Coagulation Disorders Flashcards
(117 cards)
1
Q
What components make up the virchow triad of thrombosis?
A
- endothelial injury
- thombosis - can lead to either abnormal blood flow or hyper-coagulability
2
Q
What is a very potent stimulant of the clotting cascade?
A
- thrombin
3
Q
What does the von Wildebrant factor do?
A
-platlets are pulled up against the vessel wall to establish a clot
4
Q
What proteins will inhibit the activity of 5a and 5s?
A
proteins c and s
5
Q
The activation of what allows the body to activate the fibrinolytic system here?
A
- the activation of plasminogen to plasmin
6
Q
Where is factor 8 synthesized?
A
- synthesized by the vascular endothelial wall and is released into the blood stream
7
Q
What is the only factor that is not generated by the liver?
A
- factor 7
8
Q
Factor 8C (coagulant material) participates in what pathway?
A
intrinsic pathway
9
Q
Factor 8 vWF participates in what pathway?
A
platelet pathway
10
Q
Arachidonic acid is broken down to PGI through the work of what?
A
broken down via cyclooxyrgenase
11
Q
ASA will irreversibly acetylate what enzyme to stop the activity of platelets to generate thromboxane A2 in the platelets?
A
COX (cyclooxygenase)
12
Q
What allows ASA to irrevesibly acetylate platelets?
A
- 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)
13
Q
How long will it take for COX to be regenerated in the platelets?
A
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
14
Q
What is the action of prostacyclin? (PGI)
A
PLT anti-aggregator, vasodilator
15
Q
What is the action of the TXA2 (thromboxane A2)?
A
- PLT aggregator, vasoconstrictor
16
Q
What is the action of the vWF in the vessels?
A
- 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
17
Q
What is the action of the GPIIb/IIIa receptor complex?
A
- 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
18
Q
What receptor does clopridogrel bind to?
A
- binds to the PY12 receptor- will not allow for the activation of the receptor complex
19
Q
What are the factors that predispose a person to bleeding?
A
- open vessel
- pro-clotting factor deficiencies
- platelet defects
20
Q
What is an INR or prothrombin time test?
A
- 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
21
Q
What happens in the absence of calcium in the clotting cascade?
A
- people will not clot
22
Q
How do you interpret an INR test that takes over 12 seconds?
A
- suggestive of a defective extrinsic and common pathway
- this test is sensitive to reductions in Factors 2, 7, and 10
23
Q
Warfarin reduces the synthesis of what factors?
A
- 2, 7, 9 and 10
24
Q
What factor has a very short plasma half life?
A
- factor 7
25
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
26
Will an INR be altered by thrombocytopenia or defective platelets?
- no
27
Will an INR be altered when the fibrinogen levels are low?
- yes- it will be prolonged
28
Do ASA or other NSAIDs alter the INR?
no
29
Is thrombin time affected by platelets?
- no
30
INR is the testing of the _____ generation
fibrin
31
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
32
What does an activated partial thromboplastin time over 33 seconds mean?
- suggestive of a detective intrinsic and common pathway
33
What as an activated partial thromboplastin time test sensitive to?
- sensitive to reductions in factors 2,8,9,10,11 and 12
34
Heparin immediately accelerates the binding and inactivation of activated forms of Factors 2,9,19,11,12 by ______
antithrombin-III
35
What pharmacodynamic action of heparin on PTT is ______
immediate (max effects of heparin are commonly seen after 6 hours however)
36
Can aPTT be altered by thrombocytopenia or defective platelets?
no
37
Can aPTT be altered when the fibrinogen levels are low?
yes- the aPTT is prolonged
38
Do NSAIDs affect the aPTT?
no
39
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
40
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
41
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)
42
What is a white thrombi?
- arterial thrombi
- primarily made up of platelets, but also fibrin and WBCs
- eg coronary artery thrombosis, cerebral circulation thrombi
43
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
44
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
45
What molecules are procoagulants (work with clotting)
- tissue thromboplastin
- exposed collagen
- activated factors
- thromboxane A2
- von Willebrand's factor
- factor 8 coagulant material
46
What molecules are anticoagulants (work with bleeding)
- protein C and protein S
- factor deficiencies
- antithrombin (AT)
- prostacyclin
- heparin
- tPA
- plasmin
47
What is type A hemophilia?
- deficiency in factor 8 - c; normal factor 8- vWF; referred to as classical hemophilia
48
What is type B hemophilia?
- deficiency in factor 9- referred to as Christmas disease
49
What is von Willebrand's disease?
- diminished factor 8- vWF, not normal factor 8-coagulant material (defect in the ability of the factor 8 to adhere to the vessel wall- cannot take NSAIDs here as they will make the disease worse)
50
What is disseminated intravascular coagulation?
- simultaneous clotting and bleeding- commonly seen with severe sepsis
- this is seen sometimes with postpartum women who do not stop bleeding
- in one spot, the body is consuming all of their clotting factors (in the uterus for example) but then they can have a hemorrhage somewhere else because they have run out of clotting factors but then they can have a hemorrhage somewhere else because they have run out of clotting factors. You just have to replace the clotting factors and give calcium for supportive treatment
51
How does severe liver disease affect clotting?
