Flashcards in Antithrombotics Deck (64)
difference between red clot and white clot, and what kind of drugs to treat with
red: venous slow flow (fibrin, platelets, RBCs)
white: arterial faster flow (fibrin and platelets)
Treat both with anticoagulants and
but also treat white with antiplatelets
the therapeutic range for antithrombotics is...
hemostasis : fine line between anticlotting (bleed out) and clotting (thombi/emboli)
true or false: much of antithrombosis is for treatment
false. it's mostly for prophylaxis since it doesn't break up a clot, it stops them from forming/growing
stop platelets from sticking and aggrigating in the clot
stop fibrin mesh from forming
when do you see red clots (name 3 reasons they are made)
1) Hypercoagulable states (genetics)
2) When blood pools/moves slowly (immobile post surgery, long flights, A fib)
3) With Foreign objects (vascular access device, catheter, surgical implants, central venous line)
2 clinical examples of a red clot
DVT--> pulmonary embolism
why/when we see white clots
Plaque ruptures, then white clot forms on rupture site
2) foreign objects (mechanical heart valve, Percutaneous coronary intervention)
clinical examples of white clot patents
MI, unstable angina, STEMI, nonSTEMI, CVD, TIA from plaque on carotid artery, Peripheral vascular disease
a xymogen is a ___________ and is _____ by a ____________
coagulation factors (enzymes that are inactive) and is ACTIVATED by a protease
key targets for anticoagulation
the common pathway. Goal is to diminish activity in Factors Xa &/or IIa
4 steps in common pathway to a clot
1) X-->Xa--> protrhombinase complex (XaVa)
2) this activates II-->IIa (protrombin--> thrombin)
3) which activates Fibrinogen --> fibrin
4) ---> fibrin clot 3D matrix (+platelets or RBCs depending if venous or arterial)
true or false
The grandaddy, Heparin gets rid of the clot in your grandaddy.
False. it's an anticoagulant... they only prevent them not dissolve them.
Heparin wouldn't get approved by FDA today because
it's a bunch of molecules that are stuck together... polysacharide with a bunch of acidic sulfides.
Heparin gets into the BBB to prevent ischemia (true or false)
False... highly charged, can't take orally, can't cross BBB, safe for pregnancy... stays in blood vessels
heparin's 1st mode of action
1) Heparin's pentasaccharide bind to Antithrombin (AT)
2) Xa binds to AT 1000x faster with heparin, so it deactivates the clotting cascade.
antithrombin is most potent anticlotter and called the _________
suicide bait (it fools Xa to bind covalently and deactivates it at a 1:1 ratio)
heparin's 2nd mode of action
long chain that has IIa at one side and AT at other, and they bridge and bump and bind (lessoning 3 dimensionally space to 1 dimension (a line)
how does unfractionated Heparin work differently from the other -parin's
Heparin has whole mess of polysaccharides, including the pentasacc that binds AT, and also the long chains that bind AT at end so it does both Xa and IIa
LMW Heparin does Xa and IIa
Fondaparinux is only the pentasaccharide so it only does Xa (not IIa)
IIa is also called
thrombin... so heparin knocks out thrombin with antithrombin catalization
what is enoxaparin
a low molecular weight heparin... has shorter chains than unfractionated, but deactivates Xa>>>IIa
how are the 3 heparins eliminated
unfractionated hep: liver
LMW hep: kidney
how do you know if they have too much heparin in their system, and what to do if so?
constantly monitoring for unfractionated heparin. Give Protamine to neutralize excessive bleeding.
what is HIT in regards to anticoagulants
1) Heparin-induced thrombocytopenia.
2) Antibody produced after 8+ days on Heparin because ...
3) Platelets release + charged granules (like platelet factor 4) which binds to the - heparin creating an antigen, then body sees foreign and attacks.
4) Atg binds to Aby and activates platelet to make white clot--> thrombi in terminal vessels= HIT
(sorry so long)
what is Gla
gamma-Carboxyglutamate aka "Gla" attaches coag factors and AntiCoag to platelets and includes extrinsic, intrinsic, and common pathway (Xa, VII, IX, X), and anticoag's (protein C and S)
what do Gla's do?
chelate Ca++ and enable attachment to platelet membrane,
(required to have functional coagulation factor to work)
what does Warfarin do
it blocks Gla formation, can't bind to Xa
how does Warfarin work?
It eliminates VKORC (which recycles vit K (with NADH-> NAD) back to its reduced form) so it limits Glutamate -->Gla (which needs active vit K)
what's the problem giving warfarin solo?
It takes 8-12 hours to affect INR, and days for full affect. Delayed until existing clotting factors are turned over.
Also can create pro-clotting state because inhibits protein C and S before inhibiting factors