclei and large mature cytoplasms.
  • Microscopically, this nuclear-cytoplasmic asynchrony is described as “megaloblastic.

This condition occurs due to impaired absorption rather than dietary deficiency.

  • Atrophy of gastric mucosa (leads to lack of intrinsic factor secretion).
  • Gastrectomy.
  • Resection of ileum.
  • Diverticulosis
  • Alcoholism.
  •  Medications (neomycin and colchicines).
  •  Autoimmune disorder (Graves’ disease).
  • Pallor
  • Easy fatigability.
  • Dyspnoea
  • Mild jaundice (increased destruction of erythroid progenitors).
  • Congestive heart failure.

Neurological changes:

  • Symmetric numbness.
  • Tingling and burning of feet and hands.
  • Unsteadiness of gait and loss of position sense particularly in toes.
  • Neurological lesions include demyelination of posterior and lateral columns of spinal cord & peripheral nerves.
  • Axonal degeneration in severe cases.

• Angular cheilosis.
• Mucositis.
• Stomatitis.
• Sore or burning mouth.
• Hemorrhagic gingiva.
• Halitosis.
• Epithelial dysplasia of oral mucosa.
• Oral paraesthesia.
• Detachment of periodontal fibres.
• Loss or distortion of taste.
• Glossitis oral pain.
• Ulceration.
• Ulcerative gingivitis
• Denuded tongue.
• Glossitis.
• Glossodynia.
• Tongue is “beefy,” red, smooth and glossy.
• Delayed wound healing.
• Xerostomia.
• Bone loss.
• Aphthous ulcers.

  • Decreased hemoglobin.
  • Peripheral blood smear shows macrocytic normochromic cells.
  • Increased MCV & MCH.
  • Normal MCHC.
  • Bone marrow examination shows: presence of megaloblastic marrow changes.
  • Serum assay for Vit. B12 and folate.
  • Associated neurological findings.
  • Schilling test.
  • Presence of serum antibodies to gastric parietal cells(serum anti intrinsic factor antibodies)

Measured small amount of radioactive vitamin B12 is given by mouth, followed shortly by a large flushing dose of parenteral nonradioactive vitamin B12. Because the total dose of vitamin B12 far exceeds the renal threshold for this vitamin, the excess appears in the urine within the next 24 hours. The amount of radioactivity in the urine is proportional to the amount of the orally administered vitamin B12 that has been absorbed. The normal patient excretes 7 to 30% of the radioactive B12 in 24 hours, whereas the patient with pernicious anemia excretes no more than 3%.

  • Parentral administration of Vitamin B12.
  • Large oral doses if IM infusions are contraindicated.
  • Never give folic acid therapy without diagnosing pernicious anemia as it removes a valuable diagnostic sign (low hemoglobin) and allows the neurologic changes.

This condition occurs due to dietery deficiency as well as due to malabsorption of folates.

Diet devoid of leafy vegetables (alcoholics and drug abusers)

  • Increased requirement for folate (pregnant women and young children).
  • Drugs interfering with DNA synthesis ( cancer chemotherapy)

Due to malabsorption:

  • Celic disease.
  • Tropical sprue
  • Pallor
  • Easy fatigability.
  • Dyspnoea
  • Mild jaundice (increase destruction of erythroid progenitors).

• Angular cheilosis.
• Mucositis.
• Stomatitis.
• Sore or burning mouth.
• Increased risk of candidiasis.
• Inflamed gingiva.
• Glossitis oral pain.
• Ulceration.
• Ulcerative gingivitis.
• Denuded tongue.
• Glossitis.
• Glossodynia.
• Tip or borders of tongue red and swollen.
• Aphthous ulcers.

  • Decreased hemoglobin.
  • Peripheral blood smear shows macrocytic normochromic cells.
  • Low serum assay for folic acid.
  • Normal Schilling test.
  • Low RBC folate levels.
  • Oral doses of 1 mg/day.
  • 5 mg tablet to patient with intestinal malabsorption.

Disorder characterized by suppression of multipotent myeloid stem cells with resultant anemia, thrombocytopenia and neutropenia (pancytopenia). So the term anemia is misnomer.

  • Idiopathic(50% of cases)
  • Myelotoxic drugs:
  1. Antineoplastic drugs.
  2. Benzene.
  3. Chloramphenicol and sulfonamides.
  • Whole body irradiations.
  • Viral infections(Hepatitis)

• Pallor
• Easy fatigability.
• Dyspnoea
• Petechiae.
• Ecchymosis.
• Persistant minor infections.
• Sudden onset of chills, fever and prostration.
• Marrow becomes hypocellular.
• Splenomegaly is absent.
• Reticulocytosis is absent.

  • Oral and facial petechiae.
  • Gingival hyperplasia.
  • Spontaneous gingival bleeding.
  • Oral hemorrhagic bullae.
  • Oral candidiasis.
  • Herpetic lesion.

