Thrombus and Antithrombotic Therapy in Atrial Fibrillation

Based on the mechanism of formation, thrombi are classified into 2 types:

• Platelet thrombus (so-called white thrombus)
• Fibrin thrombus (so-called red thrombus)

A detached thrombus is referred to as an embolus.

Thromboembolism is a condition in which a thrombus detaches from its site of origin, circulates in the bloodstream as an embolus, and subsequently causes an embolism (occlusion or stenosis of a vessel) at another site in the body.

Platelet thrombus (so-called white)

• Develops due to endothelial injury of blood vessels, most commonly in arteries following disruption or rupture of an atherosclerotic plaque.
• Platelets aggregate at the site of injured arterial endothelium and form the main component of the thrombus.
• Most commonly causes acute coronary syndrome or non-embolic ischemic stroke (IS).
• This type of thrombus does not develop in atrial fibrillation (AF) in the left atrial appendage.

Fibrin thrombus (so-called red)

• Develops due to blood stasis in veins or in the left atrial appendage in AF.
• During blood stasis, the coagulation cascade is activated and fibrin is formed, constituting the main component of the thrombus.
• This type of thrombus develops in AF, most commonly in the left atrial appendage.
• If it detaches, it may cause embolic ischemic stroke.
• Most commonly develops in the veins of the lower extremities.
• This thrombus most frequently embolizes to the lungs and causes pulmonary embolism.

Antithrombotic therapy is divided into 3 types:

• Antiplatelet therapy
• Anticoagulant therapy
• Thrombolysis

Antiplatelet therapy

• Inhibits platelet aggregation, thereby preventing formation of a platelet thrombus.
• Does not prevent thrombus formation in AF, because in AF a fibrin thrombus develops.
• Most commonly used drugs:
• Aspirin, Clopidogrel, Prasugrel, Ticagrelor

Anticoagulant therapy

• Inhibits coagulation factors, thereby reducing fibrin formation; prevents formation of a fibrin thrombus.
• Prevents thrombus formation in AF, because in AF a fibrin thrombus develops (most commonly in the left atrial appendage).
• Most commonly used drugs:
• Warfarin, NOAC (Dabigatran, Rivaroxaban, Apixaban, Edoxaban)
• The preferred NOAC in non-valvular AF is Apixaban

Thrombolysis

• Activates fibrinolysis, which dissolves already existing thrombi.
• It is a very aggressive i.v. therapy that dissolves a thrombus within 12–24 hours.
• Primarily dissolves fibrin thrombus, not platelet thrombus.
• It is also administered in acute ischemic stroke in patients with AF,
• within 6 hours from the onset of neurological symptoms.
• It is not administered as prevention of thrombus formation nor to dissolve a thrombus in the left atrial appendage in AF.
• If a patient with AF and a thrombus in the appendage received thrombolysis,
• the thrombus would begin to dissolve rapidly, detach, and cause ischemic stroke.
• Most commonly used drugs:
• Alteplase, Tenecteplase, Reteplase
• Major contraindications to thrombolysis include:
• Use of NOAC within the last 48 hours
• INR during Warfarin therapy > 1.7

In patients with AF, anticoagulant therapy is administered for prevention of thromboembolism.

• Anticoagulant therapy is indicated according to the CHA₂DS₂-VA score.

In AF, thrombus most commonly develops in the left atrial appendage (LAA),

• because the LAA is narrow and deep, resembling a “pouch” where blood stasis develops in AF.
• The standard LAA volume is 5–10 ml; in AF 10–20 ml
• The risk of thrombus formation can be calculated using the CHA₂DS₂-VA score.
• The main problem is that this thrombus most commonly embolizes to the cerebral arteries and causes ischemic stroke.

The right atrial appendage is wide and shallow,

• therefore blood stasis in AF in this appendage is minimal.
• The risk of thrombus formation in the right atrial appendage in AF is <1%.
• However, this thrombus embolizes to the lungs, which does not have such fatal consequences.

Paradoxical embolization is a rare situation in which a thrombus or embolus from the right side of the heart passes into the systemic circulation through an intra-/extracardiac defect:

• Patent foramen ovale
• Present in 25% of the population
• Ventricular septal defect
• Present in 30–60% of patients with congenital heart disease (which affects 1/1000 people)
• Atrial septal defect
• Present in 10% of patients with congenital heart disease (which affects 1/1000 people)
• Pulmonary arteriovenous malformation (a connection between the pulmonary artery and pulmonary veins in the left atrium)
• Present in 2/100 000 people

In paradoxical embolization, ischemic stroke may occur in AF,

• and the thrombus may not originate from the left atrial appendage but from the venous system of the lower extremities.
• These are very rare situations.

These guidelines are unofficial and do not represent formal guidelines issued by any professional cardiology society. They are intended for educational and informational purposes only.