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

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.

Hemostasis

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

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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Imbalances in hemostasis may result in what?

There are two (2) answers.

Hemorrhage (purpura)
Thrombosis

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Characterized by excessive bleeding
E.g. Thrombotic thrombocytopenic purpura, idiopathic thrombocytopenic purpura

Hemorrhage (purpura)

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Characterized by excessive clotting

Thrombosis

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

Low platelet count
Dysfunctional platelets
Clotting factor deficiency
Auto-antibodies

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

False

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

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What is the reference value of platelets?

150,000 to 400,000 µl

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

Glanzmann’s thrombasthenia

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What clotting factor is deficient in Hemophilia A?

Factor 8

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What clotting factor is deficient in Hemophilia B?

Factor 9

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What clotting factor is deficient in Hemophilia C?

Factor 11

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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

Autoantibodies

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This anticoagulant can affect PT/PTT results
This is an autoantibody of unknown cause.

Lupus Anticoagulant

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Lupus Anticoagulant

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

False

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

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

False

They are produced in the liver.

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What are the other clotting factors include?

High molecular weight kininogen (HMWK)
Prekallikrein

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Decreased clotting of blood leading to bleeding

Hypocoagulation of blood

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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)

Hypercoagulation of blood

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Molecular interactions maintain equilibrium between procoagulant and fibrinolytic activities.

Balance Mechanism

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

Clotting Activation and Bleeding

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

Endothelial Cell Function
Plateleg Plug Formation
Stagnation Effects
Protective Mechanisms

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Additional Factors that Support the Hemostatic Process

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

Endothelial Cell Function

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Additional Factors that Support the Hemostatic Process

If vascular injury exceeds platelet capacity, hemorrhage
symptoms arise

Platelet Plug Formation

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# 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.

Stagnation Effects

# 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.

Protective Mechanisms

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

Major System and Minor System

# Major or Minor System? * Vascular System * Platelets * Coagulation System * Fibrinolytic System * Serine protease inhibitors

Major System

# Major or Minor System? * Kinin System * Complement System

Minor System

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

1. Extravascular 2. Vascular 3. Intravascular

# 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.

Extravascular

# General Components of Hemostasis T or F: Heavy bleeding occurs more frequently in areas with few skeletal muscles surrounding it *(e.g. head)*

True

# Extravascular Hemostatic Component What are the (3) factors affecting hemostasis by surrounding tissues?

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

# 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)

Bulk or Amount of Surrounding Tissue

# Factors Affecting Hemostasis by Surrounding Tissues * **Skeletal muscle** is more absorbent and effective in arresting hemorrhage compared to loose connective tissue.

Type of Tissue Surrounding the Injured Vessel

# 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.

Tone of the Surrounding Tissue

# General Components of Hemostasis * Refers to the blood vessels * Diseases of the blood vessels may lead to bleeding despite having functional clotting factors

Vascular

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

1. Arteries 2. Veins 3. Small Vessels

What is the importance of collagen?

Blood vessel resiliency and platelet activation

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

True

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

Promote or prevent blood clotting

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

Provides sites for blood clotting

# General Components of Hemostasis A genetic disorder that affects collagen formation

Ehlers-Danlos and Marfan Syndrome

# General Components of Hemostasis T or F: Collagen contributes to the deactivation of platelets.

True

# General Components of Hemostasis * This is what's contained plasma

Intravascular

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

1. Platelets 2. Clotting Factors 3. Calcium

# General Components of Hemostasis What are the **three (3)** components of the intravascular component of hemostasis?

1. Platelets 2. Coagulation Proteins 3. Fibrinolysis

# General Components of Hemostasis The fibrinolytic system contains ____ which is able to dissolve the clot that was formed.

Fibrinolysin or Plasmin

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

Plasminogen

# Fibrinolysis * Responsible for activating or converting plasminogen * Can either be exogenous or endogenous

Plasminogen Activators

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

Plasmin

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

True

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

1. Whole blood clot lysis time 2. Euglobulin lysis time

What are the **two (2)** divisions of hemostasis?

