Arrest bleeding from injured

blood vessels
1a

The hemostatic mechanism is

designed to do what?
1b

Vascular constriction, platelet

plug, and blood coagulation
(thrombosis)
2a

What is involved in the

hemostatic mechanism?
2b

A complex set of interdependent

reactions between the surface,
platelets, coagulation proteins,
resulting in the formation of a clot or
thrombus that may undergo removal
by fibrinolysis. It is a localized process
at the surface

3a

What is blood coagulation?

3b

Coagulation proteins, platelets,

endothelial lining of the blood
vessel
4a

What are the key players of

hemostasis?
4b

RBCs, WBCs, and platelets

5a

What are the 3 types of blood

cells?
5b

RBCs

6a

_______are usually passive

6b

May form a large proportion of

the total thrombus mass
7a

Under low shear or venous

flow, what happens to RBCs
7b

Activate complement
coagulation and fibrinolytic and
other enzyme systems; They
interact with large surface area
devices (depletion)
8a

What do WBCs do?

8b

Arrest bleeding through

formation of platelet plugs,
stabilize the initial plugs by
catalyzing coagulation reactions
leading to the formation of fibrin
9a

What do platelets do?

9b

By the interaction between cell

surface receptors and ligands
on collagen, vWF, fibrinogen
and fibronectin
10a

How are platelets activated?

10b

Discoid shape becomes

irregular shape with spiny
pseudopods, results in release
of storage granule contents
11a

Upon activation, what happens

to platelets?
11b

1) Injury to the lining of a blood vessel

exposes collagen fibers, platelets adhere
and get sticky 2) Platelets release
substances that cause the vessel to
contract, sticky platelets form a plug and
initiate formation of a fibrin clot 3) The
fibrin clot seals the wound until the vessel
wall heals

12a

Give the 3 steps of clot

formation
12b

Promote conversion of
prothrombin circulating in
plasma to thrombin
13a

What do clotting factors do?

13b

Converts fibrinogen circulating

in plasma to fibrin
14a

What does thrombin do?

14b

Ca2+

15a

What chemical is important in

the coagulation cascade?
15b

Blood flow (dilution), rate of clotting

reaction is fast only when the reaction
is catalyzed by a surface, inhibitors of
thrombin and other coagulation
enzymes, enzymes that not only
activate coagulation factors but also
degrade cofactors

16a

What are 4 means of limiting

clot formation?
16b

Heparin/anti-thrombin III (AT II)

complex, thrombomodulin
17a

What are 2 inhibitors of

thrombin?
17b

Removal of unwanted fibrin

deposits to improve blood flow
following thrombus formation
and to facilitate healing after
injury and inflammation
18a

What is fibrinolysis?

18b

Plasmin

19a

What activates fibrinolysis?

19b

Prolonged cardiopulmonary bypass and

membrane oxygenation can produce
neutropenia; mechanical heart valves shed
emboli to the brain causing a stroke; graft
failure due to thrombosis results in ischemia
and death of downstream tissue beds; small
diameter vascular grafts cannot be made;
systemic anti-coagulant administration
introduces bleeding risk

20a

What complications result with

thrombosis? (5 examples)
20b

Fibrinogen, fibronectin,
vitronectin, and von Willebrand
factor
21a

Name 5 adhesion proteins in

the plasma for platelets
21b

IIb/IIa and Ib/IX

22a

Which receptors bind

specifically to adsorbed
proteins?
22b

Concentrating, localizing,
immobilizing effects of
adsorbed proteins at the
interface
23a

What accentuates the receptoradhesion protein interaction in

platelet adhesion
23b

Glycocalyx (mucopolysccharides/GAGs,
heparan sulfate, smoothness); heparan suflate
aids AT III to inhibit thrombin;
thrombomodulin on EC surface binds to
thrombin and activates protein C to inhibit
coagulation; secrete soluble chemical
mediators that prevent platelet aggregation or
activate plasmin to promote fibrinolysis

24a

What are the 4 roles/anticoagulative properties of the

endothelium at rest?
24b

Protective glyocalyx is compromised;

exposed ECM to reactive plasma
proteins; in response to stimuli such
as pro-inflammatory cytokines, the
intact EC surface may become
coagulatory (reduce thrombomodulin,
secrete TF and vWF)

25a

What 3 things happen to the

endothelium after injury?
25b

see book/notes

26a

What are the solutions to

thrombosis complications in
biomaterial applications?
26b

Blood variables, surface

variables, and flow variables
27a

What are the 3 cornerstones of

evaluating blood-material
interactions
27b

Species, donor, reactivity, time

interval, temperature,
anticoagulation, blood damage
28a

What are 7 blood variables to

be considered in evaluating
blood-material interactions?
28b

Fibrin formation abundant,

thrombi resemble coagulated
whole blood with entrapped
red cells resulting in a red
thrombus
29a

