Thrombosis Objectives

Question 1

List the 3 primary abnormalities that lead to thrombosis (Virchow’s triad).

Answer 1

Virchow’s triad:

1. abnormal blood flow
2. endothelial injury
3. hypercoagulability – all leads to thrombosis

Question 2

Explain how endothelial injury or dysfunction can contribute to thrombosis.

Answer 2

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.

Question 3

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

Answer 3

D. A decrease in thrombomodulin
production

Notes:
Prostacyclin-ihibits activation

Thromboxane 2- activates platets

Tissue factor-activates cascade

t-PA dissolves clots

Question 4

Describe how inflammation, such as with turbulent blood flow cause endothelial injury/dysfunction.

Answer 4

turbulent blood flow –>
damaged endothelium –> plaque
rupture and expose ECM to expose vWF

This can lead to stasis of blood also

Question 5

Explain how stasis of blood can contribute to thrombosis… What causes Stasis? (4)

Answer 5

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

Question 6

Athleroscloritic plaque

Answer 6

will cause turbulent flow because decreased Volume

Question 7

Stasis causes clotting where

Answer 7

Veins

Question 8

Differentiate between primary and secondary disorders:

Answer 8

Primary=inherited

Secondary=acquired

Question 9

Explain how a hypercoagulable state can contribute to thrombosis.

Use oral contraceptive, cancer,
myocardial infarction, immobilization, and atrial fibrillation as examples

Answer 9

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

Question 10

Compare white and red clots.

a. Where do they tend to occur (arteries or veins)?
b. What do they consist of?

Answer 10

White clots=platelet rich and happen in arteries

Red clots=venous clots which are platelet poor and red cell rich!

Question 11

List and explain the different fates of a thrombus.

4

Answer 11

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

Question 12

Mural thrombis

Answer 12

in the aorta toward the heart

Question 13

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

Answer 13

A. Endothelial injury/dysfunction

Question 14

Explain how a hypercoagulable state can contribute to thrombosis—

Use the factor V Leiden mutation

or the mutation in the prothrombin gene as examples

Answer 14

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

Question 15

Define and explain the formation of the lines of Zahn.

Answer 15

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

Question 16

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

Answer 16

C. Stasis of blood

-clotting factors activated and build up

Question 17

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

Answer 17

A. Endothelial injury/dysfunction

Question 18

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

Answer 18

B. An anticoagulant, such as heparin

adding aspirin increases risk of bleeding and adds little to treatment

Question 19

At autopsy, a blood clot is found in the abdominal aorta. How does the pathologist determine if this occurred pre or post mortem?

Answer 19

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

Question 20

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?

Answer 20

In the direction of blood flow

Arterioles are opposite

Question 21

Fat embolism caused by

Answer 21

a crushing injury to soft tissue or bone

Question 22

Thromboembolisms

deep vein thrombosis –> ends up where and symptoms

Answer 22

pulmonary embolus
(b/c hits capillary bed)

symptoms –> hypoxia

Question 23

Thromboembolism (clot that breaks off and travels) via Artery or left heart chamber ends up where

Answer 23

Systemic and go anywhere; it can lodge in an artery and cause an infarction –> coagulative necrosis

Question 24

With endothelial injury or dysfunction thrombosis,

Predict potential changes in pro and anti-thrombotic mediators with endothelial dysfunction

Answer 24

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

Question 25

What causes stasis (4)

Answer 25

Stasis can be caused by: turbulent flow, bed rest, aneurysm (a dilated artery) or a mural thrombosis

Question 26

Explain how a hypercoagulable state can contribute to thrombosis.

Differentiate between primary and secondary disorders:

Answer 26

Primary= inherited such as a gene mutation or heart problem

Secondary= acquired such as through pregnancy or cancer

Question 27

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

Answer 27

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

Question 28

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

Answer 28

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

1. Because stasis, flow can’t whisk away activated factors and
   increases chance that they will find each other

Question 29

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

Answer 29

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)