9 - Coagulation Disorders Flashcards
(112 cards)
1
Q
Describe the Virchow triad in thrombosis
A
Thrombosis can be caused by 3 things:
- Endothelial injury (ex. car accident)
- Abnormal blood flow
- Hypercoagulability
2
Q
When you expose ______ to blood it will induce clotting.
A
collagen
3
Q
Describe the intrinsic pathway
A
-exposure of collagen basement membrane
-contact activation
F12 -> F12a
F11 -> F11a
F9 -> F9a + F8C
F10 -> F10a
4
Q
Describe the extrinsic pathway
A
-tissue injury
-tissue thromboplastin (tissue factor)
F7 -> F7a
F10 -> F10a
5
Q
Describe the common pathway
A
F10 -> F10a
(through F5a) F2 -> F2a
F2 = prothrombin
F2a = thrombin
F2a converts F1(fibrin) -> soluble fibrin
F2a is converted to F13, converted to F13a, which converts soluble fibrin to insoluble fibrin strands
6
Q
In the presence of a clot, plasminogen is converted to _____
A
plasmin
7
Q
Describe how vasoconstriction can cause a clot
A
- vasoconstriction endothelial adhesion
- stasis of blood flow
- platelets
- adhesion
- release reaction
- releases ADP, TXA2, Aggregation
- vWF
- platelet thrombus
- retracted fibrin thrombus “fibrin clot”
- soluble fibrin fragments (FDPs)
8
Q
What is the only factor not generated by the liver?
A
Factor 8
*it is generated by endothelial wall
9
Q
How does aspirin work?
A
inhibits COX enzymes
-platelets cannot regenerate and so it takes about a week to until new platelets are made
*in the blood vessel wall, COX is also inhibited which means PGI is inhibited.
PGI is prostacyclin which is a platelet anti-aggregator and vasodilator
**these can regenerate very quickly therefore will turn into PGI which is good bc it’s an anti-aggregator and vasodilator
10
Q
What are examples of aDP receptor blockers?
A
clopidogrel, ticagrelor, prasugrel
11
Q
What are some factors that predispose someone to bleeding?
A
- open vessel
- pro-clotting factor deficiencies
- platelet defects
12
Q
In the absence of ______ we don’t clot
A
calcium
13
Q
What is PT?
A
prothrombin time
14
Q
What is INR?
A
international normalized ratio
15
Q
What is PT or INR?
A
A test based on the time for detection of clot formation in a test tube of the patients’ plasma after the addition of thromboplastin and calcium.
16
Q
Interpretation of PT/INR:
If it takes more than ___ seconds it is suggestive of a defective extrinsic and common pathway
A
12
17
Q
INR test is sensitive to reductions in which factors?
A
2, 7, 10
18
Q
What factors does warfarin reduce the synthesis of?
A
2, 7, 9, 10
19
Q
Factor _ is very sensitive to warfarin
A
7
20
Q
When administering warfarin, we need at least _____ hours for coverage of both pathways so we need to administer another agent.
A
48-72
21
Q
The INR or PT is not altered by thrombocytopenia or defective platelets but it prolonged when the ______ level is low
A
fibrinogen
22
Q
T or F: ASA or NSAID’s affect the INR
A
FALSE - they do not alter it
23
Q
What is the antagonist for warfarin?
A
vitamin K
24
Q
Out of factors 7, 9, 10, and 2, which has the shortest half life?
A
7
25
What is the formula for INR?
INR = {PT/PTc}^ISI
```
PT = patient's prothrombin time
Pic = mean prothrombin time for your lab control
ISI = international sensitivity index
```
26
What is the normal INR range?
0.9 - 1.1
27
White thrombi = _____ thrombi
arterial
28
Describe a white thrombi
Arterial thrombi - primarily made up of platelets but also fibrin and WBCs
29
Red thrombi = ______ thrombi
venous
30
Describe a red thrombi
Venous thrombi - primarily fibrin and RBC's and a small platelet plug
31
ASA plays no role in the treatment of prevention of _______ thrombi
venous
32
White or Red:
| Has more platelets (therefore can be treated and prevented with ASA)
White
33
Give some examples of procoagulants
- tissue thomboplastins
- exposed collagen
- activated factors
- thromboxane A2
- von Willebrand's factor
- factor 8 coagulant material
34
Give some examples of anticoagulants
- Protein C & Protein S
- factor defiiencies
- antithrombin (AT)
- prostacyclin
- heparin
- tPA
- plasmin
35
Describe Type A Hemophilia
- deficiency of Factor 8-C
- normal Factor 8 - vWF
- "Classical Hemophilia"
36
Describe Type B Hemophilia
- deficiency of Factor 9
| - "Christmas Disease"
37
Describe von Willebrand's Disease
- diminished factor 8-vWF
| - normal factor 8-C material
38
What is DIC?
Disseminated Intravascular Coagulation:
- simultaneous clotting & bleeding
- commonly seen with severe sepsis or postpartum women
39
Why does severe liver disease cause bleeding or clotting?
