Final Exam Flashcards
(207 cards)
0
Q
Neutrophilia
1) Definition
2) Type of neutrophil disorder
3) Causes
A
1) Increased number of neutrophils usually from increased BM activity
2) Quantitative
3) Chronic Myeloid Leukemia (CML); Chronic Myeloproliferative Disorders; Leukemoid Reactions (most common cause); Inflammation; Tissue damage; Metabolic disorders; Increased stress; Exercise; pregnancy; trauma
1
Q
Neutrophils
1) Function
2) Defects predispose patients to…
3) Types of disorders
A
- Phagocytic and mediate inflammation
- Recurrent bacterial infections
- Quantitative –> Number of neutrophils
Qualitative –> Correct number of neutrophils, but not functioning correctly
2
Q
Leukemoid Reactions
1) Definition
2) Characteristics of reaction
A
1) Neutrophil response to infections (bacterial)
2) Neutrophilia; Shift to the left (may see more immature); Toxic granulation (dark/larger granules); Dohle bodies; Cytoplasmic vacuolization; increased LAP
3
Q
Qualitative disorders of neutrophils
1) Types
2) Dysfunction categories
A
1) Phagocytic/Killing defects; Chemotaxis/Motility defects; Granule function & Structure defects; Adhesion defects
2) Acquired Dysfunctions –> outside, autoimmunities; pregnancy; renal disease
Inherited Dysfunctions
4
Q
Chediak-Higashi Syndrome
1) Type of neutrophil disorder
2) Characteristics
A
1) Inherited qualitative neutrophil disorder –> Defect of cytoplasmic granules
2) Release of enzymes inhibited by formation of giant lysosomal granules, defective chemotaxis and degranulation; Partially albino; Dohle bodies; vacuoles; fused/large granules
5
Q
Chronic Granulomatous Disease
1) Definition
2) Type of neutrophil disorder
A
1) Failure to make superoxide
2) Qualitative, inherited disorder –> Biochemical disturbance of respiratory burst (defect in respiratory enzymes)
6
Q
Lazy Leukocyte Syndrome
1) Type of disorder
A
1) Qualitative, inherited neutrophil disorder –> chemotaxis
7
Q
Hypersegmentation
1) Cause
A
1) Megaloblastic anemia (B12 & folate deficiency), pernicious anemia, hereditary
8
Q
Hyposegmentation (“dumbbell shape”)
1) Cause
A
1) Pelger-Huet Anomaly, Acquired (drugs, leukemia, malignancies), Inherited
9
Q
Cytoplasm Changes (WBC abnormality)
A
Alder-Reilly inclusions –> larger graunles; lipid storage disease
Toxic granulation
May-Hegglin anomaly –> hereditary, larger blue cytoplasm
10
Q
Eosinophilia
A
Parasites (helminth, invasion of tissues), allergies, malignancies (leukemias), inflammation (cystic fibrosis pneumonia)
11
Q
Basophilia (causes)
A
CML, allergies, inflammation, infection (chicken pox, influenza)
12
Q
Monocytosis (causes)
A
Chronic infections, malignancies (lymphoma), inflammation
13
Q
Absolute Lymphocyte Counts
A
Actual number of lymphocytes
14
Q
Relative lymphocyte count
A
Percentage of 100 WBC differential
15
Q
Lymphocytosis
A
Increase number of lymphocytes (greater than 40%)
16
Q
Lymphocytopenia
A
Decrease number of lymphocytes (less than 20%)
17
Q
Types of Lymphocytes
A
Resting lymphocytes
Reactive lymphocytes
Atypical/Malignant Lymphocytes
18
Q
Characteristics of resting lymphocytes
A
Smaller size (8-12 um) Scant, colorless to light blue cytoplasm Round nucleus Polyclonal No nucleoli N:C ratio- high to moderate
19
Q
Characteristics of Reactive Lymphocytes
A
- Polyclonal
- Larger (9-30 um)
- Round or indented nucleus
- Abundant and uneven stained cytoplasm with round or indented border
- Probable nucleoli
- Eccentric nucleus
- Low to moderate N:C ratio
- Azurophilic granules (pinkish granules in light blue cytoplasm)
20
Q
Causes of Reactive Lymphocytes
A
- Infectious Mononucleosis (EBV)
- Cytomegalovirus
- Other viruses–HIV/AIDS, rubella
- Bacterial–chronic infections (TB)
- Drug Reactions
- Allergic reactions
- Autoimmune diseases
- Malnutrition
21
Q
Atypical/Malignant Lymphocytes
1) Characteristics
2) Causes
A
1) Similar to reactive lymphocyte; monoclonal
2) Leukemia & lymphomas
22
Q
Leukemia
1) Definition
2) Originates in..
