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Hematology > Pathophysiology of Hemostasis > Flashcards

Pathophysiology of Hemostasis Flashcards

1
Q

When there is a break in the endothelium what forms the inital plug?

A

platelets that are circulating in the bood

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2
Q

What comes in after the platelet plug and creates a network to hold them all together?

A

fibrin

They have a natural affinity for each other to form a fibrin strand

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3
Q

Fibrin has a natural affinity for each other. How do we stop them from binding to each other while they are cicrulating in the blood?

A

fibrinogen, cap that covers a binding site

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4
Q

How does your body know when to convert fibrinogen into fibrin?

A

thrombin

is activated from its inactive form called prothrombin

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5
Q

Name the steps in the clotting factors in the intrinsic pathway.
8

A

12-11-9 and 8-10 and 5-2(thrombin)- 1(fibrin)

2 and 1 are part of both pathways and not necessarily part of each pathway

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6
Q

Each factor in the clotting casacde is not becoming one or the other. What is it doing?

A

One factor is activating the next factor. So factor 12 activates factor 11 to become factor 11a

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7
Q

Name the steps in the clotting factors in the extrinsic pathway

A

factor 3 (tissue factor)-7-10 and 5

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8
Q

What is the pathway that get activated first by the inital injury?

A

the extrinsic pathway

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9
Q

Which pathway gets most of the clotting work done?

A

the intrinsic pathway

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10
Q

What are the proteins that are secreted by the endothelium and the proteins that are newly exposed called?

A

tissue factor or factor3

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11
Q

What gets the intrinsic workhorse going in the first place?

A

thrombin (2) that was slightly activated by the extrinsic pathway

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12
Q

What factors does thrombin activate?

5

A

5, 7, 8, 11, 13

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13
Q

Whats the end goal of the clotting casade?

A

create fibin strands

and to connect all the fibrin strands that are made.

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14
Q

How are all the fibrin strands connected together?

A

factor 13 creates crosslinks that connect all the fibrin strands that are created

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15
Q

How do we stop the clotting system when we need it to?

2

A

negative feedback loop that is regulated by thrombin

  • Thrombin helps create plasmin which act directly on the mesh networks of the fibin strands and breaks them apart.
  • Thrombin stimulates the production of antithrombin which decreases the amount of thrombin produced from prothrombin and impede the production of activated 10a from 10.
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16
Q

What does antithrombin do?

2

A

decreases the amount of thrombin that prothrombin is making and impede the activatoion of 10a from 10

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17
Q

What are the three processes through which hemostasis is regulated?
3

A
  1. vascular spasm
  2. platelet plug formation
  3. coagulation
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18
Q

Describe the first step in hemostasis, vasoconstriction?

3

A
  1. direct injury
  2. chemical messengers from endothelial cells and platelets
  3. initiation of the pain reflex
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19
Q

What are the chemical messengers secreted from endothelial cells platelets?

Whats the most potent?

A

Thromboxane A2,
serotonin,
endothelin I(most potent)

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20
Q

What is primary hemostasis?

Describe the steps in the process?
3

A

Platelet plug formation

  1. injury to vascular endothelium
  2. VWF is released
  3. Proteins on platelets bind with fibrinogen causing platelets to adhere
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21
Q

Describe the effectivness of platelet plug formation?

A

quick temporary solution that lasts 12-24 hrs

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22
Q

describe the structure of a platelet?

3

A

A glycoprotein, Glycosaminoglycans
Coagulation proteins
will an outter cell membrane and no nucleus

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23
Q

Which glycoproteins bind to bridge platelets toegther?

A

GPIIb/IIIa binds fibrinogen

24
Q

Whats the lifespan of a platelet and where are they made?

A

8-12 days

Bone marrow

25
Q

What enzymes do platelets conatin?

5

A 
serotonin, 
calcium, 
ADP, 
PDGF, 
thromboxane A2
26
Q

What is the production of platelets regulated by and where does it come from?4

A

thrombopoietin from liver, kidney, smooth muscle, bone marrow

27
Q

What does an activated platelet look like?

inactivated?

