Anticoagulants and Bleeding Disorders Flashcards
(102 cards)
1
Q
What is primary haemostasis?
A
The process which recruits platelets to the site of vessel damage
2
Q
What is secondary haemostasis?
A
The process of activating coagulation factors
3
Q
Primary and secondary haemostasis occur simultaneously. T/F?
A
True
4
Q
The exposure of collagen in a damaged vessel allows the binding of which factor to facilitate platelet plug formation?
A
Von Willebrand factor
5
Q
What two factors are required in every step of the process of coagulation cascade?
A
Phospholipids
Calcium
6
Q
In the clotting cascade, tissue factor activates which factor?
A
Factor 7
7
Q
In the clotting cascade factor ten works alongside which other factor to activate prothrombin?
A
Factor 5
8
Q
What is the main action of thrombin in the clotting cascade?
A
The convert fibrinogen to fibrin
9
Q
In the clotting cascade, which factor allows cross binding of fibrin?
A
Factor 13
10
Q
Which factor in the clotting cascade activates factor 13?
A
Thrombin or factor 2
11
Q
In the intrinsic pathway of the clotting cascade, which factor does factor 11 activate?
A
Factor nine
12
Q
In the intrinsic pathway of the clotting cascade, which factor works alongside factor nine to activate factor ten?
A
Factor eight
13
Q
The production of thrombin in the coagulation cascade stimulates the activation of antithrombin. Which factors are inhibited by antithrombin?
A
Factors 2, 7 and 10
14
Q
Which molecule does thrombin bind to to activate protein C in the coagulation cascade?
A
Thrombomodulin
15
Q
Protein C alongside protein S act. to inhibit which coagulation factors?
A
Factors 5 and 8
16
Q
What action does tissue factor pathway inhibitor have on the coagulation cascade?
A
Inhibits the activation of factor 7
Inhibits factor 10
17
Q
How does the production of fibrin lead to the production of plasmin in the clotting cascade?
A
Fibrin formation results in the inactivation of plasminogen activation inhibitors which results in the conversion of plasminogen to plasmin
18
Q
Plasmin acts to dissolve the clot which creates fibrin degradation products including…?
A
D-dimers
19
Q
How is primary haemostasis assessed in vivo?
A
Bleeding time
20
Q
How is primary haemostasis assessed ex vivo?
A
FBC and platelet function tests
21
Q
What technique is used to test platelet function?
A
Light transmission aggregometry
22
Q
What tests are used to assess secondary haemostasis?
A
APTT, PT, TCT, individual clotting factor assays
23
Q
Why is citrate added to a blood sample before a PT, APTT or TCT test?
A
To chelate all the calcium to prevent clotting
24
Q
At what temperature are PT, APTT and TCT tests performed at?
A
37 degrees Celsius
25
Which part of the clotting cascade does prothrombin time stimulate?
Extrinsic pathway
26
Which part of the clotting cascade does activated partial thromboplastin time stimulate?
Intrinsic pathway
27
What Is the international normalised ratio?
A standardised form of prothrombin time used particularly to monitor oral anticoagulants
28
The INR for any given patient should be identical in any laboratory. T/F?
True
29
Briefly describe the procedure used in a prothrombin test
Patients plasma added to thromboplastin (tissue factor and phospholipids), warmed to 37 degrees celsius and the calcium added and the time taken to clot measured
30
Briefly describe the procedure used in a activated partial thromboplastin test
Patients plasma added to contact factor (kaolin or silica) and phospholipid, warmed to 37 degrees celsius and then calcium added and the time taken to clot measured
31
What does thrombin clotting time measure?
The conversion of fibrinogen to fibrin
32
Briefly describe the procedure used in a thrombin clotting time test
At 37 degrees C, patient's plasma and bovine thrombin are added and the time to clot is measured
33
Which of the three tests of the coagulation cascade is less dependent on calcium and phospholipid?
Thrombin clotting time
34
What is the general mechanism of action of anticoagulants?
Inhibit one or several components of the coagulation cascade
35
What is the mechanism of action of heparins?
These enhance the activity of endogenous antithrombin to inhibit factors 2, 7 and 10
36
Discuss the pros and cons of using low molecular weight heparin as opposed to unfractionated heparin?
