Hemodynamic Disorders and Thrombosis

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Questions and Answers

What is a significant risk posed by venous thrombi?

Causing high blood pressure.

Promoting the formation of additional thrombi.

Leading to embolization to the lungs. (correct)

Preventing blood flow in the upper extremities.

Which factor is primarily responsible for the formation of venous thrombi?

Activation of the coagulation cascade (correct)

Endothelial injury

Countercurrents in arterial flow

Perturbation of antithrombotic factors

Which type of thrombosis is most concerning for critical vascular obstruction?

Arterial thrombosis in coronary vessels. (correct)

Arterial thrombi in peripheral circulation.

Deep venous thrombosis in lower leg veins.

Superficial venous thrombosis in the saphenous system.

What is a common characteristic of arterial thrombi?

They tend to grow in a retrograde direction from the point of attachment. Signup and view all the answers

What commonly initiates arterial thrombosis?

Atherosclerosis leading to endothelial damage. Signup and view all the answers

How is primary hypercoagulability defined?

It is due to genetic mutations. Signup and view all the answers

Where do most venous thrombi primarily occur?

In the superficial or deep veins of the leg. Signup and view all the answers

What is a primary consequence of deep venous thrombosis?

Increased risk of pulmonary embolism. Signup and view all the answers

What is the role of turbulence in thrombosis?

It leads to endothelial injury and dysfunction. Signup and view all the answers

What distinguishes mural thrombi from other thrombi?

They occur on heart valves or within cardiac chambers. Signup and view all the answers

Which condition can lead to cardiac mural thrombi?

Myocardial infarction due to coronary artery disease. Signup and view all the answers

What is the primary role of endothelial cells in maintaining hemostasis?

Preventing platelet adhesion and maintaining blood flow Signup and view all the answers

Which of the following factors is produced by endothelial cells that promotes platelet adhesion during injury?

von Willebrand factor (vWF) Signup and view all the answers

Which of the following is NOT a primary disorder of hypercoagulability?

Myocardial infarction Signup and view all the answers

What defines an embolus in the context of thrombosis?

A detached mass carried by blood to a distant site. Signup and view all the answers

What are lines of Zahn?

Patterns within a thrombus visible microscopically Signup and view all the answers

Which of the following is NOT a characteristic of superficial venous thrombi?

They commonly cause life-threatening embolism. Signup and view all the answers

What are the three primary components involved in both hemostasis and thrombosis?

Endothelial cells, Platelets, Coagulation cascade Signup and view all the answers

What happens to thrombi during venous flow?

They extend in the direction of blood flow. Signup and view all the answers

How do endothelial cells exhibit antithrombotic effects?

By blocking platelets and inhibiting coagulation cascade Signup and view all the answers

Which molecule is known for contributing to the anticoagulant properties of endothelial cells?

Nitric oxide Signup and view all the answers

What initiates platelet adhesion to the extracellular matrix (ECM)?

Interaction with vWF Signup and view all the answers

Which of the following correctly describes a procoagulant effect of endothelial cells?

Production of tissue factor after injury Signup and view all the answers

What results from the activation of endothelial cells by cytokines like TNF or IL-1?

Increased production of tissue factor Signup and view all the answers

What is contained within the dense body granules released during platelet secretion?

Adenine nucleotides and serotonin Signup and view all the answers

Which statement about the role of endothelial cells in hemostasis is NOT true?

They constantly encourage platelet aggregation. Signup and view all the answers

What is a common consequence of thromboembolism in downstream tissues?

Ischemic necrosis Signup and view all the answers

What role does thrombin play in platelet aggregation?

It induces further platelet aggregation. Signup and view all the answers

Where do most pulmonary emboli originate?

Deep leg vein thrombi above the knee Signup and view all the answers

What occurs during the process of ‘viscous metamorphosis’ in platelets?

Platelets create an irreversibly fused mass. Signup and view all the answers

What is the current incidence rate of pulmonary embolism in hospitalized patients?

20 to 25 per 100,000 Signup and view all the answers

What is the ultimate goal of the coagulation cascade?

Amplify enzymatic conversions to produce thrombin Signup and view all the answers

What percentage of pulmonary emboli are clinically silent due to their small size?

60% to 80% Signup and view all the answers

How does thrombin contribute to the stability of the clot?

By converting fibrinogen to fibrin Signup and view all the answers

What can happen if the coagulation cascade is not restricted to the local site of injury?

Runaway clotting may occur. Signup and view all the answers

Which of the following is a predisposing factor for deep vein thrombosis?

Immobility and bed rest Signup and view all the answers

What are systemic thromboemboli mostly derived from?

Intracardiac mural thrombi Signup and view all the answers

What is the primary stimulus for platelet aggregation?

