Thrombosis Flashcards
Define thrombosis. Where does it frequently occur?
Pathologic formation of an intravascular blood clot. Occurs in arteries or veins. Most commonly in deep veins below knee.
How do you characterize a thrombus? What makes these characteristics important?
Lines of Zahn (alternating layers of platelets/fibrin and RBCs) and attachment to blood vessels. These distinguish thrombi from post-mortem clots.
What are the three major risk factors for thrombosis? What is the fancy name for these three risk factors?
Disruption of bloodflow (stasis, turbulence), endothelial cell damage, and hyperoagulable state. Virchow’s triad.
Give 3 examples of disruption to blood flow and whether they are characterized as static flow or turbulent flow.
Immobilization (stasis), Cardiac wall dysfunction (turbulence and/or stasis), Aneurysm (turbulence)
How does laminar flow prevent thrombi formation?
Laminar blood flow keeps factors and platelets evenly dispersed.
How does endothelium prevent thrombus formation?
Block exposure of subendothelial collagen and underlying tissue factors, produce prostacyclin (PGI2) and NO which deter platelet aggregation and promotes vasodilation, secrete heparin-like molecules which augment antithrombin III, secrete tissue plasminogen activator (tPA) (converts plasminogen to plasmin which 1) cleaves fibrin and serum fibrinogen 2) destroys coag factors 3)blocks platelet aggregation) and secretes thrombomodulin whcih causes thrombin to activate protein C which inactivtes FV and FVIII
3 causes of endothelial cell damage
Atherosclerosis, vasculitis, high levels of homocysteine
Describe the 2 mechanisms that leads to high levels of homocysteine
1) Folic acid/Vit B12 deficiency results in mildly elevated homocysteine levels. Methyl is shuttled from THF to Vit B12 to homocysteine. If FA/B12 low, shuttling cannot occur and homocysteine levels elevate 2) Cystathionine beta synthase (CBS) deficiency. CBS converts homocysteine to cystathionine
Characteristics of cystathionine beta synthase deficiency
Vessel thrombosis, mental retardation, lens dislocation, long slender fingers
General causes of hypercoagulable state and common presentation
Excessive procoagulant proteins or defective anticoagulant proteins; inherited or acquired. Recurrent DVTs usually in deep veins of legs or hepatic/cerebral arteries
Describe mechanism of protein C or S deficiency and how this deficiency leads to hypercoagulable state
Proteins C and S inactivate FV and FVIII
What is warfarin skin necrosis and how is it caused?
Thrombi that form in the skin when warfarin/coumadin is administered. FII, VII, IX, and X remain in the blood along with Protein C and S are no longer produced because of warfarin. PC and PS have shorter half-lives relative to FII, VII, IX, and X. If PC and PS deficiency exist already, there is a greater disparity between PC/PS and FII, VII, IX, and X raising the risk of skin thrombi and WSN.
What is FV Leiden and what kind of condition does it cause?
FV Leiden is a mutated FV that cannot be cleaved by PC or PS and therefore causes a hypercoagulable state.
What is Prothrombin 20210A and what condition does it cause?
Results in increased gene expression of prothrombin. Greater amounts of prothrombin result in greater amounts of thrombin and a hypercoagulable state.
What is ATIII deficiency and what condition does it cause? What is the mechanism? What is the pharmacologic intervention commonly used to maintain the desired effects of heparin?
Antithrombin III deficiency decreases protective effect of HLMs resulting in hypercoagulable state. Normally. HLMs activate ATIII which inactivates thrombin and coag factors. In ATIII deficiency, PTT does not rise with standard heparin dose because heparin normally actives ATIII. Coumadin is administered to maintain anticoagulated state.
