Vascular Disorders and Thrombosis II Flashcards
what are the major players in hemostasis?
endothelium and underlying matrix
platelets
circulating factors
what do prostacyclin and nitric oxide do with thrombosis?
inhibit platelet activation, adhesion, and aggregation
vasodilate
does ADPase promote thrombosis or prevent it?
prevents it: degrades pro-thrombotic ADP
what does tissue plasminogen activator do?
activates plasmin to digest fibrin
what are the membrane associated factors of endothelium that prevent thrombus?
thrombomodulin and circulating proteins C and S
heparin-like molecules and circulating antithrombin III
tissue factor pathway inhibitor
what does endothelin do?
vasoconstricts
what does von Willebrand Factor do?
enhances platelet binding to collagen
what does platelet activating factor do?
recruits and activates platelets
what does tissue factor (factor III) do?
initiates extrinsic coagulation pathway
what do plasminogen activator inhibitors do?
inhibit fibrinolysis
what do platelets secrete to promote aggregation?
calcium
ADP- also activation
thromboxane A2- vasoconstricts as well
what is the primary producer of most circulating clotting and anticoagulant factors?
liver
what clotting factors produced by the liver are vitamin K-dependent?
II, VII, IX, X
protein C and protein S
what is the primary initiator of the coagulation cascade in vivo?
extrinsic pathway: activated by exposure of Tissue Factor (factor III) to factor VII in circulation
what is the primary amplifier of the coagulation cascade in vivo?
intrinsic pathway: activated by negatively-charged substances, collagen, inflammatory pathways
what factors are involved in the intrinsic pathway for the coagulation cascade?
factors XII, XI, IX, VIII
when do the extrinsic and intrinsic pathways merge?
activation of factor X: factor X and V= prothrombinase complex
what is the ratio of blood to anticoagulant for a coagulation test?
9:1
what is the initiation of the cell-based model of coagulation?
circulating VIIa binds tissue factor on surface damaged endothelial cells
factor Xa and a small amount of thrombin are produced
how does thrombin amplify coagulation?
activates platelets, cleaves von Willebrand’s Factor-VIII complex, and activates factors V, VIII, XI
what do activated coagulation factors aggregating on activated platelets lead to?
production abundant Xa
what do Xa and Va produce?
abundant thrombin
what inhibits fibrinolysis?
alpha-2 antiplasmin
plasminogen activator inhibitor-1
what activates plasmin for fibrinolysis?
tissue plasminogen activator
urokinase-type plasminogen activator
what is plasmin derived from?
circulating plasminogen
what are the two major functions of plasmin?
fibrinolysis
inhibition of fibrin polymerization
what is a thrombus?
aggregate of platelets, fibrin, and blood cells
temporary patch
inappropriately large or persistent blood clot
what is thrombosis?
formation of a pathologic thrombus
what is an embolus?
thrombus or thrombus fragment is moved from its origin to a distant vessel
what are the factors leading to pathologic thrombosis?
endothelial injury
abnormal blood flow
hypercoagulable state
how can blood flow be altered in virchow’s triad?
stasis
turbulence
what can lead to hypercoagulability in virchow’s triad?
inflammation
glomerular disease
protein losing enteropathy
liver disease
endocrine disorders
neoplasia
what are the outcomes of thrombosis?
hypoxia
ischemia
infarction/infarct
what makes up a reperfusion injury?
formation reactive oxygen species
inflammation/mediators
what does the color of an infarction depend on?
whether offending thrombus arterial or venous
types of tissue
duration infarct
what can an embolus be?
detached thrombus (most frequent)
fat or bone marrow
gas bubble
tumor fragment
bacterial colonies
foreign objects
what may larger, chronic thrombi be replaced by?
granulation tissue, fibrosis +/- mineralization
recanalization
what does recanalization entain?
growth of new endothelium
formation of capillary channels
reinstitution of small amount of blood flow around/through thrombus
what is an antemortem thrombus like?
firm, adhered to vessel wall
red to tan, dull, often granular
what is a postmortem clot like?
soft, gelatinous, loosely or not adhered to vessel wall
deep red and smooth often, can be tan/yellow if red cells settle out
how can you distinguish an arterial thrombus from a venous one?
arterial is often more pale
see gross or microscopic lamellations (lines of Zahn)
how can you tell a thrombus is venous instead of arterial?
more red
less firm
should have attachment point on vessel wall
similar in appearance to postmortem clot
how does hypertrophic cardiomyopathy in cats lead to a saddle thrombus (embolism in distal abdominal aorta)?
left ventricle fills poorly, so left atrium is backed up
left atrium remodels by dilation and local endothelial damage with stretching
stasis and endothelial injury leads to clot in left atrium
dislodges
where is the defect in primary hemostatic disorders?
platelet arm of coagulation
what are the characteristics of von Willebrand disease?
decreased or absent von Willebrand’s Factor
platelet numbers and function are normal
reduces ability of platelets to bind to subendothelial collagen
what are the characteristics of hemostatic disorders?
hematomas
cavitary hemorrhage
delayed bleeding from venipuncture sites
is liver disease with loss of hepatic parenchyma and example of secondary or primary hemostatic disorders?
secondary hemostatic disorders
true/false: a patient with liver disease with loss of hepatic parenchyma is at risk for hyper- and hypocoagulabilty
true
what do vitamin K antagonist rodenticides inhibit?
factors II, VII, IX, X from binding calcium and phospholipid surface
what happens in disseminated intravascular coagulation with clotting and clotting factors?
widespread activation of coagulation in small vessels
massive consumption of platelets and clotting factors
what is hypoxanthine?
reacts with oxygen to form free radicals in reperfusion injury