LMWH has a reduced risk of heparin induced thrombocytopenia, osteoporosis and hyperkalaemia
LMWH has the same clinical efficacy as UFH
LMWH is more expensive
LMWH does not require monitoring so can be used in out-patients
37
When are heparins used?
```
Treatment of acute DVT or PE
During cardiac bypass surgery
Acute coronary syndrome
medium term after VTA in cancer patients
Prophylaxis against VTE in medical- post-op and obstetric patients
```
38
Heparin is administered orally. T/F?
False - it is administered paraenterally
39
Heparin does not cross the placenta. T/F?
True
40
What is the mechanism of action of warfarin?
Inhibits vitamin K oxide reductase which is used in the production of factors 2, 7, 9 and 10 in the liver
41
Warfarin has a delayed onset and a long half-life. T/F?
True
42
Warfarin has a narrow therapeutic window. T/F?
True
43
DOACs are generally preferred compared to warfarin. In what group of patient would warfarin be particularly useful?
Patient's who are non-compliant due to its long half-life
44
How can the effects of warfarin be rapidly reversed?
Infusion of clotting factors and vitamin K
45
When is warfarin used?
Treatment of AF, acute DVT or PE and prosthetic heart valves
46
What is one disadvantage of DOACs compared to warfarin?
There is no rapid reversing agent for DOACs
47
Give an example of a DOAC which inhibits thrombin.
Dabigatran
48
Give an example of a DOAC which inhibits factor 10
Apixaban
Rivaroxaban
Edoxaban
49
What is the general mechanism of action of fibrinolytic agents?
Enhance lysis of the fibrin clot
50
What are the two main classes of fibrinolytic agents?
Kinases
| Tissue plasminogen activators
51
What are the indications for the use of catheter directed thrombolysis?
Acute limb ischaemia
Massive DVT
blocked central line
52
What are the advantages of using catheter directed thrombolysis?
Drug is administered directly into the vessel containing the thrombosis, this has a lesser systemic effect
53
What is the mechanism of action of kinases?
These bind to plasminogen and release plasmin to enhance the breakdown of fibrin
54
Systemic fibrinogenolysis results in a significant bleeding risk in patients treated with kinases. T/F?
True
55
Streptokinase is an antigenic drug. What are the implications of this?
The drug will be ineffective if the patient has previous used it or if the patient has had a recent streptococcus infection
56
Give an example of a kinase which is not antigenic.
Urokinase
57
What is the mechanism of action of tissue plasminogen activators?
Enhance the activation of plasminogen to plasmin
58
Tissue plasminogen activators have a significant systemic effect. T/F?
False - they are relatively selective for clot bound plasminogen
59
Give examples of tissue plasminogen activators which have a short half life and so are given as a bolus and then as an infusion.
Alteplase
| Tenectplase
60
Give examples of tissue plasminogen activators which have a longer half life and so are given as a bolus only .
Reteplase
61
What are the indications for the use of alteplase (a tissue plasminogen activator)?
Acute MI for patients not suitable for percutaneous coronary intervention, within 12 hours of onset of symptoms
within 4.5 of onset of symptoms of ischaemic stroke
Massive PE with haemodynamic instability
62
There is a significant risk of haemorrhage, particularly in which organ, with the use of tissue plasminogen activators?
The brain
63
Describe the mechanism of action of clopidogrel and ticlopidine?
Irreversibly bind to a block the ADP receptor on platelets to disrupts the arachidonic pathway and inhibit platelet binding of fibrinogen by decreasing the expression of GP11B/IIIA
64
Describe the mechanism of action of abciximab and tirofiban?
Monoclonal antibodies with antagonist the GP11B/111A receptor to reduce platelet aggregation and the binding of fibrinogen
65
Describe the mechanism of action of aspirin
Irreversibly inhibits cyclooxyrgenase to block the conversion of arachidonic acid to thromboxane A2 which results in decreased platelet activation
66
What is the mechanism of action of dipyridamole?
Increases platelet concentration of cAMP which decreases the platelets responsiveness to ADP to reduce platelet aggregation
67
What is the mechanism of action of Picotamide?
Thromboxane synthesis inhibitor and receptor blocker
68
What is the mechanism of action of ifetroban?
Thromboxane receptor blocker
69
How are anti-platelet agents used in the treatment of an acute MI?
