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Pathology II > Hemodynamics Part I: hemostasis > Flashcards

Hemodynamics Part I: hemostasis Flashcards

1
Q

hemostasis occurs as the result of …

A

well regulated and balanced process of maintaining blood in a fluid state while allowing for controlled and focused clotting to prevent blood loss

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2
Q

3 general components that contribute to hemostasis

A

endothelium/vascular wall

platelts

coagulation cascade

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3
Q

sequence of clot formation (5)

A
  1. brief vasoconstriction
  2. endothelial damage exposes subendothelium casuing platelts to become activated and adhere.
  3. TF is released and activates the coagulation cascade forming fibrin
  4. platelet activation furthers coagulation
  5. fibrin and platelets form a clot thereby plugging the defect to prevent blood loss
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4
Q

factors which activate endothelium and shift the function to the procoagulant state include (4)

A

infectious agents
hemodynamic forces
cytokines
plasma mediators

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5
Q

antithrombotic mechanisms of the endothelium

A
  • acts as barrier to suendothelium
  • prostacyclin PGI2 and NO inhibit platelet aggregation (thrombin and several cytokines stimulate PGI2 and NO synthesis)
  • adenosine diphosphatase degrades ADP thereby inhibiting platelet aggregation
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6
Q

anticoagulant activites of endothelium

A
  • heparin-like molecules are cofactors to antithrombin
  • thrombomodlin converts thrombin to an anticoagulant
  • fibrinolytic (endothelial cells make tPA)
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7
Q

prothrombotic mechanisms of the endothelium

A
  • endothelial cells synthesize von Willebrand factor, which serves to firmly bind platelets to the subendothelium
  • endotoxin and some cytokines induce enothelial cells to make tissue factor
  • endothelial cells secrete plasminogen activator inhibitor
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8
Q

under normal conditions, endothelial cells inhibit platelet adherence and blood clotting

A

injury or activation of endothelial cells results in procoagulant state

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9
Q

from what do platelet cells derive?

A

magakaryocytes

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10
Q

platelet adhesion: vWF links the subenothellium to _________ on platelets

A

glycoprotein Ib receptors

this mediates firma dherence of platelets to vessel wall

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11
Q

_____- activates the platelets causing the release of their granules

A

adhesion

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12
Q

platelet granule contents

A

calcium
ADP
platelet factor 4
serotonin

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13
Q

function of calcium

A

critical coagulation cascade

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14
Q

function of ADP

A

mediates platelet aggregation which drives increasing platelet aggregation at the site (along with thromboxane)

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15
Q

function of platelet factor 4

A

binding of heparin by platelet factor 4 results in its inactivation

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16
Q

function of serotonin

A

induces vasoconstriction

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17
Q

fibrinogen links platelets via _____

A

GpIIb-IIIa

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18
Q

GpIIb - IIIa inhibitors are used to ——-

A

inhibit thrombosis

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19
Q

where does thrombin bind

A

platelet surface

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20
Q

platelet activation causes expression of __________ on surface of platelets

A

phospholipid complexes on suface of platelts which act as surfaces to bind coagulation factors and calcium –> promotes coagulation

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21
Q

actions of thrombin

A

thrombin converts fibrinogen to fibrin monomer but also effects local vasculature, inflammation and fibrinolysis

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22
Q

forms glue for platelet plug

A

fibrin crosslinks

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23
Q

when is tissue factor released?

A

when tissue is injured

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24
Q

where do the intrinsic and extrinsic pathways converge?

