Sections 1 and 2: Platelet Function Flashcards
Hemostasis definition
Process of blood clotting to arrest bleeding and re-establishment of blood flow during the healing process
Hemostasis involved parameters
- vascular
- platelets
- fibrin clot formation- coag cascade
- control (inhibitory systems)
- fibrinolysis
Abnormal bleeding vs abnormal clotting
hemorrhage and thrombosis
Primary hemostasis
- Platelet aggregation (form platelet plug)
- Capillaries
- White thrombus forms
Secondary hemostasis
- Fibrin strands form to strengthen platelet plug and RBCs get caught in mesh
- Arteries/bigger vessels
- Red thrombus
Fibrinolysis
Dissolves blood clots (initiation of wound healing)
Hemarthralgia
Bleeding in joints
Medical terms that mean bruise
- Purpura
- Ecchymoses
- Hematoma
Epistaxis
Nose bleed
List the 3 vascular layers from inside to outside
- Tunica intima
- Tunica media
- Tunica adventia
Tunica intima
Layers of broad flat endothelial cells with underlying basement membrane - collagen
Tunica media
- Elastic tissue and smooth muscle
- Controls vasoconstriction and sometimes vasodilation
Tunica adventia
Connective tissue support
How does the vasculature prevent thrombus formation in hemostasis?
- Provides physical barrier of endothelial cells covering basement membrane to prevent blood, platelets, and clotting factors from sticking
- Endothelial cells generate PGI2 (Prostacylin) and nitric oxide, which causes vasodilation and inhibits platelet adhesion to those cells
- Vasculature involved in activity of Protein C (thrombomodulin) and anti-thrombin (heparan)
- Tissue factor pathway inhibitor (TFPI) inhibits Tissue Factor/Factor VIIa complex
List steps of general hemostasis when endothelial lining is disrupted
- Vasoconstriction
- Initial stimuli of hemostasis
- Localize clot formation
- Provide activators for clearance of thrombus to break down fibrin clot
Explain the first step of hemostasis, vasoconstriction
- Blood flow slows such that platelets and coag factors easily attach to site of injury
- Shear stress pushes platelets to vessel periphery (injury site)
Explain the second step of hemostasis: initial stimuli
- Damaged endothelial cells release platelet activating factor (PAF) to activate even more platelets
- Tissue Factor III released (present in all tissues)
- Collagen is exposed such that platelets adhere to it
Explain the third step of hemostasis: localize clot formation
- Endothelial cells synthesize and release von Willebrands factor for platelet adhesion, as well as secrete ADAMTS13 to chop up vWF
- Binding sites for coag factors IXa and Xa
Explain the fourth step of hemostasis: provide activators for clearance of thrombus to break down fibrin clot
- ECs secrete tissue plasminogen activator to facilitate clot breakdown
Fill in the blank
ECs play a role in _________, ________, and _______ of the clot
formation, prevention, breakdown
Thrombopoietin (TPO) function
- Regulates megakaryocyte production and platelet release from the BM in response to thrombocytopenia
- Inhibits megakaryocyte apoptosis
- Binds receptors on circulating platelets and BM megakaryocytes, gets internalized, and degraded
Explain how TPO levels relate to platelet levels
- More platelets means less TPO (gets destroyed), so fewer megakaryocytes
- Fewer platelets means more TPO, so more megakaryocytes
Adhesion
Platelets stick to site of injury (exposed collagen)
Aggregation
Platelets stick to other platelets (helps close physical gap)
Platelet glycocalyx
- Outer layer (peripheral zone)
- Mediates platelet adhesion and aggregation
Platelet open canalicular system
- Peripheral zone, extension of platelet membrane
- Channels of membrane wind into platelet so that stuff moves in and out
Platelet cytoskeleton
- Sol-gel zone
- Helps secretion process and structural integrity
- Microfilaments made of actin and myosin
Platelet dense tubule system
- Sol-gel zone
- Plt activation and calcium storage/release
Platelet dense granules
- 6 per plt
- ADP, calcium, serotonin….etc
Platelet alpha granules
- ~55 per plt, more numerous than dense granules and give visual texture on Wright stain
- TXA2, vWF, FV, FVIII, FI, HMWK, PF4, plasminogen, PAI-1…etc)
Explain how aspirin prevents plt activation/aggregation
Aspirin inhibits cyclooxygenase-1 such that thromboxane A2 can’t be formed
Explain how a platelet adheres to collagen
- Platelets can’t directly stick to collagen, so use vWF as intermediate glue
- vWF binds GP1b receptor on plt
List steps of primary hemostasis
- Platelet adhesion
- Shape change
- Plt aggregation
- Secretion
- Primary hemostatic plug formed
Explain the process of platelet activation from start to finish of clot
- Plt adheres to collagen via vWF binding GP1b receptor
- Adhesion initiates a shape change to allow granular content secretion (serotonin, vWF, ADP…etc)
- Plts aggregate via ADP and TXA2
- Fibrinogen attaches to platelet membrane forming bridges between platelets resulting in a platelet plug (GPIIb/IIIa)
- Actin and myosin contract to pull clot in tight and stop bleeding
- Platelet plug gives foundation for clot formation
Explain process of platelet shape change
- Agonist (collagen/PAF)
- Pseudopods develop on plt surface that contain actin and myosin
- Microtubule circumferential ring contracts
- Membrane phospholipids activated
- Glycoprotein IIb/IIIa receptors appear
- Internal biochemical changes occur
- Granule secretion
List granule contents and their roles
- Serotonin = vasoconstriction
- vWF = plt adhesion
- ADP and TXA2 = plt aggregation
- Calcium = plt activation/coag cascade
- Fibrinogen = plt aggreg/coag cascade
How do ADP and TXA2 facilitate plt aggregation?
They expose the GPIIb and IIIa complex, which enables fibrinogen to come bind and crosslink plts for aggregation
Explain how platelet plug formation provides foundation for clot formation
Platelet Factor III (PF3) moves to outer surface of plt membrane to provide binding site for Vitamin K-dependent factors to support coag cascade
What is Platelet Factor 3?
It’s the whole entire primary hemostatic complex! It provides a phospholipid-rich surface to support the coag cascade