Infections:

Once diagnosis of aplastic anemia is made, thorough examination of teeth, periodontium, soft tissues, and salivary glands should be done.

Bleeding:

  • Can be reduced by systemic antifibrinolytic agents like aminocaproic acid or tranexamic acid and local hemostatic measures.
  • Tranexamic acid 20 mg/kg QID starting 24 hours before oral procedures and continuing for 3 to 4 days afterward.
  • Intramuscular injections and nerve block anesthesias to be avoided because of chances of bleeding owing to thrombocytopenia.
  • Intraligamentary anesthesia can be used.
  • Bone marrow transplantation (in non transfused patient)
  • Immunosupperesive therapy (for older, lack of donor or with multiple transfused patients).
  • Withdrawal of myelotoxic drugs.
  • Inherited aplastic anemia.
  • Manifests in early childhood.
  • Brown skin pigmentation.
  • Hypoplasia of the kidney and spleen.
  • Absent or hypoplastic thumb or radius.
  • Microcephally
  • Mental and sexual retardation.

It is defined as increase in number of WBC.

  • Severe viral infection
  • Tissue necrosis.
  • Allergic reaction.
  • Neoplastic disease.
  • Inflammatory diseases.
  • Stress and exercise (releases epinephrine).

Persistant elevation of WBC with neutrophil count above 30,000/mm3 with pronounced left shift and presence of myelocytes, metamyelocytes and bands.

These are immature neutrophils.

Increase in the number of bands entering the circulation due to increased demand is called as left shift.

Granulocytosis is to be distinguished from a leukemoid reaction by the fact that in LR, there is an orderly maturation and proliferation of all the normal myeloid elements in the bone marrow.

Granulocytopenia also called neutropenia because there is decrease in granulocytes chiefly resulting from decrease in the neutrophils.

  • The normal neutrophil count- 3,000/mm3 to 6,000/mm3.
  • Mild neutropenia, count – 1,000/mm3 to 2,000/mm3.
  • Moderate neutropenia, count – 500/mm3 to1,000/mm3
  • severe neutropenia, count – <500/mm3

The term “agranulocytosis” is used when no neutrophils are seen on a peripheral blood smear and often caused by a drug or medication that interferes with cell formation or enhances cell destruction.

  1. Deficiency of Vit B12 and folic acid.
  2. Viruses:
  • Hepatitis A and B viruses.
  • HIV-1
  • Cytomegalovirus
  • Overwhelming bacterial infection(septicemia)
  1. Systemic lupus erythematosus and Felty’s syndrome (causes sequestration of neutrophils in spleen).
  2. Drugs:

Toxic (dose related): Cancer chemotherapy, benzene, alcohol, analgesics, antibiotics.

Idiosyncratic reactions (not dose related): Phenothiazides, phenylbutazone, sulfonamides, and chloramphenicol.

  • Infection
  • General malaise (headache, discomfort, and muscle aches).
  • Swelling and pus minimal.

Common signs of infection:

  • Fever
  • Mucosal ulcers.
  • Acute pharyngitis.
  • Lymphadenopathy
  • Tachycardia

Common sites of infection:

  • Mouth (oral cavity).
  • Respiratory tract (lungs).
  • Urogenital tract.
  • Skin
  • Rectum

Common organisms:

  • Staphylococcus aureus
  • Gram-negative bacilli: Klebsiella, Pseudomonas and Proteus.
  • Painful oral ulceration: Ulcers becomes large irregular, deep which are extremely painful and characterized by necrosis.
  • Necrotic tissue gives foul smell suggesting fusospirochetal infection with Staphylococcus or gram-negative bacilli.
  • Generalized periodontal destruction.

Neutropenic ulcers differ from other oral ulcers in that they usually lack surrounding inflammation and are characterized by necrosis.

It is a rare hereditary kind of severe neutropenia. The typical symptoms, which appear since the first days of life, are abscesses located on various parts of the body: ear, cutis, lungs and oral cavity. These abscesses are due to an almost total dis-immunity typical of the neutropenia.

