The document provides an overview of the hematologic system and blood disorders. It discusses the key components of the hematologic system including blood, bone marrow, spleen, and lymph system. Several blood disorders are summarized, including anemias caused by blood loss, decreased red blood cell production, and increased red blood cell destruction. Specific disorders covered include iron deficiency anemia, thalassemia, megaloblastic anemias, aplastic anemia, and anemia of chronic disease. Diagnostic tests and treatment approaches are also outlined.

1. Hematologic System and
its pathology
Dr. Shivani Ravichinayan, MDS
19/04/2011 1

2. Hematology
 Study of blood and blood forming tissues
 Key components of hematologic system
are:
 Blood
 Blood forming tissues
 Bone marrow
 Spleen
 Lymph system
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3. What Does Blood Do?
 Transportation
 Oxygen
 Nutrients
 Hormones
 Waste Products
 Regulation
 Fluid, electrolyte
 Acid-Base balance
 Protection
 Coagulation
 Fight Infections
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4. Components of Blood
 Plasma
 55%
 Blood Cells
 45%
 Three types
 Erythrocytes/RBCs
 Leukocytes/WBCs
 Thrombocytes/Platelets
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5. Erythrocytes/Red Blood Cells
 Composed of hemoglobin
 Erythropoiesis
 = RBC production
 Stimulated by hypoxia
 Controlled by erythropoietin
 Hormone synthesized in kidney
 Hemolysis
 = destruction of RBCs
 Releases bilirubin into blood stream
 Normal lifespan of RBC = 120 days
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6. Leukocytes/White Blood Cells
 5 types
 Basophils
 Eosinophils
 Neutrophils
 Monocytes
 Lymphocytes
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7. 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
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8. Thrombocytes/Platelets
 Must be present for clotting to occur
 Involved in hemostasis
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9. Normal Clotting Mechanisms
 Hemostasis
 Goal: Minimizing blood loss when injured
1. Vascular Response
 vasoconstriction
1. Platelet response
 Activated during injury
 Form clumps (agglutination)
1. Plasma Clotting Factors
 Factors I – XIII
 Intrinsic pathway
 Extrinsic pathway
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10. Anticoagulation
 Elements that interfere with blood
clotting
 Countermechanism to blood clotting—
keeps blood liquid and able to flow
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11. Structures of the Hematologic System
 Bone Marrow
 Liver
 Lymph System
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12. Bone Marrow
 Bone Marrow
 Soft substance in core of bones
 Blood cell production (Hematopoiesis):The
production of all types of blood cells
generated by a remarkable self-regulated
system that is responsive to the demands
put upon it.
 RBCs
 WBCs
 Platelets
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13. Liver
Receives 24% of the cardiac output
(1500 ml of blood each minute)
 Liver has many functions
 Hematologic functions:
 Liver synthesis plasma proteins
including clotting factors and
albumin
 Liver clears damaged and non-
functioning RBCs/erythrocytes from
circulation
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14. Spleen
 Located in upper L quadrant of
abdomen
 Functions
 Hematopoietic function
 Produces fetal RBCs
 Filter function
 Filter and reuse certain cells
 Immune function
 Lymphocytes, monocytes
 Storage function
 30% platelets stored in spleen
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15. Pluripotential Stem Cell
Myeloid Stem Cells Lymphoid stem cells
Granulocyte;
Macrophage
Stem Cells
Granulocyte
Stem Cells
Neutrophils
Eosinophils
& Basophils
Monocytic
Stem Cells
Monocytes &
Macrophages
Megakaryocytic
Stem Cells
Megacaryocytes
& Platelets
Erythropoietic
Stem Cells
Erythrocytes Lymphocytes:
(T cells, B cells,
plasma cells)
HEMATOPOIESIS

