Ch4 - 4) Thrombosis Flashcards
What is thrombosis?
Pathologic formation of an intravascular blood clot (thrombus), Can occur in an artery or vein,
What is the most common location for thrombosis?
it is the deep veins (DVT) of the leg below the knee
What is thrombosis characterized by?
lines of Zahn and attachment to vessel wall
What are the lines of Zahn?
alternating layers of platelets/fibrin and RBCs
What distinguishes thrombus from a postmortem clot?
lines of Zahn and attachment to vessel wall
What are three major risk factors for thrombosis?
disruption in blood flow, endothelial cell damage, and hypercoagulable state (Virchow triad)
What is normal blood flow?
blood flow is normally continuous and laminar; keeps platelets and factors dispersed and inactivated
What happens to blood flow that causes an increase in the risk for thrombosis?
Stasis and turbulence of blood flow increases risk for thrombosis
What are some examples of disruption of normal blood flow?
Immobilization?increased risk for deep venous thrombosis 2. Cardiac wall dysfunction (e.g arrhythmia or myocardial infarction) 3. Aneurysm
How does endothelial cell damage increase the risk for thrombosis?
Endothelial damage disrupts the protective function of endothelial cells, increasing the risk for thrombosis
How do endothelial cells prevent thrombosis?
- Block exposure to subendothelial collagen and underlying tissue factor 2. Produce prostacyclin (PGI2) and NO, 3. Secrete heparin-like molecules, 4. Secrete tissue plasminogen activator (tPA) 5. Secrete thrombomodulin
How does endothelial cells use the secretion of tPA to prevent thrombosis?
converts plasminogen to plasmin, which (1) cleaves fibrin and serum fibrinogen, (2) destroys coagulation factors, and (3) blocks platelet aggregation
How does the secretion of thrombomodulin from endothelial cells prevent thrombosis?
redirects thrombin to activate protein C, which inactivates factors V and VIII
How do endothelial cells use the secretion of heparin-like molecules to prevent thrombosis?
augment antithrombin III (ATIII) which inactivates thrombin and coagulation factors
How does endothelial cells use the production of prostacyclin (PGI2) and NO to prevent thrombosis?
vasodilation and inhibition of platelet aggregation
What are the causes of endothelial cell damage?
atherosclerosis, vasculitis, and high levels of homocysteine
Vitamin B12 and folate deficiency result in?
mildly elevated homocysteine levels, increasing the risk for thrombosis.
What does folic acid circulate as?
methyl-THF (tetrahydrofolate, THF) in the serum,
How does THF participate in the synthesis of DNA precursors?
Methyl is transferred to cobalamin (vitamin B12) which transfers methyl to homocysteine resulting in methionine
What does a lack of vitamin B12 or folate lead to?
decreased conversion of homocysteine to methionine resulting in buildup of homocysteine
Cystathionine beta synthase (CBS) deficiency results in what?
high homocysteine levels with homocystinuria,
What does CBS do?
CBS converts homocysteine to cystathionine
CBS deficiency leads to?
homocysteine buildup
CBS deficiency is characterized by?
vessel thrombosis, mental retardation, lens dislocation, and long slender fingers
what is a hypercoagulabe state due to?
excessive procoagulant proteins or defective anticoagulant proteins; may be inherited or acquired
What is the classic presentation for a hypercoagulable state?
recurrent DVTs or DVT at a young age, usually occurs in the deep veins of the leg; other sites include hepatic and cerebral veins
What are some causes of a hypercoagulable state?
protein C and S deficiency, factor V Liden deficiency, prothrombin 20210A, ATIII deficiency, oral contraceptives
protein C or S deficiency
(autosomal dominant) decreases negative feedback on the coagulation cascade (hypercoagulable state)
Proteins C and S normally do what?
inactivate factors V and VIII
Protein C and S deficiency increases the risk for what?
warfarin skin necrosis
What does the initial stage of warfarin therapy result in?
a temporary deficiency of proteins C and S (due to shorter half-life) relative to factors II, VII, IX, and X
In preexisting C or S deficiency, what danger does the initial stage of warfarin therapy present?
a severe deficiency is seen at the onset of warfarin therapy increasing the risk for thrombosis, especially in the skin
What is Factor V Leiden?
a mutated form of factor V that lacks the cleavage site for deactivation by proteins C and S
What is the most common inherited cause of hypercoagulable state?
Factor V Leiden
What is Prothrombin 20210A?
it is an inherited point mutation in prothrombin that results in increased gene expression,
Increased prothrombin (prothrombin 20210A) results in what?
increased thrombin, promoting thrombus formation.
What does ATIII deficiency result in?
decreases the protective effect of heparin-like molecules produced by the endothelium, increasing the risk for thrombus
What do heparin-like molecules normally do?
activate ATIII, which inactivates thrombin and coagulation factors
What happens in ATIII deficiency?
PTT does not rise with standard heparin dosing.
Pharmacologic heparin works by doing what?
binding and activating ATIII
High doses of heparin in someone with ATIII deficiency results in what?
activate limited ATIII; Coumadin is then given to maintain an anticoagulated state.
How are oral contraceptives associated with a hypercoagulable state?
Estrogen induces increased production of coagulation factors, thereby increasing the risk for thrombosis
