Hemostasis Flashcards
what are the 4 steps that constrain bleeding?
- flow slowed by physical factors
- platelets form hemostatic plug
- coagulation occurs as a result of production of fibrin clot
- clot retraction occurs
flow is slowed by physical factors, what are they
- back pressure
2. vasoconstriction
what is vasoconstriction?
what are the factors involved in vasoconstricion
constricting to limit the flow, then plugging w/ activated platelets, then sealing temporarily w/ fibrin
factors: serotonin, ephinephrine
- platelets produce thromboxane A2 which increases platelet aggregation
how do underlying muscles further compress blood vessels in the uterus after birth?
contractions contineu after birth to shrink the stretched uterus and limit blood loss
what is platelet release from bone marrow (myeloid component) stimulated by
-what is it produced by
thrombopoietin which is produced by the liver parenchymal, sinusoid cells and kidney cells (it is a growth factor)
platelets adhere to each other and endothelium, forming a _______ and release granules that promote ______
physical barrier
coagulation
what factors that are located beneath the endothelial cells induce and support platelet adherence?
collagen and laminin
adherence to vessel wall induces endothelial cells to produce….
von Willebrand factor
the von willebrand factor:
forms a bridge btwn what?
important in?
not an _____; binds to proteins, particularly ___
- btwn platelet surface receptors and collagen
- platelet adhesion to wound sites
- not an enzyme; binds to other proteins, partically factor VIII
what do membrane phospholipids activate?
-this initiates cascade that ends in what? induces factor 8 to dissociate from what?
thrombin
-initiaates cascade that ends in clot formation; induces factor 8 to dissociate from von willebrand factor (normally ciculate together)
ruptured cells release _____ which causes platelets to aggregate
- when ADP binds to platelet ADP receptors, this causes what?
- drugs like ____ irreversible inhibit this receptor
ADP
- ADP binds to platelet ADP receptors; causes aggregation and thromboxane release
- drugs like plavix irreversibly inhibit this receptor
platelets are disk fragments of …..
megakaryocytes
-platelets are essentially self-contained piees of megakaryocyte cytoplasm
what block platelet activation
NO
prostacyclin
endothelial ADPase
what are the steps to platelets forming hemostatic plugs
- exposed collagen binds and activates platelets
- release of platelet factors
- attracts more platelets
- aggregate into platelet plug
coagulation produces fibrin clot
-in final common pathway, thrombin cleaves ______ into _____ monomers that assemble into ______
-factor 8 does what?
-in final common pathway, thrombin cleaves fibrinogen into fibrin monomers that assemble into ordered fibrous arrays of fibrin
- stabilizes and tightens polymerized fibrin by forming covalent bonds btwn fibrin strands
- replaces unstable platelet aggregate
coagulation factors are ________ proteases
-where do they reside?
serine proteases
-serine resides in active site of enzyme
what kind of system is the intrinsic pathway?
-initiated by contact of what?
what is the intrinsic pathway important in maintaining
amplification system
-intiated by contact of factor 7 w/ subendothelial collagen
-important in maintaining coagulation
what is the extrinsic pathway intiated by?
- tissue factor is produced by what?
- why do endothelial cells produce tissue factor?
intiated by release of tissue factor (factor 3) from injured tissue
- tissue factor is produced by subendothelial tissues like smooth muscle cells, as well as neutrophils and monocytes
- enothelial cells produce tissue factor in response to infl mediators
what is the final common pathway in the coagulation cascade
conversion of inactive factor X to its active form, factor Xa
-conversion of prothrombin to thrombin and fibrinogen to fibrin
what is the coagulation test for the extrinsic system?
-what is this used to measure? what is an example? what does this inhibit?
prothrombin time (in sec) -how long plasma takes to clot after mixed w/ tissue factor and CaCl2 (longer 11 sec fail) -used to measure effectiveness of coumarin-type anticoagulant drugs (coumadin-warfarin) =>inhibit vit k dependent symthesis of prothrombin and factors 7, 9, 10
what are the factors limited by prothrombin
2, 7, 9, 10
what is the international normalized ratio (INR)
the ratio of a pts prothrombin time to a normal (control) sample
**what is the coagulation test for the intrinsic system? what does this measure? what is the normal time? what is this used to monitor? -how?
- activated partial thromboplastin time (aPTT)
- measures clotting time from activation of factor 12 through the formation of a fibrin clot
- (normal is 25-38 sec)
- -used to monitor heparin therapy
- heparin binds to enzyme inhibitor antithrombin which inhibits thrombin and other proteases
what are kind of disorders are hypocoagulation
what are some exmaples
bleeding disorders
- thrombocytopenia: low platelet number, may be due to autoimmune disease, idiopathic thrombocytopenia purpura
* 2. von willebrand disease: reduced factor of the same name
- most common hereditary coag abnomralily in humans (1/100) - hemophila: lack of factors 8 or 9; most are inherited as x-linked recessive (most 8)
- vit k deficiency
- required for coagulation factor production by the liver
what are kind of disorders are hypercoagulation?
what are some examples
thrombotic disorders
- intravascular clot formation leading to strokes
- protein S deficiency
- regulatory protein that fucntions as anti-coagulant
* 3. hypercoagulated state in cancer
when does retraction occur
- what does it stabilize and how?
- requires what to do this?
w/in minutes or hours of clot formation
- stabilizes injured site by pulling torn edges of vessels closer together
- requires platelet actin and myosin filaments
dissolution or fibrinolysis is mainly a function of what?
- circulates as ….?
- converted to plasmin by what?
- plasmin inhibits what factors and does what to fibrin?
plasmin
- circulates as inactive proenzyme plasminogen
- converted to plasmin by tissue plasminogen activator released by activated endo cells in response to thrombin
- plasmin inhibits factors 5 and 8 and degrades fibrin
healthy endothelial cells produce what to inhibit platelets
prostacyclin
in aqueous outflow channels what is the prcoess
- tPA in aq humor
- converts plasminogen in aq humor to plasmin
- plasmin keeps outflow channels clear whcih plays a role in matrix remodeling
what is an important part of proliferative phase of healing
wound angiogenesis
during wound angiogenesis, chemoattractants attract what?
what makes these cells proliferate?
smooth muscle cells, infl cells and fibroblasts to the wound
- mitogens and growth factors induce the above cells to proliferate (platelet-derived growth factor (PDGF) and epidermal growht factor (EGF)
- VEGF is also involved