16. Effects of Aging on the Hematologic
System
 CBC Studies
 ↓ Hemoglobin (Hb or Hgb)
 ↓ response to infection (WBC)
 Platelets=no change
 Clotting Studies
 ↓ PTT
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17. Diagnostic Studies of the Hematologic
System: Complete Blood Count (CBC)
 WBCs
 Normal 4,000 -11,000 µ/ℓ
 Associated with infection, inflammation, tissue injury or
death
 Leukopenia-- ↓ WBC
 Neutropenia -- ↓ neutrophil count
 RBC
 ♂ 4.5 – 5.5 x 106
/ℓ
 ♀ 4.0 – 5.0 x 106
/ℓ
 Hematocrit (Hct)
 The hematocrit is the percent of whole blood that is
composed of red blood cells. The hematocrit is a measure
of both the number of red blood cells and the size of red
blood cells.
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18. Diagnostic Studies of the Hematologic System:
Complete Blood Count (CBC) Cont’d
 Platelet count
 Normal 150,000- 400,000
 Thrombocytopenia-↓ platelet count
 Spontaneous hemorrhage likely when count is
below 20,000
 Pancytopenia
 Decrease in number of RBCs, WBCs, and
platelets
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19. Diagnostic Studies
of the Hematologic System
 Radiologic Studies
 CT/MRI of lymph tissues
 Biopsies
 Bone Marrow examination
 Lymph node biopsies
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20. BLOOD
DISORDERS
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21. RBC disorders
WBC disorders
Platelets
disorders
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22. RBC DISORDERS
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23. Anemia
 Anemia is a reduction in the number of
RBCs, the quantity of hemoglobin, or
the volume of RBCs
 Because the main function of RBCs is
oxygenation, anemia results in varying
degrees of hypoxia
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24. Anemia
 Prevalent conditions
 Blood loss
 Decreased production of erythrocytes
 Increased destruction of erythrocytes
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25. Anemia (cont’d)
 Clinical Manifestations:
1. Pallor.
2. Fatigue, weakness.
3. Dyspnea.
4. Palpitations, tachycardia.
5. Headache, dizziness, and restlessness.
6. Slowing of thought.
7. Paresthesia.
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26. Anemia Caused By Blood Loss
 Acute Blood Loss
 Chronic Blood Loss
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27. Acute Blood Loss
 Result of sudden hemorrhage
 Trauma, surgery, vascular disruption
 Collaborative Care
1. Replacing blood volume
2. Identifying source of hemorrhage
3. Stopping blood loss
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28. Chronic Blood Loss
 Symptoms
 Pallor, glossitis, chelitis, weakness
 GI bleeding, hemorrhoids, menstrual blood loss
 Diagnostic Studies
 Identifying source
 Stopping bleeding
 Collaborative Care
 Supplemental iron administration
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29. Anemia Caused by Decreased Erythrocyte
Production
 Iron Deficiency Anemia
 Thalassemia
 Megablastic Anemia
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30. Iron-Deficiency Anemia
Etiology
1. Inadequate dietary intake
 Found in 30% of the
world’s population
1. Malabsorption
 Absorbed in duodenum
 GI surgery
1. Blood loss
 2 ml of blood contain 1mg iron
 GI, GU losses
1. Hemolysis
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31. Iron-Deficiency Anemia
 Clinical Manifestations
 Most common: pallor
 Second most common: inflammation of the tongue
(glossistis)
 Cheilitis=inflammation/fissures of lips
 Sensitivity to cold
 Weakness and fatigue
 Diagnostic Studies
 CBC
 Iron studies Diagnostics:
 Iron levels: Total iron-binding capacity (TIBC), Serum
Ferritin.
 Endoscopy/Colonscopy
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32. Iron-Deficiency Anemia
 Collaborative Care
 Treatment of underlying disease/problem
 Replacing iron
 Diet
 Drug Therapy
 Iron replacement
 Oral iron
 Feosol, DexFerrum, etc
 Absorbed best in acidic environemtn
 GI effects
 Parenteral iron
 IM or IV
19/04/2011 42

33. Thalassemia
 Etiology
 Autosomal recessive genetic disorder of
inadequate production of normal hemoglobin
 Found in Mediterranean ethnic groups
 Clinical Manifestations
 Asymptomatic  major retardation  life
threatening
 Splenomegaly, hepatomegaly
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34. Thalassemia
Collaborative Care
 No specific drug or diet are effective in
treating thalassemia
 Thalassemia minor
 Body adapts to Hgb↓
 Thalassemia major
 Blood transfusions with IV deferoxamine
(used to remove excess iron from the body)
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35. Megaloblastic Anemias
 Characterized by large
RBCs which are fragile
and easily destroyed
 Common forms of
megaloblastic anemia
1. Cobalamin deficiency
2. Folic acid deficiency
This picture shows large, dense,
oversized, red blood cells (RBCs)
that are seen in megaloblastic
anemia.
19/04/2011 46

