Lecture 7 9/10/24 Flashcards
What is primary hemostasis?
-formation of platelet plug
-adequate to stop bleeding from small vessels
What is secondary hemostasis?
-formation of stable fibrin clot
-necessary to stop bleeding from medium to large vessels
What is fibrinolysis?
breakdown of clots, necessary to restore non-turbulent blood flow in the vessel
What is clot inhibition?
prevention of unnecessary or excessive clot formation
What is the vascular phase of hemostasis?
reflex vasoconstriction that helps to prevent excessive blood loss
What is the platelet phase of hemostasis?
-von Willebrand Factor binds subendothelial collagen
-GPIb platelet adhesion molecule binds vWF
-platelets are activated, promoting platelets to bind to other platelets using fibrinogen as adhesive
What are the characteristics of secondary hemostasis?
-requires enzymes and cofactors, Ca++, and platelets
-traditional coagulation cascade occurs in vitro and is used to interpret hemostatic tests
-cell-based coagulation occurs in vivo and highlights of cell contributions
How does the intrinsic pathway differ from the extrinsic pathway?
extrinsic pathway initiates hemostasis, while intrinsic pathway amplifies hemostasis
How does in vitro hemostasis differ from in vivo hemostasis?
in vitro hemostasis requires Factor 12 for the initiation of hemostasis; in vivo, Factor 12 is not needed
Why is thrombin known as the master regulator of hemostasis?
thrombin has multiple roles throughout the different stages of hemostasis
What is the goal of the initial activation of the coagulation cascade?
to produce a small amount of thrombin that can be used to activate the intrinsic pathway and amplify thrombin production
Which steps of hemostasis occur on the fibroblast?
-exposed tissue factor and factor 7 start a reaction that leads to a small amount of thrombin production
-thrombin initiates the conversion of factor 11 into factor 11a
-factor 11a travels to platelet plug
Which steps of hemostasis occur on the platelet plug?
-intrinsic pathway activation leads to lots of thrombin formation
-thrombin converts fibrinogen in the platelet plug to soluble fibrin
-thrombin activates Factor 13 which converts soluble fibrin to crosslinked fibrin
What occurs during fibrinolysis?
fibrinogen, fibrin, and crosslinked fibrin are broken down into fragments
Which fragments are produced from fibrinogen, fibrin, and crosslinked fibrin?
-fibrinogen: FDPs
-fibrin: FDPs
-crosslinked fibrin: FDPs and D-dimers
What is plasminogen converted into?
plasmin
What is the role of plasmin?
convert fibrinogen/fibrin into its components
What is the importance of clot inhibition?
inadequate clot inhibition can lead to thrombosis
What are the characteristics of antithrombin?
-most clinically relevant clot inhibitor
-accounts for most of the anticoagulant activity in blood
-consumed as it inactivates thrombin
-small protein; can be lost in some conditions
What are the characteristics of the buccal mucosal bleeding time test?
-small cut of standard size and depth
-tests primary hemostasis only
-insensitive and difficult to standardize
Which conditions are disorders of primary hemostasis?
-thrombocytopenia: not enough platelets
-thrombopathia: platelets not working
-von Willebrand disease
What two things can lead to an inaccurate platelet count on automated CBC?
-sample handling concerns
-platelet clumping
What is the potential significance of an increased MPV/mean platelet volume?
-increased thrombopoiesis in marrow
-platelet activation or clumping
What are the characteristics of vWF antigen testing?
-evaluates concentration of vWF protein in plasma
-reported as a percentage compared to normal plasma pool
What are the requirements for activated clotting time/ACT testing?
-special tube with activator of the intrinsic coagulation pathway
-patient platelets
What are the potential causes of prolonged ACT?
-severe defects in intrinsic and/or common pathway
-very severe thrombocytopenia
What are the requirements for partial thromboplastin time/PTT?
-coagulation analyzer that adds in Factor 12 activator
-patient plasma from blue top citrate tube
What causes a prolonged PTT?
defects of intrinsic and/or common pathway
What are the requirements for prothrombin time/PT?
-coagulation analyzer that adds in tissue factor activator
-patient plasma from blue top citrate tube
What causes a prolonged PT?
defects of extrinsic and/or common pathway
How does ACT compare to PTT?
-both evaluate intrinsic and common pathways
-PTT requires a specific analyzer while ACT requires a specific collection tube
-ACT requires platelets while PTT does not
-ACT is less sensitive than PTT
What are the methods for measuring fibrinogen concentration?
-thrombin clot time (increased time = decreased fibrinogen)
-Clauss fibrinogen method
What are the requirements for measuring fibrinogen concentration?
-coagulation analyzer
-patient plasma from blue top citrate tube
Which condition is most commonly evaluated for when measuring fibrinogen conc.?
hypofibrinogenemia
What are the characteristics of D-dimers?
-produced when plasmin degrades crosslinked fibrin
-measured to detect fibrinolysis
-measured in an immunoassay
What are the characteristics of antithrombin measurement?
-requires coagulation analyzer and patient plasma from a blue top citrate tube
-reported as percentage compared to normal plasma pool
Which processes lead to excessive bleeding when they are disordered?
-primary hemostasis
-secondary hemostasis/coagulation
Which processes lead to thrombosis when they are disordered?
-fibrinolysis
-clot inhibition
