[03.05b] Hemodynamics, Thrombosis and Shock (Part 2) V2.2.pdf

Endothelial injury, stasis or turbulence of blood flow, blood hypercoagulability

What are the three primary influences that predispose to the formation of a thrombus, also known as Virchow’s Triad?

Endothelial integrity

What is considered the single most important factor for thrombosis?

Subendothelial collagen

What is exposed when endothelial injury occurs, allowing platelets to adhere via von Willebrand factor?

Platelet adherence and clot formation

What will not occur if the endothelium is intact?

Abnormal blood flow

What is a characteristic of stasis or turbulence of blood flow?

Endothelial injury

What can abnormal blood flow cause?

Independently or in combination

How may the elements of Virchow's Triad act to cause thrombus formation?

Cardiac chambers, over ulcerated plaques in atherosclerotic arteries, and vasculitis

Where is endothelial injury important for thrombus formation?

Thickening of the tunica intima, making arteries stiff and hard and their lumen narrows

What characterizes atherosclerosis?

Ulceration of formed plaques within the artery

What is one complication of atherosclerosis that can trigger thrombus formation?

Exposure of the subendothelial collagen

Why do ulcerations of atherosclerotic plaques mainly trigger thrombus formation?

No

Does the endothelium need to be denuded or physically disrupted to contribute to thrombosis?

Disturbance in the dynamic balance of pro- and antithrombotic effects of the endothelium

What generally influences local clotting events without physical disruption of the endothelium?

Excess pro-thrombotic substances or events, along with excess adhesion and aggregation

What can result in inappropriate clot formation?

Increased clotting as fibrin will persist

What is the result of a high number of anti-plasminogen activator?

Plasmin

What is supposed to degrade fibrin but is inactivated by anti-plasminogen activator?

Hemodynamic stresses of hypertension, turbulent flow over scarred valves, bacterial endotoxins, radiation injury, metabolic abnormalities, toxins absorbed from cigarette smoke

Name some settings where significant endothelial dysfunction can occur in the absence of endothelial cell loss.

Myocardial infarction (MI)

What is smoking a risk factor for?

Endothelial injury or dysfunction

How does turbulence contribute to arterial and cardiac thrombosis?

Countercurrents and local packets of stasis

What else does turbulence form, contributing to thrombosis?

Ulcerated atherosclerotic plaques

What is a common cause of turbulence that exposes vWF and tissue factor?

Glycoprotein 1b

What binds to von Willebrand factor (vWF) exposed by ulcerated atherosclerotic plaques?

Tissue factor (TF)

What initiator of the extrinsic coagulation pathway is exposed by ulcerated atherosclerotic plaques?

Atherosclerosis

What disease often has thrombosis as a consequence?

Coronary arteries

Where can plaque easily obstruct blood flow, leading to myocardial infarction?

Myocardium

What does thrombosis in coronary arteries decrease blood supply to?

Venous thrombi

What is stasis a major contributor in the development of?

Aneurysms (aortic and arterial dilatations)

What is a cause of stasis where blood enters outpocketings, disrupting laminar flow?

Fertile sites for thrombosis

What are aneurysms considered due to altered blood flow?

Deep vein thrombosis (DVT)

What common condition is associated with stasis in veins, particularly in the lower extremity?

Prolonged sitting due to obesity, pregnancy, or long flights

What can cause DVT?

Area of ischemic necrosis (cell death)

What is an infarct?

Decreased blood flow and oxygen supply

What leads to ischemia in a region of myocardium in an AMI?

Areas of non-contractile myocardium and cardiac aneurysms

What does an AMI result in?

Fibrous tissue

What replaces necrotic cardiac cells after an MI?

Permanent cells

What type of cells are cardiac cells, meaning they cannot regenerate?

Stasis and flow abnormalities

What promotes the formation of cardiac mural thrombi associated with AMI?

Endocardium

To what layer of the heart is a thrombus attached in a cardiac mural thrombus?

Left atrial dilation

What does rheumatic mitral valve stenosis result in?

Atrial fibrillation (AF)

In conjunction with what condition does a dilated atrium become a site of stasis and thrombus development?

Polycythemia vera

In what condition is hyperviscosity seen?

Increased RBC count and viscosity

What causes stasis in polycythemia vera?

Increased resistance to flow and small vessel stasis

What does hyperviscosity cause?

Vascular occlusions

What does sickle cell anemia cause?

Cannot adjust to the small caliber of capillaries

Why do sickle-shaped red blood cells cause vascular occlusions?