36. Cobalamin (Vitamin B12) Deficiency
 Cobalamin Deficiency--formerly known as
pernicious anemia
 Vitamin B12 (cobalamin) is an important water-
soluble vitamin.
 Intrinsic factor (IF) is required for cobalamin
absorption
 Causes of cobalamin deficiency
 Gastric mucosa not secreting IF
 GI surgery →loss of IF-secreting gastric mucosal cells
 Long-term use of H2-histamine receptor blockers cause
atrophy or loss of gastric mucosa.
 Nutritional deficiency
 Hereditary defects of cobalamine utilization19/04/2011 47

37. Cobalamin (Vitamin B12) Deficiency
 Clinical manifestations
 General symptoms of anemia
 Sore tongue
 Anorexia
 Weakness
 Parathesias of the feet and hands
 Altered thought processes
 Confusion → dementia
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38. Cobalamin Deficiency
Diagnostic Studies
 RBCs appear large
 Abnormal shapes
 Structure contributes to erythrocyte
destruction
 Schilling Test: a medical investigation used
for patients with vitamin B12 deficiency. The
purpose of the test is to determine if the
patient has pernicious anemia.
19/04/2011 49

39. Cobalamin Deficiency
 Collaborative Care
 Parenteral administration of cobalamin
 ↑ Dietary cobalamin does not correct the anemia
 Still important to emphasize adequate dietary intake
 Intranasal form of cyanocobalamin (Nascobal) is
available
 High dose oral cobalamin and SL cobalamin can
use be used
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40. Folic Acid Deficiency
 Folic Acid Deficiency also causes
megablastic anemia (RBCs that are large
and fewer in number)
 Folic Acid required for RBC formation and
maturation
 Causes
 Poor dietary intake
 Malabsorption syndromes
 Drugs that inhibit absorption
 Alcohol abuse
 Hemodialysis
19/04/2011 52

41. Folic Acid Deficiency
 Clinical manifestations are similar to those of
cobalamin deficiency
 Insidious onset: progress slowly
 Absence of neurologic problems
 Treated by folate replacement therapy
 Encourage patient to eat foods with large amounts
of folic acid
 Leafy green vegetables
 Liver
 Mushrooms
 Oatmeal
 Peanut butter
 Red beans
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42. Anemia of Chronic Disease
 Underproduction of RBCs, shortening of RBC
survival
 2nd
most common cause of anemia (after iron
deficiency anemia)
 Generally develops after 1-2 months of sustained
disease
 Causes
 Impaired renal function
 Chronic, inflammatory, infectious or malignant disease
 Chronic liver disease
 Folic acid deficiencies
 Splenomegaly
 Hepatitis19/04/2011 54

43. Aplastic Anemia
 Characterized by Pancytopenia
 ↓ of all blood cell types
 RBCs
 White blood cells (WBCs)
 Platelets
 Hypocellular bone marrow
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44. Aplastic Anemia
 Etiology
 Congenital
 Chromosomal alterations
 Acquired
 Results from exposure to ionizing radiation, chemical
agents, viral and bacterial infections
Low incidence
Affecting 4 of every 1 million persons
Manageable with erythropoietin or blood transfusion
Can be a critical condition
Hemorrhage
Sepsis
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45. Aplastic Anemia
 Clinical Manifestations
 Gradual development
 Symptoms caused by suppression of any or all bone
marrow elements
 General manifestations of anemia
 Fatigue
 Dyspnea
 Pale skin
 Frequent or prolonged infections
 Unexplained or easy bruising
 Nosebleed and bleeding gums
 Prolonged bleeding from cuts
 Dizziness
 headache19/04/2011 57

46. Aplastic Anemia
 Diagnosis
 Blood tests
 CBC
 Bone marrow biopsy
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47. Aplastic Anemia
 Treatment
 Identifying cause
 Blood transfusions
 Antibiotics
 Immunosuppressants (neoral, sandimmune)
 Corticosteroids (Medrol, solu-medrol)
 Bone marrow stimulants
 Filgrastim (Neupogen)
 Epoetin alfa (Epogen, Procrit)
 Bone marrow transplantation
 Preventing complications from infection and hemorrhage
 Prognosis is poor if untreated
 75% fatal
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48. Anemia caused by Increased Erythrocyte
Destruction
 Hemolytic Anemia
 Sickle Cell disease (peds)
 Acquired Hemolytic Anemia
 Hemochromatosis
 Polycythemia
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49. Hemolytic Anemia
 Destruction or hemolysis of RBCs at a rate that
exceeds production
 Third major cause of anemia
 Intrinsic hemolytic anemia
 Abnormal hemoglobin
 Enzyme deficiencies
 RBC membrane abnormalities
 Extrinsic hemolytic anemia
 Normal RBCs
 Damaged by external factors
 Liver
 Spleen
 Toxins
 Mechanical injury (heart valves)19/04/2011 61

