Primary hemostasis Flashcards

1
Q

Hemostasis definition

A

process by which the body spontaneoulsy stops bleeding and maintains blood in the fluid state within the vascular compartment

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2
Q

bleeding that doesnt stop

A

hemorrhage

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3
Q

too mcuh coagulation

A

thrombosis

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4
Q

Primary hemostasis

A

Injury

Vascular Phase

Platelet Adhesion

Platelet Aggregation

Temporary Plug

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5
Q

Secondary hemostasis

A

Coagulation cascade

Fibrin Clot Forms

Healing

Fibrinolysis

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6
Q

Major systems

A
  • Vascular
  • platelets
  • coagulation
  • Fibrinolytic
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7
Q

Minor systems

A
  • Kinin
  • Serine Protease
  • Complement
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8
Q

Blood vessel

A

smooth, continuous endothelial lining
- “nonwettable
- facilitates blood flow

Under normal conditions, hemostasis is prevented by
- endothelium as a physical barrier
- Endothelial secretions of platelet inhibitors Prostacyclin PGI2, and Nitric Oxide NO

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9
Q

Blood vessel layer composition

Inside–> Out

A

Tunica Intima
Tunica media
Tunica adventitia

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10
Q

Tunica intima

A
  • Broad flat endothelial cells
  • supports migration of cells
  • subendothelium = collagen, connective tissue and fibroblasts
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11
Q

Tunica media

A
  • Elastic tissue and smooth muscle
  • Vasoconstriction
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12
Q

Tunica adventitia

A
  • connective tissue
  • support
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13
Q

Smooth muscle constricts

A

vasoconstriction

Diverts blood flow around damaged vasculature

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14
Q

When a blood vessel is breached

A
  • sub-membranous collagen is exposed
  • platelet and coagulation factors are able to be activated = contact activation
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15
Q

Blood vessel secretes

A

cytokines

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16
Q

ADP releases from

A

Endothelium
- promotes platelet aggregation (Platelet plug)

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17
Q

Tissue thromboplastin (Tissue Factor/ Factor III) is released from

A

vessel wall

  • initiates fibrin formation through extrinsic cascade (initiates secondary hemostasis)
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18
Q

PLT count normal

A

150,000-400,000 uL

30% are sequestered in spleen as functional reserve

Aged or non-viable platelets are removed by the spleen and liver

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19
Q

Peripheral platelet zone

A

Function: adhesion and aggregation

  • Open Canilicular system - helps in releasing granules
  • Glycoproteins on surface = Glycocalyx - contains blood group and tissue compatibility antigens
  • Surface provides help with fibrin clot formation: Factor V and VIII

Membrane is former demarcation of membrane parent

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20
Q

Phospholipids

Peripheral Zone

A
  • Makes platelet sticky
  • Platelet Factor 3 - PF3 –> allows assembly of vitamin K dependent coagulation (secondary hemostasis)
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20
Q

Phospholipids

Peripheral Zone

A
  • Makes platelet sticky
  • Platelet Factor 3 - PF3 –> allows assembly of vitamin K dependent coagulation (secondary hemostasis)
21
Q

Adhesion receptors

A

GP1b –> Von Willebrand Factor (wWF)

Fibronectin

22
Q

Aggregation receptors

A

GPIIb/IIIa (normally inaccessible)
- binds fibrinogen
- ADP
- Thrombin
- Epinephrine
- Collagen
- Thromoboxane A2 (TXA2
- Serotonin

23
Q

Sol-Gel Zone

A

Function: Help support membrane

Cytoskeleton contains microfilaments and microtubules

Contractile proteins: Actin, myosin, actomyosin, and “thrombosthenin”

