Skip to ContentGo to accessibility pageKeyboard shortcuts menu
OpenStax Logo
Pharmacology for Nurses

20.1 Introduction to Clotting and Coagulation

Pharmacology for Nurses20.1 Introduction to Clotting and Coagulation

Learning Outcomes

By the end of this section, you should be able to:

  • 20.1.1 Explain the pathophysiology of thrombus formation.
  • 20.1.2 Identify the clinical manifestations of thrombus formation.
  • 20.1.3 Identify the etiology and diagnostic studies related to thrombus formation.

The ability of the blood to form clots in response to tissue damage is essential for hemostasis, or the body’s ability to stop bleeding. However, clot formation also underpins many thrombosis-related diseases such as acute myocardial infarction, stroke, and deep vein thrombosis. A client with naturally occurring decreased clotting times is described as hypercoagulable.

Blood Coagulation

Human blood moves as a fluid; however, when injury occurs, hemostasis is accomplished in two major ways: primary hemostasis and secondary hemostasis. Primary hemostasis is the process of platelet adhesion to form a platelet plug, or platelets that are aggregated on the injured vessel wall or tissues. Platelets can be activated in response to collagen released during tissue damage or by a number of other substances. A few of the substances most important for pharmacology are highlighted below and are shown in Figure 20.2:

  • Thromboxane A2, synthesized by the cyclooxygenase pathway
  • Adenosine diphosphate, which interacts with P2Y12 receptors on the platelet surface
  • Thrombin, produced in the coagulation cascade described below
  • Von Willebrand factor and fibrinogen, which bind to the glycoprotein IIb/IIIa (GPIIbIIIa) receptor to facilitate platelet adhesion to other platelets and to the blood vessel wall

Each of these activation steps represents a potential drug target in treatment of pathologic thromboses; they will be expanded upon within the text for the relevant drugs.

A diagram shows how platelet activation occurs, using thromboxane A2, adenosine diphosphate, thrombin, von Willebrand’s factor, and fibrinogen to bind to glycoprotein and form a platelet plug.
Figure 20.2 Platelet activation occurs through thromboxane A2, adenosine diphosphate, thrombin, von Willebrand’s factor, and fibrinogen, among other substances. (attribution: Copyright Rice University, OpenStax, under CC BY 4.0 license)

Upon tissue injury, secondary hemostasis can be activated via the coagulation cascade. The coagulation cascade can be thought of as a chain reaction. The coagulation cascade is made up of clotting factors, which are proteins that work to activate different parts of the coagulation cascade. The factors are named numerically with Roman numerals (e.g., factor X, factor VII). An activated form of a factor is denoted by “a” suffix (e.g., factor Xa, factor VIIa). Figure 20.3 depicts the clotting cascade; it may be helpful to follow the figure simultaneously while reading through the text.

A diagram shows the intrinsic, extrinsic, and common pathway that activates the coagulation cascade. For the intrinsic pathway, collagen activates Factor 12; X12a activates 11; 11A combines with C A 2  positive to activate factor 9. At the same time, thrombin activates factor 8. Factors 8a and 9a combine to activate Factor 10 in the common pathway. For the Extrinsic pathway, damage to endothelial tissues causes Factor 5 to activate. Factors 5a and 7a combine to activate Factor 10 in the common pathway. As Factor 10 is activated in the common pathway, Thrombin is activating Factor 5. Factor 5a and C A 2 positive combine to form Factor 2a. Factor 2a activates Factor 1. At the same time thrombin activates Factor 13 and combines with C A 2 positive to stabilize the fibrin clot.
Figure 20.3 The coagulation cascade can be activated by either the intrinsic or extrinsic pathways. Clotting factors form a chain reaction and converge on a common pathway that ends in formation of a stable fibrin clot. (attribution: Copyright Rice University, OpenStax, under CC BY 4.0 license)

The coagulation cascade can be activated by either the intrinsic pathway or extrinsic pathway, which converge on a common final pathway. Although they are discussed as separate pathways, the physiology is less linear and more complex, with significant crossover and both pathways being activated in response to tissue damage.