50. Sequence of Events in Hemolysis
Fig. 30-1
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51. Acquired Hemolytic Anemia
 Causes
 Medications
 Infections
 Manifestations
 S/S of anemia
 Complications
 Accumulation of hemoglobin molecules can
obstruct renal tubules → Tubular necrosis
 Treatment
 Eliminating the causative agent
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52. Hemochromatosis
 Iron overload disease
 Over absorption and
storage of iron causing
damage especially to
liver, heart and
pancreas
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53. Polycythemia
 Polycythemia is a condition in which
there is a net increase in the total number
of red blood cells
 Overproduction of red blood cells may
be due to
 a primary process in the bone marrow (a so-
called myeloproliferative syndrome)
 or it may be a reaction to chronically low
oxygen levels or
 malignancy
19/04/2011 66

54. Polycythemia
 Complications
 ↑d viscosity of blood
 → hemorrhage and thrombosis
 Treatment
 Phlebotomy
 Myelosupressive agents: A number of new
therapeutic agents such as, interferon alfa-2b (Intron A)
therapy, agents that target platelet number (e.g.,
anagrelide [Agrylin]), and platelet function (e.g., aspirin).
19/04/2011 67

55. WBC DISORDERS
19/04/2011 68

56. Neutropenia
 Neutropenia refers specifically to a decrease in neutrophils. It
commonly is defined as a circulating neutrophil count of less
than 1500 cells/ L.μ
 Agranulocytosis, which denotes a severe neutropenia, is
characterized by a circulating neutrophil count of less than 200
cells/ L.μ
 Neutropenia can be:
 Acquired
 Congenital
 Kostmann’s syndrome
 It occurs sporadically as an autosomal recessive disorder,
causes severe neutropenia while preserving the erythroid
and megakaryocyte cell lineages that result in red blood cell
and platelet production.
 The total white blood cell count may be within normal
limits, but the neutrophil count is less than 200/ L.μ
Monocyte and eosinophil levels may be elevated
(compensatory).

57. Acquired neutropenia
 Accelerated removal - removal of neutrophils from the circulation exceeds
production
 Inflammation
 Infection, viral or bacterial
 Increased destruction:
 Drug-induced granulocytopenia
 Treatment of cancer – chemotherapy (e.g., alkylating agents,
antimetabolites)
 Irradiation
 Autoimmune disorders or drug reactions
 May cause increased and premature destruction of neutrophils
 Splenomegaly
 Neutrophils may be trapped in the spleen along with other blood
cells
 Felty’s syndrome
 A variant of rheumatoid arthritis, there is increased destruction of
neutrophils in the spleen
 Neoplasms involving bone marrow (e.g., leukemias and lymphomas,
myeloma)

58. Acquired neutropenia
 Alcoholism
 Carentiale states:
 Folic acid
 Vitamin B12
 Iron
 Cooper
 Aplastic anemia
 All of the myeloid stem cells are affected, resulting in
anemia, thrombocytopenia, and agranulocytosis;
 Idiopathic neutropenia that occurs in the absence of other
disease or provoking influence.

59. Infectious Mononucleosis
 Self-limiting lymphoproliferative disorder
 Caused by Epstein-Barr virus (EBV)
 Most prevalent in adolescence/young adults
 Main mode of transmission → EBV-contaminated
saliva
 Pathogenesis: atypical lymphocytes proliferate
 Onset: insidious; incubation 4-8 weeks

61. Mono: Sore throat with erythema & white exudate

62. Infectious mononucleosis
 Clinical manifestations:
lymphadenopathy, hepatomegaly,
splenomegaly
 Labs:

WBC  (~ 12-18,000); 95% lymphocytes
(viral infection)
 Acute phase: 2-3 weeks
 Treatment: symptomatic & supportive

63. Leukemias
 Chronic
 CLL (chronic lymphocytic leukemia)
 CML (chronic myelocytic leukemia)
 Acute
 ALL (acute lymphocytic leukemia)
 AML (acute myelocytic leukemia)
DEFINED BY:
1.SITE OF ORIGIN
a. myeloid stem cell
b. lymphoid stem cell
2.ACUTE VS CHRONIC
a. acute
b. chronic