  • Oral ulcers, advanced periodontal disease, pericoronitis, and pulpal infections. Chances of bacteremia and septicemia which may prove to be fatal.
  • Culture and sensitivity tests are done and suitable antibiotics started generally a third generation cephalosporin.
  • Combination of topical neomycin, bacitracin, and nystatin used to reduce the risk of severe infection.
  • Topical anaesthetic mouth rinses containing 5% diphenhydramine hydrochloride mixed with magnesium hydroxide or kaolin with pectin used to reduce pain.
  • Chlorhexidine oral rinses are helpful but controversial as they increase gram-negative rods in oral flora.
  • Patient with antibodies (Ab) to neutrophils get benefit from corticosteroids.
  • Patient with Felty’s syndrome were benefitted from splenectomy.
  • Haemopoietic stem cell transplantation(in severe aplastic anemia).
  • Cyclic neutropenia was first described by Leale in 1910.
  • Cyclic neutropenia is a rare disorder characterized by episodes of neutropenia occurring at more or less regular intervals. The reported period of oscillation is 20-21 days, but intervals as short as 14 and as long as 35 days are recorded.
  • Mutation in ELANE (Elastase, neutrophil expressed), the gene that encodes neutrophil elastase.
  • Abnormality in the regulation of bone marrow precursor cells or an inhibitor of neutrophils released from monocytes.
  • Rare disorder.
  • Occurs frequently in infants and childhood, although may also occur in adults.
  • Both sexes are affected equally.
  • It is characterized by neutropenia that recurs every 14 to 35 days, although over 90 percent of patients exhibit a cycle period of 21 days.
  • Patient is healthy between neutropenic episodes, but at regular intervals the absolute neutrophil count falls quickly below 500/mm3even 0.
  • Elevation of monocyte count.
  • Fever
  • Stomatitis
  • Pharyngitis
  • Skin abscesses.
  • Lung infections
  • Urinary tract infection.
  • Rectal and vaginal ulcers.
  • Careful monitoring for infection during neutropenic periods.
  • Corticosteroids, adrenocorticotropin, or testosterone modulates sharp reduction in marrow function.
  • Granulocyte colonies stimulating factor (G-CSF) promotes maturation of neutrophil-precursor cells.
  • Ulceration of oral mucosa (recur with each new bout of neutropenia and resemble RAU major type).
  • Periodontal disease (Ranges from marginal gingivitis to rapidly advancing periodontal bone loss).
  • When either of oral disease is seen in children which cannot be explained by local factors alone, cyclic neutropenia should be ruled out.
  • Single WBC count is not sufficient to rule out cyclic neutropenia.
  • Three total WBC & DLC per week should be done.
  • Known cyclic neutropenic patient require maintenance of oral hygiene to minimize advancing periodontitis.
  • Treatment should be carried out when neutrophil count is above 2,000/mm3.
  • Described by Virchow in 1874 as “white blood,”
  • Malignant condition affecting the WBCs of the bone marrow.
  • There is differentiation and proliferation of malignantly transformed hematopoietic stem cells, leading to suppression of normal cells causing anemia, thrombocytopenia and deficiency of normally functioning leukocytes.
  1. Etiology is unknown.
  2. Predisposing factors:
  • Hereditary
  • Genetic disease.
  • Down syndrome.
  • Klinefelter’s syndrome.
  • Fanconi’s syndrome.
  1. Radiations:
  • Doses over 1 Gray.
  1. Drugs:
  • Benzene
  • Phenylbutazone
  • Chloramphenicol
  • Anticancer drugs.
  1. Acute
  • Acute lymphocytic leukemia (ALL)
  • Acute myelogenous leukemia (AML)
  1. Chronic
  • Chronic granulocytic leukemia (CGL, or chronic myelocytic leukemia [CML])
  • Chronic lymphocytic leukemia (CLL),

These are malignancies of hematopoietic progenitor cells, which consequently fail to mature and differentiate.

  • Occur at any age, but ALL is seen in children and AML in adults.
  • Sign and symptoms results either from bone marrow suppression (anemia, thrombocytopenia or decrease in number of normal functioning leukocytes) or due to infiltration of leukemic cells into other organs and tissues.
  1. Anemia causes:
  • Pallor
  • Shortness of breath
  • Fatigue
  1. Thrombocytopenia causes:
  • Petechiae
  • Ecchymoses
  • Epistaxis
  • Melena
  • Increased menstrual bleeding.
  • Disseminated intravascular disorder.
  1. Decrease number of normal functioning leukocytes causes infections of:
  • Oral cavity.
  • Upper respiratory tract
  • Skin
  • Lungs
  • Urinary tract.
  • Bone pain and tenderness.

Signs due to infiltration of organs and tissues by leukemic cells:

  • Lymphadenopathy
  • Hepatomegaly
  • Splenomegaly

Signs due to infiltration of leukemic cells in CNS or Peripheral nerves:

  • Headache
  • Vomiting
  • Parasthesia
  • Anesthesia
  • Paralysis

Localized tumors consisting of leukemic cells are called “chloromas.”

  • Mucosal pallor (anemia).
  • Spontaneous bleeding.
  • Petechial hemorrhages of gingivae, palate, tongue or lips (due to thrombocytopenia).
  • Gingival hyperplasia (due to leukemic infiltration).
  • Infections (herpes and candidiasis)
  • Chin numbness.
  • Tooth pain and mobility.
  • Cracked lips.
  • Hemorrhagic bullae on the anterior dorsum of the tongue, buccal and labial mucosa.
  • Noma-like lesion.
  • Mucosal pallor.
  • Gingival bleeding or ecchymoses.
  • Lymphadenopathy of the head and neck region.
  • Pericoronitis
  • Extensive ulcers.
  • Coated tongue.
  • Fetor oris.
  • Shallow papillae.
  • Tender oral mucosa
  • Oral mucosal infections (mucositis, candidiasis, herpes and cytomegalovirus)
  • Examination of peripheral blood: Elevated WBC count.
  • Some cases shows normal or decreased count (known as subleukemic or aleukemic leukemia).
  • Immature granulocytic or lymphocytic precursors or even stem cells may be seen PBF.
  • Bone marrow microscopic examination confirms diagnosis.

