Coag ppt Flashcards
1
Q
4 statges of hemostasis
HUGE SLIDE BUT THE BASIS AND INTRO INTO ALL THAT FOLLOWS
A
- VASCULAR CONSTRICTION- limits the flow of blood to the area of injury
- PLATELETS become ACTIVATED by thrombin and aggregate at the site if injury (temp loose PLATELET PLUG). Fibrinogen is responsible for stimulating platelet clumping (platelets bind to collagen that becomes exposed following rupture of the endothelial lining of vessles)
- Activated platelets release ADENOSINE-5’-DIPHOSPHATE (ADP) and TXA2 (which activates additional platelets), SEROTONIN, PHOSPHOLIPIDS, LIPOPROTEINS, and other proteins important for the coagulation cascade. Activated platelets change their shape to accomodate the formation of the plug.
- to insure stability of the initial loose platelet plug, a FIBRIN MESH (CLOT), forms and entraps the plug. if the plug contains only platelets it is termed WHITE THROMBUS, if red blood cells are present it is called RED THROMBUS.
The clot must be dissolved in order for normal blood flow to resume following tissue repair. the dissolution of the clot occures through the action of PLASMIN
2
Q
test that knowledge
initial phase if hemostasis
A
vascular constriction
3
Q
to test that knowledge
platelets become activated by what?
A
thrombin
4
Q
to test that knowledge
what is responsible for stimulating platelet clumping
A
fibrinogen
5
Q
to test that knowledge
activated platelets release what?
(6)
A
ADP
TXA2
Serotonin
Phospholipids
Lipoproteins
other proteins
6
Q
to test that knowledge
which protein released by activated proteins, activates additional platelets
A
TXA2
7
Q
to test that knowledge
what forms to entrap the plug to insure stability
A
Fibrin mesh (clot)
8
Q
to test that knowledge
- If the plug contains only platelets it is called what?
- If it containd RBC ot is called what
A
- white thrombus
- red thrombus
9
Q
to test that knowledge
dissolution of the clot occurs through the action of what?
A
plasmin
10
Q
Whooooo made it time for an easy question to make you feel smart again!
1+1=?
A
2
11
Q
picture time
now that you feel better. draw me a pic representation of what you want your edothelial layer to look like with a break and blood in the middle
A
keep this we’ll expand
12
Q
Physiology, pathophysiology, and pharmacology of hemostasis
what is the patho for adhesion of platelets
A
- Damage to endothelial surface → subendothelial collagen exposure
- production/release of vWF form endothelial cells
- vWF anchors platelets to subendothelial collagen vascular wall
vWF= Von Willebrad factor
13
Q
you now know the adhesion of plateletes draw it!!!
- Damage to endothelial surface → subendothelial collagen exposure
- production/release of vWF from endothelial cells
- vWF anchors platelets to subendothelial collagen vascular wall
Hint expand your 1st pic
A
14
Q
What is the most common inherited coagulation defect
A
Von Willebrands Disease
15
Q
what is tx for Von Willebrands disease
A
DDAVP- it releases vWF from endothelial cells
or
Give FFP
16
Q
Physiology, pathophysiology, and pharmacology of hemostasis
patho of the activation of plateletes
A
- prothrombin → thrombin (IIa) which activates platelets
- Shape changes and realease of mediators (TXA2 and ADP)
- TXA2 and ADP promote platelet aggregation
17
Q
now that you know the patho for activation of platelets draw it!!!
- prothrombin → thrombin (IIa) which activates platelets
- Shape changes and realease of mediators (TXA2 and ADP)
- TXA2 and ADP promote platelet aggregation
A
18
Q
Physiology, pathophysiology, and pharmacology of hemostasis
What is the patho for aggregation of platelets
A
- TXA2 and ADP “uncover” fibrinogen receptor (GPIIb/IIIa)
- this allows fibrinogen (I) to bind to the receptor and further aggregate platelets
19
Q
- TXA2 and ADP “uncover” fibrinogen receptor (GPIIb/IIIa)
- this allows fibrinogen (I) to bind to the receptor and further aggregate platelets
yep your going to draw it!!! try putting all of the drawings together
A
20
Q
After platelets aggregate , __1__ is woven into plateets and cross-linked (water soluble >stable)
the cross linkage requires fibrin stabilizing factor __2__
A
- fibrin
- XIII
21
Q
mechanism of action aspirin and NSAID’s
A
COX 1 inhibition: reduction in TXA2
22
Q
All procoagulants (clotting factors) are produced in the ___1___, with the exception of what 3? and where are they produced?