ADP and thromboxane A2 Signup and view all the answers

What treatment is commonly used for deep vein thrombosis?

Intravenous heparin Signup and view all the answers

Which factor is associated with an increased risk of fatigue embolism?

Fractures of long bones Signup and view all the answers

What primary action do antithrombins perform in the clotting process?

Inhibit the activity of thrombin and other serine proteases Signup and view all the answers

Which proteins are involved in inactivating cofactors Va and VIIIa?

Proteins C and S Signup and view all the answers

What is the primary enzyme responsible for the process of fibrinolysis?

Plasmin Signup and view all the answers

How is plasmin generated from its precursor plasminogen?

By enzymatic degradation through a factor XII-dependent pathway or plasminogen activators Signup and view all the answers

Which of the following is NOT one of Virchow's triads influencing thrombus formation?

Blood hypocoagulability Signup and view all the answers

What is the function of α2-antiplasmin in the context of fibrinolysis?

To inactivate free plasmin and prevent excessive lysis of thrombi Signup and view all the answers

Which of these coagulation assays is NOT typically used to assess fibrinolysis?

Fibrin degradation products assay Signup and view all the answers

What role does tissue factor pathway inhibitor (TFPI) have in the clotting process?

It inhibits tissue factor and prevents excessive clotting Signup and view all the answers

Study Notes

Hemodynamic Disorders, Thrombosis, and Shock

The health of cells and tissues relies on an intact circulation to deliver oxygen and remove waste products, as well as on normal fluid homeostasis.
Maintaining blood as a liquid until clot formation is necessary is a crucial aspect of normal fluid homeostasis.
Normal hemostasis is a result of tightly regulated processes keeping blood in a fluid, clot-free state in normal vessels, while simultaneously inducing rapid clot formation at the site of vascular injury.
Hemostasis and thrombosis involve three components: the vascular wall, platelets, and the coagulation cascade.

Hemostasis and Thrombosis

Vasoconstriction is the first stage, where endothelium release causes vasoconstriction, reducing blood flow to the injured area.
Primary hemostasis involves platelet adhesion, shape change, granule release (ADP, TXA2), recruitment and aggregation to form a hemostatic plug.
Secondary hemostasis involves tissue factor expression, phospholipid complex expression, thrombin activation, and fibrin polymerization to form an insoluble fibrin gel surrounding the platelets, making the plug stable.
Thrombus formation and anticlotting mechanisms involves the release of t-PA (fibrinolysis), and thrombomodulin to stop the coagulation cascade.

Endothelium

Endothelial cells play a complex role in hemostasis by modulating various opposing aspects, establishing a balance affecting thrombus formation, propagation, or dissolution.
Endothelial cells possess antiplatelet, anticoagulant, and fibrinolytic properties under normal conditions but can also exhibit procoagulant activities after exposure to injury/activation.

Antithrombotic Properties

Endothelial cells maintain a liquid blood flow environment, by preventing platelet adhesion and aggregation, by inhibiting the coagulation cascade, and by breaking down blood clots.
Intact endothelium prevents platelets and coagulation factors from interacting with thrombogenically active subendothelial ECM and by secreting prostacyclin (PGI2) and nitric oxide, along with Adenosine diphosphatase.
Endothelial-derived heparin-like molecules and thrombomodulin inhibit the clotting mechanisms.

Fibrinolytic Properties

The coagulation cascade activation also activates an opposing fibrinolytic cascade, a process regulating the ultimate clot size.
Plasmin, an enzyme, is responsible for fibrin breakdown, and interfering with fibrin polymerization.
Plasmin is produced by degrading the inactive plasminogen precursor, either through a factor XII-dependent pathway or by plasminogen activators like t-PA or u-PA.

Coagulation Cascade

The coagulation cascade is a series of enzymatic reactions that amplify the conversion of inactive proenzymes to active enzymes, culminating in thrombin.
Thrombin converts the soluble protein fibrinogen into insoluble fibrin monomers, which polymerize into a gel that ensnares platelets and other circulating cells to form the secondary hemostatic plug.
Activated coagulation cascade in the body needs to be localized to prevent a runaway effect, achieved with a variety of anticoagulants.

Antithrombins

Antithrombins like antithrombin III inhibits thrombin and other serine proteases, such as factors IXa, Xa, XIa, and XIIa.
Proteins C and S are Vitamin K-dependent proteins, responsible for inactivating cofactors Va and VIIIa, regulating the clotting cascade.
Tissue factor pathway inhibitor (TFPI) plays a vital role in controlling clotting, functioning by restricting factor activation.

Thrombosis

The pathogenesis of thrombosis has three major influences; endothelial injury, abnormal/turbulent blood flow and hypercoagulability.

