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Hematology 2 > (P) Lesson 1: Introduction to Hemostasis and Megakaryopoiesis > Flashcards

(P) Lesson 1: Introduction to Hemostasis and Megakaryopoiesis Flashcards

1
Q
  • A complex biochemical process by which the body spontaneously stops bleeding (hemorrhage) upon injury and maintains blood in a fluid state within the vessel compartment.
A

Hemostasis

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2
Q

How does the body spontaneously stop bleeding or hemorrhage upon injury?

A
  • The body makes use of platelets and clotting factor to prevent the bleeding.

Several proteins can either control their reactions and other can control the clotting of blood itself.

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3
Q

Imbalances in hemostasis may result in what?

There are two (2) answers.

A
  1. Hemorrhage (purpura)
  2. Thrombosis
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4
Q
  • Characterized by excessive bleeding
  • E.g. Thrombotic thrombocytopenic purpura, idiopathic thrombocytopenic purpura
A

Hemorrhage (purpura)

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5
Q
  • Characterized by excessive clotting
A

Thrombosis

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6
Q

What are the four (4) factors that make a person prone to these blood disorders?

A
  1. Low platelet count
  2. Dysfunctional platelets
  3. Clotting factor deficiency
  4. Auto-antibodies
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7
Q

T or F: Low platelet count is a qualitative defect while dysfunctional platelets are a quantitative defect.

A

False

Low platelet count is a quantitative defect while dysfunctional platelets are qualitative defects.

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8
Q

What is the reference value of platelets?

A

150,000 to 400,000 µl

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9
Q

This is a disorder associated with dysfunctional platelets and is characterized by impaired platelet aggregation.

A

Glanzmann’s thrombasthenia

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10
Q

What clotting factor is deficient in Hemophilia A?

A

Factor 8

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11
Q

What clotting factor is deficient in Hemophilia B?

A

Factor 9

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12
Q

What clotting factor is deficient in Hemophilia C?

A

Factor 11

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13
Q
  • Majority of these are inhibitors of clotting factors
  • They prevent the normal function of platelets and clotting factors
  • E.g. Factor 8 inhibitors and circulating anticoagulants
A

Autoantibodies

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14
Q
  • This anticoagulant can affect PT/PTT results
  • This is an autoantibody of unknown cause.
A

Lupus Anticoagulant

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15
Q

Lupus Anticoagulant

T or F: When in vitro, the anticoagulant will cause thrombosis and when in vivo, it will not clot the blood.

A

False

In vitro will not clot the blood, in vivo will cause thrombosis.

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16
Q

T or F: The majority of the clotting factors are produced in the kidney and are numbered 1 to 13.

A

False

They are produced in the liver.

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17
Q

What are the other clotting factors include?

A
  1. High molecular weight kininogen (HMWK)
  2. Prekallikrein
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18
Q
  • Decreased clotting of blood leading to bleeding
A

Hypocoagulation of blood

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19
Q
  • Uncontrolled clotting of blood leading to thrombosis (blockage in the vessel)
  • This is due to deficiencies of proteins that control the clotting factor functions (e.g. protein C and S)
  • May also be due to excessive platelets in the blood released by the bone marrow (e.g. Polycythemia vera)
A

Hypercoagulation of blood

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20
Q
  • Molecular interactions maintain equilibrium between procoagulant and fibrinolytic activities.
A

Balance Mechanism

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21
Q

What are the two (2) components of the balance mechanism for hemostasis?

A

Clotting Activation and Bleeding

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22
Q

What are the four (4) additional factors that support the hemostatic process?

A
  1. Endothelial Cell Function
  2. Plateleg Plug Formation
  3. Stagnation Effects
  4. Protective Mechanisms
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23
Q

Additional Factors that Support the Hemostatic Process

  • Blood flow changes affect endothelial cell behavior.
  • Injury to endothelium triggers hemostatic and thrombotic
    responses.
A

Endothelial Cell Function

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24
Q

Additional Factors that Support the Hemostatic Process

  • If vascular injury exceeds platelet capacity, hemorrhage
    symptoms arise
A

Platelet Plug Formation

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25
Q

Additional Factors that Support the Hemostatic Process

  • Reduced blood flow due to arterial disease or mechanical
    impedance can lead to thrombus formation and
    hypercoagulable states.
A

Stagnation Effects

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26
Q

Additional Factors that Support the Hemostatic Process

  • Intact endothelial cells are thromboresistant via receptor
    and proteoglycan interactions.
  • Coagulation proteins circulate as inactive zymogens,
    balanced by anticoagulant and fibrinolytic pathways.
  • Platelet procoagulant lipids are internalized within cells to
    maintain hemostatic balance.
A

Protective Mechanisms

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27
Q

What are the two (2) systems involved in maintaining hemostasis?

