Exam 1: Hemostasis, Thrombosis, and Hemorrhage Flashcards
What is bleeding stopped by?
Hemostasis
Describe what happens in hemostasis
Complex interaction of endothelium, platelets, and the coagulation cascade
These processes maintain blood in a fluid, clot-free state in normal blood vessels
They can also induce a rapid and localized “hemostatic plug” at the site of vascular injury
Anticoagulant activities also occur to limit the extent of the plug–process of fibrinolysis
What is the pathologic correlate to hemostasis?
Thrombosis, but it is considered to be an inappropriate activation of normal hemostatic processes
What is the sequence of events with vascular injury?
Vasoconstriction
Primary hemostasis
Secondary hemostasis
Reorganization and formation of a permanent plug
What are the different ways vasoconstriction can occur?
Transient arteriolar vasoconstriction after initial endothelial injury that exposes collagen of the subendothelial matrix (ECM)
Vasoconstriction due to local nerve reflex and release of endothelin by endothelial cells
What does vasoconstriction help do?
Limit the escape of RBCs and proteins from damaged areas
Describe primary hemostasis
Platelets adhere to exposed ECM via von Willebrand factor
Platelets undergo activation
Platelets release secretory granules (ADP and thromboxane A2, cause vasoconstriction and promote further platelet aggregation)
Form primary hemostatic plug
Describe secondary hemostasis
Local activation of the coagulation cascade
Tissue factor is secreted by adjacent endothelial cells
Thromboplastin initiate the clotting cascade
Results in fibrin polymerization and cementing platelets into a definitive secondary plug
What happens with counter-regulatory mechanisms?
Release of compounds that limit that hemostatic process to the site of injury
- –tissue type plasminogen activator (fibrinolytic)
- –thrombomodulin (interferes with the clotting cascade)
What is thrombosis?
Formation of a blood clot due to either inappropriate activation of normal hemostasis or formation of a clot in a vessel after injury
Can also be due to other abnormal processes that can block a blood vessel and lead to death
What is fibrinolysis?
The process of limiting the hemostatic process at the site of injury
Includes the release of tissue plasminogen activator and thrombomodulin by adjacent endothelium
What is endothelium?
Cells that line blood vessels
What are the antithrombotic properties of endothelium?
Normally acts as a barrier between blood and subendothelial collagen
- –Block platelet aggregation
- –Interfere with coagulation
- –Actively lyse clots
What are the prothombotic properties of endothelium?
Injury or activation of endothelial cells can result in procoagulant phenotypes that augment local clot formation
What are the effects of antithrombotic properties of endothelium?
Antiplatelet effects
Anticoagulant effects
Fibrinolytic effects
Describe the antiplatelet properties of endothelium
Intact endothelium prevents platelets and coagulation factors from meeting the highly thrombogenic subendothelial ECM
- –Non-active platelets do not adhere to the uninjured endothelium
- –Activated platelets are inhibited from adhering to surrounding uninjured endothelium by endothelial prostacyclin and NO
- –Endothelial cells also express ADPases (ADP is needed for platelet aggregation)
Describe the anticoagulant properties of endothelium
Heparin-like molecules from endothelium act indirectly with and inactivate several coagulation factors
Thrombomodulin from endothelium also acts indirectly, binding to thrombin and converting it from a procoagulant to an anticoagulant
Major source for tissue factor pathway inhibitor- a cell surface protein that complexes with and inhibits several proteins of the clotting cascade
What are the fibrinolytic effects of endothelium?
Endothelial cells synthesize tissue-type plasminogen activator
- –Promotes fibrinolytic activity
- –Clears fibrin deposits from endothelial surfaces
What are properties of platelets?
Play a central role in normal hemostasis
Smallest components of mammalian blood
They are not cells; membrane-bound smooth discs with no nucleus
Originate from bone marrow megakaryocytes as the end products of cytoplasmic and membrane protrusions
Their surface has several glycoprotein receptors called integrins that bind to exposed collagen
What do platelets do after vascular injury?
They encounter ECM constituents that are normally sequesterd beneath an intact endothelium
What are the 3 general reactions platelets undergo on contact with ECM?
