Antiplatelet Agents and Anticoagulants - Review and Key Concepts

A comprehensive set of practice flashcards covering hemostasis, coagulation cascades, antiplatelet drugs, anticoagulants, monitoring, antidotes, HIT, DOACs, fibrinolysis, and peri-procedural considerations.

What is hemostasis?

The process of maintaining blood fluidity, repairing vascular injury, and limiting blood loss while preventing thrombosis and inadequate perfusion of vital organs.

What are the three main pathways of the coagulation cascade mentioned in the notes?

Intrinsic pathway (contact activation), Extrinsic pathway (tissue factor pathway), and Common pathway.

Which coagulation factors require vitamin K for their synthesis?

Factors II, VII, IX, and X (and the natural anticoagulants proteins C and S).

What initiates platelet adhesion and aggregation?

Platelets contact exposed collagen, become activated, and aggregate; GP IIb/IIIa changes facilitate binding of fibrinogen to link platelets.

What is the role of GP IIb/IIIa receptors in platelets?

They bind fibrinogen to link platelets during aggregation, forming the platelet plug.

Which mediators promote platelet activation after contact with exposed collagen?

Thromboxane A2 (TXA2), thrombin, PAF, ADP, collagen, and platelet activation factors.

What is the end result of fibrin clot formation?

Fibrin clot formation via the coagulation cascade and subsequent fibrinolysis by plasmin.

How do arterial and venous thromboses differ in pathophysiology?

Arterial thrombosis is due to arterial wall damage/rupture and platelet-rich clot; venous thrombosis is due to slow flow with a red cell–rich clot that can embolize.

How does aspirin exert its antiplatelet effect?

Irreversible inhibition of COX-1, reducing thromboxane A2 and platelet aggregation.

What is the typical aspirin dose for antiplatelet therapy and a key perioperative consideration?

81–325 mg PO daily; typically held 2–3 days before surgery/procedure.

Name the traditional P2Y12 inhibitors and their general mechanism.

Clopidogrel, prasugrel, and ticagrelor inhibit ADP-induced platelet aggregation via the P2Y12 receptor (clopidogrel and prasugrel are prodrugs; ticagrelor is active).

Which P2Y12 inhibitor is available IV and reversible?

Cangrelor (Kengreal); IV, reversible P2Y12 inhibitor; used during infusion with avoidance of taking oral P2Y12 inhibitors during infusion.

What is the PAR-1 antagonist mentioned, and what is its clinical note?

Vorapaxar (Zontivity); inhibits thrombin-induced platelet aggregation, long half-life, contraindicated after stroke/TIA/ICH or severe hepatic impairment.

What is dipyridamole and its role in stroke prevention?

Vasodilator that inhibits platelet aggregation by preventing adenosine uptake and increasing cGMP; used as Aggrenox (with aspirin) for stroke prevention after TIA.

What is the general mechanism of fibrinolysis?

Conversion of plasminogen to plasmin by activators (t-PA, urokinase, etc.), leading to degradation of fibrin.

Name the fibrinolytics and a key use.

Alteplase (t-PA), streptokinase, reteplase, tenecteplase; indicated for life-threatening clots such as acute ischemic stroke, PE, and AMI.

What are fibrinolysis inhibitors and their primary use?

Aminocaproic acid and tranexamic acid; used to control bleeding by inhibiting plasmin formation or activity.

What is the mechanism of unfractionated heparin (UFH)?

Binds to antithrombin III and inhibits thrombin (IIa), IXa, and Xa; mixture of molecules of different weights.

What is the UFH monitoring method and antidote?

Monitoring with PTT or anti-Xa; antidote is protamine sulfate (1 mg per 100 units heparin, max 50 mg).

What is the main difference between UFH and LMWH?

LMWH mainly inhibits factor Xa with more predictable pharmacokinetics and fewer inter-patient variations; given subcutaneously, not as continuous infusion.

What is a key LMWH dosing chart feature for enoxaparin prophylaxis and treatment?

Prophylaxis: 40 mg q24h or 30 mg q12h; Treatment: 1.5 mg/kg q24h or 1 mg/kg q12h (renal impairment adjustments apply).