3) Classification basis
A
1) Malignant disease of hematopoietic tissue characterized by replacement of bone marrow with abnormal blood cells
2) Bone marrow –> malignancy taking over bone marrow
3) Based on cell type in regard to cell maturity and cell lineage
23
Q
Categories of Leukemia and onsets
A
- Acute lymphoblastic leukemia (ALL) –> Mostly children (3/4)
- Acute myeloid leukemia (AML) –> Mostly adults (80%)
- Chronic lymphocytic leukemia (CLL) –> 40-50 yrs old
- Chronic myeloid leukemia (CML) –> Any age, but > 60 yrs old
24
Leukemia Etiology
| 1) Origin
1) At genetic level and related to mutation or altered expression of oncogenes (turned on cancer genes) and tumor suppressor genes
25
Leukemia Etiology (Causes) Factors
1) Hereditary --> Increases predisposition
2) Congenital chromosomal abnormalities --> Fanconi's anemia
3) Immunodeficiency --> sex linked agammaglobinemias
4) Chronic Marrow Dysfunction --> BM shutdown, aplastic anemia
5) Environmental --> ionizing radiation, chemicals, drugs, viruses
26
Characteristics of Acute Leukemia
1) All ages
2) Sudden onset
3) Immature cells
4) Mild to severe anemia
5) Mild organomegaly
6) Untreated --> less than 6 months before fatal
27
Chronic Leukemia Characteristics
1) Adults
2) Insidious onset (few months/longer duration)
3) Mature cells
4) Mild anemia
5) Prominent organomegaly (enlarged organs)
6) Untreated --> 2-6 years until fatal
28
Acute Leukemia
1) FAB classification
2) WHO classification
3) Types
4) Signs
1) > 30% blasts in bone marrow aspirate smear
2) 20% blasts in BM and peripheral blood
3) Acute Myeloid Leukemia & Acute Lymphoblastic Leukemia
4) Fatigue, easy bruising, pallor, fever, infection, bleeding, weakness
29
Tests for Leukemia
1) Cell morphology (Auer Rods --> Diagnose AML)
2) Cytochemical Stains
* Myeloperoxidase (stains myeloid cells)
* Sudan Black B (stains for AML)
* Specific Esterase (+ for AML; neutrophil specific)
* Nonspecific Esterase (stains for monocytic cells)
* Periodic Acid-Schiff (erythroleukemias)
3) Immunological Markers (CD and TdT)
4) Cytogenetics
* Philadelphia chromosome (CML)
* Translocation T (AML)
5) Molecular Genetics
30
Treatment for Leukemia
1) Cytoreductive Chemotherapy --> gets rid of all cells; hope BM regenerates itself
2) Radiotherapy --> targeting certain area or can be whole body
3) Bone Marrow Transplant --> Kills off whole bone marrow; graft new donor bone marrow; takes up to three months
31
```
Acute Myeloid Leukemia
1) Onset
2-5) Characteristics
6) Myeloperoxidase stain result
7) Sudan black stain result
8) TdT result
```
1. Common in adults, rare in children
2. Larger, medium-large blasts
3. More cytoplasm than lymphoblast
4. Auer Rods
5. Distinct nucleoli
6. (+) Peroxidase stain
7. (+) Sudan Black stain
8. TdT negative
32
Acute Lymphoblastic Leukemia
1) Onset
2) Characteristics
3) Peroxidase stain
4) Sudan black stain
5) TdT result
1) Common in children, rare in adults
2) Variable, small-medium blasts; scarce cytoplasm; indistinct nucleoli; no Auer Rods
3) Negative Peroxidase
4) Negative Sudan Black
5) Positive TdT
33
Acute Lymphoblastic Leukemia (FAB classification)
1) L1
2) L2
3) L3
4) Based on?
1) Small, uniform lymphoblasts (cookie cutter)
2) Large, pleomorphic lymphoblasts
3) Burkitt's type; large, pleomorphic cell
4) Morphology from bone marrow aspirate
34
Acute Lymphoblastic Leukemia (WHO classification)
| 1) Based upon?
Lymphocyte stage of development using cytogenetics and immunophenotyping and molecular testing
35
Chronic Myeloproliferative Disorders
| 1. Definition
1. Malignant transformation and clonal expansion of a hematopoietic pluripotent cell line --> putting out cells that are non functional
36
Chronic Myeloproliferative Disorders
1. Characteristics
2. Age of onset
1. Hypercellular bone marrow (hyperplasia)
Increase in one or more cell lines
Splenomegaly
Extramedullary hematopoiesis
Increase platelets
Hemorrhagic and thrombotic complications
Fibroblastic proliferation in bone marrow
Cytogenetics and molecular abnormalities
2. Usually 50 years or older
37
Chronic Myeloproliferative Disorder
| 1. Types of diseases
1. Chronic Myelogenous Leukemia
2. Polycythemia vera
3. Essential Thrombocytopenia
4. Chronic Idiopathic Myeloproliferative
38
Chronic Myelogenous Leukemia
1. Definition
2. Characteristics
3. Onset
1. Clonal myeloproliferative disorder with increased production of granulocytes and their precursors
2. Philadelphia chromosome --> fusion of BCR/ABL protein
Increased leukocytosis of all granulocytes
Low to absent levels of leukocyte alkaline phosphate (LAP)
3. 30-50 years old
39
Chronic Myeloproliferative Leukemia
1. Clinical course
2. Treatment
1. Chronic (2-5 years --> if controlled by chemotherapy); Accelerated (1/2-1 1/2 years --> more blasts, shift to the left); Blastic acute (3-4 months --> nonresponsive to treatment)
2. gamma INF therapy; chemotherapy; bone marrow transplant
40
Chronic Idiopathic Myelofibrosis
1. Type of disorder
2. Characteristics
3. Treatment
1. Chronic Myeloproliferative Disorder
2. Mutation of single multipotential stem cell with bone marrow fibrosis (dry tap); chromosome abnormalities; cytokines; extramedullary hematopoiesis; splenomegaly; teardrop; poiklocytosis in peripheral blod with immature granulocytes and nucleated red blood cells; anemia (normochromic/normocytic); dysfunctional platelets; bone marrow fibrosis
3. Chemotherapy or bone marrow transplant
41
Erythrocytosis
1. Definition
2. Absolute
3. Relative
4. Types
1. Abnormal increase in number of RBCs in circulation (high hematocrit or hemoglobin levels)
2. Increased RBC mass with increase RBC
3. Normal RBC mass with decrease plasma volume (less liquid volume --> dehydration or stress)
4. Polycythemia vera, Secondary Erythrocytosis; Relative Erythrocytosis
42
Polycythemia Vera
| 1. Definition