Chemotherapy which divided into three stages:

  • Induction: Intense myelosuppressing regimen to achieve remission.
  • Consolidation: second course of intensive therapy to prevent relapse
  • Maintenance therapy: Using lower doses and continued periodically from months to years.

Supportive therapy:

  • Platelet transfusions: For hemorrhage.
  • Packed red blood cells: To counter anemia.
  • Heparin: In cases of DIC
  • Antibiotics, antiviral and antifungal.
  • Hemopoietic stem cell transplant(HSCT).

Characterized by the presence of large number of well-differentiated cells in the bone marrow, peripheral blood and tissues with a prolonged clinical course, even without therapy.

  • Chronic granulocytic leukemia (CGL or chronic myelocytic leukemia [CML])
  • Chronic lymphocytic leukemia (CLL).

CML identified by:

  • Presence of Philadelphia chromosome, this chromosomal abnormality affects the hematopoietic stem cell.
  • Reduction in leukocyte AlPO4

Two phases: chronic and blastic.

Chronic phase

Blastic phase

Increased number of granulocytes present in bone marrow and peripheral blood but they retain normal functions.

Further malignant transformation to

immature cells, which act similarly to cells in acute leukemia

Takes about 5 – 8 years for the symptoms to appear after formation of  first CML

Takes 2 – 4 years after diagnosis to transform to immature cells.

  • Occurs in between ages of 30 and 50 years.
  • No symptoms are noted during the first few years,
  • Weakness
  • Fatigue
  • Dyspnea on exertion.
  • Bone pain or abdominal pain in the upper left quadrant.
  • Petechiae, ecchymoses, and hemorrhage(due to thrombocytopenia)
  • Oral sign occurs rarely.
  • Generalized gingival overgrowth.
  • Periodontal and apical diseases.
  • Bleeding gums.
  • Granulocytic sarcoma of the jaws.
  • Elevated well differentiated WBC count.
  • Bone marrow is hypercellular.
  • Presence of Philadelphia chromosome.
  • Absence of leukocyte alkaline phosphatase.

Results from a slowly progressing malignancy involving the lymphocytes mainly B lymphocytes.

  • Occurs frequently in males.
  • Age 40 – 60 years.
  • Detected incidentally by routine hematology.
  • Asymptomatic phase and eventually symptoms of infiltration of leukemic cells in the bone marrow, lymph nodes, or other tissues appear.

Bone marrow infiltration:

  • Pallor
  • Weakness
  • Dyspnea
  • Purpura

Infiltration of other tissues:

  • Lymphadenopathy
  • Splenomegaly
  • Hepatomegaly
  • Leukemic infiltrates of skin or mucosa.
  • Cervical lymphadenopathy and tonsillar enlargement common signs.
  • Later massive lymphadenopathy causes intestinal or urethral obstruction and obstructive jaundice.
  • Hypogammaglobulinemia
  • Varicella-zoster virus infection.
  • Asymptomatic cases- No treatment
  • Treatment started only when there is progressive fatigue, troublesome lymphadenopathy or the development of anemia or thrombocytopenia.
  • Variant of CLL characterized by leukemic B lymphocytes with cytoplasmic projections and a striking 5:1 male predominance.
  • Signs include splenomegaly, vasculitis, and erythema nodosum.
  • Recurrent oral bleeding.
  • Purpura
  • Gingival bleeding.
  • Palatal enlargement.
  • Gingival leukemic infiltration.
  • Oral mucosal ulcers.
Oral Manisfestations Treatment
Gingival enlargement Meticulous oral hygiene by use of soft bristle tooth brush Topical antiseptics (chlorhexidine 0.12% mouth rinse twice a day)
Oral ulcerations Topical steroid (fluocinonide 0.05% gel) four times a day Antibiotic therapy is occasionally administered to prevent bacterial infection Biopsy if necessary
Noma and noma-like lesions Antibiotic therapy Topical antiseptics (0.12% chlorhexidine mouth rinse twice a day) Oral hygiene
Myeloid sarcoma Biopsy Antineoplastic therapy
Gingival bleeding Meticulous oral hygiene by use of soft bristle tooth brush Antifibrinolytic mouth rinse
Oral, dental and periodontal infections Infection foci removal (e.g. periodontal treatment, dental extractions). Topical antiseptics (chlorhexidine 0.12% mouth rinse twice a day) Antibiotics, antivirals and antifungals are administered to prevent and/or treat respec¬tively bacterial, virus and fungal infections Granulocyte colony-stimulating factor is administered as an adjuvant
Trismus Physiatrics/Physiotherapy
  • Chemotherapy
  • Bacterial invasion secondary to severe neutropenia.

