Anti-Thrombolytics Flashcards
1
Q
What is normal hemostasis?
A
a balance between generation of hemostatic clots and uncontrolled thrombus formation
2
Q
What is the extrinsic pathway?
A
plasma mediated, initiation of hemostasis
3
Q
What is the extrinsic pathway also known for?
A
primary hemostasis
4
Q
What is the key to the extrinsic pathway?
A
tissue factor
5
Q
What is the intrinsic pathway?
A
amplifies and propagates hemostasis
6
Q
What is the intrinsic pathway also known for?
A
secondary hemostasis
7
Q
What is the key to the intrinsic pathway?
A
thrombin
8
Q
What is the common pathway?
A
results in an insoluble fibrin clot
9
Q
Hemostasis is
A
precisely regulated by interctions between the blood vessel wall, circulating platelets, and clotting proteins in the plasma
10
Q
Fibrinolysis is
A
the orderly breakdown of a stable blood clot
11
Q
How many substances that affect blood coagulation have been identified?
A
50
12
Q
What predominates when a vessel is ruptured?
A
anticoagulants
procoagulants are activated
13
Q
What consists of normal hemostasis?
A
vasoconstriction
platelet plug
clot formation
clot dissolution
14
Q
What normally occurs in the vascular endothelium?
A
nonthrombogenic surface
15
Q
With vasoconstriction, damage to the endothelium exposes
A
the underlying extracellular matrix and elicits contraction
16
Q
What also induces pro-thrombotic endothelial changes?
A
thrombin, hypoxia, high fluid sheer stress
17
Q
How does a platelet plug form?
A
when platelets are exposed to the extracellular matrix in a damaged endothelium they undergo a series of biochemical and physical alterations
18
Q
What are the three major phases of forming a platelet plug?
A
adhesion, activation, aggregation
19
Q
What is the life of a platelet?
A
8-12 days
20
Q
What are the normal concentration of platelets?
A
150,000-400,000 per microliter
21
Q
What are platelet inhibitors?
A
adenosine
insulin
PGIE2
PGI2
22
Q
Platelet Adhesion
A
exposure to sub-endothelial matrix proteins allows platelet to undergo a conformational change to adhere to the vascular wall
23
Q
Von Willebrand Factor (vWF) is produced
A
endothelium and platelets
released by endothelial cells and by activated platelets
24
Q
What is the primary function of Von Willebrand factor?
A
bind to other proteins
25
What is particularly important about VWF?
its a bridging molecule between the subendothelial matrix and platelets forming a cross links
glycoprotein 2B/3A
glycoprotein 1B/ factor IX/ factor V receptor complex
26
GP1b-V-IX complex
binds VWf allowing platelet adhesion and platelet plug formation at sites of vascular injury
27
What is the absence of GP1b-V-IV receptor known as
Bernard- Soulier Syndrome
28
When is VWF mainly activated?
conditions of high blood flow and shear stress
29
what is type 1 vwd?
failure to secrete vWF into circulation or vWF being cleared more quickly than normal
Most common
30
What is Type 2 VWD?
qualitative defect and bleeding varies (4 subtypes)
decreased ability to bind to GP1b
decreased ability to bind to V111
31
What is type 3 vWD?
most severe, homozygous defective gene, complete absence of production of vWF
leads to extremely low levels of Viii since it does not exist to protect VIII from proteolytic degradation
32
Platelet type vWD is known as
psuedo-vWD
33
What is the platelet type vWD
a defect of the platelet's GPIb receptor
| vWF is normal, the platelet receptor GPIB is abnormal
34
What medications do we use that are GPIIb/IIIa inhibitors?
abciximab (reopro)
eptifibatide (integrilin)
tirofiban (aggrastat)
35
What do GPIIb/IIIa inhibitors do?
block the ability of fibrinogen to form around aggregated platelets
does not allow a clot to be formed
36
The biological half life of abciximab is?
12-24 hours
37
What is the biological half life of eptifibatide?
2-4 hours
38
What is the biological half life of tirofiban?
2-4 hours
39
How does platelet recruitment occur?
platelets release granular contents resulting in recruitment and activation of additional platelets
40
What are thromboxane A2 inhibitors?
aspirin and naproxen
41
Aspirin
inhibits the ability of COX enzyme to synthesize the precursors of thromboxane within platelets
42
Naproxen
nonselective COX inhibitor
43
P2Y12 receptors
further amplify the response to ADP and draw forth the completion of the aggregation
44
What are prodrugs of ADP receptor antagonist medications?
ticlopidine (Ticlid)
Clopidogrel (Plavix)
Prasugrel (Efient)
45
What are direct acting ADP receptor antagonist medications
ticagrelor (brilinta)
| cangrelor (kengrexal)
46
What ADP receptor antagonist has a safer profile?
ticlopidine
47
Platelet Aggregation includes
newly activated glycoprotein IIb/IIIa receptors on the platelet surface bind fibrinogen to provide for cross-linking with adjacent placement
48
What follows platelet adhesion, activation and aggregation?
a blood clot begins to form
49
What is converted and then produces a cross-linked stable mesh?
fibrinogen-> fibrin
50
Is fibrinogen soluble or insoluble?