1. Primary 2. Secondary

# Divisions of Hemostasis The main objective is **to form a platelet plug**

Primary

# 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.

True

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

Injury or damaged blood vessels

# 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?

1. Blood Vessels 2. Platelets 3. Von Willebrand's Factor 4. Calcium 5. Factor 1 *(Fibrinogen)*

# 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

Von Willebrand's Factor

# Primary Division of Hemostasis Deficiency of this leads to bleeding

Calcium *(Hypocalcemia)*

# Primary Division of Hemostasis Allows platelet clumping or aggregation

Factor 1 *(Fibrinogen)*

# Primary Division of Hemostasis A test that assesses/screens a possible defect in the primary division of hemostasis

Bleeding Time (BT)

# Primary Division of Hemostasis Any abnormal result in BT points to a problem in what?

Platelet plug formation

# Primary Division in Hemostasis What are the **five (5)** methods for Bleeding Time?

1. Duke's Method 2. Ivy's Method 3. Modified Ivy's Method 4. Simplate Method 5. Template Method *(Modification of Ivy's)*

The main objective is **to stabilize the plug formed to form a firm clot** ## Footnote Now involves **clotting factors.**

Secondary

# 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

Clotting Time

# Secondary Division of Hemostasis What are the **two (2)** methods for Clotting Time?

1. Lee and White method 2. Slide/drop method

# Secondary Division of Hemostasis What is the reference value of **PT** upon the addition of specific reagents?

12 to 14 seconds

# Secondary Division of Hemostasis What is the reference value of **PTT/aPTT** upon the addition of specific reagents?

20 to 45 seconds

# Secondary Division of Hemostasis What are the **three (3)** chemical processes that occur with the clotting factors to form a clot?

1. Extrinsic Pathway 2. Intrinsic Pathway 3. Common Pathway

# 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)*

Extrinsic Pathway

# 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)*

Intrinsic Pathway

# Intrinsic Pathway This factor is the most common, especially for males.

Factor 8

# 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

Common Pathway

How are platelets formed?

Megakaryopoiesis

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

Thrombopoietin

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

Interleukins 3, 6, 7, and 11

# 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

Megakaryoblast (MK 1)

# 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

Promegakaryocyte (MK 2)

# 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

Megakaryocyte (MK 3)

# 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

Metamegakaryocyte

# Phases/Stages of Development How many days does it to complete the stages of megakaryopoiesis?

5 to 7 days

# Phases/Stages of Development Megakaryopoiesis produces how many metamegakaryocytes at a time?

Only 1

# Phases/Stages of Development T or F: The cytoplasm of a metamegakaryocyte divides, not the nucleus.

False ## Footnote The cytoplasm **does not divide** but the nucleus does.

# 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

Endomitotic Division

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

1. Platelet Shedding Theory 2. Fragmentation/Budding Theory

# 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

Platelet Shedding Theory

# 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

Fragmentation or Budding Theory

* 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

Thrombocytes

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

70% are **circulating** while 30% are **sequestered or stored**

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

Increased, decrease

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

Increasing

What is the usual lifespan of thrombocytes?

**5 to 7** or **7 to 10 day** lifespan

What is the reference values of thrombocytes?

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

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

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

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

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

# Platelets This glycoprotein receptor is essential for **platelet adhesion**.

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

# Glycoprotein 1A/IX/V Defect of the glycoprotein complex leading to poor adhesion

Bernard Solier Syndrome

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

Glycoprotein 2B/3A

# Ultra-structural Zones Channels that act as openings

Open Canalicular System (OCS)

# Ultra-structural Zones Extension of the sol-gel zone

Sub-membranous Region

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

1. Microtubules and microfilaments 2. Actin Myosin/Thrombostenin

# Sol-gel Zones * Maintains the shape and appearance of the cell * It will be disrupted when activated

Microtubules and microfilaments

# Sol-gel Zones * Contractile protein that contracts upon activation to release the granuleslocated in the organelle zone

Actin Mysoin/Thrombostenin

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

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

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

(105 cards)