A
- liver
- tissue factor or thromboplastin (III)- released from traumatized cells
- Ca++(IV)- diet
- vWF (VIII:vWF)- vascular endothelial cells
23
Q
whhat are the vit K dependent factors
A
- II
- VII
- IX
- X
- protein C
- Protein S
24
Q
what are the roman numerics for the following clotting factors
- fibrinogen
- prothrombin
- tissue factor/thromboplastin
- Von Willibrands factor
A
- fibrinogen- I
- prothrombin- II
- tissue factor/thromboplastin III
- Von Willibrands factor VIII:vWF
25
tissue factor/thromboplastin (III) comes from where?
Vascular wall and extravascular cell memerane; released from traumatized cells
26
clotting cascade TISSUE FACTOR PATHWAY (Extrinsic)
(Factor III)
* Damage occurs from outside of blood vessel → triggers release of _tissue factor_
* Tissue factor comes in contact with factor _VII_
* Complexed with Ca++ on platelet → activates factor _X_
27
clotting cascade TISSUE FACTOR PATHWAY (Extrinsic)
* Damage occurs from outside of blood vessel → triggers release of tissue factor
* Tissue factor comes in contact with factor VII
* Complexed with Ca++ on platelet → activates factor X
put this whole cascasde into a picture
28
what is the primary physiologic initiator of coagulation
(in the extrinsic pathway)
tissue factor
29
the tissua factor pathway (extrinsic pathway) is measured by what?
PT test
30
how to remember the Extrensiv pathway
you can buy the extrinsic pathway for $0.37 (III, VII)
31
Clotting cascade Contact activation pathway (Intrinsic)
* Initiated when there is trauma to the vessel itself or exposure of blood to collagen
* Activation of XII→ XI→IX when complexed with platelet surface with factor VIII:C and Ca++ → factor X
32
Clotting cascade Contact activation pathway (Intrinsic)
* Initiated when there is trauma to the vessel itself or exposure of blood to collagen
* Activation of XII→ XI→IX when complexed with platelet surface with factor VIII:C and Ca++ → factor X
make it into a diagram
33
the contact activation pathway (Intrinsic) is measured by what?
PTT
34
how to remember the intrinsic pathway
you can buy the intrinsic pathway for $12 (XII) or $11.98 (XI, IX, VIII)
35
clotting cascade Final common pathway
* Activatio startes with X -\> V -\> II -\> I -\> XIII
* Thrombin converts finbrinogen (I) to fibrin and in the pressence of XIII, fibrin cross-linking occurs
* the new clot is formed now
36
clotting cascade Final common pathway
* Activatio startes with X -\> V -\> II -\> I -\> XIII
* Thrombin converts finbrinogen (I) to fibrin and in the pressence of XIII, fibrin cross-linking occurs
* the new clot is formed now
now since we know everything put it all together in one big ass diagram that encompasses the final common pathway
37
how to remember the clotting cascade common pathway?
the common pathway can be purchased at 5 (V) or 10 (X) for 1 (I) or 2 (II) dollars on the 13th (XIII) of each month
38
Hemostasis: in short
5 steps down and dirty
1. vasoconstriction
2. formation on platelet plug
3. activation of coagulation cascade
4. Formation of blood clot
5. Clot retraction and dissolution (fibrinolysis)
39
What is antithrombin III
produced in the liver and neutralizes the final common pathway _IIa & Xa_ and intrinsic factors _IX, XIa, & XIIa_
40
antithrombin III
1. strongly inhibits what factors
and
2. partially inhibits what factors
1. final common pathway IIa and Xa
2. intrinsic IXa, XIa & XIIa
41
antithrombin III os a required cofactor for what?
