MPharm Stage 2 Anticoagulants and antiplatelets

Coagulation

The process by which blood changes from a liquid to a gel, forming a blood clot.

Thrombosis

The formation of a blood clot inside a blood vessel, obstructing blood flow.

Anticoagulants

Medications that prevent blood coagulation by inhibiting specific factors in the coagulation cascade.

Arterial

Occurs under high flowconditions

• Usually due to endothelialinjury

• Pale, consisting mainly offibrin and platelets

• Adherent to vessel wall• Coronary arteries

• MI, stroke

Venous

Occurs in non-injuredveins due to stasis orhypercoagulability• Red, consisting of redcells and fibrin• Loosely attached to vesselwall• Occurs in veins of lowerlegs, portal vein• DVT, portal veinthrombosis

Antiplatelet agents

Drugs that inhibit platelet aggregation to prevent thrombus formation.

Fibrinolytic agents

Medications that dissolve blood clots by breaking down fibrin.

Deep Vein Thrombosis (DVT)

A condition in which a blood clot forms in a deep vein, typically in the legs.

Pulmonary Embolism (PE)

A blockage in one of the pulmonary arteries in the lungs caused by blood clots.

Vitamin K

A fat-soluble vitamin essential for the synthesis of clotting factors in the liver.

Heparin

An anticoagulant that inhibits thrombin and factor Xa, commonly administered via injection.

Warfarin

An oral anticoagulant that inhibits vitamin K-dependent clotting factors.

Antithrombin III

A protein in blood that inhibits several coagulation factors and plays a critical role in regulating blood clotting.

Thrombophilia

A disorder that increases the risk of thrombosis due to abnormal blood coagulation.

Platelets

Small cell fragments in the blood that are essential for blood clotting.

INR (International Normalized Ratio)

A standardized way to measure the time it takes for blood to clot, used to monitor patients on anticoagulants.

Thrombus vs. Clot

A thrombus is a clot formed in a blood vessel that remains attached to its place, while a clot can refer to any mass formed from coagulated blood.

Endothelial Injury

Damage to the inner lining of blood vessels that can lead to thrombosis.

Hypercoagulability

An increased tendency of blood to clot due to various factors, often leading to thrombosis.

Fibrinogen

A soluble plasma protein that is converted to fibrin by thrombin during coagulation.

Thrombocytopenia

A condition characterized by low platelet counts, which can increase bleeding risk.

What are the three main mechanisms within the body aimed at controlling bleeding?

Vasospasm, platelet plug formation, and coagulation

What are the three main classes of drugs developed to prevent/reverse thrombus formation?

1) Anticoagulants, 2) Antiplatelet agents, 3) Fibrinolytic agents

What is the difference between arterial and venous thrombosis?

Arterial thrombosis occurs under high flow conditions, usually due to endothelial injury, consists mainly of fibrin and platelets, and is adherent to vessel wall. Venous thrombosis occurs in non-injured veins due to stasis or hypercoagulability, consists of red cells and fibrin, and is loosely attached to vessel wall.

Where can thrombi form in the body?

In both the venous and arterial systems.

How do arterial thrombi typically present and behave?

They are firmly attached to vessel walls, rich in platelets, and often occur in arteries like coronary or cerebral arteries, causing events like myocardial infarction or stroke

What are the main characteristics of venous thrombi?

Loosely attached to vessel walls, rich in red blood cells, and commonly form in the deep veins of the lower limbs.

Why are venous thrombi dangerous during movement or change in blood flow?

They can detach due to turbulent flow as blood moves from slower to faster veins, especially in the legs.

What is the major complication of a venous thrombus detaching?

It can travel through the venous system to the lungs and cause a pulmonary embolism, a medical emergency.

What is a pulmonary embolism (PE)?

A blockage in the pulmonary artery caused by a thrombus that traveled from elsewhere in the body, often the legs.

How do the compositions of arterial vs. venous thrombi differ?

Arterial thrombi: platelet-rich (white thrombi); Venous thrombi: red cell-rich (red thrombi

What is the initial trigger for platelet adhesion during vessel injury?

Exposure of underlying collagen in the damaged vessel wall.

What happens to platelets when they adhere to exposed collagen?

They change shape from round and smooth, release various compounds, and become activated.

What is the result of activated platelets releasing compounds?

They attract and activate more platelets, amplifying the clotting response.

What cascade is triggered by vessel wall injury and collagen exposure?

