Coagulation and Dissolution of a Blood Clot Flashcards
Normal hemostasis definition
balance between generation of hemostatic clots and uncontrolled thrombus formation
Extrinsic pathway
plasma mediated, initiation of hemostasis
key: tissue factor
Intrinsic pathway
amplifies and propagates hemostasis
key: thrombin
Common pathway
results in an insoluble fibrin clot
Preoperative coagulation testing should be based on
patient’s history and planned surgery
Hemostasis is regulated by interactions between
blood vessel walls, circulating platelets, and clotting proteins in the plasma
Fibrinolysis definition
orderly breakdown of a stable blood clot
Mechanisms of normal hemostasis
vasoconstriction, platelet plug, clot formation, clot dissolution
Initiation stage of clot formation
binding of platelets to collagen tissue factor dependent
Propagation stage of clot formation
recruitment of platelets to growing thrombus, amplification of clotting cascade
Stabilization stage of clot formation
platelet- platelet interaction, fibrin deposition
Damage to the endothelium exposes the ECM and causes
vasoconstriction/contraction
What can induce prothrombotic endothelial changes?
thrombin, hypoxia, and high fluid sheer stress
3 major phases of platelet plug formation
adhesion, activation, and aggregation
Normal concentration of platelets
150,000 - 400,000 per microliter
Spontaneous bleeding can occur when platelet levels are
< 50,000 u/L, lethal is < 10,000 u/L
Life of a platelet
8 - 12 days
Where are platelets formed and what is another name for platelets?
In the bone marrow; thrombocytes
Inhibitors of platelets
adenosine, insulin, NO, PGE2, PGI2
Activators of platelets
adrenaline, cholesterol, GAS6, ICAMs, IGF1, PGE2, sCD40L, thrombopoietin, vWF
4 types of platelets
secretory, aggregating, procoagulant, coated
Platelet receptors
ADP, TXA2, fibrinogen/vWF, vW factor, collagen
Platelet adhesion mechanism
exposure to sub-endothelial matrix proteins allows platelets to undergo conformational change to adhere to the vascular wall
Von Willebrand Factor (produced, released, and primary function)
produced in the endothelium and platelets
released by endothelial cells and activated platelets
primary function is to bind to other proteins
Glycoprotein IIb/IIIa deals with
platelet to platelet
Glycoprotein Ib/factor IX/factor V receptor complex deals with
platelet to vessel wall
Glycoprotein Ib-V-IX Complex
binds von Willebrand Factor, allowing platelet adhesion and platelet plug formation at sites of vascular injury
Von Willebrand Factor is mainly activated in conditions of
high blood flow and shear stress
Which factor goes hand in hand with von willebrand factor?
factor VIII
What are 3 “red flags” that could indicate von willebrand disease?
women with heavy menstrual periods, frequent nose bleeds, and gum bleeding with teeth brushing
Type 1 vWD
failure to secrete vWF into circulation or vWF clear quickly
can be treated with DDAVP
Type 2 vWD
decreased ability to bind to GPIb and VIII
Type 3 vWD
complete absence of production of VWF
Platelet type/pseudo vWD
defect of the platelet’s GPIb receptor (vWF is normal)
What medications are GPIIb/IIIa inhibitors?
abciximab (ReoPro), eptifibatide (Integrilin), tirofiban (Aggrastat)
GPIIb/IIIa inhibitor action
blocks ability of fibrinogen to form around aggregated platelets so no platelet to platelet bridging can occur
Which GPIIb/IIIa inhibitor is irreversible?
Abciximab
Which medications do we use that are thromboxane A2 inhibitors?
Aspirin
Naproxen
Aspirin action
inhibits ability of COX enzyme to synthesize the precursors of thromboxane within platelets
What do P2Y12 receptors do?
further amplify the response to ADP and draw forth the completion of aggregation
What are ADP receptor antagonists?
ticlopidine (ticlid), clopidogrel (plavix), prasugrel (efient), ticagrelor (brilinta), cangrelor (kengrexal)
What completes the formation of a platelet plug?
platelet aggregation
blood clot formation
fibrinogen breaks down to produce fibrin that becomes cross linked into a stable mesh activating coagulation factors initiating the coagulation cascade
the key step in blood clotting is the conversion of ___ to ___ by ____
fibrinogen; fibrin; thrombin
alpha angle on ROTEM
tells how strong the clot will get
Intrinsic pathway is triggered when
blood contacts a negatively charged surface
Extrinsic pathway is activated when
blood contacts cells outside the vascular endothelium
activation of which factor converges the extrinsic and intrinsic pathways?
factor X
Which two factors are glycoproteins and not enzymes?
vWF and tissue factor III
Which two factors are NOT synthesized in the liver?
Calcium (IV) - diet
Von willebrand - endothelial and platelets
Which factors are vitamin K dependent for utilization?
factors II, VII, IX, and X
prothrombin gets activated to
thrombin
thrombin activates fibrinogen to form
fibrin
clot lysis occurs when plasminogen is activated to
plasmin
what activates plasminogen?
t-PA (tissue plasminogen activator)
plasmin digests
fibrin fibers, fibrinogen, factor V, factor VIII, prothrombin, factor XII
What is increased in DIC?
fibrinogen degradation products
thrombolytics action
possess fibrinolytic effects or enhances the body’s fibrinolytic system by converting endogenous plasminogen to plasmin
dissolves newly formed clots
prothrombin time (PT)
evaluates extrinsic pathway
reagents vary so INR is used for standardization
partial thromboplastin time (PTT)
indicates performance of the intrinsic pathway
ACT
reliable for high heparin concentrations
influenced by hypothermia, thrombocytopenia, coagulation deficiencies
Viscoelastic testing (TEG and ROTEM)
global assay for whole blood clotting
1 mg of protamine will inhibit
1 mg (100 units) of heparin
normal value for ACT
80 - 150 seconds
