lecture #1 Flashcards by carrie mathison

what is primary hemostasis mediated by

platelets

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platelets adhere to disrupted vessel wall via

receptor Ib

VWF

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platelets adhere to one another by

IIb/IIIa

fibrinogen

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two arachidonic acid vasoconstrictors

TXA2

PGs

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what gets released from platelet storage granules

ADP, serotonin (platelet agonists)
VWF, factor V
heparin binding proteins factor IV
PDGF, TGF-b, TPO

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platelet surface proves site for…

generation of thrombin

subsequent fibrin formation

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Extrinsic system

tissue factor exposed to blood

TF + VII leads to activation of VII

FT-VIIa activates X

Xa convertes prothrombin (II) to thrombin (IIa) (you need factor V as a cofactor for this)

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where is prothrombin conversion most efficient

presence of a phospholipid surface such as an activated platelet

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alternate pathway

factor IX activated by TF-VIIa complex

factor IXa and cofactor VIII activate X (thrombin)

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third coagulation pathway

factor X activates XI

XIa activates IX…leads to additional factor Xa formation

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what does thrombin do

converts fibrinogen to fibrin

activates coagulation factors and cofactors

strong activator of platelet aggregation

mediates fibrinogen cleavage

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what is the ultimate step in the coagulation cascade

Crosslinking of fibrin by factor XIII

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what are 3 natural anticoagulation mechanisms

tissue factor pathway inhibitor

protein C

antithrombin III

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what does protein C do

along with cofactor protein S, protein C degrades cofactors V and VIII

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what is protein C activated by

thrombomodulin

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what does antithrombin III do

forms complexes and inactivates thrombin and Xa

**strongly enhanced by heparin!

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where are tPA and uPA found? what activates their release?

found in endothelial cells

released by stimuli including hypoxia, acidosis

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how is fibrinolysis inhibited

activator inhibitors (PAIs)

circulating protease inhibitors (antiplasmin)

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type I VWF

reduced concentration of VWF

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type II VWF

dysfunctional VWF

IIa: defect in GP-Ib binding

IIb: gain of function in GP-Ib, excessive binding

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type III VwF

absent VWF (homozygous)

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what corrects type I and IIa VWF and how does it work

desmopressin

promotes VWF release from weibel palade bodies

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what is contraindicated for IIb VWF?

desmopressin

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after surgery on VWF pt how long should you continue desmopressin tx or replacement of transfused factors

4-7 days

initial clotting mostly platelet dependent! coagulation disease results in late rebleeding after fibrinolysis

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pts with factor VIII levels of greater than ____% will rarely spontaneously bleed but will have problems after surgery

hemophilia A: what percentage have anti FVIII antibodies?

10-15%, this is real bad

mild to moderate hemophilia A tx

DDAVP

MOA DDAVP

releases endogenous factor VIII from liver sinusoids and endothelial cells also releases VWF resulting in transient increase in FVIII MONITOR!

severe hemophilia A tx

FVIII transfusion

hemophilia B what factor is missing

F IX

Protein C and S deficiency puts you in what state

hypercoaguable

Factor V Leiden

their factor V resists being broken down by protein C, HYPERCOAG

factor V leiden present in ____% of north american caucasians

thrombocytopenia in liver failure patients a result of..

portal hypertension, and associated splenomegaly

model for end stage liver disease score based on (3):

serum bilirubin serum creatinine INR

if your MELD score is 40+ chances of survival?

71.3% dead in three months

why do patients with renal failure bleed more

impaired platelet adhesion, aggregation, release low hematocrit

what test to order for renal failure patients

platelet function assay

tx for renal disease patients with increased bleeding

desmopressin

life span of platelets

10 days

how long do you have to wait after termination of aspiring use to restore adequate platelet function

