Anticoagulants & Thrombolytics Flashcards
(149 cards)
1
Q
What type of substances promote coagulation?
A
Procoagulants
2
Q
What type of substances inhibit coagulation?
A
Anticoagulants
3
Q
What term is used to describe the prevention of blood loss?
A
Hemostasis
4
Q
What are the four phases of hemostasis?
A
Vascular constriction
Formation of platelet plug
Formation of blood clot
Clot dissolution
5
Q
What two process of hemostasis are immediate?
A
Vascular constriction and Formation of platelet plug
6
Q
How long does it take the body to form a blood clot when injury occurs?
A
15-20 seconds to 1-2 minutes
7
Q
What components are required for clot formation?
A
Vascular endothelium
Platelets
Plasma mediated hemostasis
8
Q
What roles do the platelets play in clot formation?
A
Anchoring sites for coagulation factor activation complexes
Delivery vehicles releasing hemostatically active proteins
Major structural components of the clot
9
Q
What factors induce prothrombotic endothelial changes?
A
Thrombin
Hypoxia
High fluid sheer stress
10
Q
What products in the extracellular matrix promote clot formation?
A
Collagen Von Willebrand factor Hormones Cytokines Procoagulants
11
Q
Where do platelets form and what is their normal lifetime?
A
Formed in the bone marrow and the life of a platelet is 8-12 days
12
Q
What is the normal concentration of platelets?
A
150,000-300,000 per microliter
13
Q
At what platelet count would a person more than likely being to spontaneously bleed?
A
Less than 50,000 (below 10,000 is considered lethal)
14
Q
What occurs when platelets are exposed to the extracellular matrix in damaged endothelium?
A
Adhesion
Activation
Aggregation
15
Q
What component of the extracellular matrix plays an important role in platelet adhesion to the vascular wall?
A
Von Willebrand factor
16
Q
What is the primary role of vWF?
A
It is a bridging molecule between the sub endothelial matrix and platelets
17
Q
What occurs during the activation phase of the hemostasis?
A
Platelets release granular contents (ADP, Ca, serotonin, histamine, TXA2 etc.) resulting in recruitment and activation of additional platelets
18
Q
What receptors on the surface of platelets bind fibrinogen to provide for cross-linking with adjacent platelets?
A
Glycoprotein IIb/IIIa
19
Q
What is the inactivated precursor to thrombin?
A
Prothrombin
20
Q
What is the goal of clot formation?
A
To convert a soluble to insoluble clot
21
Q
What stimulates activation of new platelets as well as increases platelet aggregation?
A
Thromboxane A2 (TXA2)
22
Q
What type of receptor is the TXA2 receptor?
A
It is a G protein coupled receptor
23
Q
Why is TXA2 important during tissue injury and inflammation?
A
It is a known vasoconstrictor
24
Q
How does TXA2 contribute to activation of new platelets?
A
It mediates expression of the glycoprotein complex IIb/IIIa in the cell membrane of platelets
25
Where are most coagulation factors synthesized?
In the liver
26
How are coagulation factors present in the body when no injury is present?
Inactive proteins
27
How are coagulation factors labeled?
With Roman Numerals in the others in which they were discovered
28
What coagulation factor is not a true factor and comes from a person's diet?
Calcium
29
Where is Von Willebrand synthesized?
In endothelial cells
30
What factors are vitamin K dependent for utilization?
II, VII, IX, and X
31
What is factor I?
Fibrinogen --> fibrin
32
What is factor II?
Prothrombin --> thrombin
33
How does the intrinsic pathway begin?
With damage to the blood vessels themselves
34
What is the common pathway?
It is common to both the intrinsic and extrinsic pathway, it depicts thrombin generation and subsequent fibrin formation
35
What is factor III?
Tissue thromboplastin
36
What is the initial step in the extrinsic pathway?
Plasma-mediated hemostasis, begins with exposure of blood plasma to tissue factor
37
What is the significance of fibrin activation?