  • The extrinsic pathway is activated by injury to blood vessels, which release tissue factor when damaged. Tissue factor works with factor VIIa to activate factor X to factor Xa, which is part of the common pathway.
  • The intrinsic pathway is activated by collagen that is exposed when there is endothelial damage. Collagen facilitates the activation of factor XII. Factor XIIa then facilitates the activation of factor XI, which in its activated form facilitates the activation of factor IX. Factor IXa and factor VIIIa work together to facilitate activation of factor X.
  • The common pathway begins with factor X. Recall from above that factor X is activated by both the intrinsic and extrinsic pathways. Factor Xa facilitates the activation of factor II, which is also known as thrombin. Thrombin facilitates the activation of fibrinogen to fibrin. Thrombin also has other roles within the clotting cascade; it activates factor VIII in the intrinsic pathway and factor V in the common pathway. Thus, activation of thrombin contributes to increased upstream activation as well, which continues down the cascade and activates more thrombin. Fibrin monomers link together to form fibers and branches that make up a solid fibrin clot.

It is noteworthy that many other substances are involved in synthesis and regulation of the clotting cascade. Vitamin K, a vitamin present in foods such as green, leafy vegetables, is a cofactor needed for synthesis of clotting factors II, VII, IX, and X. Calcium is also necessary for activation of several clotting factors.

Coagulation is in homeostatic balance with fibrinolysis, or breakdown of fibrin, as shown in Figure 20.4. This is accomplished when the enzyme tissue plasminogen activator (tPA) facilitates conversion of plasminogen to plasmin, which degrades fibrin. Other natural anticoagulants include proteins C and S, which work together to inhibit the activation of many clotting factors including factors VIIIa, Va, X, and prothrombin; antithrombin, which inhibits the action of many clotting factors including factor Xa and thrombin; and tissue factor pathway inhibitor (TFPI), which inhibits the action of factor Xa.

A diagram shows the balance between thrombosis and bleeding. Clotting occurs when the coagulation cascade combines with prothrombin to form thrombin. The thrombin combines with the fibrinogen to make fibrin. Fibrinolysis occurs when plasminogen activator combines with plasminogen to form plasmin. The plasmin combines with the fibrin to make fibrin degradation products.
Figure 20.4 Clotting and fibrinolysis are in constant balance. Excessive activation of the coagulation cascade can lead to thrombosis, the formation of a clot inside a blood vessel that can block blood flow. Excessive fibrinolysis, mediated by plasmin, can lead to bleeding. (attribution: Copyright Rice University, OpenStax, under CC BY 4.0 license)

Special Considerations

Factor V Leiden

Factor V Leiden is a blood-clotting disorder that increases the client’s risk of thrombosis. It results from a genetic mutation that causes a change in factor V, making it less susceptible to inactivation. Clients with Factor V Leiden cannot change their genetics, but they can work to minimize their other risk factors for thrombosis by maintaining a healthy weight, exercising regularly, and avoiding smoking. These clients should also be vigilant about moving and taking breaks during travel. If these clients experience a clot, they will likely need anticoagulant therapy for the remainder of their life. The National Blood Clot Alliance website provides more information.

Thrombus Formation

The pathologic formation of thrombi (plural of thrombus) occurs as the result of endothelial injury, hypercoagulability, and stasis of blood flow; this is known as Virchow’s Triad and is depicted in Figure 20.5. Endothelial injury activates clotting as described above and occurs due to events such as catheter placement, surgery, or trauma (Ashorobi, 2022). Hypercoagulability refers to a prothrombotic state due to circumstances such as an excess of clotting factors or relative insufficiency of natural anticoagulants. Abnormal blood flow can occur due to prolonged immobility (such as during travel, surgeries, or hospitalization), atherosclerosis within a blood vessel, or an abnormal heart rhythm called atrial fibrillation, where blood pools in the atria because there is no organized contraction of the chambers.

The points of Virchow's Triad are Endothelial industry, Venous stasis, and hypercoagulable state. There are double-sided arrows between each point. Moving between endothelial industry and venous stasis can occur due to surgery, trauma, indwelling catheters, atherosclerosis, and heart valve disease or replacement. Moving between venous stasis and hypercoagulable state can occur due to immobility, travel, and obesity. Moving between hypercoagulable state and endothelial injury can occur due to malignancy, pregnancy, protein C and S deficiency, and antiphospholipid antibodies.
Figure 20.5 Virchow’s Triad describes the causes of clot formation. (See Kushner, et al., 2022, and McLendon, et al., 2023; attribution: Copyright Rice University, OpenStax, under CC BY 4.0 license)

While formation of a clot can be lifesaving during bleeding events, formation of a thrombus can occlude a blood vessel, prohibiting the delivery of blood to downstream tissues. The most common types of thrombi are described below, although this list is not all-inclusive.