5-7 days

most important adverse affects of aspirin

bleeding hemorrhagic gastritis/ulceration

should you discontinue aspirin for most dental procedures

plavix metabolism

15% becomes active form in liver

half live of plavix

8 hours but effects last a platelets lifetime (binds irreversibly to P2Y12ADP receptor)

is combo of clopidogrel and aspirin better than aspiring alone for cardiac patients

yes

which results in more clinical bruising/bleeding: aspirin or clopidogrel

cloppy

should you discontinue clopidogrel for dental shit

not usually

which P2Y12 blocker has a less variable response than clopidogrel

ticlopidine (not a prodrug)

ticlopidine onset vs clopidogrel

ticlopine faster but does not last as long--reversible binding

which drug increases adenosine

ticlopidine

is dipryamidole effective for preventing thromboembolic dz

not proven in literature

what are the most potent inhibitors of platelet aggregation

glycoprotein IIb/IIIa inhibitors

MOA IIb/IIIa inhibitors

competitive inhibitors for fibrinogen binding

IV or oral for IIb/IIIa inhibitors

IV (oral does not work)

full effect of coumadin therapy in how many days

2-3 days

full restoration of normal coagulation after stopping coumadin

at least 3-5 days

why does dose-effect relationship vary widely with individuals for coumadin therapy

changes in binding to albumin variable vitamin K intake variable clearance by liver must monitor closely! INR

who is at risk for coumadin induced skin necrosis

people with low levels of protein C to begin with (net pro coagulant state results)

dabigatran brand name

pradaxa

revaroxaban brand name

xarelto

apixaban brand name

eliquis

edoxaban brand name

savaysa

do factor Xa inhibitors require monitoring

no (not affected by diet , liver function etc)

onset and half life of Xa inhibitors

rapid onset (2-3 hrs) short half life (8-12 hrs)

is there a test you can use to determine effect of Xa inhibitors

should you discontinue Xa inhibitors prior to surgery

yes 1-2 days beforehand (longer in renal patients) ask prescriber first of course

dabigatran reversal agent MOA

praxbind (idarucizamab) monoclononal antibody reverses anticoagulation immediately, peak in four hours, wears off after 24 hrs used in emergency situations

what should you not give to someone with fructose intolerance

praxbind (has sorbitol in solution)

what is andexanet alfa

factor Xa decoy protein, reverses anticoagulation in less than 5 mins (apixiban, rivaroxaban)

PER977

non specific agent for anti Xa and anti-thrombin agents (heparin)

effect of heparin after IV administration is.....

immediate

heparin must be given orally or parenterally

parenterally

low molecular weight heparins vs unfractioned

more predictable bio availability and clearance much longer half life (but not as easily adjustable)

fondaparinux is what type of molecule

pentasaccharide for DVT/PE tx anti-factor Xa

when does heparin induced thrombocytopenia show up

5-7 days if patient has never had heparin can be immediate if pt has had heparin before

long term use of heparin consequence

osteopenia less with LMWH

signs that might point to defect in coagulation

abnormal bruising petechiae splenomegaly

should you run coagulation tests for ppl with negative med hx and normal physical exam

no not unless youre doing like brain surgery

is platelet function testing clinically relevent

not really

how does PT/INR test work

mixture of calcium and thromboplastin is added to citrated blood, measure how long it takes to get a clot

PT value reflects what pathway

TF-VIIa

normal PT time

12 plus or minus 2 seconds

PT is prolonged by deficiencies in

factor VII factor X factor V prothrombin fibronogen

is INR useful for NOACs

normal PTT time

25-40 seconds

what factor deficiencies will not be detected by PTT test

VII, XIII

prolonged aPTT indicates

use of heparin antiphospholipid ab (lupsus) coag factor deficiency sepsis (coag factor consumption) ab against coagulation factors

is bleeding time a good test

no, poor sensitivity and specificity poorly reproducible technique dependent

how is platelet function measured nowadays

PFA-100 test (measures platelet response to collagen/ADP/epi) start with reaction to collagen/epi. if normal cool. if abnormal, try with collagen/ADP.

if the collagen/ADP is normal after having an abnormal collagen/EPI test....

means patient is taking aspirin if both abnormal you have platelet disfunction prob

gold standard for measuring lately function

platelet agggregometry stuff about light beams and stuff tests a lot of agonists (ADP, collagen, ristocetin, AA)