64. Leukemias
 Malignant neoplasms of cells originally derived from a
single hematopoietic cell line
 Leukemic cells:
 Are immature & unregulated
 Proliferate in bone marrow
 Circulate in blood
 Infiltrate spleen, lymph nodes & other tissues
 Disease of children & adults

65. Common feature of all leukemias:
Uncontrolled proliferation of immature leukocytes
results in crowding out of mature blood cells
including leuckocytes, red blood cells, and platelets
Pancytopenia = decrease in all functioning blood cells:
anemia, thrombocytopenia, neutropenia

66. Leukemia: Classifications
 Classified according to their PREDOMINANT CELL
type
 LYMPHOCYTIC or MYELOCYTIC AND
 whether dx is ACUTE or CHRONIC
1. Acute lymphocytic (lymphoblastic) leukemia (ALL)*
2. Chronic lymphocytic leukemia (CLL)**
3. Acute myelocytic leukemia (AML)
4. Chronic myelocytic leukemia (CML)
* Most common childhood leukemia
**Most common leukemia of older adults

67. Leukemia: Pathogenesis
 Causes:
 Unknown;  exposure to radiation
 Pathogenesis – Leukemic cells:
 Are an immature type of WBC
 Capable of  rate of proliferation/have prolonged
life span
 Cannot perform function of mature leukocytes →
are ineffective as phagocytes
 Interfere with maturation of normal bone marrow
cells (including RBC & platelets)

68. Leukemia: Acute vs Chronic
 Acute:
 Sudden, stormy onset
 S/S related to  (mature) WBC,  RBC,  platelets
 ALL 80% childhood acute leukemias→
 AML chiefly an adult disease→
 Diagnosis based on:
 Blood/bone marrow tissue presence of↔ immature WBC’s
(blasts) – may constitute 60-100% of cells

69. Leukemias: Acute vs Chronic
 Chronic
 More insidious onset
 May be discovered during a routine medical exam by a
blood count
 CLL older adults→
 Relatively mature lymphocytes that are immunologically
incompetent
 CML adults & children→
 Leukocytosis with immature cell types

70.  Hodgkin’s
disease
 Characterized by
PAINLESS, progressive,
rubbery enlargement of
a single node or group
of nodes – usually in
neck area
 Reed-Sternberg cell –
distinctive tumor cell
found with lymph biopsy
 Non-hodgkin’s
disease
 Also neoplastic disorder of
lymphoid tissue
 However, SPREADS EARLY
→ liver, spleen & bone
marrow
 Also characterized by
painless, superficial
lymphadenopathy; also
extranodal symptoms
 POORER PROGNOSIS
than Hodgkin’s
Malignant Lymphomas:
Neoplasms Of Cells Derived From
Lymphoid Tissue

71. Disorders of platelets
19/04/2011 84

72. Thrombocytopenia
 Disorder of decreased platelets
 platelet count below 150,000
 Causes
 Low production of platelets
 Increased breakdown of platelets
 Symptoms
 Bruising
 Nosebleeds
 Petechiae (pinpoint microhemorrhages)
19/04/2011 85

73. Thrombocytopenia
 Types of Thrombocytopenia
 Immune Thrombocytopenic Purpura
 Abnormal destruction of circulating platelets
 Autoimmune disorder
 Destroyed in hosts’ spleen by macrophages
 Thrombotic Thrombocytopenic Purpura
 ↑d agglutination of platelets that from microthrombi
19/04/2011 86

74. Heparin-Induced Thrombocytopenia
(HIT)
 HIT
 Associated with administration of heparin
 Develops when the body develops an antibody, or allergy
to heparin
 Heparin (paradoxically) causes thrombosis
 Immune mediated response that casues intense platelet
activation and relaese of procoaggulation particles.
 Clinical features
 Thrombocytopenia
 Possible thrombosis after heparin therapy
 Can be triggered by any type, route or amount of heparin
19/04/2011 87

75. Thrombocytopenia
Diagnostic Studies
 Platelet count
 Prothrombin Time (PT)
 Activated Partial Thromboplastin Time (aPTT)
 Hgb/Hct
 Treatment
 Based on cause
 Corticosteroids
 Plasmaphoresis
 Splenectomy
 Platelet transfusion
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76. Conclusion
 Oral manifestations of many of the blood
disorders mimics the oral lesions caused
by local etiologies such as irritations and
infections.
 Many of the dental treatments are
invasive so dental professionals must be
very careful while treating such patients.
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