Accelerated erythropoisis with varying degree of myeloid and megakaryocytic elements in hypercellular bone marrow
43
Polycythemia Vera
1. Physical Signs
2. Treatment
1. Red complexion; dizzy; verigo; thrombotic episodes (sluggish blood)
2. Myelosuppressive therapy --> suppress activity of the bone marrow
44
Polycythemia Vera Characteristics
Increased RBC mass, RBC count, Hct, Hgb, LAP score & serum B12
```
Decreased erythropoietin (key feature)
Splenomegaly
Leukocytosis
Thrombocytosis
Normal arterial oxygen saturation
Hyper-viscosity
Gradual onset
```
45
Secondary Erythrocytosis
| 1. Definition
Increased erythropoietin secretion in response to:
1. Tissue hypoxia (lack of oxygen to the tissues)
2. Inappropriate or pathological secretion with no tissue hypoxia (renal disease/tumors)
3. Defective oxygen transport (smokers, increase pollution)
46
Secondary Erythrocytosis
| 1. Characteristics
1. Increased Hct; normal LAP, B12, WBC and platelet numbers; decreased arterial oxygen saturation; no splenomegaly
47
Relative Erythrocytosis
| 1. Defintion & Characteristics
Increase hematocrit with normal RBC mass and decreased plasma volume
Normal erythropoietin; normal arterial oxygen saturation; normal LAP, B12, WBC and platelet counts; no splenomegaly
48
Relative Erythrocytosis
| 1. Cause
Dehydration -> burn patients
| Stress erythrocytosis -> obese, smokers, hypertensive, physical stress, extreme alcohol consumption, diuretic therapy
49
Essential Thrombocythemia
| 1. Characteristics
* Marked thrombocytosis and abnormal platelet function
* Hypercellular bone marrow with increased megakaryocytes
* No Ph chromosome --> rules out CML
* Absent marrow fibrosis
* Stainable iron in bone marrow --> rules out iron def. anemia
* Hemorrhage
* Thrombosis
* Splenomegaly
50
Essential Thrombocythemia
| 1. Treatment
Platelet phoresis
Aspirin
Cytokine therapy
51
In order to diagnose Essential Thrombocythemia, what must be ruled out?
1. Chronic infection
2. Trauma
3. Drugs
4. Reactive thrombocytosis
52
Myelodysplastic Syndrome
1. Definition
2. Characteristics
3. Treatment
4. Onset
1. Clonal hematological malignancies, cytopenias, dysplastic blood cells, and tendency to transform into acute leukemia
2. Abnormalities in all cell lines (peripheral blood); anemia not responsive to therapy --> Refractory Anemia; Ringed Sideroblasts in bone marrow
3. Bone marrow transplant
4. 70-80 years old
53
Lymphomas
1. Definition
2. Types
1. Group of diseases that arise from cells of lymphoid tissue (lymphocytes, histiocytes, reticulum cells)
2. Hodgkin's Lymphoma & Non-Hodgkin's Lymphoma
54
Staging of Lymphoma
| 1. Clinical Staging
--> Patient history, physical exam, chemical panel, CBC, chest x-ray
A. Asymptomatic --> no signs or symptoms
B. Symptoms --> unexplained weight loss, night sweats, low grade fever
55
Staging of Lymphoma
| 1. Pathological Staging
1. Tissue biopsy --> Lymph nodes --> what tissue and cell type
A. Microscopic evaluation
B. Histological evaluation
2. Ancillary Tests --> what stage cell is in
A. Immunphenotyping
B. Cytogenetics
56
Hodgkin's Lymphoma (1/3)
1. Onset (ages and type of distribution)
2. Characteristics
1. Biomodal distribution --> 15-35 yrs old and >50 yrs old
2. **Reed-Sternberg Cell
* Tissue Biopsy --> Classification based on growth pattern and cellular composition
* Clinical and pathological staging
57
What characteristics classify a Hodgkin's Lymphoma?
Tissue location and cell types involved
58
Non-Hodgkin's Lymphoma
1. Etiology
2. How to classify
3. Characteristic
1. Genetic damage associated with numerical or structural damage to chromosomes that would regulate growth and reproduction of cells in the immune system
2. Classify according to clinical, morphological, immunophenotype, genotype
3. Each lymphoid compartment occupied by distinct set of cells
59
Diagnostic Evaluation
1. Benign versus Malignant
2. Lymphoma versus Nonlymphoma
3. T cell versus B cell Lymphoma
4. Hodgkin's versus Non-Hodgkin's
60
Treatment of Non-Hodgkin's Lymphoma
1. Indolent --> mantle/marginal, low grade lymphoma, clinically slower progressing, incurable
2. Diffuse aggressive --> with no treatment die within 1 year, higher cure rate with aggressive treatment, more favorable
61
Chronic Leukemia
1) Definition
2) Types
1. Clonal proliferation of morphologically and immunophenotypically mature T and B cells --> slow progressing disease
2. Leukemia -> affects bone marrow and manifests in peripheral blood
Lymphoma -> affects lymph nodes (sometimes bone marrow or extramedullary sites) --> tied with leukemia (can turn into)
62
Chronic Lymphocytic Leukemia/Chronic Lymphocytic Lymphoma (CLL)
1. Onset
2. Definition
3. Characteristics of blood cells
1. Patient usually >50 years old
2. Lymphoproliferative disorder of mature lymphocytes (B-CLL or T-CLL)
3. Lymphocytosis; "Soccer Ball" appearing nuclear chromatin; Smudge cells; Hypogammaglobinemia (low antibodies)
63
Classic CLL
1. Definition
2. Characteristics
3. Immunophenotype
1. Neoplastic disorder with gradual accumulation of small mature B cells which are long lived, nonproliferating, and dysfunctional
2. Malignant B cells do not mature to plasma cells; abnormal chromosome
3. slg, CD19, CD20, CD5, CD23, CD43
64
Signs of CLL
```
Chronic fatigue
Organomegaly
Infections
Two times more common in males
Increased lymphocytosis in bone marrow
Thrombocytopenia
Decrease WBC antibody count
Monoclonal cells (cookie cutter)
```
65
Treatment options for CLL
* Chemotherapy and radiation
* splenectomy
* Increase dose gamma globulin therapy
66
Multiple Myeloma
1. Definition
2. General characteristic
3. Causes
1. Overproduction of abnormal plasma cells
2. Mutated plasmablast relocates to bone marrow and produces clone (plasmacytoma)
3. Expanding plasma cell mass; overproduction of monoclonal immunoglobulins; production of osteoclast-activating factor and cytokines
