coagulation pathophysiology - dr austin

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77 Terms

1

what is the purpose of hemostasis?

-keep blood fluid and clot-free in healthy vessels

-form a plug in injured vessels to heal and prevent blood loss

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2

what is thrombosis?

inappropriate activation of hemostatic processes

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3

what is thrombus?

solid mass of blood components that forms locally and blocks blood flow

-stays in place

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4

what is embolus?

substance that travels through blood and causes blockage away from site of origin

-when thrombus detaches

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5

what is a thromboembolus?

thrombus breaks free

-most common

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6

what is an arterial thrombosis?

-small to medium vessels

-damaged vessels

-produce platelet-rich clot

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7

what is a venous thrombosis?

-veins and venuoles

-associated with reduced blood flow (hemostasis)

-associated with inappropriate activation of coagulation cascade

-produce fibrin-rich clot

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8

what are considered white clots?

arterial clots

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9

what are arterial clots (contain, cause, treatment)?

-contain many platelets

-caused by atherosclerosis

-treated with antiplatelets

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10

what are considered red clots?

venous clots

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11

what are venous clots (contain, cause, treatment)?

-large size

-mostly fibrin and RBC components

-blood stasis and/or medications

-treated with anticoagulants

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12

what are arterial clots treated with?

antiplatelets

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13

what are venous clots treated with?

anticoagulants

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14

what kind of clot are oral contraceptives associated with?

venous clots

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15

what do antiplatelets prevent?

occurrence or growth of clot

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16

what do anticoagulants prevent?

occurrence or growth of clot

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17

what do thrombolytics do?

bust an existing clot

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18

list the thromboembolic conditions

-DVT

-PE

-stroke

-MI

-disseminated intravascular coagulation

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19

list the bleeding conditions

-vitamin K deficiency

-thrombocytopenia

-stroke

-impaired liver function

-hemophilias

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20

what thromboembolic conditions are associated with venous clots?

-DVT

-PE

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21

what thromboembolic conditions are associated with arterial clots?

-stroke

-MI

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22

list the three predisposing factors of Virchow's Triad

-endothelial injury

-stasis

-hypercoaguable state

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23

what are the three factors of thrombosis called?

Virchow's Triad

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24

what type of thrombosis is endothelial injury usually associated with?

arterial

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25

what type of thrombosis is stasis usually associated with?

venous

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26

what type of thrombosis is hypercoaguable state associated with?

-arterial

-venous

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27

which part of Virchow's triad is inadequate disease management (HTN, HLD, DM) associated with?

endothelial injury

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28

which part of Virchow's triad is afib or atherosclerotic plaques associated with?

stasis

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29

what does stasis do?

-increases endothelial cell activation and platelet proximity

-activated coagulation factors "overstay" their welcome

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30

which part of Virchow's triad may be genetic or acquired?

hypercoaguable state

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31

what are common causes of a hypercoaguable state?

-malignancy

-oral contraceptives

-HIT

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32

what is the sequence of events of coagulation?

-vasoconstriction

-primary hemostasis

-secondary hemostasis (coagulation cascade)

-resolution

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33

which part of coagulation is a reflex mechanism?

vasoconstriction

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34

what does vasoconstriction respond to?

secreted vasoconstrictors (released by damaged cells and platelets)

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35

list the vasoconstrictors

-epinephrine

-serotonin

-endothelin

-thromboxane A2

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36

what rate does vasoconstriction occur?

-immediately

-transient (not permanent)

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37

what is primary hemostasis?

platelets activate and adhere to subendothelial matrix

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38

what is secondary hemostasis?

activation of coagulation cascade leads to formation of fibrin matrix

-recruitment of more platelets

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39

what is resolution?

formation of stable plug

-activation of antithrombotic mechanisms to restrict plug to site of injury

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40

what are the three steps of primary hemostasis?

-adhesion

-granule release and activation

-aggregation

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41

how does platelet adhesion occur?

