Biochemistry - Lecture 1 - Blood Clotting

Front 1

What is the difference between Plasma and Serum?

Back 1

-They are both Liquid portions of the blood
-Plasma can clot - Has Clotting factors in it
-Serum cannot clot - Clotting factors have been removed

Front 2

What is Hemostasis?

Back 2

-Normal protective process that stops a bleed
-Limits Blood Loss
-Clot occurs

Front 3

What is Blood Clot in a Blood Vessel called?

Back 3

-Thrombus

Front 4

What is the process of dissolving a Clot called?

Back 4

Fibrinolysis

Front 5

Describe the timeline of clotting.

Back 5

Occurs very slowly and then an explosive growth (clot) occurs.

Front 6

What are the 4 Important event in Clotting?

Back 6

-Vasoconstriction
-Platelet Activation/Adhesion/Aggregation
-Fibrin Meshwork
-Fibrinolysis - Clot Dissolution

Front 7

Where do Platelets come from?

Back 7

Broken off of Megakaryocytes

Front 8

How do activated Platelets facilitate clotting?

Back 8

-They change surface properties of their membrane
-Expose new shit on the membrane
-Allows Blood CLotting Factors to Bind

Front 9

Name 2 Potent Activators of Platelets. Which shouldn't be encountered if everything is ok?

Back 9

-Collagen - this one
-Thrombin

Front 10

What is Thrombin?

Back 10

-Platelet Activator
-Last Serine Protease in the Clotting Cascade

Front 11

Name 2 Secreted Molecules that Activate other Platelets.

Back 11

-ADP
-Thromboxane A2

Front 12

How does Aspirin work?

Back 12

-Targets Cyclooxygenase
-First Enzyme in the Prostaglandin Pathway
-Would normally lead to formation of Thromboxane A2
-Without Thromboxane A2, can't activate other Platelets
-Prevents Clotting

Front 13

What is von WIllebrand Factor? Where is it released? Where is stored?

Back 13

-Adhesive Protein that Facilitiates Clotting
-Released at sites of Injury
-Stored in Platelets

Front 14

What does VWF bind to? How does it act?

Back 14

-Binds to Collagen and Cell Surface Receptors on Platelets
-Allows Platelets to Bind to Collagen and other Platelets

Front 15

What Molecule forms a bridge between activated Platelets?

Back 15

Fibrinogen

Front 16

What is the Most Common Congenital Bleeding Disorder?

Back 16

-von Willebrand Disease

Front 17

What happens in von Willebrand Disease?

Back 17

-VWF deficiency
-Defective Platelet Adhesion - Can't stick to sites of injury
-Diathesis - Abnormal propensity for bleeding

Front 18

Describe, in general, how the Clotting Cascade works.

Back 18

-Chain rxn of Enzymes
-2 Subunit Enzymes including a Serine Protease and a Regulatory Subunit or Cofactor
-They bind to each other and to Membrane Surface
-Protein is Proteolysed to become the next Protease
-Chain Reaction

Front 19

Where are most Clotting Factors Synthesized?

Back 19

Liver

Front 20

What role does Calcium play in clotting?

Back 20

Necessary for most steps in the clotting cascade

Front 21

What does Tissue Factor do?

Back 21

-Triggers the Clotting Cascade
-Binds to Factor 7 and activating it to Factor 7a

Front 22

What is Factor 7a?

Back 22

-Activated, Serine Protease Form of Factor 7
-Part of Clotting Cascade
-Activated Factors 9 and 10 - Blood Clotting Proteins

Front 23

Where is Tissue Factor found?

Back 23

Cell Surface of Tissues

Front 24

Where in most Blood Vessels is Tissue Factor very Abundant?

Back 24

-Adventitial Cells
-If blood hits these cells, we need a clot!!!

Front 25

How does Thrombin act?

Back 25

-Potent Activator of Platelets
-Removes Fibrinopeptides from Fibrinogen
-Converts Fibrinogen to Fibrin

Front 26

What does Factor 13a do? What type of Enzyme is it?

Back 26

-Chemically Cross-links Fibrin to give a stable clot
-Transglutaminase

Front 27

What Chemically Cross-links Fibrin to give a stable clot?

Back 27

Factor 13a

Front 28

What is it called when a Thrombus dislodges and causes a block downstream?

Back 28

Thromboembolism

Front 29

Where and How is Tissue Factor Expression Induced?

Back 29

-Monocytes
-In Inflammation, Monocytes begin to make lots of TF when fighting infection

Front 30

How and why does Atherosclerosis Increases the chances of a clot forming?

