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M2 Hematology > 7. Hemostasis/Coagulation > Flashcards

7. Hemostasis/Coagulation Flashcards

1
Q

components needed for hemostasis?

A
  • vessel wall/vascular endothelium
  • platelets
  • plasma coag proteins
  • physiologic protease inhibitor
  • endogenous anticoagulants
  • fibrinolytic system
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2
Q

primary hemostasis forms what

A

platelet plug

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3
Q

secondary hemostasis forms what

A

fibrin. coagulation step

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4
Q

overall steps of hemostasis?

A

primary hemostasis, secondary hemostasis, termination of coag reactions, fibrinolysis

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5
Q

what happens when the endothelium is disturbed (by injury, inflammation)?

A

shifts it from an anticoagulant to a procoagulant phenotype.

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6
Q

when not injured, vascular endothelium is procoag or anticoag?

A

anticoag.

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7
Q

besides shifting the endotheluim from anticoag to procoag, what does injury do?

A

exposes subendothelium, which is PROcoag.

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8
Q

what effect does collagen have on coagulation?

A

stimulus for platelet adhesion, activation

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9
Q

what is the very first step of primary hemostasis?

A

vasoconstriction, reduces blood flow to injured area. then formation of platelet plug.

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10
Q

what are the main things required for a platelet plug?

A

von willebrand factor
platelets
fibrinogen

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11
Q

where is vWF synthsized?

A

endothelial cells and megakaryocytes (bone marrow)

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12
Q

where is vWF stored?

A

in endothelial cells: in Weibel Palade bodies

in platelets, in alpha granules

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13
Q

what does ADAMTS-13 do?

A

cleaves vWF into smaller multimers in plasma

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14
Q

3 jobs for vWF?

A

attaches platelets to subendothelium with vascular injury
carries F VIII in blood, prolongs circulating half-life
localizes F VIII at site of injury

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15
Q

where do platelets come from?

A

megakaryocyte (bone marrow). buds from mature megakaryocytes become platelets in circulation

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16
Q

platelets: lifespan in blood?

A

7-10 days

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17
Q

platelet function in blood vessel injury?

A

adhesion
activation/degranulation
aggregation
support coagulation (fibrin)

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18
Q

fibrinogen: synthesized wehre?

A

liver

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19
Q

fibrinogen: role in primary hemostasis?

A

forms bridges between platelets during formation of platelet plug

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20
Q

fibrinogen: role in secondary hemostasis?

A

polymerizes into insoluble mesh around platelets

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21
Q

what receptor connects vWF to platelets?

A

Gp1b

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22
Q

name the elements of a platelet plug from the most internal to the most external

A 
collagen
vWF
Gp1b receptor
platelet
Fibrinogen (GpIIa/IIIb receptors)
PS/PE
coag factors
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23
Q

vWF binds what to what in a platelet plug? using what receptor?

A

collagen to platelet. receptor Gp1b

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24
Q

what prompts the activation/degran of platelets?

A

collagen, soluble agonists (such as epinephrine)