-damage or injury to vascular endothelium

-subendothelial collagen exposed to blood

-exposed collagen binds VWF and platelets

-binding interactions with glycoproteins

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42

how does granule release and activation occur?

-adhering platelets change shape

-secrete alpha and dense storage granules (ADP)

-phospholipase activation

-increased synthesis and release of TxA2

-ADP AND TxA2 activate platelets

-activation of IP3-DAG pathways

-GPIIb-IIIa converted from resting to activated state (minions--> purple minions)

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43

how does platelet aggregation occur?

-activated GPIIb-IIIa binds to fibrinogen with high affinity

-fibrinogen binds on both sides, cross-links platelets to form a mesh, becomes primary hemostatic plug

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44

what is the purpose of secondary hemostasis?

form a stable fibrin clot at the site of injury

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45

what are the pathways in secondary hemostasis?

-intrinsic

-extrinsic

-merge into common pathway

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46

when does the coagulation cascade occur?

secondary hemostasis

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47

do the two pathways of secondary hemostasis occur at the same time as eachother?

yes

same time as primary hemostasis too

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48

what are activated in the coagulation cascade?

inactive proenzymes

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49

once activated, what do inactive proenzymes serve as?

-cofactors

-enzymes for subsequent reactions

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50

how do you recognize the active form of proenzymes?

a

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51

where are proenzymes synthesized?

liver

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52

where do the reactions that activate proenzymes occur?

phospholipid protein-protein complexes

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53

what is required for proenzymes to be activated?

-phosphatidylserine

-Ca2+

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54

what part of coagulation has amplification and positive feedback?

coagulation cascade (secondary hemostasis)

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55

explain the extrinsic pathway

-initiating factor (TF) is outside of

-tissue factor (TF) is on exposed, damaged endothelium

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56

what is the primary pathway for in vivo coagulation?

extrinsic

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57

what initiates the extrinsic pathway?

TF-calcium complex

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58

what coagulation pathway also plays a role in platelet activation?

extrinsic

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59

explain the intrinsic pathway

factors are contained within blood

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60

what is the primary pathway for in vitro coagulation?

intrinsic

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61

what are the three key functions of thrombin?

-induction of platelet recruitment/activation

-conversion of soluble fibrinogen to insoluble fibrin

-activation of proenzymes --> amplification of coagulation cascade

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62

what drives positive feedback?

thrombin

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63

when does fibrin polymerization occur?

loss of solubility

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64

what is the end result of coagulation?

erythrocytes trapped in fibrin mesh

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65

what is fibrinolysis?

dissolution of clot begins shortly after it is formed

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66

what is plasminogen converted to plasmin by?

tissue-type and urokinase-type plasminogen activators

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67

are the plasminogen activators stable?

no

rapidly inactivated

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68

what does plasmin digest?

-fibrin

-fibrinogen

-factor V

-factor VIII

-prothrombin

-factor XII

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69

what characteristic of plasmin limits its activity to the local clot?

rapidly inactivated

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70

what are the limitations of clot formation?

-pro-coagulant factors are often membrane-bound

-anti-coagulant factors are soluble and secreted

-Five important substances (Antihrombin III, Proteins C and S, t-PA, PGI2, TF pathway inhibitor)

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71

why do pro-coagulant factors limit clot formation?

-membrane-bound

-localized activity

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72

what does antithrombin III do?

inactivates thrombin and other factors

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73

what enhances antithrombin III activity?

heparin-like molecules

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74

what are proteins C and S?

-vitamin K-dependent proteins

-inactivate factors Va and VIIIa

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75

what are treatment strategies for clots?

-inhibit platelet activity

-dissolve clot (clot busters)

-anticoagulants

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76

what treatment strategy prevent clots/enhance endogenous anticlotting system?

anticoagulants

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77

what treatment strategy always has bleeding as an ADR?

anticoagulants

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