A

factors IX and X

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25
what surface is best for maximum coagulation factor activity?
phospholipid surface
26
warfarin (Coumadin)
prolongs prothrombin time PT (extrinsic)
27
heparin
prolongs partial thromboplastin time PTT (intrinsic )
28
TENET XV
intrinsic longer pathway PTT
29
fibrinogen --> fibrin
via thrombin
30
3 anticoagulants
antithrombin III protein C Plasmin
31
action of antithrombin III
directly inactivates serine proteases thrombin and Xa (also IXa, XIa and XIIa)
32
what potentiates the action of antithrombin III
heparin
33
cleaves the cofactors Va and VIIIa
protein C
34
breaks down fibrin
plasmin
35
enhances the activity of protein C
protein S
36
activates protein C
thrombomodulin
37
activated by thrombin
thrombomodulin binds to thrombin to alter its conformation
38
inhibits VIIa tissue factor complex (extrinsic arm)
tissue pathway factor inhibitor
39
where is plasmin activity optimized?
at sites of fibrin deposition
40
how is free plasmin inactivated
by circulating alpha2 antiplasmin
41
what inactivates tPA
PAI plasminogen activator inhibitor
42
how do endothelial cells modulate coagulation/anticoagulation balance?
by releasing PAI
43
what increases PAI?
thrombin and various cytokines
44
what breaks down fibrin?
plasmin (from plasminogen)
45
what 3 substance activate plasminogen?
urokinase tPA streptokinase
46
prevent clot formation and extension
anticoagulants
47
interfere with platelet activty
antiplatelet drugs
48
dissolve existing thrombi
thrombolytic agents
49
blood clot that forms abnormally within a blood vessel
thrombus
50
a dislodged blood clot which travels through the bloodstream
embolus
51
naturally occurring anticoagulant produced by basophils and mast cells to prevent formation and extension of blood clots
heparin
52
does heparin disintegrate clots that have already formed?
NO
53
how is heparin given?
intravenously or by subcutaneous injection
54
how does heparin work?
binds and activates antithrombin III (inhibits thrombin, factor IXa, factor Xa)
55
how is warfarin administered?
oral medication
56
how does warfarin decrease blood coagulation?
by interfering with vitamin K metabolism
57
what are the vitamin K dependent clotting factors>
VII IX X II
58
what clotting factors does heparin attack?
9a 10a 2
59
what clotting factors does coumadin attack?
9 7 10 2
60
dabigatran
direct thrombin inhibitor
61
rivaroxaban
direct factor Xa inhibitor
62
apixaban
direct factor Xa inhibitor
63
TFPI tissue factor pathway inhibitor
new anticoagulation drug
64
extrinsic assessment of coagulation
prothrombin time PT
65
what drug increased the prothrombin time
warfarin (coumadin)
66
which factors require vitamin K for synthesis
factors II, VII, IX, X, protein C and protein S
67
describe the international normalized ratio INR
compares patient PT to the normal PT which compensates for differences in tissue factor
68
intrinsic assessment of coagulation
partial thromboplastin time PTT
69
what prolongs the PTT
heparin hemophilia antiphospholipid antibody
70
what are the only factors not included in PTT
factors VII and XIII
71
how would you distinguish between an inhibitor and factor deficiency
mixing pt sample with normal plasma: if inhibitor: no clotting if deficiency: clotting
72
low dose heparin PT and PTT
PT normal | PTT prolonged
73
high dose heparin PT and PTT
PT prolonged | PTT prolonged
74
low dose warfarin PT adn PTT
PT prolonged | PTT normal
75
high dose warfarin PT and PTT
PT prolonged | PTT prolonged
76
what is warfarin necrosis?
thighs, breasts, and buttocks multiple or single lesion, with localized pain and erythema that develops into a painful necrotic eschar low levels of protein C --> transient hypercoagulable state causing local thrombosis of dermal vessels
77
describe heparin induced thrombocytopenia
platelet factor 4 is released by plateltes and bidns heparin thus blocking its action and pormoting coagulation antibodies to heparin bind heparin/platelet factor 4 complex ----> endothelila injury and platelet activation (prothombotic state)
78
bernard-soulier diesease
platelet abnormality defect of platelet adhesion autosomal recessive lacking glycoprotein Ib
79
glanzmann's thrombasthenia
platelet abnormality: defect of platelet aggregation autosomal recessive lacking glycoprotein IIb/IIIA
80
TTP thrombotic thrombocytopenic Purpura
platelet abnormality: antibodies direct against the von Willebrand factor cleaving protease, ADAMTS-13
81
Idiopathic thrombocytopenic purpura ITP
platelet abnormality antibodies directly agianst platelets
82
aplastic anemia/ pancytopenia
platelet abnormality all the cell lines are gone- marrow destroyed
83
von Willerbrand's disease
coagulopathy deficiency of von Willebrand's antigen easily bruised, nosebleed, etc. most common bleeding disorder
84
factor VIII deficiency
hemophilia A x-linked recessive most common hemophilia
85
factor IX deficiency
hemophilia B x-linked recessive coagulopathy
86
factor XI deficiency
hemophila C mildest hemophilia associated with the EJws
87
factor XII deficiency
not clinically important neither is the presence of lupus anticoagulant
88
purpura petechia and ecchymoses are most likely
platelet deficiency
89
trouble stopping blleding most likely
coagulation factor deficiency
90
DIC
NOT a specific diagnosis widespread activation of the caogulation system (thrombin) that from tiny thrombi throughout body leading to thrombocytopenia and consumptive coagulopathy (organ failure and bleeding)
91
peripheral blood smear of DIC
observe sheared RBC
92
what do D-DIMER assays measure
plasmin-cleaved insoluble cross-linked fibrin (indirect measure of thrombin which is required for fibrin formation) used in diagnosis of DIC

Pathology II (14 decks)

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