At low flow, what happens in

blood-material interaction?
29b

Platelets are stabilized by

smaller amount of fibrin
forming a white thrombus
30a

At high flow, what happens in

blood-material interaction?
30b

Good: no adherent platelets, alternate

interpretation- platelets aggregate and
embolize downstream so they aren't seen
on the surface; bad: many adherent
platelets, alternate interpretation- many
platelets adhere but the platelets are not
activated and form passivating natural
biological layer on the surface

31a

When you measure platelet

adhesion, what results imply
good blood compatibility? Bad?
What are the alternate
interpretations
31b

Good: no adherent thrombus, alternate

interpretation: thrombus detaches and
embolizes downstream and is not seen on
the surface; bad: surface coated with
adherent thrombus, alternate
interpretation: the thrombus layer forms a
non-reactive natural biological film on the
surface

32a

When you measure mass of

adherent thrombus, what
results imply good blood
compatibility? Bad? What are
the alternate interpretations
32b

Good: no release, alternate interpretation:

release actually occurs but is diluted by the
flowing blood and released factors is never
present in physiologically significant
concentrations; bad: extensive platelet
granule release, alternative
interpretations: released factors stimulate
desirable endothelial cell growth

33a

When you measure platelet

granule release, what results
imply good blood compatibility?
Bad? What are the alternate
interpretations
33b

1) Doppler ultrasound measurement for embolization 2)

Laser scattering assay of emboli produced 3) Gamma
camera imaging for thrombus accumulation and
embolization 4) Light microscopic assessment (or SEM) for
cell attachment, activation and embolization 5) Flow
cytometric analysis of activated platelets: measure
platelet P-selectin, Mac-1 receptor, platelet activation by
annexin V, platelet microparticles 6) Fibrin production 7)
Complement activation assays, C3a and C5b-9
34a

List 7 common measurements

of blood parameters
34b

longer-term BMI

35a

In vitro assays cannot be used

to predict ________ and in vivo
outcomes.
35b

Screening materials highly

reactive to blood
36a

What are in vitro assays most

useful for in studying BMI?
36b

Whole blood clotting time: placing

whole blood (non anticoagulated or
anticoagulated with sodium citrate)
into containers made of the test
material, record the time for thrombus
to occur in reference to a control
material

37a

What is a static in vitro assay

for BMI examination?
37b

Recirculation test: circulating

heparainized or citrated blood
through a tubular device made of the
test material. Measure the platelet
deposition and protein released from
the platelet to identify highly
thrombogenic materilas

38a

What is a dynamic in vitro assay

for BMI examination?
38b

Blood flow difficult to control,

variation in implantation
trauma affect results
39a

What disadvantages are there

to in vivo assays for BMI
examination?
39b

Plasma is blood without cells,

serum is blood plasma without
clotting factors
40a

What is the difference between

blood, plasma, and serum?
40b

A-V shunt in the baboon: percutaneous

insertion of catheter into the baboon
femoral artery and vein to establish the
chronic shunt. The test materials or
devices are inserted as extension
segments or between inlet and outlet
portion of the shunt
41a

What is an example of an ex
vivo shunt model?
41b

Localized thrombus accumulation,

consumption of circulating platelets
and fibrinogen, plasma levels of
factors released by platelets and
coagulation proteins during thrombus,
embolization of microthrombi to
downstream circulatory beds

42a

What does the baboon A-V

shunt model measure?
42b

Advantages: allow sample tubes to be exposed to

blood flow, blood flow is easily controlled and
measured, native or anticoagulated blood can be
employed, the animal's physiology removes damaged
blood elements, and makes new blood, both short
term and long term, local and systemic effects can be
evaluated; disadvantages: complex surgery, high cost,
exclude modulating effects of blood vessel cells and
tissue injury
43a

What are the

advantages/disadvantages to
the baboon A-V shunt model
43b

Saphenous vein, internal

mammary artery, umbilical vein
44a

What types of materials are

used for natural vascular
grafts?
44b

Dacron and ePTFE

45a

What types of materials are

used for synthetic vascular
grafts?
45b

1) Made porous to enhance healing

2) Impregnated with connective tissue
proteins to aid clotting, reduce blood loss
through the pores and stimulate tissue
ingrowth and release antibiotics
3) Preclotting
4) Perform well in large diameter high flow,
low resistance locations

46a

What are 4 considerations for

synthetic vascular grafts?
46b

Burst pressure, compliance,

stable endothelium under
physiological shear, patency
47a

What are 4 considerations of

tissue engineered blood
vessels?
47b

see notes

48a

Draw dacron and PTFE

48b

Man-made grafts; transplanted

natural grafts
49a

_______ are more likely to be

used than___________ for large
blood vessel replacement
49b

Platelet-fibrin aggregate

50a

What is pseudointima?

50b

Fibrinogen adsorption, platelet-fibrin

aggregate, smooth muscle cells
migration and proliferation,
endothelial cell lining forms adjacent
to sutured connection, the rest is
covered by psuedointima which can
be disloged

51a

What 5 things happen in

vascular graft healing?
51b