Anticoagulants, Antiplatelets, Thrombolytics Flashcards by Nadia Uddin

Define hemostasis (patho)

a process used by the body to stop bleeding by method of clot formation

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Coagulation cascade

Series of events that take place in the formation of a clot. Anticoagulants, antiplatelets and thrombolytics all work at different points in the cascade

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Define anticoagulant

disrupt coagulation cascade (before it can start taking place)

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Define antiplatelet

disrupt platelet aggregation (sticking together)

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Define thrombolytic

breakdown of formed clots

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Which clotting factors rely on vitamin k in order to be synthesized by the liver?

Seven, Nine, Ten and Two (SNTT)

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Anticoagulant General Info

Reduce formation of fibrin

May be given p/o or parenterally

For both treatment and prevention of thromboembolism

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3 Heparin Derivative Groups

Unfractionated heparin
Low molecular weight heparin
Fondaparinux

Mech: enhance activity of antithrombin III

**These drugs have the same mechanism of action, but do not have equal effects on factor Xa and factor IIa (thrombin)

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Unfractionated Heparin (UFH)

Mech: Antithrombin III undergoes a conformation change that enhances its binding capability

Indication: Treatment of venous thromboembolism (VTE), prophylaxis of VTE< myocardial infarction, atrial fibrilation

Adverse Effects: hemmorhage, spinal/epidural hematoma, heparin-induced thrombocytopenia (HIT)

Lab Monitoring: Activated partial thromboplastin time (aPTT), Anti-factor assay

** anti-factor assay is more accurate than aPTT

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What is thrombocytopenia?

Reduced platelet count

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What medication is used in the reversal of unfractionated heparin or low molecular weight heparin?

Protamine

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Protamine (SLOW IV push or rapid admin for hypotension)

Indication: binds with heparin to inactivate, used in unfractionated heparin reversal

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What is the ratio of protamine to heparin in neutralizing/reversal of heparin or low molecular weight heparin?

1 mg of protamine neutralized 100 units of heparin

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Low Molecular Weight Heparins (LMWH) (SQ)

Enoxaparin
Dalteparin

Mech: binds to factor Xa and factor IIa (thrombin) to neutralize their activity

Indications: Prevention of DVT, treatment of venous thromboembolism (VTE), treatment of MI

Adverse Effects: hemorrhage, spinal/epidural hematoma, heparin-induced thrombocytopenia

Excretion: renally excreted, reduced doses required for pts. with renal impairment

** No lab monitoring needed

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What is the primary difference between unfractionated heparin and LMWH heparin?

smaller chain length with LMWH’s, so less binding to factor IIa (thrombin)

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What is required for the inactivation of factor IIa

binding of heparin to BOTH antithrombin II and factor IIa molecule

Fondaparinux

Mech: binds to antithrombin and causes conformational change, but ONLY binds to factor Xa and not factor IIa

Indications: prophylaxis of DVT and treatment of VTE

Adverse Effects: hemorrhage, spinal/epidural hematoma

** NO lab monitoring needed and NO risk for heparin-induced thrombocytopenia (HIT)

Which heparin derivative drug requires lab monitoring?

Unfractionated Heparin

(aPTT and anti-factor assay)

(Assay is a test to determine the presence of something )

Which heparin derivative drugs carry a risk for heparin-induced thrombocytopenia?

Unfractionated heparin and low molecular weight heparins (NOT Fondaparinux)

What type of drug is warfarin?

Vitamin K antagonist

vitamin K helps us to clot

Warfarin

Mech: decreased production of clotting factors 7, 9, 10, 2 (SNTT)

Indications: treatment and prevention of VTE, prevention of thromboembolism in patients with mechanical heart valves, prevention of thromboembolism in patients with atrial fibrillation

Pharmako: full effects seen in 3-5 days

Monitoring: International Normalized Ratio (INR)/prothtrombin time

Adverse Effects: hemorrhage, fetal hemorrhage during pregnancy (Category X)

DDI’s: other anticoagulants, drugs that decrease anticoagulant effects (phenytoin/vitamin K)

What clotting factors does the acronym SNTT represent?

7, 9, 10 and 2

Which category is warfarin for pregnancy?

Category X

Which foods should patients taking warfarin avoid and why?

mayonnaise, green leafy vegetables, soybean oil

These are high in vitamin k, so may counteract with warfarin’s anticoagulant capability

Warfarin Reversal

Vitamin K (phytonadione) and fresh frozen plasma (FFP) in life-threatening bleeds

Direct Thrombin Inhibitors (DTI)

Dabigatran (PO) Bivalirudin (IV) Argatroban (IV) Mech: bind to and inhibit factor IIa (thrombin) Adverse Effects: dyspesia ** NO need for lab monitoring with oral formulations (dabigatran)

Factor Xa Inhibitors (PO)

Rivaroxaban (PO) Apixaban (PO) Indications: prevention and treatment of VTE, prevention of thromboembolism in atrial fibrillation ** NO laboratory monitoring needed

What is the primary difference between Fondaparinux and Factor Xa Inibitors?

Fondaparinux binds to antithrombin III FIRST then binds to factor Xa, Factor Xa inhibitors bind directly

What drug is used for reversal of direct thrombin inhibitors?

Idarucizumab (Praxbind)

What drug is used for the reversal of Factor Xa inhibitors?

Adexanet-alfa

Aspirin

Mech: Irreversible inhibitor of COX-1 and COX-2, Prevents production of thromboxane A2 (TXA2), TXA2 can promote platelet aggregation Indications: ischemic stroke, transient ischemic attack (TIA), acute coronary syndrome Adverse Effects: GI bleeding and ulcers

P2Y12 Adenosine Diphosphate Receptor Antagonists

Clopidogrel (irreversible inhibitor) Prasugrel (irreversible inhibitor) Ticagrelor (reversible inhibiitor) Mech: block P2Y12ADP on platelet surface, prevents ADP stimulated platelet aggregation Indications: prevention of thrombosis of coronary stents after PCI, secondary prevention of stroke, MI and peripheral vascular disease Adverse EffectsL Dyspnea with Ticagrelor, bleeding with any of these meds DDI's: omeprazole because omeprazole inhibits CYP2C19

Which P2Y12 Adenosine Diphosphate Receptor Antagonist is actually reversible?

Ticagrelor

Glycoprotein IIb/IIIa Receptor Anatagonists

Tirofiban Eptifibatide Abciximab Mech: Reversible blockade of GIIb/IIIa receptors Indications: prevention of ischemic events in patients with acute coronary syndromes (ACS) and undergoing PCI *Typically only used in the cath lab Adverse Effects: bleeding **Used in combination with heparin during PCI

Thrombolytic (Fibrinolytic) Drugs

Alteplase Tenecteplase Indications: ischemic sroke, myocardial infarction, pulmonary embolism **HIGH. risk of bleeding associated with these medications

Alteplase (IV) ** Bolus followed by infusion

Also know as tissue plasminogen activator (tPA) Indications: acute ischemic stroke, acute myocardial infarction, acute pulmonary embolism Adverse Effects: bleeding, angioedema (hive-like reaction in deep layers of the skin) Contraindications: Prior intracranial hemorrhage, Ischemic stroke or MI in last 3 months, Active bleeding, Suspected aortic dissection

Avoiding bleeding from alteplase administration

Avoid SQ or MI injections during administration, minimize invasive procedures, minimize concurrent use of anticoagulants or antiplatelet drugs