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92 Cards in this Set

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what are the main steps of the clotting process?
1. platelet plug
2. propagation by the coag cascade
3. termination
4. fibrinolysis
What substances generated outside the platelet regulate its function by interacting with platelet membrane receptors?
collagen
thrombin
(med: GP IIb/IIIa blockers)
What substances are generated inside the platelets that regulate its function by interacting with platelet membrane receptors?
ADP
Prostaglandins
Seratonin
(med: clopidogrel)
What substances are generated within the platelet and regulate its function by acting WITHIN the platelet?
thromboxane A2

(med: ASA blocks)
What affect does thromboxane A2 have on vasculature?
vasoconstriction (and promotes further platelet aggregation)
What do ADP and seratonin do when released from the platelet following endothelial damage?
recruit additional platelets
What are two adhesive substances that are secreted from inside the platelet following endothelial damage that reinforce/stabilize platelet aggregates?
fibromectin
thrombospondin
All procoagulants except ________ are produced in the __________.
vWF; liver
What are the vitamin K dependent procoagulants?
VII, IX, X, and prothrombin
What two forms is vitamin K foundn in?
K1 (phytonadione) - a fat-soluble substance found mostly in leafy greens

K2 (menaquinone) - produced by bacteria in the GI tract
What are the vitamin K dependent anticoagulants?
Protein C
Protein S
How does vitamin K affect procoagulants?
it participates in their postribosomal modification
Which form of vitamin K must warfarin pts be warned about?
K1 - phytonadione
What activates the extrinsic clotting pathway?
tissue factor
what is the "primary physiologic initiator of clotting"?
generation or exposure of tissue factor at the wound site
What does factor X do?
converts prothrombin --> thrombin
What does thrombin do?
converts fibrinogen --> fibrin
What is the difference between fibrinogen and fibrin?
fibrinogen is a soluble plasma protein but fibrin is insoluble
What two substances are involved in termination of clotting?
antithrombin
TF pathway inhibitor
thrombin activates _______ and no longer promotes platelet aggregation of cleavage of fibrinogen.
Protein C
What inactivates factors Va and VIIIa?
Activated protein C (APC) with protein S on phospholipid surfaces
What inactivates factors IXa, Xa, XIa, XIIa?
Antithrombin (by forming irreversible complexes)
What anticoagulant is used in sepsis pts?
APC (b/c pt clots and uses it up)
what is the major activator of plasminogen in the extravascular compartment? intravascular?
extra - urokinase
intravascular - tPA
What does a d-dimer measure?
fibrin degredation products (resulting from plasmin cleaving fibrin, breaking up clot)
What does turning off COX-1 do?
can't get sticky platelets and vasoconstriction (decreased thromboxane A2)

also decreased PGs and prostacyclin
what are two ways anti-platelet drugs can lead to renal failure?
by blocking vasodilating PGs

by AIN
What 3 drugs cause AIN?
anti-platelets
nafcillin
quinolones
Where are antiplatelet drugs metabolized?
liver
Does clopidogrel have a reversible or irreversible effect on platelets?
irreversible
how does clopidogrel work?
decreases platelet aggregation by blocking ADP receptors which prevents binding at that site.
Which antiplatelet drug can cause a flu like illness?
clopidogrel
Name the glycoprotein IIb/IIIa receptor antagonists
abciximab
eptifibatide
tirofiban
What are the clinical use(s) of GPIIb/IIIa antagonists?
PCI with stent
ACS
How does warfarin work?
inhibits vitamin K dependent carboxylation of coag factors (II, VII, IX, and X) that are procoagulants

it also inhibits vitamin k dependent carboxylation of protein C and S
what occurs is warfarin is taken during the first trimester? second? third?
1st- hypoplastic nasal bridges
2nd - CNS anomalies
3rd - bleeding issues
Which pathway is initially altered by warfarin with therapy initiation?
extrinsic pathway (depresses factor VII)
Why must warfarin be overlapped with LMWH or heparain for 5-7days?
because warfarin also brings down protein C --> leaving a procoagulation state
Which drugs may make a patient need higher doses of warfarin?
rifampin
carbamazepine
St john's wort
(2C9 inducers)
What factors may make a patient need LOWER doses of warfarin?
hepatic impairment
poor nutrition
CHF
elderly
2C9 inhibitors like cimetidine, amiodarone, and fluconazole
What coag factors are assessed by the INR?
TF
VII
II (Prothrombin)
V
X
fibrinogen