Activates platelets and factor XIII
Converts inactive cofactors V and VIII to active forms
Activates factor XI
Up-regulates tissue factor
Stimulates vascular endothelium to express down regulation of fibrinolytic activity
38
What is factor IV?
Calcium
39
How does prothrombin contribute to the clotting cascade?
Attaches to receptors on the surface of a platelet
40
What is factor V?
Proaccelerin, labile factor
41
What two things would cause a deficiency of prothrombin in the blood?
Lack of vitamin K or liver disease
42
What causes the formation of fibrin?
Thrombin acts on fibrinogen to form fibrin
43
What is factor VII?
Serum prothrombin conversion accelerator, proconvertin
44
How is a meshwork in all directions of blood cells created?
Covalent bonds between fibrin molecules and cross-linking of fibers
45
What is a clot composed of?
Plasminogen
Plasmin
Fibrin and
Fibrin degradation products
46
How is plasminogen activated to plasmin?
By tissue plasminogen activator (t-PA) released from the tissue and vascular endothelium
47
What is factor VIII?
Antihemophilic A Factor
| Antihemophilic globulin
48
What does plasmin do?
It digests fibrin fibers, fibrinogen, Factor V, Factor VIII, prothrombin and Factor XII
49
What is the function of anticoagulants?
Prevent clot formation or extension of existing clot
50
What is factor IX?
Plasmin thromboplastin Component (PTC)
Christmas factor
Antihemophilic B Factor
51
What is the function of anti platelet drugs?
Reduces platelet aggregation and prevents Stroke, MI and TIA
52
What three drugs do we commonly use that are anticoagulants?
Heparin
Lovenox LMWH
Warfarin
53
What is Factor X?
Stuart-Prower Factor
| Autoprothrombin III
54
What herbal products have an effect on coagulation?
Garlic, giner, ginko, fish oil, flax seed, cranberry, black cohosh
55
How does citrate prevent blood clotting in donor blood?
Deionizes the Calcium (negatively charges citrate combines with calcium in the blood to cause an un-ionized calcium compound)
56
How is citrate metabolized when done blood is given?
Metabolized in the liver and is polymerized into glucose or metabolized
57
What is Factor XI?
Plasma Thromboplastin antecedent (PTA)
58
How does Heparin work?
Binds to antithrombin (antithrombin III) and accelerates the normally occurring antithrombin induced neutralization of activated clotting factors (Xa, XII, XI & IX)
59
What is the purpose of neutralizing thrombin?
It prevents the conversion of fibrinogen to fibrin
60
Where is heparin produced endogenously?
Basophils, mast cells and the liver
61
What are the three forms of heparin?
Bovine
Porcine
Endogenous
62
How does heparin effect the clotting cascade?
It blocks the classic intrinsic and final common pathways
63
What is the definition of a unit?
One unit of activity as the amount of heparin that maintains the fluidity of 1mL of citrated sheep plasma for 1h after re-calcification
64
How many units must heparin contain?
At least 120 USP units/mL
65
Why do we prescribe heparin in units instead of mg?
Commercial preparations varying in the number of USP units per mL
66
How does temperature affect heparin?
Decrease in body temperature prolongs its elimination half time
67
How is heparin monitored?
Biologic Activity:
PTT: 1.5-2.5 times pre drug value
ACT:
68
What is unique about heparin's dose response?
It is not linear
69
What is the typical dose of heparin and how much does it increase clotting time?
100u/kg (o.5-1mg/kg) causes blood clotting time to increase from 6 to 30 or more minutes
70
What enzyme breaks down injected heparin?
Heparinase
71
How often should ACTs be drawn on a patient receiving heparin therapy?
Baseline
3-5m post administration
30m-1h interval post administration
72
What lab value is the most widely used and reliable for high heparin concentrations?
Activated Coagulation Time (ACT)
73
What physiological processes can influence ACT results?
Hypothermia
Thrombocytopenia
Aprotinin
Coagulation deficiencies
74
How long is a typical control ACT?
80-120s
75
If a patient is on CPB what is a desirable ACT?