67
Signs and symptoms of Multiple Myeloma
* Hypercalcemia
* Kidney stones
* Mental status change
* Constipation
68
Plasmacytoma
Single tumor mass of plasma cells --> relocates to the bone marrow
69
Multiple Myeloma --> Expanding Plasma Cell Mass
1. Definition
2. Characterized by..
1. Normal bone marrow replaced by steadily growing clone of plasma cell
2. Pancytopenia with anemia, increased bleeding (decreased platelets) and increased infections (decreased WBC), bone pain (due to masses in heme rich areas of vertebrae)
70
Multiple Myeloma --> Overproduction of Monoclonal Immunoglobulins (Monoclonal Gammopathy)
1. Definition
2. Characteristics
1. Unbalanced production of free light or free heavy chains
2. *Hyperviscosity syndrome (increase in viscosity = thick blood = increased heart workload)
* Decreased production of normal Igs
* Bence-Jones Protein (increase in light chains) /Kidney damage
* Amyloidosis (accumulation of light chains in body organs)
* Bleeding disorders and cryoglobulins (increase AB components and increase in IgGs)
71
Multiple Myeloma --> Production of Osteoclast-Activating Factor and Cytokines
1. OAF increases bone resorption and calcium release (lytic or "punched out" lesions)
2. IL-6 (increases apoptosis & plasma cell growth)
3. Hypercalcemia
72
Multiple Myeloma
| 1. Signs and Symptoms
* Psychosis
* Confusion
* Bone pain
* Kidney stones
73
Multiple Myeloma
| 1. Lab results
* M-spike on protein electrophoresis
* Normocytic anemia
* Rouleaux
* Increased ESR, CRP, and Calcium
* Bone Marrow biopsy
* Radiology, CT, and MRI
74
Lipid Storage Diseases
1. Definition
2. Characterized by...
3. Types
1. Rare, autosomally inherited diseases
2. Subcellular accumulation of unmetabolized material in lysosomes of various cells
* Enzyme defect and/or deficiency affecting lipid metabolism
3. Gaucher's, Niemann-Pick, Tay-Sachs, Mucopolysaccharidosis
75
Gaucher's Disease
1. Deficiency of...
2. Result of this deficiency
3. Characteristics
1. Beta-glucocerebrosidase
2. Accumulation of unmetabolized glucocerebroside in cells of the RE system
3. Gaucher's cells (histiocytes) --> crumpled paper cytoplasm
76
Niemann-Pick Disease
1. Deficiency of..
2. Result of deficiency
3. Characteristics
1. Sphingomyelinase
2. Secondary accumulation of unmetabolized lipid sphingomyelin and cholesterol
3. Niemann-Pick cells (foamy, bubbled milk cytoplasm)
77
Tay-Sachs Disease
1. Deficiency of...
2. Results in...
3. Characteristics
1. Hexosaminidase A (increase in hexosaminidase B)
2. Accumulation of unmetabolized GM2 ganglioside in tissues
3. Macrocephaly, cherry-red spot in eye, death by 4 years of age
78
Mucopolysaccharidoses
1. Definition
2. How many different categories?
3. Characterized by..
1. Group of disorders deficient in one of the enzymes in the breakdown of mucopolysaccharides
2. MPS I-VII (7)
3. Alder-Reilly Bodies
79
Hemostasis
| 1. Definition
Maintain complete balance between clotting and bleeding
80
What are the major systems that regulate hemostasis?
* Vascular system
* Platelets
* Serine Protease Inhibitors
* Coagulation system
* Fibrinolytic system
81
What are the minor systems maintaining hemostasis?
* Kinin system
| * Complement system
82
Stages of Hemostasis
* Primary Hemostasis
| * Secondary Hemostasis
83
Primary Hemostasis
1. Initiation
2. Characterized by..
1. Initiated when blood vessel is exposed
| 2. Platelet adhesion to exposed collagen within endothelium of vessel wall and mediated by GPIb and vWF