Ulcers are characteristically large, irregular, and foul smelling, and are surrounded by pale mucosa and a lack of normal inflammatory response.

Multiple myeloma is a malignant neoplasm that is characterized by a monoclonal proliferation of plasma cells.

  • Etiology is unknown.
  • Clinical manifestations due to expanding plasma cell mass in the bone marrow and other factors produced by these cells such as monoclonal immunoglobulin, Bence-Jones proteins and osteoclast activating factors.
  • It occurs most frequently in older age group
  • Occurs in men (2:1).
  • Pain in the bone.
  • Fatigue
  • Anemia
  • Infectious diseases.
  • Bony lesions
  • Kidney disease.
  • Hypercalcemia
  • Hyperviscosity
  • Hypogammaglobulinemia
  • Swelling,
  • Orofacial pain
  • Mobility of teeth.
  • Paresthesia
  • Hemorrhage
  • Epulis formation.
  • Root resorption in the mandible, in the posterior third and angle of the jaw (greater hematopoietic activity).
  • Tongue may be enlarged and studded with small garnet-colored enlargements, including nodes on the cheeks and lips.
  • Amyloidosis
  • Multiple well‑defined “punched out” radiolucencies involving bone.
  • Radiolucent areas of bone contain the abnormal plasma cell proliferations.
  • Abnormal monoclonal plasma cells.
  • A full blood count.
  • A bone marrow biopsy.
  • Levels of M-protein in the serum or urine.
  • Clinical image consistent with multiple myeloma.
  • Serum electrophoresis identifies M-protein.
  • Urine electrophoresis may identify M-protein.

Group of malignant solid tumors involving cells of the lymphoreticular or immune system e.g.:

  1. B lymphocytes.
  2. T lymphocytes.
  3. Monocytes
  • Disease usually begins in the lymph nodes but may be first diagnosed in extra-nodal lymphoid tissue.
  • Suspicion increases when lymphadenopathy appears without signs of infection, more than one lymph node chain is involved, or a lymph node of 1 cm or greater in diameter persists for more than 1 month.

Etiology is unknown.

Risk factors:

  • Immunodeficiency states.
  • Viral infections.
  • Chemical exposure.
  • Genetics
  • Hodgkin’s Disease.
  • Non Hodgkin’s Disease

First described by British pathologist Thomas Hodgkin in 1832. Hodgkin lymphoma starts in the lymph system, usually in a lymph node.

Histologically:

  • Subgroup I: lymphocyte predominance type.
  • Subgroup II: nodular sclerosis type
  • Subgroup III: mixed cellularity type
  • Subgroup IV: lymphocyte depletion type.
  • Prognosis decreases from subgroup I to subgroup IV.

Ann Arbor Classification with Cotswolds Modification:

  • Stage I Involvement of one lymph node region or single extra-nodal site
  • Stage II Involvement of multiple lymph node regions on the same side of the diaphragm
  • Stage III (1 and 2) Involvement of lymph nodes on both sides of the diaphragm
  • Stage IV Generalized involvement

Presence or absence of significant systemic symptoms is indicated by the suffixes

A – Symptoms absent.

B – Symptoms present.

E – Extralymphatic disease.

X – Bulky disease.

  • Male female ratio is 3:2.
  • Two peaks of highest incidence: Between 2nd and 3rd decade & after 5th
  • Painless involvement of cervical lymph nodes, axillary, inguinal, and mediastinal nodes may also be involved.
  • Nodes may be non-tender and rubbery.

Younger patients:

  • Asymptomatic enlarged lymph nodes.
  • Histologically lymphocyte predominance or nodular sclerosis.

Older patients:

  • Symptomatic enlarged lymph nodes.
  • Malaise, fever, and night sweats, pruritis and weight loss
  • Histologically mixed cellularity or lymphocyte depletion.
  • Dysphagia (due to enlarged mediastinal nodes).
  • Ureteral obstruction(due to enlarged retroperitoneal nodes).
  • Pel- Ebstein fever,
  • Cyclic spiking of high fever.
  • Generalized severe pruritus.

Dental manifestations in HD result from radiotherapy or chemotherapy during tooth development such as:

  • Agenesis
  • Hypoplasia
  • Blunted or thin roots.
  • Biopsy of enlarged lymphoid tissue.
  • Presence of Reed-Sternberg cells (neoplastic giant cell).
  • Radiotherapy, chemotherapy or  combination of both,
  • Radiations of doses 3,500 to 4,500 cGy to the involved lymph node.
  • 3 fields of radiation developed:
  1. Mantle (includes submandibular region, neck, axillae, and mediastinum)
  2. Para-aortic
  3. Pelvic fields.

Malignant solid tumor arising from B or T lymphocytes.

