Anticoagulant, Antiplatelet, & Fibrinolytic Agents Drugs to Control Bleeding
Clotting Disorders
Thrombogenesis
Normal body defense
Becomes pathologic when causes vascular obstruction
Section that breaks off and travels is known as an embolus
Atherosclerosis
Hemostasis
Prevention or stoppage of blood loss from injured vessel (maintains vascular compartment
integrity)
Mechanisms involved: vasoconstriction
Formation of platelet plug (clot lysis)
Sequential activation of clotting factors
Reparation of the opening in damaged vessel
Atherosclerosis: Accumulation of lipid-filled macrophages (i.e., foam cells)
on the inner lining of arteries
Can affect any organ or tissue
Often involves arteries supplying
Heart (Thrombus may precipitate MI.)
Brain (Thrombus may precipitate stroke.)
Legs (Thrombus may precipitate DVT.) Status of blood, standing, PE is biggest risk
Consequences and clinical implications depend on location and size of thrombi/emboli.
Thrombotic and Thromboembolic Disorders
Thrombosis may occur in arteries and veins.
Arterial thrombosis
Atherosclerotic plaque, HTN
Turbulent blood flow
Damage arterial endothelium and activate platelets to initiate coagulation
Cause disease by blood flow obstruction
Ischemia, infarction- CAN CAUSE IT ANYWHERE
Antithrombotic and AntithromboembolicMedications
Anticoagulants: Used in thrombotic disorders; DVT Prevention
Primary prevention: Diet, exercise, or lifestyle modifications
Secondary prevention: when you have a clot/plaquing, prevent further damage
Antiplatelets: Used to prevent arterial thrombosis
Thrombolytics: Dissolve thrombi and limit tissue damage in thromboembolic disorders
They break down clots.
Anticoagulant drugs
Given to prevent new clot formation and extension of clots present
Does not: dissolve formed clots, improve blood flow in tissues around the clot, or prevent
ischemic damage beyond the clot
Indications for use: prevention or management of thromboembolic disorders
Thrombophlebitis, DVT, pulmonary embolism
Main adverse effect: bleeding
Anticoagulant Drugs; They work on veins
Heparins
Vitamin K antagonists
Direct thrombin inhibitors (DTIs)
Direct factor Xainhibitors
Heparin
LMWH –enoxaparin (Lovenox), dalteparin(Fragmin)
Quick-acting; HIT* in 1-3% of patients after 4-14 days; HIT (heparin induced thrombocytopenia)
IV or Subcutaneous (not absorbed in GI tract)
NOT removed in hemodialysis
Does NOT cross placenta*** & NOT in breast milk***
Used prophylactically (prevent DVT & PE)
Major surgery or illness
Immobility
Used therapeutically to prevent further thromb/emb
DVT, PE, thrombophlebitis
Disseminated intravascular coagulation (DIC); Too much clotting that puts you at risk of
bleeding. Uses the clotting factor and the rest of blood can not clot. Heparin interferes with the
clotting long enough for your body to produce more clotting factor, and the body stabilizes.
Vitamin K antagonists
Warfarin (Coumadin) –most common; Overlaps with heparin treatment
Prevents synthesis of vitamin K-dependent clotting factors
NO IMPACT on existing clotting factors; (so it takes 3-5 days for it to begin working)
Long-term mgmt. of DVT, PE, AF, Prosthetic heart valve
Attention to dietary vitamin K; Maintain Vitamin K intake; Know dietary sources of Vit. K
Direct thrombin inhibitors (DTIs)
Dabigatran (Pradaxa), argatroban, bivalirudin, desirudin
Interferes with the effect of thrombin on fibrinogen
Benefits:
Acts on BOTH circulating & clot-bound thrombin AND has antiplatelet activity
More predictable response to med; no drug monitoring required
Less incidence of immune-mediated thrombocytopenia (ITP)
Antidote - idarucizumab(Praxbind) –bleeding, emergent surgery
Beers List***; Caution with renal impairment
Use: stroke prevention with NONVALVULAR AF; Treatment/Prevention of DVT & PE
If used with valvular AF, risk of bleeding
Direct factor Xainhibitors
Rivaroxaban (Xarelto), apixaban (Eliquis), edoxaban
Inhibits thrombin production by inactivating (circulating & clot-bound) factor Xa
Less life-threatening bleeding than warfarin
Use: Treatment of secondary and Prevention of VTE and stroke with NONVALVULAR AF
Beers List*** Unsafe during pregnancy (bleeding & fetal risk)
No drug monitoring required
Anticoagulant Management
Heparin: regulated by activated partial thromboplastin time (aPTT)
Lab drawn approximately equal to 1 hour before dosing
Warfarin: regulated by international normalized ratio (INR), based on prothrombin time (PT)
Lab drawn daily until therapeutic
Therapeutic = 1.5; Hold > 3
Once therapeutic, drawn every 2 to 4 weeks for duration of anticoagulant therapy, unless dose
adjusted
Antiplatelet Drugs
Prevent one or more steps in prothrombotic activity of platelets
Act by a variety of mechanisms
Inhibit platelet activation
Inhibit platelet adhesion
Inhibit platelet aggregation
Inhibit procoagulant activity
Adverse effects depend on the medication used.