84
GPIb
Found on platelets and is a receptor for vWF
85
vWF
Secreted by endothelial and megakaryocytes
| Found on blood vessel walls
86
Secondary Hemostasis
1. Function
2. Characterized by..
1. Stabilization of platelet plug
2. Activation of coagulation proteins to produce fibrin from fibrinogen to stabilize clot
* Fibrinolysis (plasmin) and PDGF
87
Sources and Types of Bleeding
1. Arteriole, venule
2. Veins
3. Artery
1. Pinpoint petechial, hemorrhage
2. Ecchymosis --> soft tissue bleeding, blood leaking from vein
3. Rapidly expanding blowout hemorrhage
88
Vessel layers and characteristics of each layer
1. Tunica adventitia (outermost layer) --> connective tissue support
2. Tunica media (middle layer) --> controls vasodilation and constriction, smooth muscle
3. Tunica intima (inner layer) --> nonwettable surface (nonthrombogenic)
89
Vascular System's role in prevention of bleeding
1. Vasoconstriction
2. Diversion of blood flow
3. Contact activation of platelets
4. Activation of coagulation system (secondary hemostasis) leading to fibrin formation
90
Primary Hemostasis --> Platelets
1. Definition
2. Secreted by?
3. Physical characteristics?
1. Anucleated cytoplasmic fragments
2. From bone marrow megakaryocytes
3. 2-4 um and 150,000-400,000/uL --> reserved in the spleen
91
Functions of platelets in primary hemostasis
1. Provide (-) charged phospholipid surface for Factor X and prothrombin activation and binding
2. Release substances for vasoconstriction, platelet aggregation, coagulation, and repair
3. Provide surface membrane glycoproteins to attach to other platelets, endothelium
92
Platelet Structure --> what are the main areas?
1. Peripheral Zone
2. Sol-Gel Zone
3. Organelle Zone
93
Platelet structure --> Peripheral Zone (outer zone)
1. Glycocalyx
2. Platelet membrane
3. Open Canalicular system
4. Submembrane region
1. Responsible for antigens on surface (ABO/MHC)
2. Shape changes/stickiness/signal transduction
3. Moves granules
4. Microfilaments for support
94
Platelet structure --> Sol-Gel Zone (support system - cytoskeleton)
1. Microtubules
2. Microfilaments
1. Encase the whole platelet --> maintain shape
| 2. Randomly distributed --> anticipate contraction
95
Platelet Structure --> Organelle Zone
1. Granules (types)
2. Mitochondria
3. Dense Tubular System
4. Peroxisomes
1. Dense Granules (store ADP, ATP, calcium, serotonin), Alpha Granules (200/platelet), Lysosomes (neutralizing proteases), Glycogen Granules (help function in metabolism)
2. Use glycogen to get ATP
3. Sequester calcium -- site for thromboxane production
4. Nothing to know about this
96
Platelet Plug Formation Pathway (General steps)
1. Vasoconstriction
2. Adhesion
3. Platelet Activation -- Shape Change
4. Aggregation
5. Secretion (release reaction)
6. Stabilization of Platelet Plug
97
Platelet Plug Formation
| 1. Vasoconstriction
Activated by a breach in the blood vein system
98
Platelet Plug Formation
| 2. Adhesion (1-2 seconds)
1. vWF
2. GPIb
3. Collagen fibers
99
Platelet Plug Formation
| 3. Platelet Activation -- Shape Change
Altered cytosolic calcium and microtubules
100
Platelet Plug Formation
| 4. Aggregation (10-20 seconds)
Platelet to platelet interaction
* **ATP dependent, Calcium, GPIIb and IIIa, and fibrinogen
* *Primary or reversible (platelets can aggregate, but can dissociate if not needed at this point
101
Platelet Plug Formation
| 5. Secretion (Release Reaction) (1-3 minutes)
* *Platelets can no longer dissociate at this point
* *Vicious metamorphosis - platelet mass -- cannot distinguish individual platelets
* *alpha granules release beta-TG, PF4, thrombospondin, PDGF
102
Platelet Plug Formation
6. Stabilization of Platelet Plug
A. Function
B. Causes
A. Prevents blood leaking by providing structure
B Activate coagulation cascade (consolidation of plug); Formation and deposition of fibrin which interweaves with platelets; Thrombin with Factor XIII stabilizes clot
103
Fibrinolysis
1. Function
2. Pathway
1. Promotes clot dissolution (means for removing thrombi or clots)
2. Plasminogen --> Plasmin --> breaks down fibrin and fibrinogen
104
Open Canicular System
Control movement and release of stored granules and movement of calcium
105
Microtubules/Microfilaments
Platelet shape and organelle movement
106
Ionized Calcium
Shape changes (secondary hemostasis); stabilizes fibrinogen in clot
107
GPIb
Binds vWF; encourages platelet adhesion
108
PGI2
Vasodilator -- inhibits platelet aggregation
109
TXA2
Vasoconstrictor -- platelet adherence and aggregation
110
Factor XIII
Cross linking with fibrin and stabilizing clot
111
PDGF
Vascular healing and repair
112
Thrombin
Convert fibrinogen to fibrin
113
Fibrinogen
Precursor to fibrin
114
Fibrin
Stabilizes clot
115
t-PA
Primary activator of plasminogen to plasmin
116
Plasminogen
Precursor to plasmin
117
Plasmin
Destroys fibrin and fibrinogen
118
Secondary Hemostasis
| 1. Definition
Coagulation factors interact to form a fibrin clot that reinforces the platelet plug
119
Factor I
Fibrinogen
120
Factor II
Prothrombin
121
Factor III
Tissue thromboplastin
122
Factor IV
Ca++
123
Factor V
Labile Factor
124
Factor VII
Stable Factor
125
Factor VIII
Antihemophilic factor or Factor VIII:C
126
Factor IX
Christmas Factor
127
Factor X
Stuart-Prower Factor
128
Factor XI
Plasma thromboplastic antecedent
129
Factor XII
Hageman Factor
130
Factor XIII
Fibrin-stabilizing Factor
131
Fitzgerald Factor
High-molecular weight kininogen (HMWK)
132
Fletcher Factor
Prekallikrein (PK)