The coagulation cascade.

What role does fibrin play in clot formation?

Fibrin strands cross-link platelets, stabilizing the clot.

What is thromboxane A2 and its role in clotting?

A compound released by activated platelets that promotes vasoconstriction and further platelet aggregation.

What are the risks when clotting mechanisms go overboard?

Pathological thrombus formation can obstruct vessels and cause ischemic events like stroke.

How does atrial fibrillation increase the risk of stroke?

Irregular atrial contractions cause blood stasis, especially in the atrial appendage, leading to clot formation.

Why does blood stasis occur in atrial fibrillation?

The atria don't contract effectively, causing blood to pool in areas like the atrial appendage

What are the consequences if a clot formed in atrial fibrillation dislodges?

It can embolize to the brain and cause a stroke or travel elsewhere causing systemic embolism.

What is a common preventative treatment for patients with atrial fibrillation?

Anticoagulation therapy to reduce the risk of thromboembolic complications like stroke.

What are the main manifestations of thromboembolic disease?

Deep vein thrombosis (DVT), Pulmonary embolism (PE), Myocardial infarction (MI), and stroke prevention in atrial fibrillation (AF)

What are the two pathways of the coagulation cascade?

The intrinsic and extrinsic pathways.

What type of enzymes are most clotting factors?

Serine proteases.

What initiates the extrinsic pathway of coagulation?

Exposure to tissue factor (Factor III) from damaged vascular endothelium.

What is the first clotting factor activated in the extrinsic pathway?

Factor VII is converted to Factor VIIa.

What initiates the intrinsic pathway?

Exposure of blood to negatively charged surfaces such as collagen, activating Factor XII.

What is the convergence point of the intrinsic and extrinsic pathways?

Activation of Factor X to Factor Xa.

What does Factor Xa do?

Converts prothrombin (Factor II) to thrombin (Factor IIa).

What is the function of thrombin (Factor IIa)?

Converts fibrinogen into fibrin and activates platelets.

What is the structural role of fibrin in clot formation?

Fibrin forms cross-linked strands that stabilize the clot.

Which clotting factors are vitamin K–dependent?

Factors II, VII, IX, and X.

What are Protein C and Protein S?

Natural anticoagulants that inhibit clotting by degrading Factors Va and VIIIa.

How do vitamin K antagonists like warfarin affect clotting?

They inhibit the synthesis of vitamin K–dependent clotting factors and anticoagulant proteins C and S.

Which clotting factor is also known as thrombin?

Factor II.

What is another name for tissue factor?

Factor III.

What is the "common pathway" in the coagulation cascade?

The point where both intrinsic and extrinsic pathways converge at activation of Factor X, leading to thrombin and fibrin formation.

What is the role of antithrombin III in coagulation?

It inhibits thrombin and Factor Xa, reducing clot formation.

How do heparin and low molecular weight heparins (LMWH) work?

They enhance the activity of antithrombin III, thereby inhibiting thrombin and Factor Xa.[

What converts fibrin into its soluble degradation products?

Plasmin, which is activated from plasminogen.

What activates plasminogen to plasmin?

Tissue plasminogen activator (tPA) or streptokinase.

What drug class does warfarin belong to, and how does it work?

Warfarin is a vitamin K antagonist that inhibits synthesis of vitamin K–dependent clotting factors (II, VII, IX, X) and proteins C and S.

What is a serious risk of vitamin K antagonists like warfarin when first started?

Transient hypercoagulability due to early suppression of protein C and S.

Why is tPA clinically used?

To dissolve clots in acute settings like stroke or myocardial infarction by activating fibrinolysis.

What is a deep vein thrombosis (DVT) and what can it lead to?

A thrombus in a deep vein, usually in the leg, which can embolize to the lungs and cause a pulmonary embolism (PE).

What is the most serious complication of DVT?

Pulmonary embolism (PE), which can be fatal.

Why are patients with atrial fibrillation (AF) given anticoagulants?

To prevent thrombus formation in the atria and reduce the risk of stroke.

What does NICE recommend regarding anticoagulation in AF?

The stroke prevention benefit of anticoagulation outweighs the bleeding risk, even in patients prone to falls.

What inherited condition can predispose young people to thromboembolism?

Thrombophilia (e.g., Factor V Leiden or antithrombin/protein C/S deficiency), often with family history.

How does blood flow velocity change in veins as blood moves proximally toward the heart?

