Thrombosis Objectives Flashcards
List the 3 primary abnormalities that lead to thrombosis (Virchow’s triad).
Virchow’s triad:
- abnormal blood flow
- endothelial injury
- hypercoagulability – all leads to thrombosis
Explain how endothelial injury or dysfunction can contribute to thrombosis.
activation, adhesion, and formation of a clot
-If there is damage you expose the ECM including the collagen and vWF which allows platelets to adhere.
Endothelial dysfunction that promotes clot development, would most likely be associated with:
A. An increase in prostacyclin production
B. A decrease in thromboxane A2
production
C. A decrease in tissue factor production
D. A decrease in thrombomodulin
production
E. An increase in t-PA production
D. A decrease in thrombomodulin
production
Notes:
Prostacyclin-ihibits activation
Thromboxane 2- activates platets
Tissue factor-activates cascade
t-PA dissolves clots
Describe how inflammation, such as with turbulent blood flow cause endothelial injury/dysfunction.
turbulent blood flow –>
damaged endothelium –> plaque
rupture and expose ECM to expose vWF
This can lead to stasis of blood also
Explain how stasis of blood can contribute to thrombosis… What causes Stasis? (4)
In stasis, since there is no flow, activated factors will not get washed away which means there is an increased chance of them finding one another and clotting.
Stasis can be caused by:
turbulent flow
bed rest
aneurysm (a dilated artery)
dilated
atrium and atrial fibrillation to produce a mural thrombus, which is during atrial fibrillation there is just quivering, there is no coordinated contraction
Athleroscloritic plaque
will cause turbulent flow because decreased Volume
Stasis causes clotting where
Veins
Differentiate between primary and secondary disorders:
Primary=inherited
Secondary=acquired
Explain how a hypercoagulable state can contribute to thrombosis.
Use oral contraceptive, cancer,
myocardial infarction, immobilization, and atrial fibrillation as examples
an abnormality of blood coagulation that increases the risk of thrombosis (blood clots in blood vessels).
These are all Secondary, or acquired
Oral contraceptives or pregnancy –> increased synthesis of clotting
factors
Cancers –> releases procoagulant tumor products
The others may cause stasis
Compare white and red clots.
a. Where do they tend to occur (arteries or veins)?
b. What do they consist of?
White clots=platelet rich and happen in arteries
Red clots=venous clots which are platelet poor and red cell rich!
List and explain the different fates of a thrombus.
4
Resolution
Propagation to heart
Fibrous Scar
Embolous
1.) Resolution: t-PA generates plasmin, degrades fibrin
2.) Thrombus propagation TOWARD HEART! (in the direction of blood
flow)
– Propagating venous thrombus has a tail –> poorly attached to
vessel wall so risk of clot breaking away and embolizing
3.) Become organized and recanalized into fibrous scar
–Endothelial cells, smooth muscle cells, fibroblasts move in
–Form small, narrow channels called cannulas so there is some
blood flow through scar tissue
4.) Become an embolus: flowing via blood
—Intravascular solid, liquid, or gaseous mass that is carried by
the blood to a site distant from its point of origin
—Thromboembolisms
Mural thrombis
in the aorta toward the heart
The main precipitating event for the development of arterial clots, such as from atherosclerotic plaque rupture is most likely:
A. Endothelial injury/dysfunction B.Hypercoagulability C. Stasis of blood
A. Endothelial injury/dysfunction
Explain how a hypercoagulable state can contribute to thrombosis—
Use the factor V Leiden mutation
or the mutation in the prothrombin gene as examples
Mutation in cofactor V gene = Factor Leiden mutation
Factor V is resistant to protein C which is an endogenous anticoagulant
Mutation in prothrombin gene:
in untranslated region —> increased
transcription of prothrombin –> increased risk of development of
thrombin and clot
Define and explain the formation of the lines of Zahn.
platelet/fibrin rich layer next to a red blood cell rich layer
from flowing blood –
this is how to tell if thrombus occurs pre or post mortem
Venous clots can occur with immobility, such as with prolonged bed rest. The main precipitating event with this type of clot is:
A. Endothelial injury/dysfunction
B. Hypercoagulability C. Stasis of blood
C. Stasis of blood
-clotting factors activated and build up
The main precipitating event for the development of arterial clots, such as from atherosclerotic plaque rupture is most likely:
A. Endothelial injury/dysfunction
B.Hypercoagulability C. Stasis of blood
A. Endothelial injury/dysfunction
What would be the most effective therapy for a deep vein thrombosis (DVT)?