133
Physical Properties Classification of Factors --> Contact
1. Factors?
2. Consumed in the reaction?
3. Vitamin K dependent?
1. XII, XI, Prekallikrein, HMwK
2. Not consumed in the reaction
3. Not vitamin K dependent
134
Physical Properties Classification of Factors --> Prothrombin
1. Factors?
2. Consumed in the reaction?
3. Vitamin K dependent?
1. II, VII, IX, X
2. Not consumed in the reaction except for II
3. Vitamin K dependent
135
Physical Properties Classification of Factors --> Fibrinogen Group
1. Factors?
2. Consumed in the reaction?
3. Vitamin K dependent?
1. I, V, VIII, XIII
2. Consumed in reaction
3. Not vitamin K dependent
136
Coagulation Pathways
| 1. Types
Extrinsic, Intrinsic, Common
137
Extrinsic Coagulation Pathway
1. Factors
2. Test
1. III, VII --> goes into common pathway --> X, V, II, I
| 2. Prothrombin Times (PT)
138
Intrinsic Coagulation Pathway
1. Factors
2. Test
1. XII, XI, IX, VIII --> Goes into common --> X, V, II, I
| 2. Activated Partial Thromboplastin Time (APTT)
139
Common Coagulation Pathway
1. Factors
2. Tests
1. XIII, X, V, II, I
| 2. APTT or PT
140
If platelet count and morphology are normal, how do you determine if it is a factor deficiency or factor inhibitor causing the problem?
Mixing studies with pooled normal plasma to determine the cause
141
PT is abnormal, but is corrected with pooled normal plasma
| APTT is normal
Deficiency of Extrinsic Factor
142
PT is abnormal, but is NOT corrected with pooled normal plasma
APTT is normal
Inhibitors to Extrinsic Factors
143
PT is normal
| APTT is abnormal, but is corrected with pooled normal plasma
Deficiency of Intrinsic factors
144
PT is normal
| APTT is abnormal, but is NOT corrected with pooled normal plasma
Inhibitors to Intrinsic Factors
145
PT and APTT is abnormal, but are corrected with pooled normal plasma
Deficiency of Common Factors
146
PT and APTT are abnormal, but are NOT corrected with pooled normal plasma
Inhibitors to Common Factors
147
Test Results for Vascular Disorder:
1. PT
2. APTT
3. TT
4. Platelet Count
5. Template or Ivy Bleeding Time
6. PFA-100 Assay (Platelet Function Assay)
1. Normal
2. Normal
3. Normal
4. Normal
5. Abnormal
6. Abnormal
148
Test Results for Quantitative Platelet Disorder:
1. PT
2. APTT
3. TT
4. Platelet Count
5. Template or Ivy Bleeding Time
6. PFA-100 Assay (Platelet Function Assay)
1. Normal
2. Normal
3. Normal
4. Abnormal
5. Abnormal
6. Abnormal
149
Test Results for Qualitative Platelet Disorder:
1. PT
2. APTT
3. TT
4. Platelet Count
5. Template or Ivy Bleeding Time
6. PFA-100 Assay (Platelet Function Assay)
1. Normal
2. Normal
3. Normal
4. Normal
5. Abnormal
6. Abnormal
150
Test Results for Factor Deficiency Common Disorder:
1. PT
2. APTT
3. TT
4. Platelet Count
5. Template or Ivy Bleeding Time
6. PFA-100 Assay (Platelet Function Assay)
1. Abnormal
2. Abnormal
3. Normal
4. Normal
5. Normal
6. Normal
151
Test Results for Factor Deficiency Intrinsic Disorder:
1. PT
2. APTT
3. TT
4. Platelet Count
5. Template or Ivy Bleeding Time
6. PFA-100 Assay (Platelet Function Assay)
1. Normal
2. Abnormal
3. Normal
4. Normal
5. Normal
6. Normal
152
Test Results for Factor Deficiency Extrinsic Disorder:
1. PT
2. APTT
3. TT
4. Platelet Count
5. Template or Ivy Bleeding Time
6. PFA-100 Assay (Platelet Function Assay)
1. Abnormal
2. Normal
3. Normal
4. Normal
5. Normal
6. Normal
153
Test Results for Factor I Deficiency:
1. PT
2. APTT
3. TT
4. Platelet Count
5. Template or Ivy Bleeding Time
6. PFA-100 Assay (Platelet Function Assay)
1. Abnormal
2. Abnormal
3. Abnormal
4. Normal
5. Normal
6. Normal
154
Thrombin
| 1. Main Functions
1. Converts fibrinogen to fibrin
2. Activates XIII
3. Enhances activity of V and VIII -- enhance coagulation
4. Induces platelet aggregation and activation
5. Aids in tissue repair and healing (induces WBC adhesion, increases vascular permeability)
155
Fibrinolytic System
1. Definition
2. Pathway
1. Removal of fibrin deposits with enzymatic cleavage to reestablish blood flow
2. Plasminogen with t-PA --> Plasmin --> splits fibrin into FDPs
156
Fibrinolytic System
| 1. Plasmin function
1. Destroys fibrinogen and fibrin; produce FDPs; Destroys some coagulation factors; cleaves C3; liberates kinins
157
Kinin System
1. Function
2. Systems that activate it...
1. Inflammation, permeability, vasodilation, and chemotaxis
| 2. Activated by coagulation and fibrinolytic systems
158
Protease Inhibitors
| 1. Function
1. Eliminate kallikrein and plasmin
159
Other Systems involved in Hemostasis
1. Kinin System
2. Protease Inhibitors
3. Complement System
160
Diagnosis of Hemostatic Disorders
1. Patient history
2. Platelet count
3. Peripheral blood smear
4. Template Bleeding time
5. Prothrombin time (PT)
6. Activated Partial Thromboplastin Time (APTT)
7. Thrombin Time (TT)
161
Thrombin Time
Time for thrombin to convert fibrinogen to fibrin
162
Disorders of Primary Hemostasis
1. Definition
2. Clinical symptoms
3. Tests used to determine..
1. Quantitative and qualitative platelet disorders and defects of blood vessel wall
2. Ecchymosis, petechiae, purpura and mucosal bleeding
3. Platelet count; Peripheral blood smear; bleeding time; vWF studies; Platelet antibody testing; platelet aggregation; Bone marrow aspirate and biopsy
163
Types of Quantitative Platelet Disorders
Thombocytopenia and Thrombocytosis
164
Thrombocytopenia
| 1. Causes (3)
1. Deficient Platelet Production
2. Abnormal Platelet Distribution
3. Increased Platelet Destruction
165
Thrombocytopenia --> Deficient Platelet Production
| 1. Causes
1. Myelophthisic (bone marrow, leukemia/lymphoma)
2. Aplasia (aplastic anemia)
3. Ineffective Erythropoiesis (Increase alcohol consumption)
4. Congenital disorders
166
Thrombocytopenia --> Abnormal Platelet Distribution
1. Hypersplenism (hyperactive spleen)
| 2. Hemangiomas (large tumors in blood vessels that accumulate platelets
167
Thrombocytopenia --> Increased Platelet Destruction
1. Immune (primary)
2. Immune (secondary)
3. Microangiopathic thrombocytopenia
4. Pregnancy (associated)
1. Idiopathic thrombocytopenic purpura; posttransfusion purpura, isoimmune neonatal; drug-induced; heparin therapy
2. Lymphoproliferative disorders; collage vascular disorders; viral infection
3. Thrombotic thrombocytopenia purpura; Hemolytic Uremic syndrome; Disseminated Intravascular Coagulation
4. Gestational; Preeclampsia; Eclampsia
168
Thrombocytosis
| 1) Types
1. Primary Thrombocytosis --> Due to myeloproliferative disorders
2. Reactive Thrombocytosis --> Acute hemorrhaging
169
Qualitative Platelet Disorders
| 1) Types
1. Platelet Membrane Defects
2. Platelet Release (Secretion) Defects
3. Defects in Platelet Coagulant Activity
4. vonWillebrand's Disease
170
Qualitative Platelet Disorders --> Platelet Release (Secretion) Defects --> Causes
1. Storage Pool Deficiencies
2. Primary Secretion Defects
1. Granule defect; Chediak-Higashi & Wiskott-Aldrich
| 2. Enzymatic pathway defects
171
Qualitative Platelet Disorders --> vonWillebrand's Disease --> Causes
* Inherited deficiency of vWF
* vWF promotes secondary hemostasis by functioning as carrier for Factor VIII
* Platelet adhesion depends on vWF, GPIb, vascular endothelium (collagen), and other adhesive proteins
172
Causes of acquired qualitative platelet disorders
1. Renal disease
2. Liver disease
3. Paraproteinemias
4. Myeloproliferative disorders
5. Acquired vWF disease
6. Cardiopulmonary bypass
7. Acquired storage pool deficiencies
8. Drug Therapy
173
Vascular Disorders --> Purpora
1. Definition
2. Primary
3. Secondary
1. Bleeding
2. Simple bruising, mechanical (sneezing can cause a bruise on the face, senile, factitious, Schamberg's
3. Result of other disease --> Infectious (strep), allergic, metabolic, psychogenic, secondary to dysproteinemia (lack of protein), vascular and connective tissue disorders
174
Disorders of Plasma Clotting Factors
1. Causes
2. Characteristics
3. Types
1. Decrease in factor synthesis, Produce abnormal molecules that interfere with coagulation pathway; loss or consumption of factors; inactivation of factors by inhibitors or antibody
2. Prolonged clot formation; Increased bleeding time or clot; Delayed pathway activation
3. Inherited or acquired
175
Factor I (Fibrinogen)
1. Function
2. Pathway
1. Fibrinogen combines with thrombin to form fibrin / Acute phase reactant (inflammation reactant)
2. Common pathway
176
```
Factor I (Fibrinogen) Deficiency
1. Types
```
Afribinogenemia --> low levels of fibrinogen (increase in PT, APTT, TT)
Hypofibrinogenemia
Dysfibrinogenemia --> Dysfunction in fibrinogen (increase in PT, TT, APTT)
177
Treatment options for factor deficiencies
1. Fresh frozen plasma --> gives coagulation factors
| 2. Cryopercipitate --> high concentration of coagulation factors (esp. 8)
178
Factor II (Prothrombin)
1. Characteristics
2. Function
3. Pathway
1. Vitamin K dependent
2. Prothrombin with Xa, Va, Ca++, and phospholipid cofactor forms thrombin
* Can also bind platelets and initiate platelet charge
179
Factor II (Prothrombin) Deficiency
* Hypoprothrombinemia --> low levels
* Dysprothrombinemia --> dysfunctional prothrombin
* Prothrombin mutation --> most common cause of thrombosis
**APTT, PT, TT tests
180
Factor V (Proaccelerin/Labile Factor)
1. Function
2. Pathway
3. Diseases/Deficiencies
1. Cofactor of prothrombin --> thrombin
2. Common Pathway (APTT, TT, PT)
3. Parahemophilia (congenital) or Factor V mutation (affects protein C)
181
Factor VII (Proconvertin/Stable Factor)
1. Characteristic
2. Pathway
3. Function
4. Deficiency types
5. Test
1. Vitamin K dependent
2. Extrinsic Pathway
3. VIIa and tissue factor activate factors IX and X
4. Congenital and acquired
5. PT test abnormal
182
Factor VIII (Anti-hemophilic Factor)
