cell based model

Question 1

cascade model
contact activation sequence:
intrinsic (within blood vessel)

Answer 1

XII - XI - IX - (VIII) - X

Question 2

extrinsic - outside of blood vessel:

Answer 2

VII, tf Ca++ - X

Question 3

common:

Answer 3

X - V - II (prothrombin) - I (fibrinogen)

Question 4

XIII
Tenase complex
prothrombinase complex:

Answer 4

VIIIa-IXa

Xa-Va

Question 5

vit K dépendant

Ca++ cofactor

Answer 5

II, VII, IX, X

II, VII, IX, X XI

Question 6

limitations of cascade model:

Answer 6

1. assume redundant and indep. -not the case
   - yet Hagmeman def >PTT but no clinical bleeding
2. in vitro not in vivo

Question 7

2 fundamental paradigm shifts w cell based model:

Answer 7

1. TF primary initiator of coagulation (not contact activation/intrinsic path)
2. coagulation is localized and controlled on cellular surfaces

Question 8

G1a glutamic acid residues allow for what?:
must be carboxylated by:
vit K antagonists prevent G1a

Answer 8

binding of Ca++
vit K dependent epoxside reductase
G1a glutamic acid residue binding (II,VII,IX,X)

Question 9

1. role of cell membrane surface:

external leaf is neutral - composed of:

Answer 9

1. sphingomyelin
2. sphingolipids
3. PC phosphatidyl-choline

Question 10

cell membrane surface:

internal leaf - composed of:

Answer 10

1. PS - phospatidyl-serine

2. PE - phosphatidyl-ethanolamine

Question 11

resting state: Flippase:
Floppase:

injury: scramblase:

Answer 11

PS returned to internal
PC returned to external

PS & PE to external
(phospatidyl-serine/ethanolamine)

Question 12

2. role of microparticles:
   what is MP:
   derived from:

activated by:

Answer 12

intact vesicles derived from cells
size 2–20% of the size of a RBC
arise when activated or apopototic cells shed bits of membrane
derived from plt, endothelial cells, and monocyte - in inflam also RBC and granulocytes

Cytokines (TNFa, IL-6), thrombin, shear stress, and hypoxia can stimulate MP formation

Question 13

MP contain:

Answer 13

cell surface proteins similar to those found on their parent cell (eg, ultra large vWF monomers on endothelial cell-derived MPs, P-selectin on platelet-derived MPs, TF on monocyte-derived MPs)

can participate in coagulation reactions, especially when the MP expresses a procoagulant membrane

Question 14

Hypercoagulability, or thrombophilia, describes:

Causes may include:

Answer 14

a propensity for inappropriate thrombus formation

1. increases in procoagulant elements
2. altered blood flow
3. endothelial barrier disruption
4. decreases in endogenous anticoagulants
5. decrease in fibrinolysis

Question 15

endothelial barrier disruption
inflammation thins:
4. decreases in endogenous anticoagulants
5. decrease in fibrinolysis

Answer 15

EGC

1. = < heparan sulfate (most abundant anticoagulant)
2. TFPI TF pathway inhib also found in EGC

Question 16

Increase procoag:

Answer 16

1. exposed TF
2. microparticles
3. plt - integrin AIIbB3

Question 17

decreased endogenous anticoag:

Answer 17

TFPI, AT, protein C

Question 18

what are the 3 anticoagulant proteins expressed on the endothelial membrane:

Answer 18

1. HSPG heparan sulfate proteoglycan
2. Thrombomodulin
3. TFPI tissue factor pathway inhibitor

Question 19

what does HSPG-bound AT do?:

what does heparin-AT drug do?

Answer 19

inactivate II (thrombin)
non-membrane bound, low dose inactivates Xa
high doses inactivate II directly and IX,X,XI,XII

Question 20

what does thrombomodulin on EC do?

Answer 20

combines with thrombin
-thrombomodulin-thrombin complex activates
-protein C (+ cofactor protein S) = aPC
-aPC (with its cofactor protein S [ProS])
1. irreversibly cleaves FVa and FVIIIa, preventing II
2. inactivates PAI-1 plasmingen activator inhibitor
= upregulates fibrinolysis

Question 21

what does TFPI do?

Answer 21

1. irrev. bind Xa

2. forms quaternary complex TFPI-Xa-VIIa-TF