A

Major System and Minor System

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28
Q

Major or Minor System?

  • Vascular System
  • Platelets
  • Coagulation System
  • Fibrinolytic System
  • Serine protease inhibitors
A

Major System

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29
Q

Major or Minor System?

  • Kinin System
  • Complement System
A

Minor System

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30
Q

What are the three (3) general components of hemostasis?

A
  1. Extravascular
  2. Vascular
  3. Intravascular
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31
Q

General Components of Hemostasis

  • Mainly the tissue surrounding the damaged BVs (e.g. skeletal and smooth muscles)
  • These can contract to prevent further bleeding
  • Provide back pressure on the injured vessel through
    swelling and trapping of escaped blood.
  • Increased tissue pressure tends to collapse venules and
    capillaries.
A

Extravascular

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32
Q

General Components of Hemostasis

T or F: Heavy bleeding occurs more frequently in areas with few skeletal muscles surrounding it (e.g. head)

A

True

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33
Q

Extravascular Hemostatic Component

What are the (3) factors affecting hemostasis by surrounding tissues?

A
  1. Bulk or Amount of Surrounding Tissue
  2. Type of Tissue Surrounding the Injured Vessel
  3. Tone of the Surrounding Tissue
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34
Q

Factors Affecting Hemostasis by Surrounding Tissues

  • A wound in a fleshy area (e.g., thigh) will not bleed as
    profusely as an identical wound in an area with less tissue
    (e.g., scalp)
A

Bulk or Amount of Surrounding Tissue

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35
Q

Factors Affecting Hemostasis by Surrounding Tissues

  • Skeletal muscle is more absorbent and effective in
    arresting hemorrhage compared to loose connective
    tissue.
A

Type of Tissue Surrounding the Injured Vessel

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36
Q

Factors Affecting Hemostasis by Surrounding Tissues

  • Tissue elasticity affects the amount of bleeding.
  • Identical wounds in a 17-year-old with great tissue
    elasticity tend to bleed less than those in a 71-year-old with
    less tissue elasticity.
A

Tone of the Surrounding Tissue

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37
Q

General Components of Hemostasis

  • Refers to the blood vessels
  • Diseases of the blood vessels may lead to bleeding despite having functional clotting factors
A

Vascular

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38
Q

What are the three (3) components of the vascular system?

A
  1. Arteries
  2. Veins
  3. Small Vessels
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39
Q

What is the importance of collagen?

A

Blood vessel resiliency and platelet activation

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40
Q

T or F: When a cut occurs, collagen is exposed which initiates platelet function.

A

True

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41
Q

What is the contribution of chemicals released by blood vessels to clotting?

A

Promote or prevent blood clotting

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42
Q

What is the contribution of the surfaces of the blood vessels to clotting?

A

Provides sites for blood clotting

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43
Q

General Components of Hemostasis

A genetic disorder that affects collagen formation

A

Ehlers-Danlos and Marfan Syndrome

44
Q

General Components of Hemostasis

T or F: Collagen contributes to the deactivation of platelets.

45
Q

General Components of Hemostasis

  • This is what’s contained plasma
A

Intravascular

46
Q

What are the three (3) components in the intravascular system needed for blood coagulation?

A
  1. Platelets
  2. Clotting Factors
  3. Calcium
47
Q

General Components of Hemostasis

What are the three (3) components of the intravascular component of hemostasis?

A
  1. Platelets
  2. Coagulation Proteins
  3. Fibrinolysis
48
Q

General Components of Hemostasis

The fibrinolytic system contains ____ which is able to dissolve the clot that was formed.

A

Fibrinolysin or Plasmin

49
Q

Fibrinolysis

The inactive form that circulates the body when it is not needed

A

Plasminogen

50
Q

Fibrinolysis

  • Responsible for activating or converting plasminogen
  • Can either be exogenous or endogenous
A

Plasminogen Activators

51
Q

Fibrinolysis

The active form that can digest the clot to allow for wound healing of damaged tissue

52
Q

Fibrinolysis

T or F: Excessive activity of plasmin can easily dissolve the clot, making it soft and harder to heal.

53
Q

Fibrinolysis

What are the two (2) manual methods for determining plasmin action?

A
  1. Whole blood clot lysis time
  2. Euglobulin lysis time
54
Q

What are the two (2) divisions of hemostasis?

A
  1. Primary
  2. Secondary
55
Q

Divisions of Hemostasis

The main objective is to form a platelet plug

56
Q

Primary Division of Hemostasis

T or F: Hemorrhaging does not only mean that blood needs to come out of the body, it can also occur internally.

57
Q

Primary Division of Hemostasis

It is only upon this certain circumstance that the components mentioned in the primary division of hemostasis will be activated.