Antiplatelet Drugs; They work on arteries
Adenosine diphosphate receptor antagonists
Thromboxane A2 inhibitors
Glycoprotein IIb/IIIa receptor antagonists
Phosphodiesterase-3 enzyme inhibitor
Adenosine diphosphate receptor antagonists
clopidogrel (Plavix), prasugrel, ticagrelor, cangrelor
Blocks ADP receptor on platelet cell surface
Cons:
Blocking action is irreversible(no antidote), permanent action; Platelet transfusion if something
goes wrong
Delayed onset of action
Significant variability in platelet response
Use: Prevention of stroke, MI, vascular ischemia in ACS, AF (in patients who cannot take
warfarin), after stent (with ASA)
Caution with hepatic impairment, pregnancy, lactation
Thromboxane A2 inhibitors 1/2
acetylsalicylic acid (Aspirin)
Inhibits synthesis of prostaglandins and prevents thrombus formation
Irreversible –lasts the life of the platelet (no antidote)
Use: Prevention of MI, stroke, heart valve pts; Treatment of MI, TIA,evolving thrombotic strokes
Main S/E: risk of bleeding
Thromboxane A2 inhibitors 2/2
NSAIDs -ibuprofen
Inhibits synthesis of prostaglandins and prevents thrombus formation
Reversible –effect on platelet stops when drug removed
Not typically used as antiplatelet, but if patient takes ibuprofen daily, they may not need
additional ASA
*Tylenol usually does not affect platelets
Glycoprotein IIb/IIIa receptor antagonists
abciximab(ReoPro) –monoclonal antibody that prevents the binding of fibrinogen, von
Willebrand factor to GPIIb/IIIa platelet receptors, thus inhibiting platelet aggregation
eptifibatide (Integrilin), tirofiban (Aggrastat) –same action
Use: Prevention of thrombosis of arteries after PTCA or atherectomy
Action stops when drug stopped
Contraindications: h/o stroke, bleed, surgery or trauma in past 30 days; h/o aneurysm, av
malformation, ICH ever
Phosphodiesterase-3 enzyme inhibitor
Cilostazol (Pletal) –used for intermittent claudication
Takes 2-12 weeks to work
Inhibits phosphodiesterase, which inhibits platelet aggregation and produces vasodilation
BLACK BOX WARNING: Not for use in patients with HF
Anagrelide –used for essential thrombocythemia (Too many platelets)
Dipyridamole –used in combination (Aspirin/Warfarin) for heart valve replacement and
Prevention of stroke
Thrombolytic Agents; Clot Buster
Given to dissolve thrombi
Usually stroke patients, and we must know there normal, work best on newer clots
Stimulate conversion of plasminogen to plasmin (enzyme that breaks down fibrin)
Management of acute, severe thromboembolic disease
MI, PE, iliofemoral thrombosis
Goal: reestablish blood flow as quickly as possible, prevent/limit tissue damage
Main adverse effect: bleeding
Thrombolytic Therapy
Recombinant tissue plasminogen activators (rtPA) alteplase (Activase), Tenecteplase (TNKase)
Performed only by experienced personnel in ICU or diagnostic/interventional setting with cardiac
monitoring in place
Baseline laboratories (INR, aPTT, platelet count, fibrinogen) needed preadministration
Factors in bleeding decrease include: careful selection of recipients, avoiding invasive
procedures, omitting anticoagulants or antiplatelets during use.
Use in Special Populations
Children, Older adults, Renal impairment, Hepatic impairment, Home care, Herbal and dietary
supplement use
Monitor for accumulation effect, make sure they are excreting the medications
Nurse Considerations:
Monitor for bleeding and patient education; Medical jewelry
Take medication at the same time, each day. Be more conscious when performing activities.
Drugs Used to Control Bleeding (Antidotes)
Warfarin → vitamin K (Mephyton)
Warfarin (urgent) → PT complex (Kcentra)
Heparin → protamine sulfate
Dabigatran → idarucizumab(Praxbind)
tPA → aminocaproic acid (Amicar)
Thrombolytics → tranexamic acid (TXA)