soluble
51
Is fibrin insoluble or soluble?
insoluble
52
What is the key step in blood clotting?
the conversion of fibrinogen (I) to fibrin (Ia) by thrombin (2a)
53
Define the coagulation cascade
a classic description of coagulation that includes initiation of this chain reaction via either the intrinsic or extrinsic pathway
54
What triggers the intrinsic pathway?
when blood contacts a negatively charged surfcae (exposed to subendothelial collagen)
55
What activates the extrinsic pathway?
when blood contacts cells outside the vascular endothelium
56
What protein do nonvascular cells express that initiate the extrinsic pathway?
tissue factor (III)
57
What is the common pathway?
intrinsic and extrinsic pathways converge with the activation of factor X
58
What are 2 glycoproteins?
tissue factor (III) and vWF
59
Where are most coagulation factors synthesized?
The liver
60
What are the two coagulation factors not synthesized in the liver?
calcium (IV) comes from diet
| vWF synthesized in endothelial cells and platelets
61
What factors are dependent in Vitamin K for activation?
2 7 9 10
62
Do factors circulate in an active or inactive state?
inactive
63
Fibrinogen is clotting factor #
I
64
What is the function of fibrinogen?
clot formation
65
What is the clotting factor # of prothrombin?
II
66
What is the function of prothrombin?
Activation of I, V, VII,XI,XIII, protein C and platelets
67
What is the clotting factor # of Tissue factor?
III
68
What is the function of tissue factor?
co factor of VIIa
69
What is the clotting factor # of calcium?
IV
70
What is the function of calcium in the clotting cascade?
facilitates the coagulation factor binding to phospholipids
71
What is the clotting factor # for Stuart-Power Factor?
X
72
What is the function of Stuart-Power factor?
prothrombinase complex with factor V and activates factor 2
73
What is the clotting # of vWF
factor XVI
74
What is the function of vWF
binds to VIII, mediates platelet adhesion
75
How does the intrinsic pathway of coagulation start?
contact activation system
| begins with damage to the BV themselves
76
Intrinsic Pathway of coagulation
formation of primary complex on collagen and thrombin generation by way of factor XII and utimately merges to the common pathway an activates factor X
77
Extrinsic Pathway of Coagulation
Tissue factor pathway
initial step in plasma-mediated hemostasis
following the damage to the BV, factor VII comes into contact with tissue factor adn forms TF-VIIa complex
78
When TF-VIIa circulates the plasma it
activates factor X to promote the conversion of X to Xa
79
What is the common pathway of coagulation
its common to both extrinsic and intrinsic
it depicts thrombin generation and subsequent fibrin formation- prothrombin (II) is cleaved by activated factor X to produce thrombin (IIa)
signal amplification and thrombin activity
80
Describe the steps (2) of a blood clot
prothrombin gets activated to thrombin
| thrombin activates fibrinogen to form fibrin
81
How does clot lysis occur?
When plasminogen is activated to plasmin
82
How does the activation from plasiminogen to plasmin occur?
tissue plasminogen activator (t-PA)
83
tPA
is released form tissue, vascular endothelium, plasma and urine
84
Plasmin
is an enzyme which digests fibrin fibers, fibrinogen, factor V, factor VIII, prothrombin and factor XII
85
Thrombolytics
possess inherent fibrinolytics effects or enhances the body's fibrinolytic system by converting endogenous pro-enyzme plasminogen to the fibrinolytic enzyme plasmin
86
What do thrombolytics work the best on?
more capable of dissolving newly formed clots (platelet rich and weaker fibrinogen bonds)
87
Prothrombin time
evaluates the extrinsic pathway
sample of blood plasma is incubated w/tissue factor in the presence of excess Ca2+
it is particularly sensitive to three of the four vitamin-K dependent factors (II,VII, X).
88
Partial Thromboplastin time (Ptt)
indicates the performance of the intrinsic pathway
| sample of blood is triggered by adding an activator surface plus phospholipid and CA2+
89
ACT
performed by mixing of whole blood with an activated substance to initiate activation of the clotting cascade. Widely used and reliable for high heparin concentrations
influenced by hypothermia, thrombocytopenia, coagulation deficiencies
90
THromboelastometry & rotational thromboelastimetry (ROTEM)
a global assay for whole blood clotting including coagulation factors, inhibitors, anticoagulation drugs, platelets, and fibrinolysis
91
Bleeding time
sensitive test of platelet function
92
Heparin concentration measurements
increasing concentrations of protamine are added to samples of heparin containing blood
time to clot is measured in which heparin and protamine are most closely matched will clot first
(1mg protamine will inhibit 1mg (100u) of heparin
93
Platelet function tests
the classic method involves centrifugation of patient blood to obtain platelet- rich plasma, which is then analyzed in a cuvette at 37 placed between a light source and photocell
94
Bleeding time
3-10 min
95
Platelet count
150-350k mm3
96
prothrombin time (pt)
12-14 seconds
97
INR
0.9-1.2
98
Activated partial thromboplastin time (aPTT)
25-35 seconds
99
Thrombin time (TT)
<30 seconds
100
Activate coagulation time (ACT)
80-150 seconds
101
Fibrinogen
>150mg/dl
