blood clotting Flashcards
(103 cards)
1
Q
what is haemostasis
A
to prevent blood loss
by stopping of blood flow
2
Q
what is clotting (coagulation)
A
the conversion of liquid blood to a solid,
3
Q
what is an anticoagulant
A
compounds that prevent blood clotting
4
Q
what are factors in terms of clotting
A
Factors in this specific context, clotting factors are enzymes/proteins required for clot formation. As new ones were discovered they were given numbers
5
Q
what are platelets
A
small pieces
acellular
, small pieces budded from special cells, found in whole blood which when activated play an important role in clotting
6
Q
explain proteolysis
A
cleavage of peptide bonds in proteins. In blood clotting, many of the factors are very specific proteases, which cleave only certain peptide bonds in their substrates
7
Q
define thrombus
A
a blood clot, often used to designate a clot which will cause damage, disease; a clot formed where it is not wanted
8
Q
define thrombus
A
formation of dangerous clots
9
Q
define thrombin
A
an enzyme (clotting factor) which forms clots
10
Q
what happens if coagulation does not occur
A
tissues may not be perfused, and there may be significant blood loss which can lead to haemorrhage, shock and can be life-threatening
11
Q
list the 3 stages of haemostasis
A
1.Vasoconstriction
2.Formation of a platelet plug
3.Coagulation
12
Q
briefly explain function of vasoconstriction
A
reduces the blood flow to the injured area
13
Q
what part of the haemostasis does coagulation fit in
A
formation of the platelet plug
14
Q
what should coagulation lead to
A
the formation of fibrin and a more stable clot
15
Q
list the 3 divisions of the coagulation cascade
A
intrinsic
extrinsic
common pathway
16
Q
how are coagulation factors represented
A
in roman numerals
17
Q
how is the extrinsic pathway initiated ?
A
by tissue factor which is normally due to damaged tissue
18
Q
where is tissue factor expressed ?
A
many cells found outside blood vessels but not on the surface of circulating blood cells or the endothelium
19
Q
when the endothelium is damaged, what occurs ?
A
tissue factor comes into contact with blood
20
Q
after the tissue factor comes into contact with blood what occurs
A
tissue factor combines with circulating factor VII to form a complex that leads to the activation of factor X
21
Q
what does factor X to trigger
A
the common pathway
22
Q
how is the activation of the extrinsic pathway tested
A
in the lab by a test called the prothrombin time, abbreviated to PT
23
Q
what is the intrinsic pathway activated by ?
A
initiated by activated platelets
24
Q
how does the extrinsic pathway activate the intrinsic pathway
A
using thrombin from the activation of the extrinsic pathway
25
what does the series of reactions in the intrinsic pathway lead to ?
initiation of the common pathway
26
what does each coagulation factor lead to ?
catalysation and activation of the next coagulation factor in the sequence
27
what is the term when certain reactions activate other reactions
cascade
28
intrinsic pathway: what does surface contact activate
factor XII which is activated into factor XIIa
29
intrinsic pathway: what does factor XIIa activate
Factor XIIa activates factor XI -> factor XIa
30
intrinsic pathway: what does factor XIA activate ?
IX -> IXa
31
what does factor IXa activate
factor X
32
what does factor IXa combine with to activate the next factor
factor VIIIa, platelet membrane phospholipid and Ca2+ ions to activate factor X
factor X -> factor Xa
33
what does factor Xa activate
the common pathway generating more thrombin
34
what is the common pathway
the final stage of the coagulation cascade and leads to the formation of thrombin and fibrin.
35
in the extrinsic pathway what leads to the production of factor X
factor VII to factor VIIa
36
final common pathway
what does factor Xa combine with to produce thrombin
factor V .
37
what does thrombin convert
insoluble fibrin from soluble fibrinogen.
38
how is thrombin formed
active enzyme thrombin is formed from inactive prothrombin in the final common pathway
39
what does soluble fibrinogen allow
allows change from soluble to insoluble which leads to the gel-like consistency of the clot.
