Primary hemostasis Flashcards
Hemostasis definition
process by which the body spontaneoulsy stops bleeding and maintains blood in the fluid state within the vascular compartment
bleeding that doesnt stop
hemorrhage
too mcuh coagulation
thrombosis
Primary hemostasis
Injury
Vascular Phase
Platelet Adhesion
Platelet Aggregation
Temporary Plug
Secondary hemostasis
Coagulation cascade
Fibrin Clot Forms
Healing
Fibrinolysis
Major systems
- Vascular
- platelets
- coagulation
- Fibrinolytic
Minor systems
- Kinin
- Serine Protease
- Complement
Blood vessel
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
Blood vessel layer composition
Inside–> Out
Tunica Intima
Tunica media
Tunica adventitia
Tunica intima
- Broad flat endothelial cells
- supports migration of cells
- subendothelium = collagen, connective tissue and fibroblasts
Tunica media
- Elastic tissue and smooth muscle
- Vasoconstriction
Tunica adventitia
- connective tissue
- support
Smooth muscle constricts
vasoconstriction
Diverts blood flow around damaged vasculature
When a blood vessel is breached
- sub-membranous collagen is exposed
- platelet and coagulation factors are able to be activated = contact activation
Blood vessel secretes
cytokines
ADP releases from
Endothelium
- promotes platelet aggregation (Platelet plug)
Tissue thromboplastin (Tissue Factor/ Factor III) is released from
vessel wall
- initiates fibrin formation through extrinsic cascade (initiates secondary hemostasis)
PLT count normal
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
Peripheral platelet zone
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
Phospholipids
Peripheral Zone
- Makes platelet sticky
- Platelet Factor 3 - PF3 –> allows assembly of vitamin K dependent coagulation (secondary hemostasis)
Phospholipids
Peripheral Zone
- Makes platelet sticky
- Platelet Factor 3 - PF3 –> allows assembly of vitamin K dependent coagulation (secondary hemostasis)
Adhesion receptors
GP1b –> Von Willebrand Factor (wWF)
Fibronectin
Aggregation receptors
GPIIb/IIIa (normally inaccessible)
- binds fibrinogen
- ADP
- Thrombin
- Epinephrine
- Collagen
- Thromoboxane A2 (TXA2
- Serotonin
Sol-Gel Zone
Function: Help support membrane
Cytoskeleton contains microfilaments and microtubules
Contractile proteins: Actin, myosin, actomyosin, and “thrombosthenin”
Capable of contracting within seconds
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)
Alpha granules
most numerous (up to 200/plt)
- PLT specific proteins
- Plasma proteins
PLT specific proteins
Stay on membrane post secretion
Platelet factor 4
inhibits heparin
beta-thromboglobulin and platelet derived growth factor
promotes vessel smooth muscle vessel
thrombospondin
promotes PLT-PLT interaction
plasma proteins
become soluble post secretion
- Albumin
- vWF
- Fibrinogen
- Plasminogen
- a2 antiplasmin
vWF
promotes adhesion
Fibrimogen, Factor V, Factor III, high molecular weight kiniogen
coagulation
Plasminogen
fibrinolysis
alpha2 antiplasmin
inhibits fibrinolysis
Dense granules
- 2-10/plt
- nonmetabolic ATP
- nonmetabolic ADP - promtotes aggregation
- calcium - regulates PLT activation/aggregation
- serotonin - vasoconstriction
Lysosomes
Proteases
- breaks down protein/peptide
Hydrolyases
- uses water to break a chemical bond
Bactericidial enzymes
Platelet plug formation
Adhesion
Shape change
aggregation
Secretion Release
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
Platelet plug - shape change
PLT becomes activated and changes from circle disc to “spiny” sphere-pseudopods Thromboplastin) to be accessible
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
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
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
Effects of Aspirin
- inhibits enzyme cyclo-oxygenase
- this inhibits endoperoxide and Thromboxsane A2 synthesis
- When thromboxane A2 synthesis is blocked, this prevents aggregation
Platelet plug only provides temporary hold, so we need to reinforce it with fibrin
secondary hemostasis
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
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
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
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
Platelet markers
Provides proof of platelet activation
virtually absent in normal plasma
Ex:
- Beta Thromboglobulin
- Platelet Factor 4
- Thrombospondin
- Platelet Derived Growth Factor
Ultimate goal of coagulation cascade
Convert main substrate: fibrinogen (aka Factor I) into fibrin
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.
