Coags Flashcards
What happens with platelets when they encounter endothelial injury?
They stick to the subendothelial collagen matrix, release thromboxane A2, causing other platelets to adhere and degranulate
Factors released by degranulation of platelets
Serotonin and histamine (vasoconstriction)
TXA2 (causes aggregation and degranulation of platelets)
ADP (activates the GP IIb/IIIa binding site, making the platelet more sticky)
Clotting factors 5, 8, 9
Platelet Factor 4 (heparin neutralizing factor-enhances clotting)
Fibrinogen (links platelets)
End product of the coagulation cascade
Fibrin
The intrinsic pathway is measured by ____ and the extrinsic is measured by ______
PTT
PT
Examples of natural anticoagulents that our bodies make
Prostacyclin II
Antithrombin II
Heparin
Proteins C and S
Remember that coagulation is a balance in our bodies. There are constantly micro-clots being formed as endothelial damage occurs. We need natural anticoagulents to make sure that we’re just making clots all the time.
Examples of oral antiplatelet meds
ASA (COX inhibitor) Ticlopidine Clopidogrel (Plavix) Prasugrel Ticagrelor
IV antiplatelet meds
Abciximab
Eptifibatide (Integrellin)
Tirofiban
All of these work by inhibiting GP IIb/IIIa
How does ASA work?
It’s a COX inhibitor. It prevents the formation of thromboxane A2, which decreases platelet aggregation and degranulation)
In general, what are antiplatelets used for?
For the prevention of recurrent ischemic events (stroke, MI)
Precautions associated with ASA
Children (Reye’s syndrome)
Pregnancy (placental bleeding)
Increases leukotriene production (risk for asthmatics)
Decreases effectiveness of ACE inhibitors, B-blockers, and diuretics
How do the oral antiplatelets work (excluding ASA)?
They block the ADP receptor. Normally, binding of ADP causes GP IIb/IIIa activation and formation of fibrinogen links between platelets.
When might you use ticlopidine (Ticlid) instead of ASA?
ASA intolerance
However, ticlopidine (Ticlid) is rarely used because it can cause neutropenia and thrombotic thrombocytopenic purpura (TTP)
When must clopidogrel be stopped before surgery?
At least 5 days prior.
Which is better for monotherapy, ASA or plavix?
Plavix. However, ideal is dual therapy with ASA.
People who are genetically predisposed not to respond to plavix will be placed on
Prasugrel
Prasugrel compared to plavix
Prasugrel works better than plavix, but it’s expensive and has higher risk of fatal events. Risk of bleeding is 4x higher than plavix
These oral antiplatelets should not be given to patients with a recent CVA due to risk of hemorrhagic conversion
Clopidogrel, Prasugrel and Ticagrelor
Examples of IV antiplatelets
Abciximab
Eptifibatide
Tirofiban
When might you want to use IV antiplatelets?
ACS (Acute coronary syndrome)
PCI (percutaneous coronary intervention)
How do IV antiplatelets work?
By blocking the GP IIb/IIIa receptor, thus preventing platelet aggregation.
When should antiplatelet therapy resume after surgery?
24 hours post-op as long as hemostasis is achieved
What about stopping antiplatelet therapy for those with high risk for cardiac events?
Maintain on ASA therapy if surgeon allows, and stop plavix 5 days prior to surgery.
Basic way that antithrombotics work
Activation of antithrombin III (which will go on to inhibit thrombin IIa and Xa). This prevents secondary hemostasis.
Antiplatelets were concerned with preventing primary hemostasis.
When would you want to use an antithrombotic?
ACS
DVT and PE prevention/treatment
Is heparin able to inhibit clot-bound thrombin?
No. Heparin doesn’t dissolve clots, it just prevents them from occurring/growing.
What is heparin induced thrombocytopenia (HIT)?
Basically, the body makes IgG against the heparin, resulting in a complex that activates platelets, causing them to aggregate and form clots.
HIT shows the initial drop and platelets, and can predispose to HITT, which is when a thromboemolism occurs. HITT is associated with 25-30% mortality and 25% amputation rate.
How to test for HIT
ELISA (looks at IgG)
C-serotonin release assay (detects platelet activation)
Do not delay treatment waiting for tests to come back.
Treatment for HIT
Immediately stop all heparin
Look for unrecognized sources of heparin (flushes, etc)
Start on non-heparin anticoagulant (Argatroban)
If someone experiences HIT, switch them to this non-heparin anticoagulant
Argatroban
These medications can be reversed with protamine
UF Heparin
Enoxaparin (only provides 60% reversal)
What is fondaparinux and why is it not really used?
It’s another antithrombotic in the same class as heparin and enoxaparin. It’s not used because it is very expensive, and there are NO REVERSAL AGENTS.
Factor IIa is also known as
Thrombin. Hence, this is why the antithrombotics are called such. They activate antithrombin III, which inhibits factor IIa (thrombin).
How excited are we for the test?
So excited.
Argatroban and bivalrudin are examples of
Direct thrombin (IIa) inhibitors.
Argatroban is commonly used in HIT
Bivalrudin is commonly used for PCI and WHC is the largest consumer of bivalrudin in the entire US! How fucking cool is that??
What’s the problem with direct IIa inhibitors and direct Xa inhibitors?
They have no known antidote. We just futilely attempt to throw everything them to make them stop bleeding (Facor VII, ffp, platelets, cryo
How to stop warfarin before surgery
Stop five days prior. Bridge with heparin for 1-2 days and stop 4-6 hours prior to surgery. Resume warfarin 12-24 hours post-op.
How to treat bleeding with warfarin
Vitamin K or ffp (need to replace those clotting factors!)
Length of warfarin therapy for an uncomplicated DVT
3 months
Why don’t we really use streptokinase anymore as a fibrinolytic?
Because a high incidence of an anaphylactic reaction
When do we use fibrinolytics?
STEMI
Acute CVA
Can you get tPA if you’re on your period?
Yes