A

Injury or damaged blood vessels

58
Q

Primary Division of Hemostasis

What are the five (5) components needed in order for platelets to clump together at a damaged site to form a plug?

A
  1. Blood Vessels
  2. Platelets
  3. Von Willebrand’s Factor
  4. Calcium
  5. Factor 1 (Fibrinogen)
59
Q

Primary Division of Hemostasis

  • Allows platelet adhesion to the blood vessel’s collagen
  • The disease associated with this have different types depending on the cause
A

Von Willebrand’s Factor

60
Q

Primary Division of Hemostasis

Deficiency of this leads to bleeding

A

Calcium (Hypocalcemia)

61
Q

Primary Division of Hemostasis

Allows platelet clumping or aggregation

A

Factor 1 (Fibrinogen)

62
Q

Primary Division of Hemostasis

A test that assesses/screens a possible defect in the primary division of hemostasis

A

Bleeding Time (BT)

63
Q

Primary Division of Hemostasis

Any abnormal result in BT points to a problem in what?

A

Platelet plug formation

64
Q

Primary Division in Hemostasis

What are the five (5) methods for Bleeding Time?

A
  1. Duke’s Method
  2. Ivy’s Method
  3. Modified Ivy’s Method
  4. Simplate Method
  5. Template Method (Modification of Ivy’s)
65
Q

The main objective is to stabilize the plug formed to form a firm clot

Now involves clotting factors.

66
Q

Secondary Division of Hemostasis

  • A test that assesses and screens a possible defect in the clotting factors
  • Not confirmatory for what specific clotting factor is impaired
  • Is requested in tandem with Bleeding Time
A

Clotting Time

67
Q

Secondary Division of Hemostasis

What are the two (2) methods for Clotting Time?

A
  1. Lee and White method
  2. Slide/drop method
68
Q

Secondary Division of Hemostasis

What is the reference value of PT upon the addition of specific reagents?

A

12 to 14 seconds

69
Q

Secondary Division of Hemostasis

What is the reference value of PTT/aPTT upon the addition of specific reagents?

A

20 to 45 seconds

70
Q

Secondary Division of Hemostasis

What are the three (3) chemical processes that occur with the clotting factors to form a clot?

A
  1. Extrinsic Pathway
  2. Intrinsic Pathway
  3. Common Pathway
71
Q

Secondary Division of Hemostasis

  • Involves Factor 7
  • Requires a specific reagent to activate this pathway
  • It uses PT to assess any defects (also applies to the common pathway)
A

Extrinsic Pathway

72
Q

Secondary Division of Hemostasis

  • Involves Factors 8, 9, 11, 12, HMWK, and Prekallikrein
  • Requires a specific reagent to activate this pathway
  • Uses PTT to assess any defects (also applies to the common pathway)
A

Intrinsic Pathway

73
Q

Intrinsic Pathway

This factor is the most common, especially for males.

74
Q

Secondary Division of Hemostasis

  • The activation of the either the extrinsic or intrinsic pathway to form a clot
  • Involves factors 1, 2, 5, 10, and 13 (cannot be assessed by either PT/PTT)
  • Utilizes both PT and PTT depending on what pathway is activated
A

Common Pathway

75
Q

How are platelets formed?

A

Megakaryopoiesis

76
Q
  • This is produced by the liver
  • When this hormone goes through the bone marrow, it activates stem cells to produce platelets
A

Thrombopoietin

77
Q

Megakaryopoiesis

These are needed for the successful maturation of platelet-producing cells.

A

Interleukins 3, 6, 7, and 11

78
Q

Phases/Stages of Development

  • 20 to 45 µm
  • Has an NC ratio of 4:1
  • The nucleus is oval to kidney-shaped, placed either centrally or eccentrically, and has red-purple fine chromatin granules
  • Has 1-2 nucleoli
  • The cytoplasm is basophilic, non-granular, and has pseudopodia
  • Has cytoplasmic tags (protrusions on the surface) due to immaturity
A

Megakaryoblast (MK 1)

79
Q

Phases/Stages of Development

  • 20 to 80µm
  • An NC ratio of 4:1 to 1:1
  • The nuclei (2) are oval and indented, placed either centrally or eccentrically, and have increased red-purple fine chromatin granules
  • Gas 0-1 nucleoli
  • The cytoplasm is basophilic, with fine azurophilic granules, and with abundant pseudopodia
  • Whenever the granules are forming, cytoplasmic channels (aka the demarcating membrane system) also start to get formed
A

Promegakaryocyte (MK 2)

80
Q

Phases/Stages of Development

  • 30 to 100µm
  • Has an NC ratio of 1:1 to 1:12
  • The nuclei (2 or 4) are lobulated, interconnected (fused), granulated, and with a central blue purple color
  • Has no nucleoli
  • The cytoplasm is pale blue with an abundance of pink
  • They are not really cells, these are merely fragments of the cytoplasm of one big cell
    -The minimum number of nuclei needed to release platelets is 4
  • Does not contain cytoplasmic tags anymore
A