Heparin
42
Heparin binds to antithrombin III and enhances AT III by ______ x's
1000
43
which anticoagulant drug is an inhibitor of clotting factor synthesis include what drug
Coumadin
44
Which anticoagulant drugs are known as a thrombin inhibitor
Heparin
Lepirudin (refludan)
45
what are 3 ANTIcoagulant drugs
1. coumadin
2. Heparin
3. Lepirudin (Refludan)
46
name 8 anti-platelet drugs
1. aspirin
2. NSAIDs
3. Ticlid
4. Plavix
5. Persantine
6. Integrilin
7. reopro
8. aggrastat
47
anti-platelet drugs
how does ASA work
inhibits cyclooxygenase: duration of action is life of platelet (due to covelent bond)
48
anti-platelet drugs
how do NSAIDs work
same as ASA but depression of TXA2 is shorter 24-48 hours
49
anti-platelet drugs
how do the drugs
ticlid
plavix
and
Persantine work
inhibit ADP
50
anti-platelet drugs
how do the drugs
Integrilin
reopro
aggrastat work
Antifibrinogen receptor (GPIIb/IIIa)
51
what are 2 thrombolytics currently in use
1. tPa
2. streptokinase
52
what is an antifibrinolytic drug not in use due to fear of law suits
Aprotinin
53
what is an antifibrinolytic drug currently in use for CPB and acute hemmorrhage
amicar
54
Anticoagulants
MOA: heparin
* binds/activates ANTITHROMBIN III
* which inhibits SERINE PROTEASES of the coag cascade
55
Anticoagulants
Heparins response to injury
* heparin is abundant in granules of the mast cells taht line the vasculature
* in response to injury, heparin is released and inhibits coagulation
* * * side note heparin is also present in basophils and liver
56
Anticoagulants
MOA: Coumadin
* inhibits the VITAMIN K dependent y-carboxylation reactions necessary to thr function of thrombin, and factors II, VII, IX and X as well as protein C
57
antiplatelet drugs
MOA: ASA
* inhibits the activity of cyclooxygenase, ASA reduces the production of TXA2
* ASA also reduces endothelial cell production of PGI2 (an inhibitor of platelet aggregation and a vasodilator)
* since endothelial cells regenerate active COX faster than platelets teh net effect of ASA is more in favor of endothelial cell-mediated inhibition of coagulation cascade
58
antiplatelet drugs
MOA: Gylcoprotein IIb/IIIa inhibitors
(Repro, Integrilin, Aggrastat)
* inhibits the integrin gylcoprotein IIb/IIIa receptor in the membrane of platelets, inhibits platelet aggregation
* * * side note--used inACS in ACLS protocol
59
is a thrombolytic agent an anticoagulant?
***_fuck no_*** like is like saying you have a god damn dissecting aneurysm just not fucking possible
60
Thrombolytic agents
MOA: tPa
* Highly selective for degradation of fibrin in clots, it is extremly useful in restoring the patency of coronary arteries following thrombosis, in particular during short periods following MI
61
Thrombolytic agents
MOA: Streptokinase
* an enzyme from the streptococci bacterium
* less selective than tPA, being able to activate circulating plasminogen as well as plasminogen to a fibrin clot
62
what do all anticoagulants do? very basic
delay or prevent clotting
63
do anticoagulants work on clots already formed?
NOOOOOOOOOOOOOOOOOOOO!!!!!! they have no effect on clots that have already formed
64
what are 3 ex of anticoagulants that we frequently use?
1. Heparin
2. Enoxaparin (lovenox)
3. COUMADIN
65
Heparin can be fractionated into 2 parts using affinity chromatography with immobolized antithrombin what are the 2 and what do they do?
* the high-affinity fraction is responsible for nearly all of the anticoagulant activity
* the other fraction, low-affinity heparin, has virtually no anticoagulant activity
66
low molecular weight heparin (LMWH) is prepared by what process
fractionation
67
heparin in prepared form what?
bovine lung and bovine/ porcine intestine
68
what is the duration of use of heparin?
unlimited
69
what is the only contraindication of heparin?
HIT
70
pts with what d/o are receiving heparin and develop antibodies to antigens on platelets. and leads to thrombocytopenia
HIT
71
down and dirty patho of hit (3 steps)
heparin antibodies -\> platelet aggregation -\> thrombocytopenia
72
going off the last definition!! HIT is also called what?
HIPA
heparin induced platelet activation
73
tx for HIT
D/C heparin
74
steps to diagnose HIT?