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25
what happens once platelets are activated?
-develop pseudopods and degranulate
26
what 2 types of granules are involved in platelet degranulation?
alpha granules | dense granules
27
what's in alpha granules?
``` adhesive proteins (fibronectin, vWF) coag proteins (fibrinogen, FV) growth factors ```
28
how does Thromboxane A2 enter the picture? where does it come from?
secreted by activated platelets
29
what does Thromboxane 2 do?
vasoconstriction, platelet aggregation & activation
30
when platelets aggregate, what holds them together? what receptor?
fibrinogen tethers them together, using receptor GpIIb/IIIa
31
what agonists stimulate platelets to aggregate?
ADP, epinephrine, collagen, thrombin, serotonin, Thromboxane A2
32
how do platelets support coagulation?
exposure of phosphatidyl serine (PS) and PE on platelet surface allows coag factors to bind to surface.
33
what is the exposure of PS/PE on platelet surface called?
platelet factor 3 (PF3) activity.
34
defect in PF3 is known as what?
Scott syndrome
35
secondary hemostasis is dependent on what ion?
calcium!!
36
what does fibrin look like?
spaghetti
37
what is the ultimate goal of the coagulation cascade?
conversion of fibrinogen to fibrin
38
where are most coag factors synthesized?
liver
39
where is FVIII syntheisized?
both liver and vasc endothelium
40
where is vWF synth?
megakaryocytes (bone marrow) and vasc endothelial cells
41
which coag factors are dependent on Vit K?
2, 7, 9, 10
42
what anticoag factors are dep on Vit K?
Protein S, C, Z
43
what happens to monocytes in response to vasc injury?
stimulated to produce TF on cell surface
44
what does TF do?
initiates the coag cascade with F VIIa
45
draw the coag cascade...
on paper!
46
two ways in which TF/VIIa initiates coag?
direct: X to Xa indirect: IX to IXa, then X to Xa in presence of VIIIa and Ca2+
47
Extrinsic pw: starts with what?
X to Xa
48
intrinsic pw: starts with what?
IX to IXa
49
intrinsic pw v extrinsic pw: which is more efficient?
INTRINSIC. by 100,000x
50
overall, why do people with hemophilia bleed?
deficient in VIII or IX, can't run intrinsic pw.
51
what is it about the intrinsic pw that makes it more efficient?
uses VIIIa and Ca2+ as cofactors.
52
where does F V come from, what does it do?
released from platelets. cofactor (with Ca2+) for prothrombin to thrombin.
53
what's the prothrombinase complex? what does it do?
Xa, Va, Ca2+ | bindns to platelet surface, activates prothrombin --> thrombin
54
where is secondary hemostasis occuring?
on surface of platelets
55
what catalyzes fibrinogen to fibrin?
thrombin
56
where does fibrinogen come from?
platelets
57
what's the Thrombin Burst?
thrombin activates FXI -> XIa; very efficient way to run the intrinsic pathway
58
what does thrombin activate?
platelets, V, VIII, IX, XIII
59
what factor stabilizes fibrin?
XIII (thirteen)
60
can thrombin protect clot from fibrinolysis?
yes!
61
can thrombin inhibit coag when needed?
yes!
62
how does thrombin work to form/stabilize fibrin?
Converts fibrinogen to a monomer (fibrin) by cleaving off peptides A and B. Monomer then self-associates/polymerizes into spaghetti formation.
63
4 ways that coagulation is controlled?
- hemodilution - hepatic clearance - endogenous anticoagulants - fibrinolysis
64
what is hemodilution?
activated coag factors are diluted by systemic circulation
65
hepatic clearance in regards to control of coagulation?
activated coag factors are cleared by the liver
66
what are 4 endogenous anticoagulants?
activated protein C/protein S antithrombin tissue factor pathway inhibitor (TFPI) protein Z
67
what does protein Z do?
inactivates factor Xa
68
if there is much less circulation than usual, how can that effect control of coagulation?
may form a big clot due to absence of hemodilution.
69
what are the MAJOR control points of coagulation?
Xa and thrombin: both controlled by anti-thrombin.
70
what does anti-thrombin do (AT)?
inhibits Xa and thrombin.
71
what does TFPI do?
tissue factor pathway inhibitor: inhibits VIIa and Xa
72
what does APC/S do?
inhibits V and VIII
73
where is antithrombin produced?
liver, endothelial cells
74
what drug increases the activity of antithrombin?
heparin
75
how does thrombin inhibit coagulation?
binds thrombomodulin on endothelial cells. now thrombomodulin can activate Protein C. APC and its cofactor (S) can INACTIVATE factors Va and VIIIa.
76
what does APC/S do?
inactivates factors Va and VIIIa, thus slowing coagulation
77
where is TFPI produced?
endothelial cells
78
what does TFPI do?
binds/inactivates Xa. then the TFPI/Xa complex inactivates the TF/VIIa complex.
79
overall process of fibrinolysis?
plasminogen converted to plasmin by TPA/UPA. Plasmin is the scissors that cleaves fibrin to degradation products
80
what can cause deficiency in things that STOP the fibrinolytic agents? what is the state that this causes?
result in bleeding disorders. deficiency in PAI-1 (stops TPA), alpha-2-antiplasmin (stops Plasmin).
81
plasma: definition
fluid fraction of unclotted whole blood. contains coag factors.
82
serum: def
fluid remaining after blood has been allowed to clot. does NOT contain coag factors
83
coag studies performed with plasma or serum?
PLASMA
84
what does a blue top tube contain? how does that help? how are the labs performed?
contains citrate, which binds calcium and makes it unavailable for coag reactions. in lab, Ca is added back to make coag reactions go
85
electrolytes tested in plasma or serum?
plasma, with heparin
86
antibodies, other proteins assayed in plasma or serum?
serum.
87
cells assayed in what form of blood? how does EDTA help?
whole blood. EDTA preserves morphology of cells
88
what is thrombocytopenia?
decr platelet count
89
what is associated with thrombocytopenia?
spontaneous bleeding, if count is lower than 10k/uL

M2 Hematology (15 decks)

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