Coagulation Disorders Flashcards
What components make up the virchow triad of thrombosis?
- endothelial injury
- thombosis - can lead to either abnormal blood flow or hyper-coagulability
What is a very potent stimulant of the clotting cascade?
- thrombin
What does the von Wildebrant factor do?
-platlets are pulled up against the vessel wall to establish a clot
What proteins will inhibit the activity of 5a and 5s?
proteins c and s
The activation of what allows the body to activate the fibrinolytic system here?
- the activation of plasminogen to plasmin
Where is factor 8 synthesized?
- synthesized by the vascular endothelial wall and is released into the blood stream
What is the only factor that is not generated by the liver?
- factor 7
Factor 8C (coagulant material) participates in what pathway?
intrinsic pathway
Factor 8 vWF participates in what pathway?
platelet pathway
Arachidonic acid is broken down to PGI through the work of what?
broken down via cyclooxyrgenase
ASA will irreversibly acetylate what enzyme to stop the activity of platelets to generate thromboxane A2 in the platelets?
COX (cyclooxygenase)
What allows ASA to irrevesibly acetylate platelets?
- there are no nuclear apparatus in the platelets - they cannot regenerate the COX enzyme (this is not like COX in the blood vessel wall that can be regenerated before cell death)
How long will it take for COX to be regenerated in the platelets?
COX enzyme regenerates in about a week in the platelets - have to wait for the life of the platelets to be over before we can generate more COX enzymes
What is the action of prostacyclin? (PGI)
PLT anti-aggregator, vasodilator
What is the action of the TXA2 (thromboxane A2)?
- PLT aggregator, vasoconstrictor
What is the action of the vWF in the vessels?
- vWF allows the platelets to bind to the collagen as well as to the collagen on the vessel walls. vWF is the way that you get the platelets to adhere to the vessel wall
What is the action of the GPIIb/IIIa receptor complex?
- the receptor here latches down on the fore of the fibrin
- the fibrin strand here will contact and will pull the platelets together
- the pulling together of the platelets occur when the activation of the GPIIb/IIIa receptor
What receptor does clopridogrel bind to?
- binds to the PY12 receptor- will not allow for the activation of the receptor complex
What are the factors that predispose a person to bleeding?
- open vessel
- pro-clotting factor deficiencies
- platelet defects
What is an INR or prothrombin time test?
- a test based on the time for detection of clot formation in a test tube of the patient’s plasma after the addition of the thromboplastin and calcium
What happens in the absence of calcium in the clotting cascade?
- people will not clot
How do you interpret an INR test that takes over 12 seconds?
- suggestive of a defective extrinsic and common pathway
- this test is sensitive to reductions in Factors 2, 7, and 10
Warfarin reduces the synthesis of what factors?
- 2, 7, 9 and 10
What factor has a very short plasma half life?
- factor 7
What is the effect of warfarin on factors 7, 2 and 10?
- factor 7- very sensitive to warfarin (have a very short plasma half life)
- there may not be adequate reductions of factors 2 and 10
- the PT (or INR) may become rapidly prolonged during warfarin therapy
- a thrombotic state may still be evident due to a continued activation of factors 2 and 10 via the intrinsic pathway
Will an INR be altered by thrombocytopenia or defective platelets?
- no
Will an INR be altered when the fibrinogen levels are low?
- yes- it will be prolonged
Do ASA or other NSAIDs alter the INR?
no
Is thrombin time affected by platelets?
- no
INR is the testing of the _____ generation
fibrin
What is the activated partial thromboplastin time (aPTT)?
- a test based on the time for detection of clot formation in a test tube of patients plasma after the addition of an activating agent and calcium
What does an activated partial thromboplastin time over 33 seconds mean?
- suggestive of a detective intrinsic and common pathway
What as an activated partial thromboplastin time test sensitive to?
- sensitive to reductions in factors 2,8,9,10,11 and 12
Heparin immediately accelerates the binding and inactivation of activated forms of Factors 2,9,19,11,12 by ______
antithrombin-III
What pharmacodynamic action of heparin on PTT is ______
immediate (max effects of heparin are commonly seen after 6 hours however)
Can aPTT be altered by thrombocytopenia or defective platelets?
no
Can aPTT be altered when the fibrinogen levels are low?
yes- the aPTT is prolonged
Do NSAIDs affect the aPTT?
no
What is the main difference of heparin and warfarin summarized?
- heparin: binds the activated forms of the clotting factors (you are immediately affecting the clotting pathway and stopping the activation of the clotting cascade)
- warfarin: decreases the synthesis of certain clotting factors
How is INR calculated?
INR = {PT/PTc} ISI
- PT: patient’s prothrombin time
- PTc: mean prothrombin time for your lab control
- ISI: international sensitivity index
What is the normal INR range for someone that is not medicated?
0.9-1.1 (the higher the INR, the higher the potential for bleeding)
What is a white thrombi?
- arterial thrombi
- primarily made up of platelets, but also fibrin and WBCs
- eg coronary artery thrombosis, cerebral circulation thrombi
What is a red thrombi?
- venous thrombi
- primarily made of fibrin and RBCs and a small platelet plug
- eg. deep vein thrombi, pulmonary emboli, ischemic limbs
Where does ASA have an effect? (venous or arterial thrombi?)
- ASA will have absolutely no effect in a venous thromboembolism
- is has an effect on the arteries (if someone has a heart attach or a stroke) but not have an effect on the veins
What molecules are procoagulants (work with clotting)
- tissue thromboplastin
- exposed collagen
- activated factors
- thromboxane A2
- von Willebrand’s factor
- factor 8 coagulant material
What molecules are anticoagulants (work with bleeding)
- protein C and protein S
- factor deficiencies
- antithrombin (AT)
- prostacyclin
- heparin
- tPA
- plasmin