Capable of contracting within seconds

24
Organelle Zone of platelet
Function: metabolic reserve Contains storage granules Aid in protaglandin/Thromboxane A2 Synthesis Dense tubular system Mitochondroa - 10-60/platelet - Has glycogen (storage form of glucose)
25
Alpha granules
most numerous (up to 200/plt) - **PLT specific proteins** - **Plasma proteins**
26
PLT specific proteins
Stay on membrane post secretion
27
Platelet factor 4
inhibits heparin
28
beta-thromboglobulin and platelet derived growth factor
promotes vessel smooth muscle vessel
29
thrombospondin
promotes PLT-PLT interaction
30
plasma proteins
become soluble post secretion - Albumin - vWF - Fibrinogen - Plasminogen - a2 antiplasmin
31
vWF
promotes adhesion
32
Fibrimogen, Factor V, Factor III, high molecular weight kiniogen
coagulation
33
Plasminogen
fibrinolysis
34
alpha2 antiplasmin
inhibits fibrinolysis
35
Dense granules
- 2-10/plt - nonmetabolic ATP - nonmetabolic ADP - promtotes aggregation - calcium - regulates PLT activation/aggregation - serotonin - vasoconstriction
36
Lysosomes
Proteases - breaks down protein/peptide Hydrolyases - uses water to break a chemical bond Bactericidial enzymes
37
Platelet plug formation
Adhesion Shape change aggregation Secretion Release
38
Platelet plug - adhesion
Reversible process where platelets stick to foreign surfaces Subendothelium is exposed due to injuty - composed of adhesive molecules: collagen, vWF and others **vWF attaches to platelet membrane GPIb = adhesion**
39
Platelet plug - shape change
PLT becomes activated and changes from circle disc to "spiny" sphere-pseudopods Thromboplastin) to be accessible
40
Platelet Plug - aggregation 1st wave (GPIIb/IIIa-Fibrinogen-GP IIb/IIIA)
Energy dependent process - requires ATP Fibrinogen binds to the now usuable GPIIb/IIIa receptors Bridges of fibrinogen and Ca2+ form between GPIIb/IIIa recepors on adjacent platelets = **aggregation**
41
Platelet plug - 2nd wave
Secretiojn requires a strong stimulus - thrombin (from coagulation) is great candidate Platelets secrete their granules - promotes Thromboxane A2 synthesis Irreversible form, this point Result = **Viscous metamorphosis-transformation** of irreversibly aggregated platelets into a mass of degenerative platelet material without membranes
42
Thromboxane A2 (TXA2)
- Recruits more platelets (amplification) and activates them in helping to promote aggregation - Once TXA2 is used up, it becomes the inactive form TXB2
43
Effects of Aspirin
- inhibits enzyme cyclo-oxygenase - this inhibits endoperoxide and Thromboxsane A2 synthesis - When thromboxane A2 synthesis is blocked, this prevents aggregation
44
Platelet plug only provides temporary hold, so we need to reinforce it with fibrin
secondary hemostasis
45
Platelet aggregeometry
PLT rich plasma and exogenous aggregating agents are added in a cuvette **As platelets aggregate and clump, more light is transmitted = decreasing optical density (absorbance)** % transmittance is recorded creating a pattern
46
Plt count and peripheral smear
- PLT decrease in number in platelet count and visually on smear - Giant platelets - RBC fragments present from fibrin cutting in circulation
47
Clot retraction
After clot formaiton, the blood clot retracts (shrinks) and serum begins to seperate from the clot - contractile proteins in platelet are responsiblr for clot retraction Decreased/abnormal retraction can be due to - thrombocytopenia - Glanzmann's Thrombasthenia
48
Platelet Function Assays
Screens for platelets ability to adhere to collagen and aggregate together. Whole blood is added to cartridges containing collagen and either ADP or epinephrine Used as a screen for von Willebrand Disease, drug-related platelet inhibition and hereditary platelet defects. Also produces abnormal results with vascular disorders
49
Platelet markers
Provides proof of platelet activation virtually absent in normal plasma Ex: - Beta Thromboglobulin - Platelet Factor 4 - Thrombospondin - Platelet Derived Growth Factor
50
Ultimate goal of coagulation cascade
Convert main substrate: **fibrinogen (aka Factor I) into fibrin**
51
All factors are synthesized in the liver except
vWF PLT contents (alpha granules) are believed to have orig. from the plasma and not truly synthesized in the platelet.