>400-450s
76
What is a desirable ACT in patients that are not on CPB but had a vascular procedure done?
>200-300s
77
How is an ACT preformed?
Mixing whole blood with an activated substance to initiate activation of the clotting cascade
78
What is significant about the size of lovenox?
1/3 size of heparin and can cross placenta
79
Why is it that low molecular weight heparin only has to be given once a day?
There is less binding to the endothelial cells and therefore a longer half life
80
What are some advantage of using lovenox over heparin?
Lack in need of monitoring
More predictable
Fewer effects on platelet function
Reduced risk of HIT
81
What is the mechanism of action of lovenox?
It binds to and accelerates antithrombin III, inhibits factor Xa and IIa
82
What is factor XII?
Hageman factor, glass factor, contact factor
83
How much lovenox should be administered for DVT prophylaxis?
30mg SQ Q12H
84
What is one of the most important risk factors of an epidural hematoma?
Anticoagulant therapy/length of use
85
How does heparin induce thrombocytopenia occur (HIT)?
Heparin-dependent antibodies that agglutinate platelets and produce thrombocytopenia
86
What is considered mild HIT syndrome?
Platelet count of less than 100,000 cells/mm
| 30-40% of heparin treated patients
87
What is considered severe HIT syndrome?
Platelet count of less than 50,000 cells/mm
| 0.5% -6% of patients treated with heaprin
88
When would it be okay to administer Heparin to a patient with a history of HIT?
If remote history and no loner can demonstrate antibodies
89
What medication is not effective if a patient has an antithrombin deficiency?
Heparin, no antithrombin nothing for heparin to bind to
90
What is the treatment for antithrombin deficiency?
2-4 units FFP in adults OR
| Antithrombin concentrate 1,000 units in adults
91
What drug can be given for heparin reversal?
Protamine
| can also give FFP & prothrombin complex concentrate
92
What is the mechanism of action of protamine?
The positively charged alkaline protamine combines with the negatively charged acidic heparin to form a stable complex void of anticoagulant activity
93
How is the Heparin-Protamine complex removed from the body?
Removed by Reticuloendothelial system (phagocytosis)
94
What is the dose of protamine?
1mg for every 100 units of Heparin
| It can be guided by last ACT and estimated amount of heparin within the last two hours
95
If protamine is given too rapidly what can occur?
Histamine release causing HoTN, facial flushing and tachycardia
96
What effect can the Heparin-protamine complex have on the pulmonary vasculature?
Can cause vasoconstriction --> Pulmonary HTN
97
What population is at risk for protamine allergy?
Diabetics, insulin contains protamine and chronic exposure to low dose protamine may produce antibodies against protamine
98
What is another indication for having a protamine allergy?
Fish allergy (protamine derived from salmon sperm)
99
What is population has the highest actual risk of having a protamine allergy?
Patients that have previously had a reaction to protamine (could be from bypass surgery)
100
What is the mechanism of action of Coumadin?
Competitively inhibits vitamin K dependent coagulation proteins (Factors II, VII, IX, X)
Inhibits protein C and S which prevent extensive clot formation
101
How are Coumadin levels measured?
PT/INR
102
What is the goal of the INR in patients on Coumadin therapy?
2-3
103
What is the typical dose of Coumadin?
5-10mg orally
104
Why is Coumadin contraindicated in pregnancy?
It crosses the BBB and is severely teratogenic
105
How long does it take to see an effect in the patients INR with Coumadin use?
8-12h due to depletion of factor VII, however full clinical effects are not appreciated for several days
106
What is factor XIII?
Fibrin stabilizing factor, fibrinase
107
How is the INR calculated?
INR = Platelets PT
| Control PT
108
What is the normal INR range?
0.9-1.2
109
How often is the INR repeated while on Coumadin therapy?
4-6 weeks
110
What are INR goals with Coumadin therapy?
2-3 (may be higher with mechanical valve and recurrent MI)
111
When should Coumadin be discontinued for minor surgery?
D/c 1-5 days prep for PT 20% within baseline
112
What can be given to offset the effects of Coumadin if emergency surgery is required?