A

activated is all crunched up and stringy so it can latch onto endothelium and to each other

inactivated looks like potato chips

28
Q

Describe the steps in primary hemostasis

5

A
  1. platelet adhesion
  2. shape change of platelet
  3. platelets release granules (ADP anf TXA2) in order to
  4. recruit more platelets
  5. aggregation or hemostatic plug
29
Q

What does clopidogrel inhibit?

A

ADP

30
Q

What does aspirin inhibit?

A

TXA2

31
Q

Primary hemostasis/platelet plug formation is defective when what happens?
3

A

Low platelets
Decreased vWF
Medications that inhibit platelets

32
Q

What medications inhibit the platelet plug formation?
And how do they do this?
2

A

Aspirin (inhibits prostaglandin synthesis including thromboxane A2)
Clopidrogel (inhibits the ADP pathway)

33
Q

What does VWF do?

2

A
  1. acts as a glue and binds platelets to the endothelium/collagen.
  2. It also prolongs the life of factor 8 (usually only lasts for a few seconds and with vwf it can last for a few min)
34
Q

What is secondary hemostasis?

A

coagulation

35
Q

How is the clotting pathway activated?

2

A
  1. a defect in the vessel endothelium or

2. disruption in the vessel wall.

36
Q

What is the intrinsic pathway activated by?

2

A
  1. Exposed collagen in the vessel. 2. This sets forth the catalyst to activate factor XII (Hageman factor)
37
Q

What is hagemen factor?

A

factor 7

38
Q

What are the important factors of the intrinsic pathway?

5

A

Hageman factor, factors VIII, IX, XI and calcium

39
Q

What are important factors in the extrinsic pathway?

3

A

Tissue factor III, VII and calcium

40
Q

What is tissue factor activated by?

3

A

inflammatory cytokines, cell injury and vessel injury (bleeding into the tissue)

41
Q

Common pathway starts and ends with what?

Describe how it gets from start to finish
7

A

Starts with 10 and ends with fibrin (10-prothrombin-thrombin-fibrinogen- fibrin- fibrin strands-corsslinked fibrin strands)

42
Q

How fast is clot formation completed?

A

3-6 minutes

43
Q

What is clot retraction?

A

when the platelets contract and draw the edges of the blood vessel closer together

44
Q

Why is fibrinolysis necessary and how long does it take to happen?

A
  1. necessary to remove clots as the blood vessel heals

2. Within 2 days of clot formation and continues until clot is fully dissolved

45
Q

What is the formaiton of plasmin dependant on?

3

A
  1. activation of plasminogen by tPA, XIIa and thrombin.
46
Q

What would be some things that activate plasminogen?

4

A

vasoactive drugs,
venous occlusion ,
increased body temp,
exercise

47
Q

What does plasmin do?

A

digests the fibrin in the clot and breaks it up

48
Q

What regulatory mechanisms are in place to limit clot growth?
2

A
  1. Removal of clotting factors (dilutional)
  2. Inhibition of activated clotting factors
    - antithrombinIII
    - protein C
    - protein S
49
Q

What does antothrombin III inhibit?

2

A

Inactivates thrombin and X

50
Q

What does protein C inactivate?

A

Inactivates V and VIII

51
Q

What does protein S activate?

A

Accelerates the action of Protein C

52
Q

How does heparin work?

Heparin is produced from where?3

A

binds to AT (antithrombin II) causing a conformation change activating it. This then inactivates factor 10a and thrombin

mast cells, basophils, and surface of endothelium

53
Q

Why does liver damage affect hemostasis?

A

most of the clotting factors are synthesized in the liver

54
Q

What vitamin is required for synthesis of 4 clotting factors and what are these factors?

A
  1. vitamin K

2. 2, 7, 9, 10

55
Q

What is the role of calcium in the clotting cascade?

A

Calcium helps to activate multiple clotting factors throughout the entire coagulation cascade.

Hematology (18 decks)

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