Adhesion and shape change
Secretion (release reaction)
Aggregation
What are the 2 types of granules that platelets contain?
Alpha granules and dense bodies (delta granules)
Describe alpha granules
Express the adhesion molecule P-selectin
Contain fibrinogen, fibronectin, factor V, Factor VIII, vWF, PDGF, and TGF-β
Describe dense bodies
Contain ADP, ATP, ionized Ca, histamine, serotonin, epinephrine
What do activated plates have?
Spiny processes that protrude from cell membranes
Describe platelet activation
Activated platelets undergo change in shape
Secrete granule contents and express surface phospholipid complex
Aggregate and form reversible primary hemostatic plug
—Thrombin binds to surface receptors and binds to fibrinogen to integrins on surface
Contract irreversibly to form secondary hemostatic plug
—Thrombin converts fibrinogen to fibrin
—FIbrin “mortars” in place
What is thrombocytopenia?
Lack of platelets
Describe the coagulation cascade
Secondary hemostasis
A blood clot forms through the action of a cascade of proteolytic reactions
Third component of the hemostatic process
Major contributor to thrombosis
Cascade of enzymatic conversions that turn inactive proenzymes into activated enzymes
Culminates in the formation of thrombin
Thrombin then converts the soluble plasma protein fibrinogen precursor into the incoluble protein fibrin
What does each reaction in the coagulation cascade result from?
The assembly of a complex composed of an enzyme (activated coagulation factor), a substrate (proenzyme form of coagulation factor), a cofactor (reaction accelerator)
How are the components that result it in the coagulation cascade assembled?
Assembled on a phospholipid complex and held together by Ca ions
What is the intrinsic pathway initiated by?
Initiated in vitro by activation of the Hageman factor (factor XII)
What is the extrinsic pathway initiated by?
Tissue factor (a cellular lipoprotein exposed at site of tissue injury)
Besides coagulation, what does the activation of the clotting cascade also initiate?
The fibrinolytic cascade that limits the final size of the clot
What happens to plasminogen in fibrinolysis?
Plasminogen is in circulation and is cleaved to plasmin by tissue plasminogen activator
What does plasmin do?
Breaks down fibrin and interferes with its polymerization
What can fibrin split products act as?
Weak anticoagulants
What is an important process in the regulation of hemostasis?
Fibrinolysis
What is extravasation?
Escape of blood from blood vessels
What is hemorrhage per rhexis?
Rapid flow of blood through breaks in vessel wall
What is hemorrhage per diapedesis?
Oozing of blood through holes in the vessel wall
What is a hematoma?
Enclosed accumulation of blood in a tissue (bulging, rounded area of hemorrhage)
What is petechiae?
1-2 mm hemorrhage in the skin, mucous membranes, or serosal surface of an organ
What is petechiae associated with?
Locally increased intravascular pressure, thrombocytopenia, defective platelet function, or clotting factor deficits
What are ecchymoses?
2mm - 1cm SQ hemorrhage
What is ecchymoses associated with?
Locally increased intravascular pressure, thrombocytopenia, defective platelet function, or clotting factor deficits, especially trauma
What is purpura?
More than 1 cm hemorrhage in the skin, mucous membrane, or serosal surface
What is purpura associated with?
Locally increased intravascular pressure, thrombocytopenia, defective platelet function, or clotting factor deficits
Also trauma, local vasculitis, increased vascular fragility
What is paintbrush hemorrhage?
Hemorrhage along a natural plane
What is suffusive hemorrhage?
Hemorrhage along a natural plane
What is hemorrhage?
A large accumulation of blood in a blood cavity
What is the fate of hemorrhage?
RBCs are phagocytized and enzymatically degraded by mφ
Porphyrin release from hemoglobin produces color
Clot
What is the process of color changes with hemorrhage?
Hemoglobin (red-blue)
Bilirubin (blue-green)
Hemosiderin (gold-brown)
What is a clot?