Endothelial Injury

Endothelial injury is crucial in thrombus formation, and disruption in the dynamic balance between prothrombotic and antithrombotic functions contribute to local clotting events.
Endothelial injury is relevant in thrombus formation, particularly in the heart or arterial circulation.

Alterations in Blood Flow

Turbulence in blood flow causes endothelial injury or dysfunction, contributes to arterial and cardiac thrombosis.
Blood stasis is a crucial contributor to venous thrombi development.

Hypercoagulability

Hypercoagulability is defined as alterations in coagulation pathways that increase the susceptibility to thrombosis.
This can be further classified into primary (genetic) and secondary (acquired) disorders.

Morphology

Thrombi can originate anywhere in the cardiovascular system, including heart chambers, valves, arteries, veins or capillaries.
Thrombi develop focally on the underlying vascular surface and may propagate in the direction of blood flow, with arterial thrombi propagating retrogradely and venous thrombi propagating towards the heart.
Thrombi can have distinct laminations known as Zahn lines, and heart or aortic thrombi are categorized as mural thrombi.
Arterial thrombi are often occlusive and are primarily composed of platelet activation and coagulation activation, featuring a meshwork of platelets, fibrin, erythrocytes and degenerating leukocytes.
Venous thrombi are almost always occlusive, having a cast of the lumen, primarily due to the coagulation cascade and containing enmeshed erythrocytes; called red or stasis thrombi

Fate of Thrombus

Thrombi can propagate, embolize or dissolve.
Thrombi organization and recanalization can eventually occur.

Clinical Correlations

Thrombi can significantly obstruct arteries and veins, causing emboli.
Venous thrombi are more concerning due to their potential to embolize to the lungs causing death.
Arterial thrombi can lead to tissue infarctions and are clinically more significant when obstructing critical blood vessels.

Venous Thrombosis

Most venous thrombi arise from superficial or deep leg veins, often in the saphenous system (particularly in the presence of varicosities).
Superficial venous thrombi typically cause local congestion, swelling, pain, and tenderness.
Deep venous thrombi, arising in larger leg veins above the knee joint (e.g., popliteal, femoral, iliac) can embolize and be more serious.

Cardiac and Arterial Thrombosis

Atherosclerosis is a critical contributor to arterial thrombosis, related to loss of endothelial integrity and altered vascular flow.
Cardiac mural thrombi can arise from myocardial infarction, leading to dyskinetic myocardial contraction or endocardium damage.
Rheumatic heart disease can lead to atrial mural thrombi due to mitral valve stenosis, accompanied by left atrial dilation and atrial fibrillation.

Embolism

An embolus is a detached intravascular solid, liquid, or gaseous mass that is transported by blood to a distant site.
Almost all emboli (99%) are thromboemboli.
Other rare forms include fat droplets, air bubbles, atherosclerotic debris, tumor fragments, bone marrow and foreign bodies like bullets.

Pulmonary Thromboembolism

Pulmonary embolism (PE) has a rate of approximately 20-25/100,000 hospitalized patients with a fatality rate of 6% to 2%, though its prevalence is lower post-mid 20th century.
Most pulmonary emboli (60-80%) are clinically silent because of their small size. Deep leg vein thrombi above the knee joint are the main origin of venous emboli.

Systemic Thromboembolism

Most systemic thromboemboli originate from intracardiac mural thrombi.
Commonly associated with left ventricular wall infarctions and dilated left atria (e.g., secondary to mitral valve disease and potentially leading to embolization to lower extremities (75%) and brain (10%).

Deep Veins Thrombosis - Predisposing Factors

Immobility, pregnancy and postpartum states, post-operative, severe burns, heart failure, and disseminated cancer increase the risk of deep vein thrombosis (DVT).

Prevention and Treatment of DVT

High risk patients must identify themselves and be offered prophylaxis.
Treatment of DVT generally includes intravenous heparin and/or warfarin .

Fat Embolism, Air Embolism, and Amniotic Fluid Embolism:

Fat embolism syndrome, characterized by pulmonary insufficiency, neurological symptoms, anemia and thrombocytopenia, arises following long bone fractures or soft-tissue trauma.
Air embolism can occur due to large amounts of air entering the circulation, often from obstetric procedures or chest wall injury and can frequently cause distal ischemic injury.
Amniotic fluid embolism (AFE) is a serious complication of labor and the immediate postpartum period with an unusually high mortality rate.

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Description

Explore the critical concepts of hemodynamic disorders, thrombosis, and shock. Understand the processes of hemostasis, including vasoconstriction and the roles of platelets and coagulation in maintaining fluid homeostasis. This quiz assesses your knowledge of vascular injury responses and clot formation.