  • Low-grade NHL – localized form, respond to radiotherapy alone.
  • Intermediate NHL.
  • High-grade NHL
  • Painless persistent enlargement of multiple peripheral lymph nodes eg: waldeyer’s ring, mesentric nodes etc.
  • Common above 40 years, but can occur at any age.
  • Renal obstruction
  • Neurologic impairment.
  • Liver infiltration.
  • Skin infiltration.
  • Bone marrow involvement.
  • Palate most commonly involved
  • Rapidly growing swellings which ulcerate.
  • Large, fungating, necrotic, foul-smelling masses.
  • Pain is a variable feature.
  • Tooth mobility and pain.
  • Paresthesia of the face, and major salivary gland enlargement.

Hodgkins disease

Non Hodgkins disease

Localized to single group of nodes, eg:cervical, mediastinal, para aortic etc.

Involve multiple peripheral lymph nodes

Spreads orderly by contiguity

Non contiguous spread

Mesenteric nodes and waldeyer’s ring rarely involved.

Mesenteric nodes and waldeyer’s ring commonly involved.

Extranodal involvement is uncommon.

Extranodal involvement is common.

Reed Sternberg cells present.

Reed Sternberg cells present

Pel- Ebstein fever

Fever is uncommon

High grade Non-Hodgkins Lymphoma (NHL) that is characterized histopathologically by a mass of diffuse small non-cleaved B cell lymphocytes.

  • Geographical location/climate.
  • Immunosuppression
  • Chromosomal abnormalities.
  1. African or endemic burkitt lymphoma
  • Associated with low socioeconomic status, undernourishment, malaria holoendemicity and Epstein Barr virus (EBV) infection.
  • Age range is 2-16 years but also occur in 4-7 years.
  • Male: female ratio of 2:1.
  • Lesion involves bones of the jaw and other facial bones, kidneys, gastrointestinal tract, ovaries, breast and other extranodal sites.
  1. Non-African (sporadic).
  • Accounts for 1-2% of lymphoma in adults and up to 40% in children
  • Abdomen especially the ileo-caecal area is common site of involvement.
  1. Immunodeficiency associated Burkitt lymphoma
  • Occurs mainly in HIV patients.
  • The endemic BL affects children of age 2-16 years with a mean age of 7 years.
  • Occurs in the jaw and in the retroperitoneum, bilateral involvement of kidneys and ovaries or a para spinal tumor.
  • The non-endemic cases affect age range (up to 35 years) with mean age of 11 years.
  • Males most affected in both in both endemic and non-endemic areas.
  • Swelling of the mandible or maxillae (1-4 quadrants), which is the commonest presentation in Africa.
  • Earliest sign is the loosening of child’s molar or premolar.
  • Proptosis may be marked but not usually painful.
  • Intra-abdominal tumors, especially retroperitoneal lymph nodes or ovaries.
  • Extradural lesion causing spinal cord compression and paraplegia.
  • Enlargement of the parotid glands, breasts (usually both), testis, thyroid and kidneys.
  • Lymph node enlargement is also uncommon except in the abdomen.
  • However, the child’s general condition is usually remarkably good.
  1. Cytologic appearance

The cytoplasm form a thin rim round the nucleus, it is basophilic, non granular and contains some small vacuoles corresponding to lipid droplets.

The nucleus is slightly indented and has 2-5 nucleoli, evenly distributed chromatin and occasionally mitosis is seen.

  1. Histological appearance

Starry Sky appearance indicating sheets of monomorphic small non cleaved cell with bluish cytoplasm interspersed by cellular debrisladen macrophages.

  1. Immunophenotyping
  • The Burkitt’s cell is terminal deoxynucleotidyl transferase (Tdt) –ve, but CD10, CD19, CD20, CD22, CD24, CD 37, CD 38 and SIgM positive.
  • In most African BL cases, the cells are CD21 positive but negative in American BL cases.

Cyclophosphamide

  • To be given for six (6) cycles at an interval of two (2) weeks.
  • Dose: give 40mg/kg body weight or 1200mg/m² in 250 dextrose 5% within 30 min to 1 hr.

Methotrexate

  • Intravenous (IV) Methotrexate (50mg/2mls vials)
  • To be given for 6 cycles at an interval of two weeks.
  • Dose: 75mg/m2 slow push.

Note:

  • IT(Intra-theca) Methotrexate is given weekly.
  • If there is no CNS involvement – it should be given prophylactically in the first three cycles at weekly interval i.e. 6 doses.
  • If there is CNS involvement: IT Methotrexate is given in all six cycles i.e. 12 doses at weekly interval.
  • Remember to take CSF for cytology before giving IT Methotrexate until the result is negative on two successive tests.

