Thrombosis Flashcards
What is Virchow triad?
disruption in blood flow
endothelial cell damage
and hypercoagulable state
Where is the most common location for thrombosis? What are characteristic findings on imaging? What are three risk factors?
DVT of the leg below the knee. Characterized by 1. Lines of Zahn (alternating layers of platelets/fibrin and 2. Attachment to vessel wall
Risk factors - disruption in blood flow, endothelial cell damage, and hypercoagulable state (Virchow triad)
What are three examples of normal blood flow disruption?
Immobilization
Cardiac wall dysfunction due to arrhythmia or MI
Aneurysm
What are 5 ways that endothelial cells prevent thrombosis?
- Block exposure to sub endothelial collagen and underlying tissue factor
- Produce prostacyclin (PGI2) and NO to cause vasodilation and inhibit platelet aggregation
- Secretion of heparin like molecules to augment antithrombin 3
- Secrete tPA
- Secrete thromobomodulin which redirects thrombin to activate protein C which inactivates factors V and VIII
What are some causes of endothelial cell damage?
Atherosclerosis,vasculitis and high levels of homocysteine.
What is the result of cystathionine beta synthase deficiency? How is it characterized?
CBS converts homocysteine to cystathionine. Enzyme deficiency leads to buildup of homocysteine. Characterized by vessel thrombosis, mental retardation, lens dislocation and long slender fingers.
A 16 year old high schooler presents to your office. Her chart shows that she has significant history of recurrent DVTs of the leg, hepatic and cerebral veins. What condition does she have?what usually causes it? Is this an inherited condition?
She has a hypercoagulable state. Usually due to excessive pro coagulant proteins or defective anticoagulant proteins. It may be inherited or acquired.
Deficiency in which protein causes hypercoagulable state? What is the mechanism? How is it inherited? What does it increase the risk of? How is this risk caused?
Protein C or S deficiency which is an autosomal dominant decreases negative feedback on factors V and VIII. Increased risk for warfarin skin necrosis. Initial stage of warfarin therapy results in reduced proteins C and S compared to the other factors particulary if there was a previous deficiency. This leads to an increased risk of thrombosis in the skin.
What is the most common inherited cause of hypercoagulable state? What is an inherited point mutation that promotes thrombus formation?
Factor V Leiden which lacks the cleavage site for deactivation by proteins C and S. Prothrombin 20210A is an inherited point mutation in prothrombin causing increased gene expression.
What medications are associated with a hypercoagulable state?
Estrogen oral contraceptives
How does heparin inactivate thrombin and coagulation factors? What happens to PTT when there is AT3 deficiency? What is the dosing of the heparin medication in AT3 deficiency?
Heparin like molecules normally activate AT3 which inactivates thrombin and coagulation factors. PTT does not rise with standard heparin dosing. High heparin dose activates limited AT3, Coumadin is then given to maintain an anti-coagulated state.
