Ch 4 Pathoma - Thrombosis/Embolism Flashcards
Thrombosis
pathologic formation of an intravascular blood clot
Lines of Zahn
alternating layers of platelets/fibrin and RBCs characteristic of thrombosis (thrombi are also attached to vessel walls)
How can you tell a thrombus from a postmortem clot on autopsy
lines of zahn
Virchow’s Triad
disruption in blood flow (turbulent or static), endothelial cell damage, hypercoaguable state
3 examples of disruption in normal blood flow
Immobilization, cardiac wall dysfunction (arrhythmia or MI), aneurysm
5 ways endothelial cells prevent thrombosis normally
Block exposure to sub endothelial collagen, produce prostacyclin (PGI2) and NO, secrete heparin-like molecules, secrete tPA, secrete thrombomodulin
Prostacyclin (PGI2) and NO (ways endothelial cells prevent thrombosis)
vasodilation and inhibition of platelet aggregation
Heparin-like molecules (ways endothelial cells prevent thrombosis)
augment antithrombin III (ATIII), which inactivates thrombin and coag factors
Tissue plasminogen activator (tPA) (ways endothelial cells prevent thrombosis)
converts plasminogen to plasmin which (1) cleaves fibrin and serum fibrinogen, (2) destroys coagulation factors, (3) blocks platelet aggregation
Thrombomodulin (ways endothelial cells prevent thrombosis)
redirects thrombin to activate protein C, which inactivates factors V and VIII
3 causes of endothelial damage
atherosclerosis, vasculitis, high levels of homocysteine
Two ways to have elevated homocysteine
vitamin B12/folate deficiency and cystathionine beta synthase (CBS) deficiency
How Vitamin B12/Folate deficiency –> Homocysteine buildup
folic acid (aka tetrahydrofolate, THF) circulates in serum as methyl-THF –> methyl transfered to cobalamin (B12) –> (THF can participate in synthesis of DNA precursors) –> cobalamin transfers methyl to homocysteine resulting in methionine
Cysthationine beta synthase deficiency
cbs converts homocysteine to cystathionine; characterized by vessel thrombosis, mental retardation, lens dislocation, and long slender fingers (also results in homocystinuria)
4 genetic causes for hypercoagulability
Protein C or S deficiency, Factor V Leiden, Prothrombin 20210A, ATIII deficiency
Protein C or S deficiency
- autosomal dominant
- normally they inactivate factors V and VIII
- increased risk for warfarin skin necrosis
Factor V Leiden
mutated form of factor V that lacks the cleavage site for deactivation by proteins C and S
- most common inherited cause of hypercoagulable state
ATIII deficiency
- ATIII inactivates thrombin and coagulation factors
In ATIII deficiency does PTT rise/fall/stay the same with standard heparin dosing
stays the same (heparin works by binding and activating ATIII) –> give high dose heparin to activate the limited ATIII and coumadin to maintain anticoag state (can stop high dose heparin when you pass skin-necrosis warfarin window)
Estrogen induces ______ production of coagulation factors (increased/decreased)
increased (oral contraceptives = increased risk for thrombus)
Embolism
intravascular mass that travels and occludes downstream vessels
5 types of emboli
thromboembolus, atherosclerotic embolus, fat embolus, gas embolus, amniotic fluid embolus
Embolus characterized by presence of cholesterol clefts
atherosclerotic embolus (formed by atherosclerotic plaque that dislodges)
Embolus associated with bone fractures
Fat embolus