Vincristine

To be given for 6 cycles at an interval of two weeks Dose: 1.4mg/m2 slow push for 5 minutes

NB: Vincristine needs to follow the pharmaceutical cold chain

Supportive Treatment

  • Ensure hydration- 3liters/m2 in 24 hrs, starting 12 – 24 hours prior to   chemotherapy and continue for 24 – 48 hours post chemotherapy depending on child’s condition.
  • Tabs Allopurinol 300mg/m2 as single daily dose to start one (1) day before chemotherapy and continue for 5 days after chemotherapy.
  • Monitor vital signs (temperature, respiration and pulse) for at least six (6) hour starting 24 hours prior to chemotherapy.
  • Watch for:
  1. Anemia (pallor), mucositis, candidiasis.
  2. Excessive vomiting or diarrhea.
  3. Urine output.
  4. Tumour Lysis Syndrome.

Management of BL Patient During Acute Distress:

  • Resuscitate as necessary:
  • If Hb <7.0g/dl then transfuse first
  • Ensure hydration with IV fluids
  • Diagnose and treat co-existing infections; for example sepsis, pneumonia,malaria, and cellulitis.
  • If airway obstruction is impending:
  1. Immediately give Cyclophosphamide 40 mg/kg IV bolus as soon as possible (do not wait on arrival of other drugs), with plenty of hydration (i.e. 3liters/m2 IV normal saline in 24 hours).
  2. Commence Allopurinol 300 mg/m2 a day as soon as the child is able to swallow for 5 days.
  3. Always complete standard treatment with three drugs regimen as soon as other drug as are available.
  4. Notify anesthetist and have emergency tracheostomy kit at bedside.
  1. Sembulingam K, Sembulingam P. Blood and body fluids In, Dr. TK ParthaSarthy (ed). Essentials of Medical Physiology, 6th edition. New Delhi, Jaypee Brothers Medical Publishers (P) Ltd, 2012;(51-148).
  2. Solberg LA Therapeutic options for essential thrombocythemia and polycythemia vera. Semin Oncol 2002;29:10-15.
  3. Gilbert Modern treatment strategies in polycythemia vera. Semin Hematol 2003;40:26-29.
  4. Michiels JJ, Berneman Z, Van Bockstaele D, van der Planken M, De Raeve H, Schroyens W. Clinical and laboratory features, pathobiology of platelet-mediated thrombosis and bleeding complications, and the molecular etiology of essential thrombocythemia and polycythemia vera: Therapeutic implications. Semin Thromb Hemost 2006;32:174-207.
  5. Greenberg MS, Glick M. Hematologic diseases. Burket’s Oral medicine diagnosis and treatment.10th Hamilton, Ontario. BC Decker Inc; 2003;429-53.
  6. Sarma PR Red cell indices. Available from: https://www.ncbi.nlm.nih .gov/books/NBK260/pdf/ Bookshelf_NBK260.pdf.
  7. Yates JM, Logan EC, Stewart RM. Iron deficiency anaemia in general practice: clinical outcomes over three years and factors influencing diagnostic investigations. Postgrad Med J 2004;80:405-410.
  8. Rector WG Jr. Pica: its frequency and significance in patients with iron-deficiency anemia due to chronic gastrointestinal blood loss. J Gen Intern Med 1989;4:512-513.
  9. Clark, S.F. Iron deficiency anemia: Diagnosis and management. Curr Opin Gastroenterol 2009; 25: 122-
  10. Looker A.C., Dallman, P.R., Carroll, Gunter, E.W. and Johnson, C.L. Prevalence of iron deficiency in the United States. JAMA 1997; 277: 973-
  11. Pearson TC. Apparent polycythemia. Blood Rev 1991;5:205–13.
  12. Besa EL, Kim PW,Havran FL. Treatment of primary defective iron-reutilization syndrome: revisited. Ann Hematol 2000;79:465–8.
  13. Novacek G Plummer-Vinson syndrome Orphanet Journal of Rare Diseases 2006;36:1-4.
  14. Hemolytic Anemia. Available from: https://www.ncbi.nlm. nih.gov/pubmed health/PMHT0022026/.
  1. Socie G, Mary JY, deGramont A, et al. Paroxysmal noncturnal hemoglobinuria: long-term follow up and prognostic factors. Lancet 1996;348:573–7.
  2. Steinberg MH. Genetic etiologies for phenotypic diversity in sickle cell anemia. Sci World J 2009;9:46-49.
  3. Williams TN, Uyoga S, Macharia A, Ndila C, McAuley CF, Opi DH, et al. Bacteraemia in Kenyan children with sickle cell anaemia: a retrospective cohort and case-control study. Lancet 2009;374:1364-1369.
  4. Rouse LE, Hays GL: Dental considerations in sickle cell anemia. Gen Dent 1979;27:18-19.
  5. Pace BS, Zein S. Understanding mechanisms of gamma-globin gene regulation to develop strategies for pharmacological fetalhemoglobin induction. Developmental dynamics 2006; 235:1727-1737.
  6. Hebbel RP, Osarogiagbon R, Dhananjay K. The endothelial biology of sickle cell disease: inflammation and a chronic vasculopathy. Microcirculation 2004;11:129-51.
  7. Madhok S, Madhok S. Dental considerations in Thalassemic patients. Journal of Dental and Medical Sciences. 2014;13:57-62.
  8. Trent RJ. Diagnosis of the haemoglobinopathies. Clin Biochem Rev. 2006; 27: 27-38.
  9. Tunaci M, Tunaci A, Engin G, Ozkorkmaz B, Dinçol G, Acunaş G, et al. Imaging features of thalassemia. Eur Radiol. 1999;9:1804-09.
  10. Adeyemo TA, Adeyemo WL, Adediran A, Akinbami AJ, Akanmu AS. Orofacial manifestations of hematological disorders: Anemia and hemostatic disorders. Indian J Dent Res. 2011;22:454-61.
  11. Waters HM, Dawson DW, Howarth JE, Geary CG. High incidence of type II autoantibodies in pernicious anemia. J Clin Pathol 1993;46:45–7.
  12. Carmel R, Herbert V. Intrinsic factor antibody in saliva of a patient with pernicious anemia. Lancet 1967;1:80–1.
  13. Faccini JM. Oral manifestations of vitamin B12 deficiency. Br J Oral Surg 1968;6:137-40.
  14. Field EA, Speechley JA, Rugman FR, Varga E, Tyldesley WR. Oral signs and symptoms in patients with undiagnosed vitamin B12 deficiency. J Oral Pathol Med 1995;24:468-70.
  15. Sepúlveda E, Brethauer U, Rojas J, Le Fort P. Oral manifestation of Aplastic anaemia in children. J Am Dent Assoc 2006;137:474-8.
  16. Stroncek DF. Drug-induced immune neutropenia. Tranfus Med Rev 1993;7:268–74.
  17. Welte K, Dale D. Pathophysiology and treatment of severe chronic neutropenia. Ann Hematol 1996;72:158–65.
  18. Andrews RG, Benjamin S, Shore N, Canter S. Chronic benign neutropenia of childhood with associated oral manifestations. Oral Surg Oral Med Oral Pathol 1965; 20: 719-725.
  19. Barrett AP. Neutropenic ulceration. A distinctive clinical entity. J Periodontol 1987; 58: 51-55.