(extrinsic path and common path)
How often should the INR be checked if pt on warfarin?
q3-4 wks once stable (or more if concominant meds that interfere)
How do you reverse hemorrhage from warfarin?
FFP
Why should IV vitamin K be given slowly?
can cause dyspnea, CP, and death
What ABX could alter warfarin metabolism?
erythromycin
quinolones
What drugs decrease absorption of warfarin?
antacids
bile acid sequestrants
What is purple-toe syndrome?
cholesterol emboli --> chokes off small vessels (often goes to the toes but other organs/areas possible)

usually won't amputate
What drug is associated with "purple-toe syndrome"?
warfarin
Explain skin necrosis/gangrene associated with warfarin.
paradoxical thrombosis that occurs in the first few days of administration (probably mediated by rapid reduction in protein C)

probably more common if protein C deficiency

usually affects breast, penis, or extremities
WHat drug is made from porcine intestinal mucosa and bovine lung?
heparin
How does heparin work?
complexes with antithrombin --> turns it into a rapid inactivator of thrombin (IIa) and Xa (also XIIa, XIa, and IXa)
Which factor does antithrombin affect the most?
II
What factors are assessed by the aPTT?
XII, VIII, IX, XI
II, V, X

(intrinsic and common)
Is the aPTT standardized like the INR?
no
What is the half-life of heparin?
30-60min
For reversal of heparin what is the maximum dose/speed at which protamine can be given?
No more than 20mg/min
AND
no more than 50mg in 10min
Who is at increased risk of anaphylaxis from protamine?
pts who have received it previously

diabetics on NPH
What should be given to pt that is hemorrhaging on heparin?
FFP
What is the initial dose of FFP?
15mL/kg
What needs to be monitored when pt is on heparin?
aPTT
heparin level (possible)
Platelet counts
WHat are the risk factors for hemorrhaging on heparin?
IE
congenital bleeding disorder
active ulcerative GI disease
Severe HTN
post brain/eye/spinal surg
use of other anti-coagulants
advanced liver disease
WHat anti-coagulant may lead to alopecia?
heparin
What anti-coagulant may lead to osteoporosis if given for >6mo?
heparin (but not much with LMWH)
Why does heparin lead to osteoporosis?
increases osteoclast number and activity
What is the difference between HIT Type I and HIT type II?
HIT I - transient decrease in platelets that has no clinical significance

HITII - more serious
What is HIT Type II?
Heparin binds to platelet factor 4 complex on platelet and IgG responds by tagging it --> removed from system

Some of these patients will clot at the same time (looks like DIC)
Which patients is HIT Type II more likely?
Those on SQ/IV heparin
Name 3 LMWHs.
enoxaparin
dalteparin
tizaparin
How do LMWHs work?
inactivate factor Xa
Unlike unfractionate heparin, LMWH does not prolong which test?
aPTT
No labs must be monitored with LMWH except in which population? What needs to be monitored?
pg women; monitor anti-Xa levels 4 hours after SQ injection

(want it 0.5-1.2 U/mL)
LMWH dose needs to be adjusted for what?
creat clearance
What is the difference between reversal of heparin and reversal of LMWH?
reversal of LMWH is not as complete

no easy test to see how much FFP/protamine to give
What is Tinzaparin
newer LMWH - fewer indications
Which anticoag drug may cause injection site pain and hematoma?
LMWH
What is fondaparinux?
a synthetic analog of heparin that binds to antithrombin with higher affinity
Why can't you get HIT with fondaparinux?
it doesn't interact with platelet/PF4
What is the name of the heparin analog that cannot currently be reversed?
fondaparinux
How do you monitor anticoagulation with fondiparinux since it doesn't alter the aPTT, PT, or BT?
anti-Xa assay
What lab values should be monitored if pt is on Fondaparinux?
CBC
Creat (not well studied in creat >1.8)
Stool occult blood
Are heparin, LMWH, and fondaparinux direct or indirect thrombin inhibitors?
indirect
Name 2 direct thrombin inhibitors.
Hirudin
Lepirudin
What anti-coag drugs besides fondaparinux cannot be reversed?
hirudin, lepirudin, and argatroban (the direct thrombin inhibitors)
How are the direct thrombin inhibitors monitored?
aPTT
What drugs are approved for the treatment of HIT Type II?
lepirudin (Refludan)
argatroban
direct thrombin inhibitor
What patients do you want to be careful when using lepirudin?
renal dysfunction
Which direct thrombin inhibitor should be used to treat HIT Type II if patient has renal dysfunction?
argatroban
Does warfarin cross the placenta?
yes
When is fetal teratogenicity from warfarin most likely during gestation?
6-9wks
Can nursing mothers be on warfarin?
yes
Does heparin cross the placenta?
no
What teratogen category is heparin?
C