Anticoagulants

How do we measure the "extrinsic pathway?"

Prothrombin Time (PT) International Normalized Ratio (INR)

Fondaparinux [Atrixtra]

Selective inhibitor of factor Xa ***same risks as heparins

Venous thrombosis vs. arterial thrombosis

anticoagulants = venous thrombosis prevention antiplatelet drugs = arterial thrombosis prevention

Which factors are vitamin K dependent?

factors VII, IX, X, and II (prothrombin) ***these factors are affected by warfarin

Drugs that activate ANTITHROMBIN

heparin (unfractionated) LMW heparins 1. enoxaparin (Lovenox) 2. dalteparin (Fragmin)

Plasmin

Plasmin is an enzyme that degrades fibrin Plasmin is produced through activation of its precursor, plasminogen

Direct Factor Xa Inhibitors

rivaroxaban [Xarelto] apixaban [Eliquis] edoxaban [Savaysa] ***thromboembolism/stroke prophylaxis (in patients with afib) ***DVT prophylaxis in patients undergoing knee/hip replacement Black Box: spinal/epidural hematoma

What are the two main steps in hemostasis?

(1) formation of platelet plug (2) reinforcement of platelet with fibrin

How do anticoagulants work?

(1) inhibit synthesis of clotting factors; OR (2) inhibit the ACTIVITY of clotting factors (factor Xa, thrombin/IIa, or both)

LMW heparins (adverse effects)

***bleeding ***thrombocytopenia ***BLACK BOX WARNING: epidural/spinal hematoma risk

Stage I: Formation of Platelet Plug

1. blood vessel wall damaged 2. collagen released 3. platelet activation in contact with collagen 4. platelet activation --> platelet aggregation 5. fibrinogen bridges between GP IIb/IIIa ACTIVATED receptors between platelets ***Platelet plug is UNSTABLE and must be reinforced with fibrin (Stage II)

Heparin (unfractionated) mechanism, route, monitoring, setting

Binds to antithrombin and inactivates: 1. thrombin (IIa) 2. factor Xa ***generally IV, monitor aPTT, HOSPITAL

Anticoagulant (definition)

By definition, anticoagulants are drugs that REDUCE FIBRIN formation

Stage II: Coagulation (definition)

Definition: the production of FIBRIN ***Intrinsic pathway ***Extrinsic pathway ***Converge at FACTOR Xa***

Which factors are inactivated by antithrombin?

IXa, Xa, XIa, XIIa, and thrombin (factor IIa) ***these factors are affected by heparin

How do we measure the "intrinsic pathway?"

activated partial thromboplastin time (aPTT)

Direct Thrombin Inhibitors

bivalirudin [Angiomax] desirudin [Iprivask] argatroban [Argotroban] dabigatran [Pradaxa] ***idarucizumab [Praxbind] approved to REVERSE the effects of dabigatran

What factors ACTIVATE GP IIb/IIIa platelet receptors?

collagen thromboxane A2 (TXA2) thrombin platelet activation factor adenosine diphosphate (ADP)

Heparin (low-molecular weight) mechanism, route, monitoring, setting

same as unfractionated except prefers to inactivate factor Xa ***subQ only, no monitoring required, hospital/home

warfarin [Coumadin]

vitamin K antagonist that blocks biosynthesis of factors VII, IX, X and prothrombin (factor II) ***monitor INR ***vitamin K for overdose ***Pregnancy category X