See also Drug Delivery of anti-thrombotic agents.

Each year, about 795,000 persons in the U.S. experience a stroke. There are 2 major types of stroke: ischemic stroke and hemorrhagic stroke.

In the normal or healthy states, an equilibrium exists between fibrin formation (coagulation) and fibrin dissolution (fibrinolysis). However, when this hemostatic process is impaired, coagulation and fibrinolysis are pathologically expressed as thrombosis and hemorrhage, respectively. The clinical manifestations of pathological thrombosis or thrombotic disease are extremely diverse and include disseminated intravascular coagulation (IC), deep vein thrombosis (DVT), arterial and venous thrombosis. Thromboeembolism and thrombotic complications of other vascular disease (e.g., atherosclerosis) can result in occlusion of major arteries leaidng to organ ischemia and the life threatening conditions such as crebrovascular accidt (stroke), myocardial infarction, etc. (Gargan, 5,837,540).

Blood clots when thrombin cleaves two pairs of small peptides from fibringoen to yeild fibrin monomers (Matsueda, 4,916,070).

Ischemic Stroke (see outline)

Hemorrhagic Stroke: See outline

Pathology

Atherosclerotic plaque: progresses in discrete stages, entailing multiple episodes of rupture and healing that ultimately culminate in a complete obstruction, leading to stroke or an acute heart attack. Microdeposits of fibrin are the hallmark of the unstable lesion. Numerous cellular and molecular processes play a role including macrophages and other inflammatory cells which secrete matrix metalloproteinases (MMPs) that can dissolve fibrous omponents, and large lipid cores that induce prothrombotic tissue factor and destabilize lesions by distributing stress to rupture prone regions. 

Treatment:

ELIQUIS (NDA 202155) relates to drug products containing the active ingredient apixaban in a tablet composition. Apixaban is in the drug class Factor Xa inhibitors (a type of anticoagulant) and is used to lower the risk of stroke and to prevent deep vein thrombosis (DVT). Factor Xa inhibitors work by blocking the activity of clotting factor Xa. ELIQUIS is used to treat nonvalvular atrial fibrillation and blood clots. The study includes ELIQUIS because it was one of the twelve top grossing drugs of 2017.