Lecture 10: Vascular Disorders: Hemorrhage, Emboli and Shock

What pathological outcomes can result from failure of hemostasis, and what underlying issue with the four major factors typically leads to hemorrhage?

Failure of hemostasis can cause hemorrhage, thrombosis, or both (in some disease states). Hemorrhage occurs when there is damage, loss, or abnormal function of any of the four major factors influencing hemostasis:

- Endothelium

- Blood vessel integrity

- Platelets

- Coagulation factors

If a dog presents with spontaneous bleeding and a prolonged bleeding time but normal coagulation factor assays, which major hemostatic factor is most likely affected, and why?

Platelets — because prolonged bleeding time with normal coagulation assays suggests a primary hemostasis defect due to thrombocytopenia or decreased platelet function.

How could infectious agents cause hemorrhage in veterinary patients, and what is a disease example involving immune complexes?

Infectious agents (bacterial, viral, fungal) can damage blood vessels or trigger inflammation that disrupts hemostasis. Immune complex deposition (e.g., feline infectious peritonitis — FIP) can damage the endothelium and increase vascular permeability, leading to hemorrhage.

In terms of gross pathology, how might trauma-induced hemorrhage differ in appearance from hemorrhage caused by thrombocytopenia?

Trauma-induced hemorrhage often presents as larger, localized hematomas or overt external bleeding, while thrombocytopenia tends to cause petechiae or ecchymoses (small pinpoint or blotchy hemorrhages) in mucous membranes, skin, and serosal surfaces.

Which hemostatic factor is most likely compromised in a patient with severe liver disease, and how do toxins such as anticoagulants exacerbate this problem?

Coagulation factors — the liver produces most clotting proteins. Anticoagulant toxins (e.g., rodenticides) inhibit vitamin K-dependent clotting factors, compounding the coagulopathy.

A horse with septicemia develops widespread microthrombi and secondary bleeding at multiple sites. What is the diagnosis, and how does it relate to hemorrhage?

Disseminated intravascular coagulation (DIC) — excessive clot formation consumes platelets and clotting factors, leading to secondary hemorrhage due to depletion of these hemostatic components.

How could a collagen disorder lead to hemorrhage, and which hemostatic factor's integrity is most directly impaired?

Collagen disorders weaken vascular structure, making vessels fragile and prone to rupture. This primarily affects blood vessel integrity within the four major hemostatic factors.

Why might hemorrhage occur in neoplasia, and which hemostatic factor(s) can be disrupted?

Neoplasia can directly invade blood vessels, cause ulceration, or produce procoagulant factors leading to secondary consumption of clotting factors (paraneoplastic coagulopathy). This may disrupt endothelium, vessel integrity, platelets, and/or coagulation factors.

What are the three general mechanisms that cause thrombocytopenia, and provide an example for each.

1. Decreased platelet production - e.g., estrogen toxicity, radiation/drug toxicity, viral infections, liver failure.

2. Increased platelet destruction - e.g., immune-mediated thrombocytopenia (autoimmune).

3. Increased platelet use - e.g., disseminated intravascular coagulation (DIC) causing platelet and coagulation factor consumption.

A dog undergoing chemotherapy develops thrombocytopenia. Which mechanism is most likely responsible, and what is the pathophysiology?

Decreased platelet production — cytotoxic drugs damage bone marrow megakaryocytes, reducing platelet synthesis.

How does DIC cause thrombocytopenia, and what is the paradoxical bleeding/clotting pattern seen?

DIC triggers intravascular coagulation, leading to widespread microthrombi that consume platelets and clotting factors. This results in both thrombosis (from excess clotting) and hemorrhage (from depletion of hemostatic components).

What are the major causes of decreased platelet function, and which is the most common inherited cause in dogs?

Causes include:

- Inherited defects (often alongside coagulation factor deficiencies)

- Von Willebrand's disease (most common inherited platelet function disorder in dogs)

- Autoantibodies against vWF

- Uremia

- NSAID use

- Aspirin therapy

How does von Willebrand's disease impair platelet function?