1. Pathway and test
2. Function
3. Disease associated
4. Treatment of Disease
1. Intrinsic pathway (APTT test)
2. Circulates with vWF/cofactor in converting X --> Xa
3. Hemophilia A --> sex linked defect or absence of FVIII:C/(procoagulant portion) with normal levels of vWF
5. Cryopercipitate
183
vonWillebrand's Disease
1. Factor associated with this disease
2. Characterized by...
3. Normal function of vWF
4. Abnormal...
1. Factor VIII
2. Autosomal defect of vWF with decreased platelet adhesion; vWF in Weibel-Palade bodies in endothelial cells and alpha platelet granules
3. Carrier for Factor VIII
4. Abnormal bleeding time and platelet adhesion
184
Factor IX (Christmas Factor)
1. Characteristic
2. Pathway
3. Normal function
4. Disease associated
1. Vitamin K dependent
2. Intrinsic pathway (APTT test)
3. Cofactor in activating Factor X --> Xa
4. Hemophilia B --> Sex linked inherited
185
Factor X (Stuart-Prower Factor)
1. Characteristic
2. Pathway
3. Function
1. Vitamin K dependent
2. Common pathway (increase in APTT and PT)
3. Activates prothrombin to thrombin
186
Factor XI (Plasma Thromboplastin Antecedent)
1. Pathway
2. Function
3. Disease associated with it...
1. Intrinsic pathway (APTT)
2. Converts Factor IX --> Factor IXa
3. Hemophilia C --> Inherited Jewish population
187
Factor XII (Hageman Factor)
1. Normal function
2. Disease and symptoms
1. Starts with intrinsic pathway as contact factor with collagen
2. Hageman Trait --> Increase chances of thrombotic diseases; Increase thrombosis; APTT is abnormal
188
Factor XIII (Fibrin-Stabilizing Factor)
1. Special characteristic
2. Normal function
3. Pathway
4. Disease characteristic
1. Only one that is not a serine protease
2. Formation of stable fibrin clot
3. Common Pathway
4. Normal test results, but about 36 hours after platelet plug formation person will bleed due to inability to stabilize the clot
189
High-Molecular-Weight Kininogen (Fitzgerald Factor)
1. Pathway
2. Function
1. Intrinsic pathway (APTT)
| 2. Contact activator cofactor with Factor XIIa and prekallikrein
190
Inhibitors of Coagulation (Major types)
1. Specific Factor Inhibitors
| 2. Nonspecific Inhibitors
191
Specific Factor Inhibitors
| 1. Types
1. Antibodies --> directly inhibit or neutralize or cause increased clearance by binding
2. Factor VIII:C inhibitor --> Most common; alloantibody; result of transfusion
192
Nonspecific Inhibitors
| 1. Example
Antiphospholipid Antibody Syndrome --> lupus anticoagulants and anticardiolipin antibody)
193
Fibrinolytic System Function
Breaking down blood clot
194
Fibrinolytic System Parts
1. Plasminogen
2. Plasminogen Activators --> t-PA
3. Plasminogen Activator Inhibitor-1 (inhibits t-PA)
4. Plasmin
5. Plasmin Inhibitors
6. Fibrinogen and Fibrin (plasmin substrates)
7. Thrombomodulin --> Regulates thrombin -- inhibits thrombin
8. Thrombin-activatable fibrinolysis inhibitor
195
Plasmin Inhibitors
1. Function
2. Type
1. Grade reaction
2. Alpha2-antiplasmin inhibitor --> primary, irreversible
Alpha2-macroglobulin --> secondary
196
Fibrinolytic System Abnormalities
| 1. Types
1. Congenital and Acquired
197
Acquired Fibrinolytic System Abnormality
1. Disseminated Intravascular Coagulation (DIC)
| 2. Primary Fibrinolysis
198
Disseminated Intravascular Coagulation
Acquired Fibrinolytic system abnormalities
--> Coagulation factors and platelets are consumed with thrombus in microcirculation; diffuse hemorrhage and/or ischemic tissue damage with vascular occlusion
199
Primary Fibrinolysis
Acquired Fibrinolytic System Abnormality
| --> Plasmin formed in absence of coagulation process
200
Thrombosis
1. Definition
2. Causes
1. Development or formation of a blood clot or thrombus
| 2. Stroke, myocardial infractions, pulmonary embolism
201
Thrombosis
| 1. Factors influencing Thrombosis
* Role of Blood Vessel
* Flow of blood within the vessel
* Chemistry of blood
* Role of Endothelium
- -> Prothrombotic Properties
- -> Antithrombotic Properties
* Platelets
* Procoagulant Factors and generation of thrombin
202
Anticoagulant Therapy
| 1. Types
* Unfractionated Heparin
* Low-Molecular-Weight Heparin
* Oral Anticoagulants
* Factor Xa Inhibitors
* Antiplatelet Agents
* Thrombolytic Therapy
203
Unfractionated Heparin
Initial acute treatment for thrombosis
* binds thrombin
* APTT (70-100 seconds)
204
Oral Anticoagulants
1. Type of treatment
2. Examples and function
3. Test
1. Long term treatment
2. Coumarin (Warfarin) --> Inhibits vitamin K
3. PT
205
Antiplatelet Agents
| 1. Example and function
1. Aspirin --> inhibits cyclo-oxygenase for TXA2 production and inhibits prostaglandin synthesis; inhibits platelet aggregation
206
Thrombolytic Therapy
1. Function
2. Examples
1. Lyse clots
| 2. Urokinase, Streptokinase, t-PA
