Hemostasis

Question 1

intrinsic clotting pathway

Answer 1

factors 12, 11, 9, 8

Question 2

extrinsic pathway

Answer 2

factor 7
VII:TF complex
Ca required
K dependent

Question 3

K+ dependent factors

Answer 3

2, 7, 9, 10, C, S

Question 4

common pathway

Answer 4

10, 5, 2 (pro/thrombin)

Question 5

effects of thrombin

Answer 5

1) activate platelets
2) cleaves fibrinogen –> fibrin
3) activates factor 13 (crosslinks fibrin)
4) activates cofactors 5, 8, 9

Question 6

thromboplastin tissue factor

Answer 6

• glycoprotein
• sub endothelial cells
• exposed if vasc damage
• major activator of coagulation system
• complexes with 7 (VII:TF) –> activate X

Question 7

factor VIII (8)

Answer 7

• produced in endothelial cells, megakaryocytes
• bound to vWF –> stabilizes

(vascular injury –> released –> intrinsic pathway)

Question 8

factor XIII (13)

Answer 8

• crosslinks fibrin
• stabilizes fibrin plug
• requires Ca cofactor
• activated by thrombin

Question 9

factor XII (12)

Answer 9

• activates factor XI (11)

- activated by contact with negative charges (basis for PTT)

Question 10

warfarin

Answer 10

vitamin K antagonist

anticoagulant

Question 11

kinins

Answer 11

• vasodilate, incr vasc permeability, pain
• produced by factor XII (12)
• degraded by ACE, C1 inhibitor (ACEi incr kinin levels –> angioedema)

Question 12

antithrombin III

Answer 12

• coagulation inhibitor
• serine protease inhibitor (serpin)
• inhibits factors II, VII, IX, X, XI, XII (2, 7, 9, 10, 11, 12)
• produced in liver
• activated by endothelium (heparin sulfate)

Question 13

protein C

Answer 13

• coagulation inhibitor
• liver glycoprotein
• activated = APC
• thrombomodulin + thrombin –> activates to APC
• cofactor: protein S

-inactivates V, VIII (5, 8)

Question 14

TFPI

Answer 14

• coagulation inhibitor
• tissue factor pathway inhibitor
• inactivates X (10)
• binds directly to X, or binds to TF:VII to prevent activation of X
• heparin increases plasma levels of TFPI

Question 15

plasminogen

Answer 15

• active enzyme: plasmin
• breaks down fibrin
• also breaks down clotting factors, fibrinogen
• activated by: tPA, urokinase

Question 16

sources of vitamin K

Answer 16

• green leafy vegetables

- bacterial synthesis in gut

Question 17

PT

Answer 17

prothrombin time

• extrinsic system
• common pathway, factor VII (7)

Question 18

PTT

Answer 18

partial thrombin time

• intrinsic pathway
• common pathway, factors VIII, IX, XI, XII (8,9,11,12)

Question 19

What is not reflected in PT or PTT?

Answer 19

vWF, factor XIII (13)

Question 20

von Willebrand Factor

Answer 20

• glycoprotein
• endothelial cells (Weibel Palade bodies) and megakaryocytes (alpha granules in platelets)
• released on vascular injury

1) carrier protein for factor VIII (8)
2) binds platelets to damaged endothelium (adhesion)
3) binds activated platelets together (aggregation)

Question 21

platelet adhesion

Answer 21

• vascular damage exposes collagen
• subendothelial damage binds vWF
• vWF binds GPIa on platelets

damaged wall/collagen can bind platelet directly via GPIa/IIa receptor

Question 22

GPIb

Answer 22

• on platelets
• binds vWF
• platelet adhesion

Question 23

GPIIb/IIIa receptor

Answer 23

-mediates aggregation

• once platelet activated, GPIIb/IIIa changes shape –> binds fibrinogen or vWF
• links platelets together

Question 24

platelet secretion

Answer 24

activated by

• binding subendothelial collagen
• binding activating substances
• secretion of stored activators causes more activation

Question 25

alpha granules

Answer 25

in platelets - fibrinogen (aggregation) - thrombospondin (aggregation) - vWF (adhesion/aggregation) - factor V (fibrin clot) - platelet factor 4 (heparin antagonist, promotes fibrin clot) - beta thromboglobulin (recruits fibroblasts) - PDGF (recruits fibroblasts) - P selectin (adhesion to phagocytes)

Question 26

dense granules

Answer 26

in platelets - ADP - Ca (cofactor for fibrin formation) - serotonin (vasoconstriction)

Question 27

P2Y1

Answer 27

- platelet receptor - adenosine binds - Ca release - platelet shape change

Question 28

P2Y13

Answer 28

- platelet receptor - adenosine binds - platelet degranulation - more aggregation

Question 29

effects of ADP

Answer 29

P2Y1 - Ca release - shape change of platelet P2Y12 - platelet degranulation - more aggregation

Question 30

thromboxane A2

Answer 30

- platelet activator - cell membrane lipids --> AA --> TXA2 -last step by COX (inhibited by ASA

Question 31

production of platelets stimulated by

Answer 31

GM-CSF IL-3 IL-6 TPO

Question 32

GPIa/IIa receptor

Answer 32

- on platelets | - collagen from damaged wall can bind to platelet directly

Question 33

platelet activating agents

Answer 33

- thrombin - thromboxane A2 - epinephrine - ADP - collagen - AA

Question 34

platelet shape change

Answer 34

- discoid --> spherical | - long pseudopods

Question 35

major tests for platelet function

Answer 35

Aggregation: -platelet rich plasma plus platelet agonists light transmission Aggregation + Adhesion -PFA 100

Question 36

PFA-100

Answer 36

- tests platelet adhesion and aggregation - time to clot formation between 2 membranes coated with activators -affected by thrombocytopenia, anemia

Question 37

tissue factor pathway inhibitor (TFPI)

Answer 37

-regulates TF/FVIIa pathway (extrinsic)

Question 38

anti-thrombin III (AT-III)

Answer 38

inhibits thrombin, FIX, FX, FXI (intrinsic and common)

Question 39

protein C

Answer 39

- inhibits FV and FVIII (intrinsic and common) | - vitamin K dependent