Deficiency or functional defect in von Willebrand factor (vWF) reduces platelet adhesion to subendothelial collagen and decreases platelet aggregation.

A cat with chronic kidney disease has normal platelet numbers but prolonged bleeding time. Which defect is most likely and what is the mechanism?

Uremia-induced platelet dysfunction — uremic toxins impair platelet adhesion and aggregation despite normal platelet counts.

Why can NSAIDs and aspirin cause platelet function defects, and how do their mechanisms differ?

Both inhibit cyclooxygenase (COX), decreasing thromboxane A₂ synthesis, which impairs platelet aggregation. Aspirin's effect is irreversible for the platelet's lifespan, while most NSAIDs are reversible inhibitors.

What is thrombosis, and what cellular and molecular components make up a thrombus?

Thrombosis is the formation of an excessive or inappropriate thrombus (blood clot) within an injured vessel. A thrombus contains platelets, fibrin, erythrocytes, and inflammatory cells adhered to the vascular wall (blood or lymphatic vessel).

What are the three major determinants of thrombosis described in Virchow's triad, and which is the most important?

1. Endothelial injury - most important; potent stimulus for platelet aggregation and coagulation.

2. Abnormal blood flow - includes turbulence and stasis.

3. Hypercoagulability - imbalance in pro- and anti-coagulant factors.

Why is endothelial injury considered the most important factor in Virchow's triad?

It exposes subendothelial collagen and tissue factor, triggering platelet adhesion, activation, and coagulation — initiating the hemostatic cascade.

In which vascular beds is reduced blood flow most significant for thrombosis risk, and why?

Most significant in veins, where baseline flow is slow. Stasis allows accumulation of activated coagulation factors and prolonged contact with platelets and the endothelium.

How can abnormal blood flow promote thrombosis through turbulence versus stasis?

- Turbulence disrupts laminar flow, causing platelets and coagulation factors to contact endothelium and potentially injure it.

- Stasis prolongs contact time between activated factors and the endothelium, allowing local clot propagation.

Give two anatomic sites where reduced blood flow may predispose to thrombosis, and explain why.

Dilated heart chambers and dilated vessels — both create areas of stasis where coagulation factors and platelets accumulate.

What is hypercoagulability, and what is the most common cause in animals?

Hypercoagulability is an increased tendency to clot due to excessive activation or decreased degradation of hemostatic proteins (coagulation factors, inhibitors, or fibrinolytic proteins). Inflammation is the most common cause in animals.

What are the gross morphologic features of arterial thrombi, and why are they typically paler than venous thrombi?

Features: Tapering tail, pale red to tan, dull, friable, loosely adherent to vessel wall or endocardium.

Reason for paler color: Formed under high pressure/high flow → fewer RBCs trapped compared to venous thrombi.

What are the gross morphologic features of venous thrombi, and what conditions favor their formation?

Features: Molded to vessel wall, dull mottled dark red with pale tan-red regions, loosely adherent, often occludes entire lumen, rarely has a tapering tail.

Form under: Low pressure and stasis → more RBCs incorporated.

How can you differentiate an antemortem thrombus from a postmortem blood clot on gross exam?

Antemortem thrombus: Dull, friable, variably colored, adherent to vessel wall.

Postmortem clot: Smooth, shiny, gelatinous, non-adherent, often forms "chicken fat" (yellow) and "currant jelly" (red) portions due to RBC settling.

What is the primary mechanism for resolving small thrombi, and why might larger thrombi require a different process?

Small thrombi: Removed via thrombolysis.

Large thrombi: Often incompletely cleared; phagocytes remove debris, fibroblasts invade, and recanalization (new vascular lumen formation) occurs.

What is recanalization, and why is it clinically significant?

Formation of new vascular channels through an organized thrombus, allowing partial restoration of blood flow. Clinically important because it can restore some perfusion but rarely returns the vessel to normal function.