Platelet count drops during or after heparin therapy
plt \< 50% baseline or \<100,000
no other cause of thrombocytopenia indentified
Clinical diagnosis of HIT
D/C all heparin
Assess risk of thrombosis
If indicated, initiate alternatinve therapy (anticoag)
75
of a pt has HIT what is wrong with each of teh folloing alternative therapies
1. LMWH
2. Danaparoid (a heparinoid)
3. Warfarin
1. contraindicated -nearly 100% corss-ractivity to heparin- antibodies
2. Has a rate of 10-15% cross-reactivity and is contraindicated
3. takes several days for its onset of activity, and therefore althernatives must be used in conjunction
76
heparin dosing prior to vascular occlusion
3000-7500 units IV
77
protamine reversal dose
25, 50, 100 mg
1-1.3 mg/100U heparin
78
protamine sulfat can be found where?
salmon sperm
79
1 mg protamine neutralizes \_\_\_mg heparin
1 mg
80
how fast do you want to administer heparin
5-10 min IV
81
how does protamine neutralize heparin
***_electrostatically_*** binds heparin
protamine (+) + Heparin (-) = HP (~)
82
what will occur if protamine is given in absence of heparin
anticoagulation
83
SE of protamine
* antihemostatic
* Hypotension (histamine release)
* Pulm HTN or bronchoconstriction
* Hypersensitivity
* Fish allergy (not shell)
84
how do you give protamine oif pt is at risk w/ hypersensitivity
* 1 mg/50ml test dose over 10 min
* steroid and antihistamine pretreatment
* give slower
85
lovenox (LMWH) is derived from what?and how?
heparin by chemical depolymerization to yeild 1/3 the size of heparin (WM" 4K to 5K daltons)
86
advantages of lovenox (LMWH) over heparin
* binds less avidly to proteins
* More predictable anticoagulant response
* better DVT protection
* Longer elimination half-time
87
coumadin blocks conversion of _____ \_\_\_\_ _____ to _____ \_\_\_\_\_
vitamin K epoxide
Vitamin KH2
88
what is coumadin used for
prosthetic heart valves
afib
cva prevention
recurrent MI
89
what is the target INR while on coumadin?
2.0-3.0
90
when do you want to d/c coumadin prior to sx and why that time frame
* d/c 1-3 days b4
* elimination 1/2 time 24-36 hours
91
if your pt is takinf coumadin and is having emergency sx what 3 things can you give to help reverse it?
* Vit K
* Fresh whole blood
* FFP
92
platelets tell me what you know
normal levels
needs further workup
increased risk of bleeding
spont bleeding
* 200,000 - 400,000 (+/- 50,000)
* \<100,000
* \<50,000
* \<20,000
93
PT detectsdefects in what what pathway?
extrinsic pathway
94
what coag test is indispensable for monitoring patients on oral anticoags
PT
95
normal PT
10-12 sec
96
PTT or aPTT
detects deficiency in clotting factors of what pathway
intrinsic
97
what coag test is most commonly used for monitoring heparin therapy
PTT, aPTT
98
levels of PTT, aPTT
normal 24-30
abnormal \>35
99
what are chelating agents
agents which bind Ca++ therby preventing activation of the coagulation cascade
* _By many stages of teh total cascade require the availability of Ca++_
100
what is a comercial prothrombin time reagent
INR
101
activated clotting time (ACT)
it is similar to what other test?
Normal Values?
PTT
90-120
102
thrombin time
measures what?
screening tool for assessing what?
Normal levels
prolonged if what is occuring?
* conversion of fibrinogen to fibrin
* end stage of coag cascade
* 10-12
* low fibrinogen, elevated fibron degradation products, heparin tx
103
Fibrinogen
Normal levels?
less than what is asscoiated with bleeding
low levels found in what d/o?
increased levels found when?
* 200-400
* \<100 mg/ml
* DIC
* following sx or trauma
104
what is a more precise measurment for detection of fibrinolysis
fibrin degradation products (FDPs) or fibrin split products
105
FDPs or FSPs are produced when fibrin is split by what?
plasmin
106
Normal level of FDPs or FSPs
\<5ug/ml
107
the presence of FSPs or FDPs means that they have what effect
that they have an anticoagulant effect and actually inhibit clotting circulation
108
causes of DIC
trauma
snake bite
amniotic fluid
imcompatable blood
burns
neoplasms
109
what is the diffuse consumptive coagulopathy that leads to formation of small clots in teh blood vessel, that eventually consumes clotting factors/ platelets
dissrupion of normal coagulation and increases in bleeding
DIC
