Blood Coagulation and Wound Healing Flashcards
what are the steps to blood clotting (coagulation)
-injury or damage
- vessel contracts
- platelet plug
-fibrin clot
what happens in primary hemostasis
-vasoconstriction and platelet response
-platelet aggregation at the site of injury is mediated by platelet receptors, platelet derived agonists, platelet derived adhesive proteins and plasma derived adhesive proteins
what happens in secondary hemostasis
- clotting cascade
- coagulation of serine proteases that results in cleavage of soluble fibrinogen by thrombin. thrombin cleavage generates insoluble fibrin that forms a cross-linked fibrin mesh at the sit of injury
when does fibrin generation occur
simultaneously to platelet aggregation
what happens when platelets bind to collagen
-undergo a release reaction where they secrete ADP, serotonin, and TXA2.
-serotonin and TXA2 cause vasoconstriction
-ADP and TXA2 attract platelets and make them stick to the collagen in the broken vessel to make the platelet plug
why is calcium important
clotting cascade cant take place without it
what does serotonin come from
tryptophan
what is serotonin secreted by
enterochromaffin cells
how are platelets formed
arachindonic acid is converted into endoperoxides by cyclooxygenase (prostaglandin synthase) which then gets converted into TXA2 by thromboxane synthetase which gets converted into plateletes (TXAB2)
how are endothelial cells formed
arachindonic acid is converted into endoperoxides by cyclooxygenase (prostaglandin synthase) which then gets converted into prostacylin by prostacyclin synthase which gets converted into 6 keto PGF 1 alpha (endothelial cells)
what is the initial binding of platelets to vWF mediated by
glycoproteins that are necessary for platelet tethering (GPIIb/IIIa) but dont promote strong adhesion
what is responsible for firm adhesion of platelets to the subendothelia
GPIIb/IIIa
what happens to GBIIb/IIIa upon platelet activation
GBIIb/IIIa undergoes a conformational change that reveals a binding site for vWF or fibrinogen. vWF binds at the subendothelial surface to promote strong adhesion to the vessel wall
what is the delay in platelet activation
platelets activate before releasing ADP
what do aggregometer tracings do
record the aggregation of platelets in platelet rich plasma in response to an aggregation agent
how does ADP affect platelet aggregation
the higher the ADP the longer it can sustain platelet aggregation
what is the extrinsic pathway activated by
external trauma that causes blood to escape from the vascular system
what factor is involved in the extrinsic pathway
factor 7
which pathway is the clotting cascade is quicker
the extrinsic
what is the intrinsic pathway activated by
trauma inside the vascular system activated by platelets, exposed endothelium, chemicals, or collagen
what factors are involved in the intrinsic pathway
factors 12, 11, and 9
which pathway is the clotting cascade is more important
the intrinsic pathway
what factors does the common pathway involve
factors 1,2 5, and 10
what does activated partial thromboplastin time test measure
the intrinsic pathway
what does the prothrombin time test measure
extrinsic pathway
what are the fat soluble vitamins
- vitamin D
- vitamin E
- vitamin A
- vitamin K
what are the vitamin K dependent factors
2, 7, 9, and 10
what does the fibrin mesh do
laid down to reinforce and strengthen the platelet plug since thats not strong enough itself to prevent further bleeding
what catalyzes the crosslinking of fibrin
transglutaminase or factor 7
where are peptide bonds formed
between lysine and glutamine domains of fibrin molecules by transglutaminase
how does fibrin polymerization and breakdown occur
plasmin breaks peptide bonds and destroys mesh
what is plasmin derived from
plasminogen
what converts plasminogen to plasmin
tissue plasminogen activator and urokinase, factor 11a, 12a, and kallikrein
what is wound healing
complex process in which skin or other tissue repairs itself after injury
what are the 4 phases of wound healing
-hemostasis
- inflammatory
-proliferative
-remodeling
what happens in hemostasis
within minutes post-injury, platelets aggregate at the injury site to form a fibrin clot which acts to control bleeding
what happens in inflammatory phase
bacteria and debris are phagocytosed and removed from the wound site, factors are released that cause migration and division of cells involved in the proliferative phase
what happens in the proliferative phase
angiogenesis, collagen deposition, granulation, tissue formation, epithelialization and wound contraction
what happens in the remodeling phase
collagen is remodeled and realigned along tension force lines and cells no longer needed are removed by apoptosis
what cells are involved in coagulation
platelet/fibrin deposition
what cells are involved in the inflammatory phase
neutrophil, monocyte, macrophage
what cells are involved in the proliferation phase
-fibroblast/collagen deposition
-endothelial cell/angiogenesis
- keratinocyte/re-epithelialization
what is the plasma form of fibronectin secreted by and what does it do
secreted by hepatocytes and modulates platelet function
what is the cellular form of fibronectin secreted by and what does it do
secreted by cells as part of the ECM and functions as a scaffold protein
what is ACD anticoagulant
acid citrate dextrose solution- solution of citric acid, sodium citrate and dextrose in water
how does citrate work as an anticoagulant
citrate in the form of sodium citrate or acid-citrate dextrose is used to disrupt the coagulation cascade and prevent clotting. they bind to the calcium in blood, thus no regulation of binding and cascade cannot begin
what is the prothrombin time test used for
to help detect and diagnose a bleeding disorder or excessive clotting disorder.
what is the INR calculated from and what does it measure
calculated from a prothrombin time test and used to monitor how well the blood thinning medication, warfarin, is working to prevent blood coagulation
what does the prothrombin time measure
the integrity of the extrinsic pathway and final common pathways of the coagulation cascade. consists of tissue factor and factors 7,2,5,10, and fibrinogen
what is prothrombin time measured in
seconds
why is the INR an important tool
is allows for easier comparisons of test results from different labs
what is a healthy INR
1.1 or below
what is an effective therapeutic range of INR for people taking warfarin
2.0-3.0
what does a higher INR mean
blood clots more slowly than desired
how does warfarin work
competetively inhibits the vitamin K epoxide reductase complex 1
- depletes vitamin K reserves and reduced the synthesis of active clotting factors 2,7,9, and 10, coagulation regulatory factors protein C and protein S
how can effects of warfarin be neutralized
massive doses of vitamin K
what targets factor 10a
rivaroxaban (xarelto, eliquis)
what targets thrombin
dabigatran etexilate (pradaxa)
what are hemophilia A and B caused by
an X-linked recessive genetic mutation
what is hemophilia A caused by and how do you treat it
caused by decreased synthesis of factor 8 and treat with recombinant factor 8
what is hemophilia B caused by and how do you treat it
caused by decreased synthesis of factor 9 and treat with recombinant factor 9
what form of hemophilia is X-mas disease
hemophilia B
