Hemostasis and Thrombosis Flashcards
ecchymoses
larger bruises that color change as hemoglobin is broken down
petechiae
tiny hemorrhages
purpura
medium hemorrhages
hematoma
accumulation of blood in a tissue
hemarthrosis
hemorrhage into a joint
hemostasis by definition
stopping the flow of blood
3 stages of hemostasis
1) reflex vasoconstriction
2) primary hemostasis
3) secondary hemostasis
reflex vasoconstriction
baroreceptors detect low BP and vessels automatically constrict to roughly stop bleeding / increase BP
7 steps of primary hemostasis in general
1) endothelial injury
2) exposure of subendothelial vWF + collagen
3) platelet adhesion to vWF
4) change in platelet shape + receptor affinity change
5) secretion of granule contents
6) platelet recruitment and aggregation
7) platelet plug
what is primary hemostasis?
platelet plug
How do platelets adhere to vWF?
through Gp1B receptors
What does a change in platelet shape change affinity for?
GpIIb / II a affinity
What are platelets derived from?
megakaryocytes
what 3 receptors do platelets express? What are they for?
1) fibrinogen - GpIIb/a
2) vWF - Gp1B
3) collagen - a2B1
What do activated platelets express at their surface?
phosphatidylserine
how can you assess platelet function?
measure closure time
closure time
time it takes for blood to plug a small hole
what type of granules do platelets contain?
alpha and dense-core granules
What molecules is an activator of platelets?
ADP
*induces conformation change
Thromboxane A2
potent vasoconstrictor that promotes platelet aggregation and activation
How does aspirin work
inhibits COX
by inhibiting COX, you have less thromboxane A2 and less platelet activation
COX
normally catalyzes production of thromboxane A2
Plasminogen activator inhibitor (PAI)
secreted by endothelial cells
limits fibrinolysis and favors thrombosis
vWF
large protein in subendothelial tissue that allows platelets to bind
What links primary and secondary hemostasis?
vWF allows platelets to bind
vWF also stabilizes Factor VIII
What is the end product of secondary hemostasis?
fibrin clot
What is the first step of secondary hemostasis?
vascular injury expresses Tissue Factor which binds to and activates factor VII
tissue factor
activates factor VII
membrane protein that is synthesized by “activated” endothelial cells, fibroblasts, and smooth muscle cells
What are the coagulation factors?
a series of serine proteinases
What does thrombin do?
converts fibrinogen to fibrin
triggers positive feedback
What blood test measures the extrinsic pathway and common pathway?
PT
What blood test measures the intrinsic pathway and common pathway?
PTT
What does a long PT or PTT indicate?
clotting problem
takes too long to clot
INR
compares PT to standard
High INR indicates …
high likelihood of bleeding
What is hemophilia associated with?
absence of factor VII
After tissue factor activates, factor VII what happens?
factor IX is activated
What factors does thrombin activate as part of positive feedback loop
factor 13, 11, 8 and 5
Factor XIII
stabilizes fibrin clot by cross-linking fibrin
important for clot stabilization
What can elevated D-Dimer indicate?
you had or have a clot somewhere that is currently being degraded
Problems with D-dimer
use when suspicion is low/moderate as a screening test
not the best test
How does D-dimer arise physiologically?
plasmin degrades the fibrin clot into D-dimers
t-PA
converts plasimonogen to plasmin
*plasmin breaks down fibrin
alpha2-antiplasmin
prevents plasmin by sequestering it
allows the clot to remain for longer
what occurs at the same time as activation of the coagulation cascade?
fibrinolytic cascade is also set in motion
urokinase
also converts plasminogen to plasmin, like tPA
what regulates plasmin activity?
alpha2-antiplasmin
heparin-like molecule
activates antithrombin which inhibits thrombin
difference in fibrinolysis and anti-thrombosis
fibrinolysis = breakdown of fibrin clot
anti-thrombosis = clot never forms to begin with
What is another term for thrombin?
factor II
What else does heparin inhibit, in addition to thrombin?
factor X
protein C/S network
inactivates Va and VIIIa and thereby quells the common/intrinsic pathways for coagulation
heparin
anticoagulant
combines with antithrombin to inhibit the activity of thrombin and Xa
What type of drug is aspirin?
NSAID
clopidogrel
antiplatelet
blocks ADP receptors which inhibits platelet activation
xarelto / rivaroxaban
anticoagulant
directly inhibits factor Xa, thus inhibiting coagulation
warfarin / coumadin
anticoagulant
inhibits vitamin K-dependent clotting factor synthesis
cannot produce clotting factors in the liver
VKORC1
enzyme that activates vitamin K stores in the liver
needed to synthesize clotting factors
Virchow triad
endothelial injury
abnormal blood flow
hypercoagulability
*risk factors for thrombosis
lines of zhan
only thrombi show lines of Zahn
blood clots lack lines of Zahn
layers of fibrin admixed with layers of aggregated platelets and blood cells
Factor V leiden
in-born hypercoagulable state
factor V is resistant to inactivation by protein C+S
therefore, factor V stays on for longer and there is more clotting
definition of embolus
any bolus that moves
ex: thrombosis = clot embolus