Because all factors (except 8) are made by the liver.
- Causes decreased synthesis of Factors 1-13 (except 8)
* DIC may also occur
* NOTE: there is also a decrease in synthesis of AT, plasminogen, and alpha 2-antiplasmin
THEY COULD EITHER BLEED OR CLOT
40
__________ = platelet count < 100,000
Thrombocytopenia
41
What could cause thrombocytopenia?
- a decrease in bone marrow production
| - increased peripheral (i.e. circulating blood) destruction
42
What are a few known thrombogenic risk factors? (i.e. risk factors that would increase your risk for clotting)
- obesity
- age > 40
- malignancy
- immobilization
- major surgery
- AMI (acute MI)
- multiple trauma
43
What type of deficiency results in heparin not working?
anti thrombin 3
44
How does unfractionated heparin (UF) work?
binds with AT and neutralizes activated forms of factors 2, 9, 10, 11, 12
45
How do low molecular weight heparins (LMWH) work?
binds with AT and neutralizes activated forms of factor 10 (some 2a)
46
Give a few examples of LMWH
- enoxaparin
- dalteparin
- tinzaparin
47
How does warfarin work?
Impairs the synthesis of clotting factors 2, 7, 9, and 10 (vitamin K dependent clotting factors)
**REMEMBER - works on factor 7 initially
- warfarin also depletes the synthesis of protein C, a physiological anticoagulant (theoretically increasing clotting initially)
* this is why warfarin is never given alone for the first few days
48
How do ASA/NSAIDs work?
Inhibit TXA2 synthesis decreasing platelet aggregability
49
How does TNKase (tenecteplase) work?
Increased fibrinolysis; converting plasminogen to plasmin (called a thrombolytic)
50
How does DDAVP (desmopressin) work?
Increased release of factor 8-vWF and thus enhancing platelet aggregabililty .... thus a "pro platelet aggregation effect"
51
How do Bivalrudin & Argatroban work?
Factor 2a (thrombin) inhibitors
52
How does Dabigatran work?
```
Factor 2a (thrombin) inhibitor
(DOAC)
```
53
DOAC
direct oral anticoagulant
54
How does Rivaroxaban work?
Factor 10a inhibitor (DOAC)
55
How does Fondaparinux work?
Factor 10a inhibitor
56
How does Apixaban work?
Factor 10a inhibitor (DOAC)
57
****If it has an 'x' in the generic name, it inhibits factor ___.
X (10)
58
Describe DVT (deep vein thrombosis)
- unilateral, warm, swollen, painful leg
- usually starts in the calf (distal DVT)
- may progress, moving up the thigh (proximal DVT)
- positive Homan's sign (pain upon dorsiflexion of the foot)
59
Describe PE (pulmonary embolism)
- generic symptoms (tachypnea, chest pain, dyspnea, tachycardia)
- commonly found in patients with recent history of a DVT chest X-ray findings, EKG, and blood gases may appear normal
- these tests are performed to rule out other causes of the symptomatology
ex. pneumonia, pneumothorax, AMI, aortic dissection, or PUD
60
What does Atrial fibrillation result in?
stasis of blood within the atria, often resulting in atrial thrombus formation (mural thrombus)
61
What does A. Fib increase the risk of?
cerebral embolization
62
CHADS2 or CHA2DS2-VASc:
| Score of 0 = ?
ASA 81 mg daily alone
63
CHADS2 or CHA2DS2-VASc:
| Score of 1 = ?
ASA OR a DOAC or warfarin (targeting INR of 2-3)
64
CHADS2 or CHA2DS2-VASc:
| Score of > 2 = ?
a DOAC or warfarin (targeting INR of 2-3)
65
When are DOAC's recommended?
for all forms of non-valvular atrial fibrillation
66
What are forms of valvular a. fib?
- mitral regurgitation
- aortic stenosis
- aortic regurgitation
67
Do not use DOAC in ?
- mitral stenosis
| - prosthetic valve disease
68
Patients with prosthetic heart valves are at an increased risk of ??
developing valvular thromboembolism (TE)
69
Embolization is greater with _____ than bioprosthetic valves.
mechanical
70
What are types of mechanical valves?
bileaflet or tilting disc
71
Describe the pharmacotherapy for mechanical valves in aortic position.
Warfarin INR target of 2.5 (2-3) is recommended for valves in aortic position (AVR) and NO risk factors for TE. If they have risk factors then 3.0 (2.5-3.5)
72
Describe the pharmacotherapy for mechanical valves in mitral position.
Warfarin INR target of 3.0 (2.5 - 3.5) is recommended for valve in mitral position (MVR)
73
What should we add to the pharmacotherapy for pts with mechanical valves?
Add ASA 75-100 mg to all with mechanical valves
74
Bioprosthetic valves are generally at lower risk for systemic ________.
embolization
75
Should pts with bioprosthetic valves get ASA 75 - 100 mg as well?
yes - this is reasonable
76
What is the target INR for pts on warfarin with bioprosthetic valves?