A. An antiplatelet agent, such as aspirin B. An anticoagulant, such as heparin
C. Both aspirin and heparin
B. An anticoagulant, such as heparin
adding aspirin increases risk of bleeding and adds little to treatment
At autopsy, a blood clot is found in the abdominal aorta. How does the pathologist determine if this occurred pre or post mortem?
Look at lines of Zahn:
platelet/fibrin rich layer next to a red blood cell rich layer from flowing blood – how to tell if thrombus occurs pre or post mortem
Thrombi propagate toward the heart.
Will a venous clot ‘grow’ or propagate in the direction of blood flow, or the opposite direction of blood flow?
Arteriole?
In the direction of blood flow
Arterioles are opposite
Fat embolism caused by
a crushing injury to soft tissue or bone
Thromboembolisms
deep vein thrombosis –> ends up where and symptoms
pulmonary embolus
(b/c hits capillary bed)
symptoms –> hypoxia
Thromboembolism (clot that breaks off and travels) via Artery or left heart chamber ends up where
Systemic and go anywhere; it can lodge in an artery and cause an infarction –> coagulative necrosis
With endothelial injury or dysfunction thrombosis,
Predict potential changes in pro and anti-thrombotic mediators with endothelial dysfunction
Administer aspirin to inhibit thromboxane A2 (which activates platelets), antiplatelet and heparin which is an anticoagulant to decrease the thrombin- note that plasmin will still work to remove the clot too
What causes stasis (4)
Stasis can be caused by: turbulent flow, bed rest, aneurysm (a dilated artery) or a mural thrombosis
Explain how a hypercoagulable state can contribute to thrombosis.
Differentiate between primary and secondary disorders:
Primary= inherited such as a gene mutation or heart problem
Secondary= acquired such as through pregnancy or cancer
Considering
atherosclerosis
rupture of an atherosclerotic plaque causing a myocardial infarction
AND
a deep vein thrombosis (DVT), or a mural thrombus.
Compare the
a) main causes
ADD on to this/break it up
Arterial clots are caused by endothelial damage/dysfunction…
Deep vein thrombosis: prolonged rest/immobility –> slow moving
blood or stasis –> build up of activating clotting factors –> activates
the coagulation cascade
Considering
atherosclerosis
rupture of an atherosclerotic plaque causing a myocardial infarction
AND
a deep vein thrombosis (DVT), or a mural thrombus.
Compare the
b) type of clot (what are they made of) and location
endothelial damage
A plaque forms in artery –> turbulence –> rupture and exposes ECM which leads to a WHITE SPOT PLAQUE
Deep vein thrombosis:
stasis –> clotting factors build up–> RED CLOTS B/C MADE OF RBC NOT PLATELETS
- Because stasis, flow can’t whisk away activated factors and
increases chance that they will find each other
Considering
atherosclerosis
rupture of an atherosclerotic plaque causing a myocardial infarction
AND
a deep vein thrombosis (DVT), or a mural thrombus.
Compare the
c) clinical problems
d) treatment of a clot associated with
Clot in arteries –>
Would administer aspirin (to inhibit thromboxane A2,
antiplatelet) and heparin (anticoagulant to decrease thrombin)
to prevent clot expansion, but PLASMIN still dissolves clot
Venous Clot –>
Since these do not contain many platelets DO NOT use aspirin, RBC are caught in fibrin mesh so use ANTICOAGULANT (HEPARIN)