Blood flow becomes faster as it moves proximally, especially near the inferior vena cava.

Why are venous thrombi often described as "thread-like"?

Because they are long, fibrous, and loosely structured, like stretched cotton wool, allowing them to fragment and embolize easily.

What happens if a venous thrombus dislodges?

It can embolize and travel through the venous system to the lungs, potentially causing a pulmonary embolism

Why is the structure of venous thrombi significant for embolization?

Their fragile, thread-like nature allows pieces to break off and travel through circulation.

Do veins have smooth muscle to assist blood flow?

No, venous blood return relies on skeletal muscle contraction and valves rather than intrinsic muscle in the vein walls

What are two key factors assisting venous return to the heart?

Skeletal muscle pump and venous valves to prevent backflow.

What prevents blood in the leg veins from flowing backward when muscle contraction stops?

Venous valves prevent backflow by closing after blood is pushed upward.

What are common local effects of a deep vein thrombosis (DVT)?

Pain, oedema from tissue fluid leakage, and surface vasodilation due to blood diversion

How can DVT damage veins long-term?

Thrombus movement through valves can damage the vessel wall, potentially causing chronic venous insufficiency.

What happens when a DVT embolizes to the lungs?

It causes a pulmonary embolism, blocking pulmonary circulation and potentially leading to fluid/blood leakage into lung tissue

What are classic symptoms of pulmonary embolism?

Cough, shortness of breath, and possibly haemoptysis (coughing up blood).

How is suspected DVT assessed clinically?

Using scoring systems like the Wells Score, which includes symptoms and signs around the tibial tuberosity.

What diagnostic tools are used for suspected DVT?

Ultrasound imaging and D-dimer testing.

What is "pitting oedema" and what does it indicate?

Swelling where pressing leaves an indentation, indicating fluid accumulation—commonly seen in DVT or immobility (e.g., long flights).

How does DVT presentation differ between distal and proximal involvement?

Proximal DVTs (extending to the thigh) carry a higher risk of embolization and may require higher INR targets for anticoagulation.

What are the long-term risks of DVT despite treatment?

Persistent leg swelling, asymmetry, or post-thrombotic syndrome due to vein damage.

What visible signs might suggest a leg DVT?

Swelling, redness, warmth, shininess, and asymmetry compared to the other leg.

How does a pulmonary embolism (PE) occur?

A thrombus (usually from a DVT) travels via the venous system into the right atrium, right ventricle, and pulmonary artery, where it lodges in the lung vasculature.

Why is PE a medical emergency?

It obstructs blood flow in the lungs, impairing gas exchange and potentially causing respiratory collapse or death.

What is the path of an arterial embolism that causes a stroke?

A clot from the left atrium (e.g., in atrial fibrillation) can enter the left ventricle, then the aorta, and travel into cerebral arteries (via carotids), causing a stroke.

Why are patients with atrial fibrillation at increased risk of stroke?

Atrial stasis from fibrillation promotes thrombus formation in the left atrial appendage, which can embolize to the brain.

Why are some patients still maintained on warfarin rather than DOACs?

Some patients (e.g. with mechanical heart valves or severe renal impairment) are unsuitable for DOACs and require warfarin for effective anticoagulation.

Which patients may still be maintained on warfarin (Warf)?

Patients with protein C/S deficiency, factor V Leiden, or antithrombin III deficiency, especially if DOACs are unsuitable.

What is protein C deficiency and why is it significant?

It's a hereditary thrombophilia that impairs natural anticoagulation, increasing VTE risk.

What is Factor V Leiden?

A genetic mutation that makes Factor V resistant to degradation by activated protein C, leading to a prothrombotic state.

What is antithrombin III deficiency?

A hereditary or acquired condition reducing the inhibition of thrombin and factor Xa, increasing clotting risk.

How does malignancy lead to hypercoagulability?

Cancer induces a prothrombotic state via inflammation, tissue factor expression, and immobility, increasing risk of spontaneous VTE.

Why are patients undergoing surgery at high risk of VTE?

Due to endothelial injury, immobility, and inflammatory changes; managed with compression stockings and prophylactic heparin.

What makes pregnancy a hypercoagulable state?

Hormonal changes and venous stasis increase clotting tendency to prevent postpartum haemorrhage but increase VTE risk.

What VTE prophylaxis is used in orthopaedic surgeries?

Compression devices and post-operative low-molecular-weight heparin or DOACs (unless contraindicated).