40
what is the role of fibrinogen
to produce fibrin
41
what does fibrin allow to be formed
. A lattice of fibrin forms, which traps blood cells and forms a soft clot. Cross-links then form between the fibrin strands which leads to a more stable hard clot.
42
a soft clot can form what ?
a hard clot
43
what is plasmin
an enzyme
44
what is the role of plasmin
it will slowly lyse the clot once it has formed
45
this continuous cycle of the clotting cascade allows for what
vast amounts of thrombin can be generated from a single initial stimulus and a thrombus can be formed quickly after injury to limit blood loss.
46
what is the role of thrombin in the intrinsic pathwayb
thrombin generates a positive feedback loop by initiating the intrinsic pathway
production of thrombin leads to the formation of more thrombin
47
how does fibrin turn into cross linkked fibrin
through factor XIIIa (8)
48
how is plasmin produced ?
from plasminogen
49
without regulatory mechanism in coagulation what can be caused
the positive feedback loop triggered by thrombin in the intrinsic pathway would continue indefinitely and cause dangerous levels of clotting in the blood.
50
give brief overview of intrinsic pathway
51
give a brief overview of the extrinsic pathway
52
what is the enzyme plasmin formed from
plasminogen
53
what does fibrin have to combine with to form cross linked fibrin and therefore a hard clot
XIIIa
54
both the extrinsic and intrinsic pathways require what
clotting factors
calcium ions
surfaces
55
why is sodium citrate added to the plasma
.sodium citrate is a chelating agent. Chelates calcium and inhibits clot formation (used in blood donation)
56
. Why is the plasma a mixture of plasmas from a large number of donors?
Individual clotting times will vary; by pooling plasma, a reproducible average clotting time can be determined
57
what is Phospholipid/kaolin (K
suspension of negatively charged phospholipid adsorbed on particles of kaolin (an aluminium silicate clay), which is required to initiate the cascade.
58
what is phospholipid micmicking ?
the negatively charged surface of activated platelets. When activated platelets change shape from spherical to finger-like projections
59
compare cscl2 solution used in the lab to normal plasma calcium levels
(25 moles L-1) - very much more concentrated than normal plasma calcium levels.
60
what is the role of EDTA in calcium levels
EDTA chelates the calcium (bounds it together)
until the concentration of free Ca++ ions is about 10-5 mmoles L-1
61
why is EDTA an effective chelator
the four carboxyl groups and the two nitrogen atoms form bonds with the calcium ion and trap it within a cage formed by the EDTA anion.
62
what does heparin solution contain
sulphated polysaccharide heparin.
63
what charges does heparin carry
Negative charges
64
what is the role of trypsin
highly specific endopeptidase
cleaves polypeptides on the carboxyl side of basic amino acid residues such as arginine and lysine.
65
how does the trypsin bind to the polypeptide
it has a pocket with a negative charge that binds the positively charged side chain of the basic amino acid in the polypeptide substrate.
66
explain why these two compounds (benzamidine and -aminocaproic acid) are competitive inhibitors of trypsin?
same charge and structure of side chain that will fit into the active pocket for trypsin cleavage.
67
what is trypsin ?
a protease
68
what are most clotting factors?
proteases
69
how can clotting factor be inhibited
if they are proteases, they can be inhibited by compounds that fit into their active site
70
Which basic amino acid side chains do benzamidine and ɛ-aminocaproic acid most closely resemble?
lysine and arginine
71
what is the role of plasmin
removing clots after they have served their purpose
72
what is Streptococci
group of pathogenic bacteria some members of which secrete an enzyme streptokinase
73
explain what streptococci does
acts in a similar way to human enzymes, such as urokinase or tissue plasminogen activator, which convert inactive plasminogen to active plasmin
74
what is the role of fibrin in an infection of bacteria such as streptococci
the formation of a fibrin clot round the site of infection plays a role in limiting the spread of the bacteria.