- bleeding is secondary to factor deficiencies
- decreased hepatic synthesis of factors 1-10, except factor 8; DIC may also occur
- there is also decreased synthesis of AT, plasminogen, and alpha 2-antiplasmin
- people can have elevated liver tests and can still throw a clot- you should ignore the results of the liver test
52
What is thrombocytopenia?
- platelet count < 100,000
- a decreased platelet count from either a decrease in line marrow production or due to increased peripheral (ie. circulating blood) destruction
(platelets can start to fall rapidly between 5-10 days of starting heparin)
53
What are the known thrombogenic risk factors/disease states?
- obesity
- age eg >40 yrs
- malignancy
- immobilization (ie. with CVA, hip surgery, limb paralysis, etc)
- major surgery
- AMI
- multiple trauma
54
What is the action of heparin?
- binds to AT and neutralizes the activated forms of factors 2,9,10,11, and 12
55
What are examples of LMWH's?
- enoxaparin, dalteparin, tinzaparin
| - bind to AT and neutralize activated forms of factor 10 (some 2a)
56
What is the effect of warfarin?
- impairing the synthesis of clotting factors 2,7,9,19 as known as the vitamin K dependent clotting factors
- this also depletes the synthesis of protein C, a physiological anticoagulant (theoretically increasing clotting initially)
-- warfarin blocks the production of protein C
(you can actually form more clots within the first few days of starting warfarin than you normally would- typically in the distal limbs- warfarin toe)
57
What is the action of ASA/NSAIDs?
- inhibition of thromboxane A2 synthesis decreasing platelet aggregability
58
What is the action of TNKase (tenecteplase)?
- increased fibrinolysis; converting plasminogen to plasmin (called a thrombolytic)
59
What is the action of DDAVP? (desmopressin)
- increased release of factor 8-vWF and thus enhancing platelet agreeability... thus a pro-platelet aggregation effect
(this assists more with platelets adhering up against the vessel wall)
60
Bivalrudin and argatroban are factor ____ inhibitors
2a (thrombin)
61
Dabigitran is a factor _____ inhibitor
2a (thrombin)
62
Rivaroxaban, fondaparinux and apixaban are all factor ____ inhibitors
10a
63
What is deep vein thrombosis?
- unilateral, warm, swollen, painful legs
- usually starts in the calf (distal DVT)
- may progress, moving up the thigh (proximal DVT) - into the femoral and iliac veins from the calf veins
- a positive Homan's sign (pain upon dosiflexion of the foot)
64
What is the classical clinical presentation of pulmonary embolism?
- tachypnea, chest pain, dyspnea, tachycardia
65
Pulmonary emboli are typically found in patients with a recent history of ____
DVT
66
Are chest X-rays, EKG and blood gases good ways to diagnose pulmonary embolism?
- no! they are good ways to rule out other causes of the symptomatology (e.g. pneumonia, pneumothorax, AMI, aortic dissection, or PUD)
67
What is the definition of atrial fibrillation?
- a fib results in stasis of the blood within the atria- often results in an atrial thrombus formation (mural thrombus) increases the risk of cerebral embolization (most commonly detected site)
68
What test helps decide what therapy to give for an atrial fibrillation?
- CHADS2 or CHA2DS2- VASc
69
_____ are recommended of all forms of non-valvular atrial fibrillation
DOACs (direct oral anticoagulants)
70
What are some forms of valvular atrial fibrillation?
- mitral regurgitation
- aortic stenosis
- aortic regurgitation
71
DOACs should not be used in what cases?
- in mitral stenosis or in prosthetic valve disease
72
Patients with prosthetic heart valves are at an increased risk of developing what?
- developing valvular thromboembolism
73
What kind of valves are embolization most common with?
- most common with mechanical rather than bioprosthetic valves
74
What is the target warfarin INR for valves in the aortic position (AVR) and NO risk factors for TE?
2.5 (range of 2-3)
| if the person has risk factors for TE then the INR target should be 3.0 (2.5-3.5
75
What is the target warfarin INR for valves in the mitral position (MVR)
3.0 is the target (range 0f 2.5-3.5)
76
What drug should be added on as an adjunct to those with mechanical heart valves?
ASA
77
What is the advantage of using bioprosthetic valves?
- lower risk of systemic embolism
78
What should the warfarin INR goal be in the first 3-6 months after bioprosthetic valve surgery?
INR should be at 2.5 (range of 2-3)
79
What is the advantage of using heparin as an anticoagulant?
- gives an immediate anticoagulant effect (should check the aPTT every 6 hours initially for the first 24 hours)
- check platelet count daily
80
When should warfarin be started?
warfarin should be started at day 1 at a dose of 5 mg - subsequent doses should be adjusted according to the INR goal
81
When can heparin be stopped?
- heparin can be stopped when there has been at least 5 days of combined therapy (warfarin and heparin) and when the INR is greater than the target for at least 2 consecutive days)
82
What are the exceptions to the amount of time that heparin has to be used with warfarin after an embolism?