Megakaryocyte (MK 3)

81
Q

Phases/Stages of Development

  • 30 to 100µm
  • Has an NC ratio of 1:1 to 1:12
  • The nuclei (4 or more; even numbers up to 32) are lobulated (2 or more lobes)
  • The cytoplasm is granular, with demarcation lines, pale blue with an abundance of pink, and contains numerous fine azurophilic granules
  • The platelets are ready to be deployed/fragmented out of the cytoplasm
A

Metamegakaryocyte

82
Q

Phases/Stages of Development

How many days does it to complete the stages of megakaryopoiesis?

A

5 to 7 days

83
Q

Phases/Stages of Development

Megakaryopoiesis produces how many metamegakaryocytes at a time?

84
Q

Phases/Stages of Development

T or F: The cytoplasm of a metamegakaryocyte divides, not the nucleus.

A

False

The cytoplasm does not divide but the nucleus does.

85
Q

Phases/Stages of Development

  • Division of the nucleus only but still with a complete set of 23 chromosomes each which causes the cytoplasm to expand
A

Endomitotic Division

86
Q

What are the two (2) release of platelets theories?

A
  1. Platelet Shedding Theory
  2. Fragmentation/Budding Theory
87
Q

Release of Platelets Theories

  • Megakaryocytes will squeeze a portion of their cytoplasm through blood vessels in the bone marrow via pseudopodia
  • Due to the blood flow, the cytoplasmic sheath will be cut with the platelets inside
  • The fragmented portion will be dragged along the circulation
  • Enzymes in our plasma will dissolve the sheath, releasing the platelets
A

Platelet Shedding Theory

88
Q

The Release of Platelets Theories

  • The platelets will fragment in the cytoplasm of the metamegakaryocyte
  • It will eventually enter the sinuses/blood vessels in the bone marrow before being dragged through the circulation
A

Fragmentation or Budding Theory

89
Q
  • 2 to 4µm
  • A blue cell with fine azurophilic granules—whatever we see in the cytoplasm of the metamegakaryocyte, it is the same for the platelet
  • Is anucleated without a golgi and rough ER
  • Approximately takes 1 week to produce
A

Thrombocytes

90
Q

____ are circulating while the ____ are sequestered or stored in the spleen.

A

70% are circulating while 30% are sequestered or stored

91
Q

In cases of splenomegaly, the (increased/decreased) size will attract more platelets causing a (decrease/increase) in plasma platelets.

A

Increased, decrease

92
Q

In cases of a splenectomy, all platelets will now be found in the circulation therefore (increasing/decreasing) in number.

A

Increasing

93
Q

What is the usual lifespan of thrombocytes?

A

5 to 7 or 7 to 10 day lifespan

94
Q

What is the reference values of thrombocytes?

A

50-350 (or 140-400)x 10^9/L or 150,000-350,000 cells per µm

95
Q

What are the three (3) zones in the ultra-structural zones?

A
  1. Peripheral Zones
  2. Sol-Gel Zones (Cytoskeleton)
  3. Organelle Zones
96
Q

What are the five (5) components under the peripheral zones?

A
  1. Glycocalyx
  2. Glycoprotein Receptors
  3. Platelet Membranes
  4. Open Canalicular System
  5. Sub-membranous Regions
97
Q

Platelets

This glycoprotein receptor is essential for platelet adhesion.

A

Glycoprotein 1A/IX/V (1A-9-5)

98
Q

Glycoprotein 1A/IX/V

Defect of the glycoprotein complex leading to poor adhesion

A

Bernard Solier Syndrome

99
Q

Platelets

This glycoprotein receptor is essential for platelet aggregation. (e.g. Glanzzman Thrombasthenia)

A

Glycoprotein 2B/3A

100
Q

Ultra-structural Zones

Channels that act as openings

A

Open Canalicular System (OCS)

101
Q

Ultra-structural Zones

Extension of the sol-gel zone

A

Sub-membranous Region

102
Q

What are the two (2) components of the sol-gel zones?

A
  1. Microtubules and microfilaments
  2. Actin Myosin/Thrombostenin
103
Q

Sol-gel Zones

  • Maintains the shape and appearance of the cell
  • It will be disrupted when activated
A

Microtubules and microfilaments

104
Q

Sol-gel Zones

  • Contractile protein that contracts upon activation to release the granuleslocated in the organelle zone
A

Actin Mysoin/Thrombostenin

105
Q

Hi, please study the platelet granules and overview of hemostasis.

A

Good job sa first lesson, see you next week. <3

Hematology 2 (10 decks)

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