34.  Defraia E, Marinelli A. Oral manifestations of congenital neutropenia or Kostmann syndrome. J Clin Pediatr Dent. 2001 Fall;26(1):99-102

  1. Lowenberg B, Downing JR, Burnett HA. Acute myeloid leukemia. N Engl J Med 1999;341:1051–62.
  2. Grimwade D. The importance of diagnostic cytogenetics on outcome in AML: analysis of 1612 patients entered into the MRC AML 10 Trial. Blood 1998;92:2322–33.
  3. Kurzrock R, Gutterman JU, Talpaz M. The molecular genetics of Philadelphia chromosome positive leukemias. N Engl J Med 1988;319:990–8.
  4. Sawyers CL. Chronic myeloid leukemia. N Engl J Med 1999;340:1330–40.
  5. Faderl S, Talpaz M, Estrov Z, et al. The biology of chronic myeloid leukemia. N Engl J Med 1999;341:164–72.
  6. Carolina Favaro Francisconi et alLeukemic Oral Manifestations and their Management.Asian Pacific Journal of Cancer Prevention 2016;17:911-15.
  7. Lee SH, Huang JJ, PanWL, Chan CP. Gingival mass as the primary manifestation of multiple myeloma: Report of two cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1996;82:75-9.
  8. Shibata M, Kodani I, Doi R, Takubo K, Kidani K, Sakai H, et al. Multiple myeloma presenting symptoms in the oral and maxillofacial region. Yonago Acta medica 2003;46:77-81.
  9. Deliliers G L, Bruno E, Cortellezzi A, Fumagalli L, Morosini A. Incidence of jaw lesions in 193 patients with multiple myeloma. Oral Surg Oral Med Oral Pathol 1988;65:533-7.
  1. Zhao XJ, Sun J, Wang YD, Wang L. Maxillary pain is the first indication of the presence of multiple myeloma: a case report. Mol Clin Oncol. 2014;2:59–64. 
  2. Khanna R, Burrows SR, Moss DJ (1995) Immune regulation in Epstein-Barr virus-associated diseases. Microbiol Rev1995; 59: 387-405.
  3. Diebold J Burkitts lymphoma. In: Jaffe E, Harris N, Stein H et al., (Eds.), Pathology and Genetics of Tumors of haematopoietic and Lymphoid tissues. Washington, DC: IARC Press 2001;181-184.
  4. Boerma EG, van Imhoff GW, Appel IM, Veeger NJ, Kluin PM, et al. Gender and age-related differences in Burkitt lymphoma–epidemiological and

clinical data from the Netherlands. Eur J Cancer 2004;40: 2781-2787.

  1. Blum KA, Losanski G, Byrd JC Adult Burkitt leukemia and lymphoma.

Blood 2004;104: 3009-3020.

  1. Ferry JA Burkitt’s lymphoma: clinicopathologic features and differential

diagnosis. Oncologist 2006;11: 375-383.

error: Content is protected !!