IV Vitamin K
| FFP or PCC
113
What is the mechanism of action of antiplatelet drugs?
Suppress platelet function (inhibit platelet aggregation)
114
What are three well known antiplatelet drugs given?
ASA
Plavix
NSAIDs
115
What is the mechanism of action of Aspirin?
Inhibits platelet aggregation by irreversibly inhibiting COX-1, via acetylation, the effects last the life of the platelet (8-12days)
116
What is the typical dose of Aspirin?
81-325mg
117
What is the importance of COX-1 in the conversion of arachidonic acid to thromboxane A-2?
COX-1 is the rate limiting enzyme for the conversion
118
What is ASA utilized for in primary prophylaxis?
Used for prevention in the absence of an established diagnosis of CV disease
119
What is ASA utilized for in secondary prophylaxis?
Treatment with ASA in the presence of overt CV disease or conditions conferring particular risk.
120
What are the general guidelines for taking ASA prior to surgery?
It should be continues in both primary and secondary prophylaxis prior to and day of surgery unless surgical procedure has a high EBV
121
What is the mechanism of action of Plavix?
Inhibits platelet activation and aggregation through the irreversible binding of its active metabolite P2Y12 class od ADP receptors on platelets
122
What is significant about patients with liver disease taking plavix?
Plavix must be metabolize by CYP enzymes to produce the active metabolite that inhibits platelet aggregation (prodrug)
Liver failure may not get full effects
123
What laboratory value should be drawn when a patient is taking plavix?
P2Y12 point of care assay, can measure actual level of drug
124
Which type of stent requires longer use of plavix?
Medicine releasing, delayed healing
125
How do ASA and plavix act when used in combination?
Synergistically
126
What is the mechanism of action of NSAIDs in relation to antiplatelet therapy?
Reversibly depress thromboxane A2 production by platelets --> more temporary (24-48h)
127
What are the two mechanisms in which thrombolytics work?
Process inherent fibrinolytic effects OR
| Enhance the body's fibrinolytic system
128
What is the main use of thrombolytics?
To restore circulation through a previously occluded vessel
129
What are contraindication to thrombolytic therapy?
Trauma
Severe HTN
Active bleeding
Pregnancy
130
What is the most common risk of thrombolytic use?
Hemorrhage or bleeding
131
What is the mechanism of action of tPa?
It converts plasminogen to the active form, plasmin and plasmin breaks down fibrin
132
What reaction allows plasminogen to become plasmin?
t-Pa cleaves the plasminogen peptide bond into the serine protease plasmin
133
Why do we typically seen t-PA given as a bolus and followed by a gtt?
It has a short half life of only about 5 minutes
134
What agent could you coadminister with t-PA to prevent re-thrombosis?
Heparin
135
What is significant about the age of the clot?
Older clots have more cross linking and are more compacted = more difficult to dissolve
136
What are direct thrombin inhibitors?
Class of medications that act as anticoagulants by directly inhibiting the enzyme thrombin (factor II)
137
What is a benefit to using DTI?
Does not require a cofactor and may be used if patient has a positive history for HIT
138
What is a major disadvantage to using DTIs?
There is no reversal
139
What is a major disadvantage to using DTIs?
There is no reversal
140
What is the mechanism of action of bivalent DTIs?
Block simultaneously the active site and secondary binding site (exosist 1) and act as competitive inhibitors of fibrin
141
What is the mechanism of action of univalent DTIs?
Block only the active site and can therefore both inhibit unbound and fibrin-bound thrombin
142
What is the normal bleeding time?
3-10m
143
What is the normal prothrombin time?
12-14s
144
What is the normal INR?
0.9-1.2
145
What is the normal aPTT?
25-35s
146
What is the normal thrombin time?
less than 30 seconds
147
What is the normal ACT?
80-150s
148
What is the normal amount of fibrinogen?
greater than 150mg/dL
149
Why is TXA2 important during tissue injury and inflammation?
It causes vessel wall vasoconstriction initially after injury