What is the major boxed warning for LMWH?

Spinal/epidural hematomas with neuraxial anesthesia or procedures; hold LMWH before and after spinal procedures.

What is the HIT acronym and its clinical relevance?

Heparin-Induced Thrombocytopenia; immune-mediated thrombocytopenia with heparin exposure; risk higher with UFH; risk 1–4% after 5 days; can cause thrombosis (HITT).

How is HIT diagnosed and managed?

Diagnosis via 4T score; discontinue all heparin; initiate a non-heparin anticoagulant (argatroban, bivalirudin); consider fondaparinux in select cases; once platelets recover, start warfarin.

What is warfarin’s mechanism of action and its major considerations?

Vitamin K antagonist reducing synthesis of factors II, VII, IX, X and proteins C and S; delayed onset; multiple drug/food interactions (CYP enzymes and VKORC1); monitor with INR; antidote is vitamin K.

What is the target INR for most warfarin patients?

INR goal generally 2.0–3.0.

What is bridging in warfarin therapy and why is it required?

Temporary overlap of warfarin with a parenteral anticoagulant (UFH/LMWH) until INR is therapeutic for two consecutive days; typically at least 5 days due to initial prothrombotic state from depletion of proteins C and S.

How should an elevated INR be managed acutely?

If INR >10 without bleeding, hold warfarin and monitor; if bleeding, reverse with vitamin K; for any clinically significant bleeding, administer vitamin K (dose and route per protocol).

Which vegetables are high in vitamin K and can affect warfarin dosing?

Kale, spinach, turnip greens, collard greens, Swiss chard, parsley, mustard greens.

Name the direct oral anticoagulants (DOACs) that are direct Xa inhibitors and their reversal agent.

Rivaroxaban, apixaban, edoxaban (Xa inhibitors); reversal agent: andexanet alfa (Andexxa) or PCC in some settings.

Name the direct thrombin inhibitors (DTIs) and their common clinical uses.

Dabigatran (oral); argatroban and bivalirudin (IV, used for HIT and procedural anticoagulation). Reversal for dabigatran is idarucizumab (Praxbind).

What is the reversal agent for dabigatran?

Idarucizumab (Praxbind).

What is the reversal approach for factor Xa inhibitors in emergency settings?

Andexanet alfa (Andexxa) is the specific reversal agent; PCC can be used in select cases.

What are common parameters used to monitor UFH vs warfarin therapy?

UFH: PTT or anti-Xa levels; Warfarin: INR (PT/INR). Platelets and CBC are monitored for HIT and safety.

What is the role of platelets and GP IIb/IIIa inhibitors in periprocedural settings?

GP IIb/IIIa inhibitors (abciximab, eptifibatide, tirofiban) reduce platelet aggregation; ASRA guidelines detail timing for neuraxial procedures around thrombolytics and GP IIb/IIIa inhibitors.

Which agents fall under antiplatelet therapy vs anticoagulants in the DOAC context?

DOACs include direct thrombin inhibitors (DTIs like dabigatran) and Xa inhibitors (rivaroxaban, apixaban, edoxaban); these are anticoagulants, whereas aspirin, P2Y12 inhibitors, PAR-1 antagonists, and dipyridamole are antiplatelet agents.

What is a key consideration for DOACs in renal impairment?

Many DOACs should be avoided or dose-adjusted in renal impairment; apixaban has data supporting use in CKD 4/5 and dialysis; others require caution or avoidance.

What are common peri-procedure guidelines mentioned for neuraxial anesthesia with antithrombotics?

ASRA guidelines provide timing recommendations after last dose and before catheter placement/removal for thrombolytics, GP IIb/IIIa inhibitors, and neuraxial procedures; neuraxial techniques are generally avoided during thrombolytic therapy.

What is the general teaching point about DOACs and bridging at initiation/holding?

DOACs have rapid onset and often do not require IV bridge at initiation; if temporarily held, bridging with IV anticoagulant may be considered in select high-risk patients, but not universally recommended.