Anticoagulant, Antiplatelet

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Anticoagulant, Antiplatelet Thrombolytic Drugs

• Julie Balk NP, MS
• Nsg 220

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Hemostasis

• Stage One
• Platelet Plug
• Stage Two
• Coagulation

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Platelet Plug

• Damaged blood vessel
• Platelets come in contact with collagen
• Platelets adehere
• Platelets activate
• Platelets aggregate

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Platelet Aggregation

• GPIIb/IIIa receptors
• Fibrinogen bridges on adjacent platelets
• GPIIb/IIIa Activation
• Thrombaxane A2 (TXA2)
• Thrombin
• Collagen
• Platelet activatin factor
• ADP
• Platelet Plug
• Unstable

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Coagulation

• Production of Fibrin
• Protein that reinforces the platelet plug
• Clotting Cascade
• Instrinsic system
• All factors are present within the vascular
  system
• Extrinsic system
• Tissue thromboplastin required (located outside
  vascular system)
• Common Pathway

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Instrinsic System

• XII into XIIa
• (a represents activated form)
• XI into XIa
• IX into IXa
• X into Xa

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Extrinsic System

• VII into VIIa
• X into Xa
• Common Pathway
• Prothrombin to Thrombin
• Fibrinogen into Fibrin (monomer)
• Ultimately forms Fibrin (polymer)

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Thrombus/Embolus

• Arterial Thrombosis
• Localized tissue injury owing to lack of
  perfusion
• Venous Thrombosis
• Injury occurs secondary to embolization at a
  distant site
• Embolus

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Anticoagulants

• Anticoagulants
• Heparin and warfarin
• Most effective against venous thrombosis

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Heparin

• Enhances the activity of antithrombin
• Inactivates thrombin and Xa
• Rapid acting, Injectable only
• Mixture of long polysaccharide chains
• Active region is unique pentasacharide sequence
  found randomly along the chain

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Heparin (Cont)

• Inactivation of thrombin and Xasuppression of
  the formation of fibrin
• DVT proophylaxis
• Fibrin forms the framework of thrombi in veins
• Because it directly inhibit clotting factor
  activity it works very quickly (minutes)

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Heparin (Cont)

• Therapeutic Uses
• PE Stroke DVT Devices DIC MI Pregnancy
• Complications
• Bleeding 10 (protamine sulfate) HIT
  Hypersensitivity
• Drug Interactions
• Drugs that depress platelet function

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Heparin (Cont)

• Laboratory Monitoring
• PTT (partial thromboplastin time)
• Administration
• IV continuous IV intermittent Sub q
• Measured in units

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Low Molecular Weight Heparins

• Heparin preparation composed of molecules that
  are shorter than those found in unfractioned
  heparin
• Advantages
• Fixed-dose schedule no PTT monitoring less
  likely to cause HIT

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LMWH

• MOA-same as unfractionated heparin except since
  molecules are short dont have same effect
• Preferentially inactivate factor Xa
• Much less able to inactivate thrombin
• Therapeutic Uses
• DVT prevention, tx ischemic strokePE NonQMI

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LMWH (Cont)

• Higher bioavailability than standard Heparin
• Longer half-lives
• Dosage based on body weight
• Adverse Effects
• Bleeding (protamine sulfate)

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Direct Thrombin Inhibitors

• Direct inhibition of thrombin
• Continuous IV infusion
• Only utilized in hospitalized pts
• Bivalirudin (Angiomax)USA w/aspirin
• Lepirudin (Refludan)--HIT
• Argatoban (Acova)--HIT

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Oral Anticoagulants

• Warfarin
• MOA-supresses coagulation by acting as an
  antagonist of vitamin K (VII, IX, X
  prothrombin)
• By antagonizing vitamin K warfarin blocks the
  biosynthesis of these vitamin K dependent factors
• Highly protein bound (99) to albumin
• Basis for several drug interaction
• Only inhibits clotting factor synthesis
• Delay in onset of action, delay in return to nl
  clotting

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Warfarin

• Therapeutic Uses
• DVT PE prevention Prevention of
  thromboembolism in pts with prosthetic heart
  valves prevention of thrombolembolism during
  atrial fib

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Warfarin (Cont)

• Monitoring
• PT INR
• Recommended ranges
• Adverse Effects
• Bleeding
• Fetal Hemorrhage and Teratogenesis
• Drug Interactions
• Overdosage
• Vitamin K

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Antiplatelet Drugs

• Aspirin (ASA)
• Irreversible inhibition of cyclooxygenase (life
  of platelet 7-10 days)
• Thromboxane A2 (TXA2)
• Therapeutic Uses
• Primary prevention of MI secondary prevention of
  MI prevention of stroke in pts with h/o TIAs
• Adverse Effects
• GI bleeding

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ADP Receptor Antagonists

• Ticlopidine Clopidogrel
• Irreversible blockade of ADP receptors on
  platelet surface (prevents aggregation)
• Therapeutic Uses
• Secondary prevention MI, ischemic stroke, other
  vascular events and post stent placement
• Adverse Effects
• Bleeding TTP Neutropenia

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IIb/IIIa Antagonists

• Reversible blockade of platelet GP IIb/IIIa
  preventing final step in aggregation
• Abciximab, Tirofiban, Eptifibatide
• Therapeutic Uses
• ACS Percutaneous Coronary Interventions
• Adverse Effects
• Bleeding

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Thrombolytics

• MOA-remove thrombi that have already
  formedFibrinolyticsClot Busters
• Therapeutic Uses
• AMI DVT Massive PE
• Adverse Effects
• Bleeding
• Varied cost between agents