What is an embolus, and how does it differ from a thrombus?

An embolus is a free-floating foreign material within a vessel, whereas a thrombus is a stationary mass adhered to the vessel wall.

List at least six types of emboli found in veterinary patients.

- Thromboemboli (most common)

- Bacterial

- Parasitic

- Fat

- Fibrocartilaginous

- Neoplastic

- Air

Why is a saddle thrombus considered an embolus?

A saddle thrombus originates as a thrombus in another location (often the heart) and travels through the bloodstream until lodging at a vascular bifurcation (e.g., aortic bifurcation in cats), making it a thromboembolus.

What are two non-thrombotic causes of emboli that could occur after trauma or invasive procedures?

Fat emboli (e.g., from long bone fractures) and air emboli (e.g., from catheter placement or surgery).

Define shock and describe the cascade of events it triggers at the cellular level.

Shock (cardiovascular collapse) is a circulatory dyshomeostasis leading to hypotension, impaired tissue perfusion, and cellular hypoxia. This causes a shift to anaerobic metabolism, resulting in cellular degeneration, death, and — if persistent — irreversible cell injury and organ failure.

What are the three major types of shock, and what is the unifying pathophysiologic outcome among them?

Cardiogenic, hypovolemic, and blood maldistribution shock — all lead to impaired tissue perfusion and cellular hypoxia.

What are common causes of cardiogenic shock, and how do they impair perfusion?

Caused by failure of the heart to pump adequately (↓ stroke volume, ↓ cardiac output). Examples: myocardial infarction, ventricular tachycardia, fibrillation, advanced cardiomyopathy, and obstruction of blood flow (pulmonary thromboembolism, pulmonary/aortic stenosis, caval syndrome).

How much acute blood loss can typically be compensated for before dramatic hemodynamic collapse occurs in hypovolemic shock?

Up to 10% loss is usually well compensated; 35-45% loss causes severe drops in blood pressure and cardiac output.

What are the two major mechanisms leading to hypovolemic shock, and give examples of each.

Hemorrhage (trauma, surgery, GI bleeding)

Fluid loss (vomiting, diarrhea, burns)

What are the three main categories of blood maldistribution shock, and what unites them pathophysiologically?

1. Anaphylactic shock - IgE-mediated hypersensitivity; histamine release → peripheral vasodilation + bronchoconstriction.

2. Neurogenic shock - trauma, electrocution, or fear → autonomic discharge → vasodilation, venous pooling, hypoperfusion.

3. Septic shock - bacterial/fungal products (e.g., LPS) → massive inflammatory mediator release → peripheral vasodilation, hypotension, hypoperfusion.

4. Common mechanism: Decreased peripheral vascular resistance → pooling of blood in peripheral tissues.

Why is septic shock the most common form of blood maldistribution shock in veterinary patients, and what organism type is most often involved?

Septic shock is most common because bacterial and fungal infections are frequent in clinical settings. Gram-negative bacteria are the most frequent cause due to lipopolysaccharide (LPS) in their cell walls, which triggers endotoxic shock via excessive proinflammatory and procoagulant responses.

What are the hallmark cardiovascular and respiratory signs seen in shock?

Hypotension, weak pulse, tachycardia, hyperventilation often with pulmonary rales.

What renal and thermoregulatory changes occur in shock, and why?

Reduced urine output from renal hypoperfusion and hypothermia from decreased metabolic heat production and peripheral vasoconstriction.

What characterizes the late decompensated stage of shock, and why is it often irreversible?

Organ and system failure due to prolonged hypoperfusion and widespread irreversible cell injury.

What defines the nonprogressive stage of shock, and what is its clinical significance?

The nonprogressive stage involves compensatory mechanisms (e.g., baroreceptor reflexes, RAAS activation, catecholamine release) that temporarily counteract hypoperfusion, allowing potential recovery if the cause is corrected early.