w5- coagulation

Question 1

what triggers the activation of a hard and soft clot

Answer 1

Cleavage of fibrinogen (coagulation factor I) to fibrin (factor Ia) by thrombin results in aggregation to form a “soft clot.” Cross linking between Lys & Gln in an enzyme-mediated transamidation reaction subsequently transforms the soft clot to a “hard clot.”

Question 2

what is Virchow’s triad

Answer 2

• Blood flow (stasis or impaired flow) - Composition of the blood (hypercoagulability) - Changes in the vessel wall (endothelial activation or damage important for venous thrombosis

Question 3

how does tx of arterial and venous thrombosis differ

Answer 3

arterial- anti-platelet venous- anti-coat

Question 4

would hyper coagulation encourage venous or arterial thrombosis

Answer 4

venous

Question 5

how does deoxygenation impact stasis

Answer 5

 Deoxygenation increases chance of forming blood clots  Recirculation of blood  very important for anti coag prop

Question 6

how does hypoxia impact venous thrombosis

Answer 6

 Cells in the vessel walls become inflamed  Bleb of microvesicles that express tissue factor  coag cascade

induces expression of P-selectin, which acts as a docking site for tissue-factor-positive microparticles, platelets, and leukocytes

Question 7

differentiate TPA from an anti-plasmin drug

Answer 7

o TPA- targets plasminogen o Antiplasmin- targets plasmin and prevents its conversion of fibrin to degredation products

Question 8

what phase of the arterial cycle does vWVF impact and how

Answer 8

 von Willebrand factor (vWF) mediates the adhesion in response to injury by changing its MW at sites of injury recognize the change and platelets bind

deficit = bleeding disorder (most common inherited cause of bleeding disorders)

Question 9

what are the four steps of arterial thrombus

Answer 9

adhesion

activation

secrection

aggregation

Question 10

name 3 things that are secreted during arterial thrombosis

Answer 10

Thombin (enforces activation)

ADP

thromboxin A2

Question 11

what are the targets of aspirin and clopidogrel

Answer 11

Aspirin is an irreversible cyclooxygenase-1 (COX-1) inhibitor that blocks production of TXA2 from arachidonicacid.

Clopidogrelis an ADP receptor blocker.

Question 12

what phase of the arterial thombosis cycle influences microvascular constriction and immune mediators

Answer 12

secrection

Question 13

what 2 phases does thrombin act on

Answer 13

activation and aggregation (clot formation by converting fibrin)

speds up the conversion of V, VIII, IX (feedback

Question 14

outline the process of aggregation

Answer 14

Upon activation, interaction between platelets is promoted by increased surface area due to shape changes. Thrombin converts fibrinogen to fibrin. Fibrin and vWFform cross-bridges between activated platelets and stabilize the thrombus

Question 15

what causes tissue factor from the extrinsic pathway to be present

what is its function

Answer 15

endothelial damage

activates XI and X

Question 16

what is the function of factor 10

what activates it

what does it interact with and how

Answer 16

function: forms complex with V to convert prothrombin to thrombin

activates: tissue factor and VII, IX and VIII

interacts with PS

X has post translational modification of carboxyl groups that allow interaction of calcium ions which bring between neg charge of PS and -carboxyglutamic acid

Question 17

which factors contain γ-carboxyglutamic acid residues and can be bound with citric chelator

Answer 17

VII, IX, X, prothrombin

Question 18

what is the target of coumadin a VIT K antagonist

Answer 18

block -carboxyglutamic acid residues post trans modifications

Question 20

difference between the intrinsic and extrinsic pathway

Answer 20

Xii –> XI –> IX

indep of tissue factor

can be initiated by foreign surface such as dialysis tube or trauma/surgery and works in parallel with extrinsic

Question 21

what is the deficit in hemophillia A and B

Answer 21

A- VIII (cant activate X)

B- IX

(cant activate X)

Question 22

what activates antithombin and what does it block

Answer 22

heparin

blocks: thrombin, Xa, IXa

Question 23

what is blocked by the Tissue factor pathway inhibitor (TFPI)

Answer 23

VIIa and Xa

Question 24

what is the protein C pathways and what does it block

Answer 24

feedback loop mediated by thrombomodulin TM

TM turns on ability of thrombin to activate protein C by proteolytic cleavage.

Blocks VIII and Va

turns on TPA, blocka PAI (which inhibits TPA)

Question 25

what would a mutation in factor V result in

Answer 25

4-7x increase in risk of venous thrombosis

factor V Leiden

DO NOT TEST FOR, low penetrance

Question 26

what does pro and partial thombin time measure

Answer 26

Prothrombin time measures the extrinsic pathway + common pathway

• dietary malabsorption*
• sepsis*

monitor patients on oral anti-coagulants such as warfarin.

• Partial prothrombin time* intrinsic pathway + common pathway
• antiphospholipid antibodies*
• hemophilia*
• sepsis*

monitor patients on heparin

Question 27

how do neutrophils impact clotting

Answer 27

Neutrophil elastase cleaves thrombomodulinfrom endothelium, making it less effective in activating protein C

Bound, activated leukocytes sequester platelets which trigger the clotting cascade

Monocyte activation leads to tissue factor expression on their surface and trigger clotting cascade

Question 28

what are 2 ways to break down a clot

Answer 28

TPA and Streptokinase

convertes plasminogen to plasmin