Deep Vein Thrombosis and Pulmonary Embolism

A deep vein thrombosis (DVT) is a blood clot that forms within a vein. It most commonly occurs within the legs but can occur elsewhere, such as the pelvis and arms. The clot can break off, travel through the circulatory system, and lodge within the lungs, causing a pulmonary embolism (PE), which can be life-threatening. Risk factors for DVTs include stasis of blood flow caused by confinement to a bed, limited movement, sitting for a long time (such as during travel), or paralysis; increased estrogen caused by oral contraception or pregnancy; certain medical conditions such as cancer; personal or family history of DVT; increased age; obesity; catheter placement; or genetic clotting disorders. Clients with a DVT may experience swelling, pain, redness, and tenderness at the site of the clot (usually in the leg). Clients with a PE often describe chest or back pain and have difficulty breathing, tachycardia, hemoptysis (coughing up blood), and if severe, hemodynamic instability (Centers for Disease Control and Prevention [CDC], 2020). Clients who experience a deep vein thrombosis typically need to be treated with anticoagulant medications. A pulmonary embolism is commonly diagnosed with a computed tomography pulmonary angiogram (CTPA), a specialized type of x-ray that allows visualization of the pulmonary vessels. A ventilation/perfusion scan (also known as a VQ scan) is another type of imaging test that can help diagnose a pulmonary embolism by assessing air flow (ventilation) and blood flow (perfusion) in the lungs.

Ischemic Stroke (Cerebral Infarction)

When a clot obstructs blood flow to the brain, it can cause an ischemic stroke. Two types of ischemic stroke are atherosclerotic and embolic. An atherosclerotic ischemic stroke can be caused by a buildup of fatty substances, cholesterol, and other substances that can narrow the artery and cause blood clots to form. Risk factors for atherosclerotic stroke include male sex, family history of premature cardiovascular disease, hypercholesterolemia, cigarette smoking, hypertension, diabetes mellitus, obesity, and physical inactivity. Clients who experience an atherosclerotic ischemic stroke may also need antiplatelet therapy in addition to treatment of any contributing disease states.

An embolic ischemic stroke (also known as a cerebral embolism) occurs from a blood clot that forms elsewhere in the body. It can be caused by a dysrhythmia called atrial fibrillation (American Stroke Association, 2021) or by clots that form on prosthetic heart valves. In atrial fibrillation, abnormal blood flow within the left side of the heart can lead to clot formation, which can travel out the aorta and lodge within the blood vessels of the brain, occluding blood flow. In clients with atrial fibrillation, the CHA2D2-VASc score (Parsons et al., 2017) can help estimate stroke risk. The scale includes a point system for the following variables: age, sex, heart failure, hypertension, personal history of thromboembolism, vascular disease, and diabetes. It can be calculated by hand or by using an online stroke risk calculator. Clients who have atrial fibrillation or certain prosthetic heart valves usually are treated with an anticoagulant to decrease the risk of embolic stroke. A computed tomography (CT) scan of the brain with contrast allows visualization and diagnosis of both types of stroke.

Myocardial Infarction and Coronary Artery Disease

Clients with atherosclerosis in their coronary arteries are said to have coronary artery disease. The disease states of coronary artery disease and myocardial infarction are expanded upon in the chapters Antihypertensive and Antianginal Drugs and Cardiac Emergency and Shock Drugs. Clients with acute myocardial infarction and coronary artery disease usually are treated with antiplatelet medications. This is especially true after a coronary artery stent is placed. A coronary artery stent is a wire caging that props open a narrowed coronary artery. These require treatment with two concomitant antiplatelet medications for a period of time after stent placement to prevent clots from forming on the stent. While there are many ways to detect a myocardial infarction or coronary artery disease, clots can be directly visualized using coronary angiography during a left-heart catheterization.


This book may not be used in the training of large language models or otherwise be ingested into large language models or generative AI offerings without OpenStax's permission.

Want to cite, share, or modify this book? This book uses the Creative Commons Attribution License and you must attribute OpenStax.

Attribution information
  • If you are redistributing all or part of this book in a print format, then you must include on every physical page the following attribution:
    Access for free at
  • If you are redistributing all or part of this book in a digital format, then you must include on every digital page view the following attribution:
    Access for free at
Citation information

© May 15, 2024 OpenStax. Textbook content produced by OpenStax is licensed under a Creative Commons Attribution License . The OpenStax name, OpenStax logo, OpenStax book covers, OpenStax CNX name, and OpenStax CNX logo are not subject to the Creative Commons license and may not be reproduced without the prior and express written consent of Rice University.