Normal blood flow is laminar

What is a characteristic of normal blood flow in vessels?

Platelets and other blood elements flow centrally, separated from endothelium by plasma

How do blood elements flow in laminar blood flow?

Endothelial activation

What do stasis and turbulence promote?

Enhances pro-coagulant activity and leukocyte adhesion

What does endothelial activation lead to?

Disrupt laminar flow

What do stasis and turbulence do to blood flow?

Prevent washout and dilution of activated clotting factors

What do stasis and turbulence prevent?

Abnormally high tendency of the blood to clot

What is hypercoagulability?

Alterations in coagulation factors

What causes hypercoagulability?

Venous thrombosis

Where do hypercoagulable states play important roles?

Primary (genetic) and secondary (acquired) disorders

What are the two main types of hypercoagulable disorders?

Point mutations in the factor V gene and prothrombin gene

What are the most common inherited causes of hypercoagulability?

Site of endothelial injury or turbulence

Where do arterial or cardiac thrombi typically occur?

Sites of stasis

Where do venous thrombi (phlebothrombosis) typically occur?

Retrograde direction from the point of attachment

In what direction do arterial or cardiac thrombi grow?

Direction of blood flow

In what direction do venous thrombi grow?

Occlusive

What characteristic is shared by both arterial/cardiac thrombi and venous thrombi regarding blood flow?

Coronary arteries, cerebral arteries, femoral artery

Name common sites for arterial or cardiac thrombi.

Veins of the lower extremity (90%)

Where do venous thrombi most commonly occur?

Heart chambers or aortic lumen

Where do mural thrombi occur?

Stasis secondary to MI

What causes cardiac mural thrombi?

Fibrous noncontractile scar post-MI

What is seen in the heart that promotes cardiac mural thrombi?

Abnormal MI or endomyocardial injury

What promotes cardiac mural thrombi?

Ulcerated atherosclerotic plaque and aneurysmal dilation

What are precursors for aortic thrombi?

Laminations in thrombi

What are Lines of Zahn?

Grossly and microscopically in the heart or aorta

Where are Lines of Zahn seen?

Alternating pale layers of platelets admixed with fibrin and darker layers of red cells

What do Lines of Zahn appear as?

White

What color does fibrin appear in Lines of Zahn?

Red

What color do red cells appear in Lines of Zahn?

Thrombosis at a site of blood flow

What do Lines of Zahn imply?

Antemortem thrombosis from bland non-laminated clots that occur postmortem

What do Lines of Zahn distinguish?

Gelatinous with dark red dependent portion and yellow chicken fat supernatant

What is the character of postmortem clots?

Firmer

What is the character of venous thrombi?

Not attached to underlying wall

Are postmortem clots attached to the vessel wall?

Almost always have a point of attachment

Are venous thrombi attached to the vessel wall?

Absent

Are Lines of Zahn present in postmortem clots?

Present

Are Lines of Zahn present in venous thrombi?

Accumulate more platelets and fibrin, leading to vessel occlusion

What happens during propagation of a thrombus?

Plasmin

What degrades fibrin?

Plasminogen

From what is plasmin derived?

tPA alteplase

What drug can be given in early MI or stroke?

Dislodge and travel to other sites

What happens during embolization of a thrombus?

Embolus

What is a dislodged thrombus called?

Form new lamina to facilitate blood flow

What can thrombi do during organization and recanalization?

Fibrinolytic activity

How may thrombi be removed during dissolution?

Inflammation and fibrosis

What may thrombi induce during organization and recanalization?

New lamina

What can thrombi form during organization and recanalization to reestablish vascular flow?

Dislodged thrombus

What is an embolus, primarily?

Detached intravascular solid, liquid, or gaseous mass that is carried by the blood to a site distant from its point of origin

What is the full definition of an embolus?

Partial or complete vascular occlusion

What is the result when an embolus lodges in vessels too small to permit further passage?

Ischemic necrosis or infarction

What does occlusion of an artery due to an embolus lead to?

Cell death

What happens to cells or tissue with persistent ischemia?

Coronary artery or pulmonary circulation

Where can an embolus or thromboembolism lead to infarction and cell death?

Deep leg vein thrombi above the level of the knee

Where do pulmonary thromboembolisms most commonly originate?

Venous thrombi, phlebothrombosis, red or stasis thrombus

What type of thrombus is a deep leg vein thrombus?

Stasis due to prolonged periods of time without movement of the lower extremities

What causes deep leg vein thrombi?