- patients with a major pulmonary embolism or iliofemoral vein thrombosis- run heparin forum to 10 days and start warfarin after a delay of 4 days
83
What is available as thrombolytic therapy for DVT?PE?
- alteplase (tPA)
84
What are the main possible indications for the use of tPA?
a) pulmonary embolism with shock
| b) massive DVT with limb gangrene
85
What is the logic behind waiting for 5 days of consecutive treatment with both heparin and warfarin?
- want to be sure that we have knocked out both the intrinsic and extrinsic pathways
86
What would we do with someone that was on warfarin and need to go in for surgery?
- we would slow their warfarin and wait until it went down below 1.5
87
What would we do with a patient that was responding poorly to warfarin and needed to be switched to another DOAC?
- we would stop their warfarin and wait until their INR went down before 2.1, then we would start the patient on another anticoagulant
88
In what cases would you continue heparin on for longer (i.e. over 10 days)?
- would continue in those with a massive pulmonary embolism or iliofemoraal vein thrombosis
89
How long should you stay on warfarin when you have a provoked VTE? What is the target INR?
- warfarin should be continued for 3 months
| - target INR here is 2.5 (2-3)
90
How long should you stay on warfarin for for unprovoked VTE?
therapy is recommended for over 3 months - can be taken for up to 2.5 years
** warfarin can be continued indefinitely if the patient has risk factors (e.g. malignancy, AT deficiency, etc). If a patient has thrombotic/embolic recurrence despite anticoagulation, then continue warfarin INDEFINITELY , with an INR target of 3.0
91
How long should you stay on warfarin for for unprovoked VTE?
therapy is recommended for over 3 months - can be taken for up to 2.5 years
** warfarin can be continued indefinitely if the patient has risk factors (e.g. malignancy, AT deficiency, etc). If a patient has thrombotic/embolic recurrence despite anticoagulation, then continue warfarin INDEFINITELY , with an INR target of 3.0 (2.5-3.5)
92
What are the target factors that LMWH work on?
- work on factora Xa and IIa
93
What are the indications for LMWH?
- ACS
- knee, hip prophylaxis
- DVT/PE
- bridging therapy
94
LMWH should be avoided with a CrCl less than what?
- less than 30 mL/min/72kg
95
What DOACs are inhibitors or inducers of CYP3A4?
-rivaroxaban and apixaban
96
What is the indication for protamine?
- protamine reverses heparin and does so immediately- does not work as well with LMWH
97
What is vitamin K a reversal agent for?
- vitamin K is a reversal agent for warfarin
98
What is the action of FFP (fresh frozen plasma)?
- provides you with all of the clotting factors that may have been consumed
99
What is the action of rFVIIa (recombinant factor VIIa)?
- this is a factor 7 that is synthesized- used only when people are bleeding out and are almost dead
100
What is the action of idarucizumab?
- a new monoclonal antibody fragment that is specifically targeted at dabigatran
101
What is warfarin indicated to treat?
- treatment of major thrombosis
102
What clotting factors do warfarin act on? What is the action?
- causes clotting factor depletion
| - works on factors 2, 7, 9 and 10
103
How long does warfarin take to have full effect in the body?
- warfarin takes over a week for full effect
104
How long before planned surgeries should warfarin be stopped?
- stop 1 week before any planned surgeries
105
What drugs can be used for reversing warfarin?
- vitamin K
- FFP
- rFVIIa
- 4-PCC
- dialysis is not effective in overdose
106
What dabigatran indicated for?
- indicated for the prevention of stroke with a fib
107
What clotting factor does dabigatran work on?
- binds to and inhibits thrombin IIa
108
What test will dabigatran alter?
- dabigatran will increase the aPTT test - not recommended for monitoring however
109
How long before surgery should dabigatran be stopped?
- should be stopped 1-2 days before surgery
110
Dabigatran is contraindicated when the creatinine clearance is below what?
- CI'ed if it is below 30 mL/min
111
What are the reversal agents associated with dabigatran?
- hemodialysis
- rFVIIa
(no role for FPP because dabigatran works by inhibition not by clotting factor depletion
- octaplex is also not effective
112
What is the indication for rivaroxaban and apixaban?
- prevention of stroke with a fib
113
What test with rivaroxaban and apixaban alter?
- they will increase the INR test (not recommended for monitoring according to the manufacturer)
114
How long before surgery should rivaroxaban/apixaban be stopped?
- should be stopped 1-2 days prior to surgery
115
What are the reversal agents that will act on rivaroxaban/apixaban?
- 4PPC (octaplex)
- dialysis NOT effective
- no role for FPP with these drugs because these agents provide anticoagulation by inhibition, not by clotting factor depletion
116
What is a greenfield filter?
- a mechanical device that is placed in the inferior vena cava to "filter" emboli originating from the lower extremities
117
When is the greenfield filter most commonly used?
- when there is a possible contraidication to anticoagulant therapy
- when there is a recurrent PE despite adequate anticoagulation