Back 30

-Oxidized LDLs can be found in the Subendothelial Space
-Monocytes are attracted to them and take up LDLs via Scavenger Receptor
-This Activates Monocytes and upregulates Inflammatory Response and TF Production by Monocytes
-Recruits other Leukocytes and essentially get a benign tumor growing
-Cells may die
-These Cells are now getting close (1 Layer) from the Lumen and May Rupture

Front 31

What happens in atherosclerosis when rupture occurs?

Back 31

-Exposes TF to the blood
-Causes Clot to form

Front 32

What is Progression?

Back 32

-When the Damage to a Clot is repaired
-Another Clot may occur
-Can occur multiple times and lead to an occlusion

Front 33

What is Hemophilia?

Back 33

Bleeding Disorder that involves the Clotting System

Front 34

What are the most common types of Hemophilia? How are these 2 related?

Back 34

-Factor 8a and 9a
-They are 2 halves of the same enzyme

Front 35

Why in Hemophilia is there more bleeding in joints?

Back 35

-There is lots of TF in the skin so the pathway is usually fine there
-Very little TF in Joints
-Causes bleeding in Joints

Front 36

How do we test for the Integrity of the Plasma Clotting System?

Back 36

-PT test - Prothrombin Time
-aPTT test - activated Partial Thromboplastin Time

Front 37

How does the PT test work?

Back 37

-Draw Blood
-Remove Plasma
-Mix with excess calcium and TF
-Measure time it takes to Clot

Front 38

What is the PT Test Sensitive to?

Back 38

-Prothrombin
-Fibrinogen
-Factos 5, 7, and 10

Front 39

What is INR? What is a normal INR? What is abnormal?

Back 39

-Ratio of a Patient's Clot time to a Normal Clot time
-1 is normal
->2 is considered to be Prolonged

Front 40

What is the Intrinsic Pathway? What is another name for it? What is its importance?

Back 40

-Clotting activated by artificial surfaces
-Contact Pathway
-We don't know what its role is and it doesn't seem like its necessary

Front 41

How does the aPTT test work?

Back 41

-take Plasma
-Add Calcium
-Use Artificial Activators - typically Clay
-Tells us if Clotting is working

Front 42

What is the aPTT test sensitive to?

Back 42

-Factors 5, 8, 9, 10, and 12
-Prothrombin
-Fibrinogen
-HK
-PK

Front 43

Which test can detect Hemophilia A and B?

Back 43

aPTT test

Front 44

What can we do to monitor Heparin Therapy?

Back 44

aPTT test

Front 45

Describe the structure of Fibrin.

Back 45

Dimer of Trimers

Front 46

Describe how Fibrin Polymerizes.

Back 46

-Fibrinopeptides are on Fibrin and keep it from Polymerizes
-Thrombin cleaves them off
-Spontaneously Polymerizes and forms a clot

Front 47

What is Antithrombin?

Back 47

-Natural Anticoagulant
-It is a Serine Protease Inhibitor

Front 48

How does Antithrombin work?

Back 48

-It is a Serine Protease Inhibitor
-Irreversibly Inactives Serine Proteases
-Not a very good inhibitor - needs Heparin

Front 49

What are the main targets of Antithrombin?

Back 49

Factor 10a and Thrombin

Front 50

What does Heparin do?

Back 50

-Interacts with Antithrombin
-Makes it more of an anticoagulant
-Accelerates ability of Antithrombin to Inactivate Factor 10 and Thrombin
-Make Clotting Cascade harder to run

Front 51

What is Warfarin? How does it work?

Back 51

-Anticoagulant drug
-Vitamin K helps Blood Proteins get Calcium, which they need for clotting
-Warfarin Depresses the Vitamin K Dependent Carboxylation of Clotting Factors
-Prothrombin, Protein S, Factors 7, 9, and 10
-Can be very dangerous

Front 52

Why is Warfarin Potentially Dangerous

Back 52

-It affects lots of Enzymes in the Clotting Pathway

Front 53

What is Argatroban? Why might it be safer than Warfarin?

Back 53

-Direct Thrombin Inhibitor
-Only acts on 1 enzyme

Front 54

What is Plasmin? What activates Plasminogen and turns it into Plasmin?

Back 54

-Plasmin digests Blood Clots during Wound-Healing
-tPA – Tissue-Type Plasminogen Activator
-uPA – Urinary-Type Plasminogen Activator (Urokinase)

Front 55

What do Thrombolytics do? Name a few.

Back 55

-Drugs that help digest Clots.
-Activase - tPA
-Abbokinase - uPA
-Streptase - Streptokinase