75
what are the symptoms of streptococci
infections that give rise to boils and pimples
76
Why might streptokinase be an advantage to these bacteria?
. Strep tend to live on skin, once clot is made, the streptokinase will help to break down the clot (plasmin) and allow access to underlying tissue
77
what should be the time for clot formation
1-2 minutes
78
What do you observe after the addition of the plasmin solution?
Slower process (15-30 for partial lysis) Probably several hours for complete digestion (similar to what you should expect in body),
79
When clots are formed naturally they are red, why is this so?
A11. Trap RBCs
Trapped RBCs
80
. Would a plasma sample from a patient with a lack of Factor VIII give a clotting time shorter or longer than normal ?
Longer, factor VIII part of intrinsic so APTT assay delayed
81
. Would a plasma sample from a patient with a lack of Factor VII give a clotting time shorter or longer than the one in experiment
no effect because testing intrinsic pathway and factor VII is in the extrinsic pathway
82
Would you expect a plasma sample from a patient with a disease causing the spontaneous formation of thrombi to give a clotting time shorter or longer than the one you obtained?
these types of diseases are complex and in reality, APTT may not be shortened.
83
how is heparin used monitored
using APTT assay
84
what is the importance of monitoring heparin use and anticoagulant use in general
effects can vary widely across individuals – needs to be monitored regularly so that clotting is not too fast and not too slow (danger of cerebral hemorrhage).
85
how is warfarin monitored
requires the PT test as it affects vitamin K-dependent clotting factors in extrinsic pathway.
86
how is protein c produced
in response to thrombin binding to the receptor thrombomodulin on the vascular endothelium.
87
what does protein c activate
protein s
88
what does the activation of protein S do ?
breaks down factors Va and VIIIa in a negative feedback loop.
89
what is antithrombin
a natural anticoagulant that is produced by the liver and destroys factors XIa, Xa and thrombin.
90
what does heparin do
an anticoagulant
. enhance the natural effects of antithrombin in inhibiting thrombin and factor Xa.
91
explain Tissue factor pathway inhibitor
a protein that binds to and inactivates factor VIIa and factor Xa.
92
what is warfarin
Warfarin is a vitamin K antagonist which prevents the synthesis of vitamin K-dependent clotting factors (II, VII, IX and X).
93
why is heparin prescribed with warfarin
vitamin K is also required for the synthesis of the natural anticoagulants protein C and protein S so Warfarin may inhibit their production initially.
94
what do coagulation screening tests involve
adding triggers to a sample of reversibly anticoagulated plasma (by citrate) and measuring the time taken for fibrin to form.
95
what does prothrombin time (PT) measures
time taken for fibrin to form via the extrinsic pathway.
96
what specific factors are measured in PT
factor VII; factor X; factor V; prothrombin and fibrinogen.
97
what are causes of prolonged PT
Disseminated intravascular coagulation (DIC)
Vitamin K deficiency
Chronic liver disease
98
what does activated thromboplastin time measure
time taken for fibrin to form via the intrinsic pathway.
99
what specific factors are measured in APTT
actor XII, factor XI, factor IX, factor VIII, factor X, factor V, prothrombin and fibrinogen.
100
what are causes of prolonged APTT
Disseminated intravascular coagulation (DIC)
Clotting factor deficiencies (e.g. haemophilia A or B)
Lupus anticoagulant
Von Willebrand’s disease
101
why may the pt test is not accurate
does not account for the fact that in vivo (within circulating blood) large amounts of thrombin are produced via a positive feedback loop through the intrinsic pathway
102
Erythropoietin (Epo) is a peptide growth hormone that stimulates the production of erythrocytes (red blood cells).
in which organ is the majority of this hormone produced?
the kidney
103
explain the relevance of sodium citrate in blood donation
Sodium citrate added to donated blood allows blood to be stored for some time before being given to patients
