Squier

Question 1

Megakaryocyte regulation

Answer 1

Platelets can bind THPO to down regulate platelet formation

Question 2

Platelet activation

Answer 2

ET damage causes collagen exposure (and vWF)
Platelet adheres to form plug (vWF)
Platelet aggregation via GP to fibrin
Platelet activation releases ADP and TXA2 to increase GP expression

Question 3

vWF

Answer 3

Between ET and BM
Crosslinks collagen and platelets
Binds to FVIII in Plasma

Question 4

ADP platelet release

Answer 4

ADP binding activates scramblase, resulting in phosphatidylserine (PS) on outer membrane (creates negative surface charge to stimulate intrinsic pathway of blood coagulation)

Question 5

ASA inhibits what

Answer 5

COX1/2

Prevents Arachidonic acid to PGH2 formation

Question 6

Cloting cascade

Answer 6

F7 binds F10——F10a acts to converts prothrombin to thrombin
Thrombin cleaves fibrinogen to fibrin

Question 7

What does Thrombin activate in the extrinsic pathway?

Answer 7

Converts fibrinogin to fibrin
Further activate F7 to feed forward rxn
Activate F13 which causes soft clot to cross linked fibrin clot
Also activates F5 which increases prothrombin cleavage by 300,000 fold

Question 8

Factor 13

Answer 8

Is a transglutamase which crosslinks glutamine to lysine to stabilize fibrin to make a hard clot
Activated by Thrombin, stabilized by Ca

Question 9

Intrinsic pathway activation

Answer 9

Contact Activation of FXII Promotes Cleavage of Prekallikrein (PK) to Form Kallikrein (K)
Kallikrein Proteolytically Activates FXII to Form FXIIa
FXIIa Proteolytically Activates FXI to Form FXIa
FXIa Proteolytically Activates FIX to Form FIXa

Prekallikrein (PK) and FXI Circulate in Plasma in Complex with High-Molecular-Weight Kininogen (MMWK), which brings Zymogens in Contact with Bilayer (Lesion)
FIXa + FVIIIa (Proteolytically Activated by Thrombin) Activates FX (Integration Step Involving Common Pathway – Tissue Factor)

Question 10

Vitamin K and Formation of Gamma Carboxyglutamic Acid (Calcium Binding Sites)

Answer 10

ɣ-Glutamyl Carboxylase Acts on Prothrombotic Factors Prothrombin, VII, IX, and X and on Antithrombotic Regulatory Proteins C and S.
Vitamin K Epoxide Reductase Reduces Vitamin Koxidized (KO) and is Blocked by Competitive Inhibitor Warfarin

Question 11

Antithrombin III

Answer 11

(major targets are thrombin and Xa (also IX, XI, XII, thrombin, VIIa, kallikrein, and plasmin

Question 12

Antithrombin

Answer 12

Blocks Active Site of Protease (e.g., Thrombin).

Serpin (serine protease inhibitor)

Stoichiometric Binding Occurs Through Reactive Site Loop (without Subsequent Hydrolysis; t½ = 3 days).

Heparin (highly sulfonated oligosaccharide) Stabilizes Complex to Favor Rapid Inactivation of Proteases.

Question 13

Tissue Factor Pathway Inhibitor (TFPI)

Answer 13

TFPI Specifically Interacts with TF-FVIIa-FXa Complex.

Intracellular Degradation of FVIIa Following Internalization(Inactive Alone).

Question 14

Thrombomodulin (TM)

Answer 14

TM is a Membrane Protein That Specifically Binds Thrombin
TM-Thrombin Complex Activates Protein C

Protein C in the Presence of Protein S Proteolytically Inactivates Factors Va and VIIIa

Question 15

Clot Dissolution (Fibrinolysis)

Answer 15

Proteolysis (Inactivation) of Plasminogen Activatable Inhibitor
(PAI-1 and PAI-2)
Release of Inhibition of tissue type plasminogen activator
(t-PA)