Contracts which causes separation of serum from coagulum
Describe coagulum
Lysed and removed
Can become organized by connective tissue
Describe serum
Reabsorbed and removed
Form seroma (large area of fluid in a tissue)
Seromas can be excellent growth media for bacteria
What does the significance of a hemorrhage depend on?
Amount, rate, and location
What happens if more than 1/3 of blood volume is lost quickly?
Hypovolemic shock which leads to exsanguination
What happens if less than 1/3 of blood volume is lost quickly?
Possible compensation and survival
What happens with slow blood loss?
Compensatory changes
What happens if the location of the hemorrhage is in the brain, pericardium, or lungs?
Interference with organ normal function
How much blood volume can be lost if blood is lost slowly?
As much as 1/2 of blood volume over weeks to months and the animal is able to compensate
What occurs when an animal is trying to compensate for blood loss?
RR may increase to help oxygenate better
Hematopoiesis in bone marrow
Extramedullary hematopoiesis
Animals will limit exercise to keep O2 consumption low
What is thrombosis?
Pathological formation of a clot with the cardiovascular system
What may thrombosis lead to?
Interference with blood flow
—Turbulence and stasis
What may thrombosis result in?
Infarction, passive congestion, or embolism (fragment of thrombus that breaks off and lodges somewhere distal
What are causes of thrombosis?
Change in blood flow (slow down) Change in blood viscosity Loss of vascular endothelial smoothness Endothelial injury Hyper reactive states of platelets Proteinuria
Describe what happens with endothelial injury
Endothelial cell damage and exposure of subendothelial collagen
Vasoconstriction follows and then platelet adhesion, aggregation, and activation of the clotting cascade
A platelet plug is formed which is often held together by polymerized fibrin
What does turbulence of blood flow contribute to?
Arterial and cardiac thrombosis by causing endothelial injury and by forming countercurrent and local areas of stasis
What is stasis?
A major factor in the development of venous thrombi
What do stasis and turbulence do?
Disrupt laminar flow and bring platelets into contact with endothelium
Prevents dilution of clotting factors by fresh flowing blood
Retard inflow of clotting factor inhibitors
Describe secondary blood hypercoagulability
Disseminated intravascular coagulation (DIC)
Disseminated cancers- release of procoagulant tumor products
Certain glomerular diseases (loss of anti-thrombin III)
What is a postmortem (PM) clot?
When an animal dies, blood clots in vessels and forms a mold in the shape of the vessel
Describe what a PM clot is like
Shiny and gelatinous
Fills entire chamber
Removes easily
Usually red, but may have yellow plasma near the surface and be red at the base
Describe thrombus
Rough surface and attached to vessel wall
Difficult to remove
Usually pale color due to protein and fibrin
Early thrombi may be red
What is a current jelly clot?
Homogenous red
What is a chicken fat clot?
Homogenous yellow (plasma)
What is the microscopic appearance of thrombus?
Attached to wall
Lamination- alternating pale layers of platelets admixed with some fibrin and darker layers containing more RBCs
Where does a venous thrombi\us usually occur?
At sites with blood stasis, extending in the direction of blood flow
Where does an arterial thrombus begin?
At site of endothelial injury or turbulence
Where is a vegetative thrombus most common? Where else can one occur?
On mitral (left AV) valve and it tends to travel in general circulation (kidneys) It can also occur on semilunar and R AV valves and it tends to travel to lungs or general circulation
What is verminous thrombus caused by?
Parasites
What is a mural thrombus?
Attached to endocardium
What is a septic thrombus?
Bacterial colonization of a thrombus; causes or is a result if bacteremia
What are the outcomes of thrombosis?
Propagation
Embolization
Dissolution/resolution
Organization and recanalization
What is propagation?
Thrombus may accumulate more platelets and fibrin leading to vessel obstruction
What is embolization?
Thrombus may dislodge and travel to other sites, forming thromboemboli
What is dissolution/resolution?
Thrombi may be removed by fibrinolytic activity
What may organization and recanalization induce?
Inflammation and fibrosis and eventually become recanalized (re-established blood flow or be incorporated into a thickened vascular wall)
What happens with recanalization?
Thrombus converted to fibrous connect tissue
May contract over time