Thombosis Flashcards
What are 2 characteristics of a thrombus, these characteristics allow us to distinguish a thrombus from what, and what are the three major risk factors for developing a clot?
Lines of Zahn which are alternating lines of RBC and fibrin platelet.
Attachment to the vessel wall.
These two features also distinguish it from a postmortem clot.
Disrupted blood flow, endothelial damage, hypercoagulable state
What is the main principle behind disruption of blood flow and what 3 situations can cause disruptions?
Laminar vs. turbulent. Keeps platelets away from the wall and being activated.
Immobilization, cardiac wall dysfunctions like arrhythmias and MI
Aneurysm because there is a pocket to have turbulent flow
5 things the endothelial wall does to protect itself from being damaged or from clot forming on it?
The endo layer itself is a protected layer from exposing collagen
secretes PGI2 and NO for vasodilation and inhibiting platelet aggregation
Secretes heparin like molecules which leads to production of AT3 which takes out thrombin and clotting factors
Secretes TPA
Secretes thrombomodulin which redirects thrombin to activate protein C which activates 5 and 8
3 causes of endothelial damage to remember?
Atherosclerosis, vasculitis, and high homocysteine levels
What are three causes of high homocysteine levels?
Folate deficiency, b12 deficiency, and CBS deficiency.
What is the problem with CBS deficiency, what two things does it lead to, and what are 4 clinical symptoms of it?
High homocysteine levels with homocysteine in the urine
Thrombosis, mental retardation, lens dislocation and long slender fingers
Two big picture reasons why we would have a hypercoagulable state?
Either too much of clotting side of things or not enough anti clot. Balance is way off.
What is the classic presentation of people who have hypercoagulable states?
Recurrent DVTs at a young age
Explain what is going on with Protein C or S deficiency and how warfarin affects this disease?
C and S inactivate factors 5 and 8, so no C or S and these guys agents turned off.
Now, when we give warfarin to a patient, it takes out epoxide reductase which takes out vitamin k. Now we will start to see a drop in 27910 and c and s. However, c and s have much shorter half life so they go first leaving the clotting factors at a high level and at risk for activation and clot. We give heparin at this increased risk time. A person with a c and s deficiency already really has a big risk because c and s go fast. Increased risk for warfarin skin necrosis.
What is the most common inherited cause of a hypercoagulable state?
Factor 5 Leiden mutation where 5 is mutated in such a way that it cannot be cleaved/inactivated by protein c and s.
What is the problem with prothrombin 20210A?
Point mutation in prothrombin that results in increased gene expression so you’re going to get way more thrombin, leading to more thrombus.
What’s the main problem with AT3 deficiency and how do we anticoagulate these patients?
The protective effect of the heparin like molecules coming out of the endothelium is gone because they work through AT3. Also, this is how heparin works.
Need to give a high dose of heparin to activate any AT3 that’s in there and then give Coumadin
What was the last cause of a hypercoagulable state he mentioned and why?
Oral contraceptives because they increase the production of clotting factors
