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Flashcards in Coag ppt Deck (109):
1

4 statges of hemostasis

HUGE SLIDE BUT THE BASIS AND INTRO INTO ALL THAT FOLLOWS

 

  1. VASCULAR CONSTRICTION- limits the flow of blood to the area of injury
  2. 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)
  3. 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.
  4. 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

test that knowledge

initial phase if hemostasis


vascular constriction

3

to test that knowledge

platelets become activated by what?


thrombin

4

to test that knowledge

what is responsible for stimulating platelet clumping


fibrinogen

5

to test that knowledge

activated platelets release what?

(6)


ADP

TXA2

Serotonin

Phospholipids

Lipoproteins

other proteins

6


to test that knowledge

which protein released by activated proteins, activates additional platelets

TXA2

7


to test that knowledge

what forms to entrap the plug to insure stability


Fibrin mesh (clot)

8

to test that knowledge

  1. If the plug contains only platelets it is called what?
  2. If it containd RBC ot is called what

  1. white thrombus
  2. red thrombus

9

to test that knowledge

dissolution of the clot occurs through the action of what?


plasmin

10


Whooooo made it time for an easy question to make you feel smart again!

1+1=?

2

11

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

keep this we'll expand

A image thumb
12

Physiology, pathophysiology, and pharmacology of hemostasis

what is the patho for adhesion of platelets

 

  1. Damage to endothelial surface → subendothelial collagen exposure
  2. production/release of vWF form endothelial cells
  3. vWF anchors platelets to subendothelial collagen vascular wall

vWF= Von Willebrad factor

13

you now know the adhesion of plateletes draw it!!!

  1. Damage to endothelial surface → subendothelial collagen exposure
  2. production/release of vWF from endothelial cells
  3. vWF anchors platelets to subendothelial collagen vascular wall

Hint expand your 1st pic

A image thumb
14


What is the most common inherited coagulation defect


Von Willebrands Disease

15

what is tx for Von Willebrands disease

DDAVP- it releases vWF from endothelial cells

or

Give FFP

16

Physiology, pathophysiology, and pharmacology of hemostasis

patho of the activation of plateletes

  1. prothrombin → thrombin (IIa) which activates platelets
  2. Shape changes and realease of mediators (TXA2 and ADP)
  3. TXA2 and ADP promote platelet aggregation

17

now that you know the patho for activation of platelets draw it!!!

  1. prothrombin → thrombin (IIa) which activates platelets
  2. Shape changes and realease of mediators (TXA2 and ADP)
  3.   TXA2 and ADP promote platelet aggregation

A image thumb
18

Physiology, pathophysiology, and pharmacology of hemostasis

What is the patho for aggregation of platelets

  1. TXA2 and ADP "uncover" fibrinogen receptor (GPIIb/IIIa)
  2. this allows fibrinogen (I) to bind to the receptor and further aggregate platelets

19

  1. TXA2 and ADP "uncover" fibrinogen receptor (GPIIb/IIIa)
  2. 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 image thumb
20

After platelets aggregate , __1__ is woven into plateets and cross-linked (water soluble >stable)

the cross linkage requires fibrin stabilizing factor __2__

 

  1. fibrin
  2. XIII

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21


mechanism of action aspirin and NSAID's


COX 1 inhibition: reduction in TXA2

 

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22


All procoagulants (clotting factors) are produced in the ___1___,  with the exception of what 3? and where are they produced?

 

  1. liver
  • tissue factor or thromboplastin (III)- released from traumatized cells
  • Ca++(IV)- diet
  • vWF (VIII:vWF)- vascular endothelial cells

23


whhat are the vit K dependent factors

 

  • II
  • VII
  • IX
  • X
  • protein C
  • Protein S

24


what are the roman numerics for the following clotting factors

  • fibrinogen
  • prothrombin
  • tissue factor/thromboplastin
  • Von Willibrands factor

  •     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

A image thumb
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

A image thumb
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

A image thumb
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

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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