lecture #1 Flashcards
what is primary hemostasis mediated by
platelets
platelets adhere to disrupted vessel wall via
receptor Ib
VWF
platelets adhere to one another by
IIb/IIIa
fibrinogen
two arachidonic acid vasoconstrictors
TXA2
PGs
what gets released from platelet storage granules
ADP, serotonin (platelet agonists)
VWF, factor V
heparin binding proteins factor IV
PDGF, TGF-b, TPO
platelet surface proves site for…
generation of thrombin
subsequent fibrin formation
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)
where is prothrombin conversion most efficient
presence of a phospholipid surface such as an activated platelet
alternate pathway
factor IX activated by TF-VIIa complex
factor IXa and cofactor VIII activate X (thrombin)
third coagulation pathway
factor X activates XI
XIa activates IX…leads to additional factor Xa formation
what does thrombin do
converts fibrinogen to fibrin
activates coagulation factors and cofactors
strong activator of platelet aggregation
mediates fibrinogen cleavage
what is the ultimate step in the coagulation cascade
Crosslinking of fibrin by factor XIII
what are 3 natural anticoagulation mechanisms
tissue factor pathway inhibitor
protein C
antithrombin III
what does protein C do
along with cofactor protein S, protein C degrades cofactors V and VIII
what is protein C activated by
thrombomodulin
what does antithrombin III do
forms complexes and inactivates thrombin and Xa
**strongly enhanced by heparin!
where are tPA and uPA found? what activates their release?
found in endothelial cells
released by stimuli including hypoxia, acidosis
how is fibrinolysis inhibited
activator inhibitors (PAIs)
circulating protease inhibitors (antiplasmin)
type I VWF
reduced concentration of VWF
type II VWF
dysfunctional VWF
IIa: defect in GP-Ib binding
IIb: gain of function in GP-Ib, excessive binding
type III VwF
absent VWF (homozygous)
what corrects type I and IIa VWF and how does it work
desmopressin
promotes VWF release from weibel palade bodies
what is contraindicated for IIb VWF?
desmopressin
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
pts with factor VIII levels of greater than ____% will rarely spontaneously bleed but will have problems after surgery
5%
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
5%
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
no
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
no
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
no
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)