For the first 3 up to 6 months after bioprosthetic valve surgery (MVR or AVR) warfarin INR of 2.5 (2-3)
77
What is the dose for heparin?
80 units/kg IV load
THEN
18 units/kg/hr IV
78
Describe some goals/monitoring with heparin
- Heparin provides for an immediate anticoagulant effect
- Check aPTT's q6h initially and adjust heparin infusion to maintain aPTT within desired range as early as possible (within 24 hours)
- Check platelet count daily
- Start warfarin on day 1 at 5mg for at least 2 days
- Adjust subsequent doses according to INR goal
- Stop heparin after at least 5 days of combined therapy and when INR is great than target for at least 2 consecutive days
79
What are the parameters for monitoring therapy for UFH, LMWH or warfarin
aPTT, INR, Hgb, PLTS & clinical signs of bleeding at least daily
80
What are clinical signs of bleeding?
- melena (dark, tarry stools)
- hematuria (blood in urine)
- ecchymosis (discolouration of skin from bleeding underneath)
- hematemesis (vomiting blood)
- hemoptysis (coughing up blood)
- epitaxis (nose bleed)
81
What is the lab goal range for aPTT's?
59 - 99 seconds
82
High INR = ?
risk of bleeding
83
Low INR = ?
risk of clotting
84
What is the recommended pharmacotherapy of DVT & PE?
- UFH or LMWH and start on warfarin at the same time.
- UFH or LMWH is usually discontinued after 5 days, provided that the INR has been therapeutic range (i.e. INR > 2 for at least 24 hours)
85
What type of patients should heparin be continued longer in? (10 days)
patients with massive pulmonary embolism or iliofemoral vein thrombosis
86
For ______ VTE, continue warfarin for 3 months maintaining INR target of 2.5 (2-3).
provoked
87
For idiopathic or unprovoked VTE, therapy is recommended for ??
> 3 months (up to 2.5 years)
*continue warfarin indefinitely if patient has risk factors (ex. malignancy, AT deficiency, etc.)
88
If a pt has had a clot recurrence despite anticoagulation, what is the protocol?
continue warfarin indefinitely but at an increased intensity of INR target of 3.0 (2.5 - 3.5)
89
How does LMWH (enoxaparin, dalteparin) work?
inhibits factors Xa and 2a
90
Who should LMWH be avoided in?
its with CrCl < 30
91
Dabigatran (Pradaxa) is ___& really excreted
80
92
Antidote for heparin?
Protamine
93
Antidote for warfarin?
Vitamin K
94
What is FFP?
fresh frozen plasma (provides you with clotting factors to replace all the clotting factors that were consumed)
95
What is rFVIIa?
recombinant factor VIIa
96
What is 4-PCC?
4 factor prothrombin complex concentrates (also referred to as Octaplex)
97
What is Idarucizumab?
a new monoclonal antibody fragment specifically targeted at dabigatran
98
How early before surgeries should warfarin be stopped?
1 week
99
If a patient is renally impaired can they get normal doses of warfarin?
yes
100
What options do we have for reversing warfarin?
- vitamin K
- FFP
- rFVIIa
- 4-PCC
101
Is dialysis an option to remove warfarin in an overdose?
no
102
What is dabigatran indicated for?
preventing stroke with A. fibrillation
103
Full effects of dabigatran take?
3 days
104
When do you need to stop dabigatran before surgeries?
1-2 days before
105
If a patient is renally impaired can they get normal doses of dabigatran?
No. Dabigatran is contraindicated in patients with ClCr < 30
106
What options do we have for reversal of Dabigatran?
- hemodialysis
- rFVIIa
* no role for FFP bc dabigatran provides anticoagulation by inhibition not by clotting factor depletion
* 4-PCC (Octaplex) NOT effective
-Idarucizumab 5 grams = 1st line reversal agent for Dabigatran
107
What is Rivaroxaban/Apixaban used for?
the prevention of stroke with atrial fibrillation
108
How early before surgeries do you need to stop Rivaroxaban/Apixaban ?
1-2 days
109
Can you use normal doses of Rivaroxaban/Apixaban in the renally impaired
NO. Use is contraindicated if Clcr < 30
110
Options for reversing Rivaroxaban/Apixaban ?
4-PCC (Octaplex)
* dialysis NOT effective
* no role for FFP bc these agents provide anticoagulation by inhibitor, not by clotting factor depletion
111
What is a Caval Interruption - Greenfield Filter?
A mechanical device placed in the inferior vena cava to filter emboli origination from the lower extremities (i.e. proximal vein thrombosis)
Possible indications:
- a contraindication to anticoagulant therapy (eg. bleeding PUD)
- recurrent PE despite adequate anticoagulation
112
How often are people monitoring their INR?
they will be undergoing weekly or biweekly monitoring of their blood INR values with their clinic visits, in order to ensure adequate warfarin anticoagulation