Aspirin is used indefinitely
Clopidogrel is for up to 12 months after an acute MI
Tirofiban can be used acutely for an acute MI
70
Which anti-platelet agent is used for the secondary prevention of cardiovascular disease?
Aspirin
71
Which anti-platelet agent is used for the treatment of secondary prevention of an acute stroke or TIA?
Clopidogrel or dipyridamole is clopidogrel is not tolerated
72
Which anti-platelet agent is used for the treatment of peripheral vascular disease?
Clopidogrel
| Or aspirin if clopidogrel is not tolerated
73
Disseminated intravascular coagulation is an acquired consumptive process. T/F?
True
74
What can caused disseminated intravascular coagulation?
```
Sepsis
Malignancy
Massive haemorrhage
Severe trauma
Pregnancy complications e.g. pre-eclampsia, placental abruption, amniotic. fluid embolism
```
75
When would protein C be given in the treatment of disseminated intravascular coagulation?
Meningococcal sepsis
76
How is disseminated intravascular coagulation treated?
By treating underlying cause
Fresh frozen plasma if there is bleeding
Activated protein C, protein c concentrate or AT concentrate can be used
Heparin is thrombotic phenotype
77
Explain the pathophysiology of disseminated intravascular coagulation
Acquired, consumptive process where there is abnormal activation of the coagulation cascade causing the formation of mciro thrombi and later exhausting the cascade and causing bleeding
78
How does liver disease cause coagulopathy?
Clotting factors are produced. in the liver
Vit K deficiencies can contribute
Poor clearance of activated coagulation factors can lead to DIC, hypersplenism and reduced thrombopoietin synthesis
79
Haemophillia A is a deficiency in which clotting factor?
Factor 8
80
Severe haemophilia A causes spontaneous bleeds, What level of factor 8 is classified as 'severe haemophilia'?
<1iu/dl
81
Moderate haemophilia A causes bleeding with minor trauma. What level of factor 8 is classified as 'moderate haemophilia'?
1-5iu/dl
82
Mild haemophilia A causes bleeding with surgery, What level of factor 8 is classified as 'mild haemophilia'?
6-10iu/dl
83
What mode of inheritance is exhibited by haemophilia A?
X linked recessive
84
What effect will haemophilia A have on PT, APTT and TCT?
PT and TCT normal
| APTT prolonged
85
If a patient with haemophilia A is still capable of producing some factor 8, how is this treated?
Desmopressin.
86
What mode of inheritance is exhibited by von willebrand disease?
Autosomal dominant
87
Which clotting factor is commonly reduced in von willebrand disease?
Factor 8
88
What pattern of bleeding results from von willebrand disease?
Mucosal bleeding pattern
89
Describe types 1, 2 and 3 of von willebrand disease?
Type 1 - partial quantitative deficiency of vWF
Type 2 - qualitative deficiency of vWF
Type 3 - virtually complete deficiency of vWF
90
What is the cause of glansmanns thromboplasthenia?
Absent or defective GPIIB/IIIA
| Normal platelet count but platelets cannot function properly
91
What is the cause of Bernard soupier syndrome?
Absent of defective GPIB/V/IX which causes macrothrombocytopaenia
92
How can severe inherited platelet disorders such as Bernard soupier syndrome and glansmanns thromboplasthenia be treated?
```
Applying pressure
Tranexamic acid
Desmopressin
Platelet transfusion
rFVIIa
```
93
How does the Factor V Leiden mutation result in thrombophillia?
APC and prothrombin gene resistance
94
Antithrombin deficiency increases the chances of developing DVT. T/F?
True
95
What causes thrombophillia?
A deficiency of natural anticoagulants such as antithrombin, protein C and protein S
96
The presence of lupus anticoagulant will falsely prolong which test of secondary haemostasis?
APTT
97
Lupus anticoagulant antibody is associated with an increased bleeding risk. T/F?
False - this is associated with a prothrombotic state
98
What is antiphospholipid syndrome?
Combination of persisting lupus anticoagulant and thrombosis or recurrent foetal. loss
99
Why is it important not to use blood or blood products to treat DIC caused by meningitis?
DIC is a consumptive process and so given blood would worsen the process and cause thrombus
100
What is a heterophiles antibody?
An antibody developed by a human which has the capability to react to antigens in a different species
101
What test is used to diagnose infectious mononucleosis?
Monospot test
102
What is the causative organism of infectious mononucleosis?
Epstein barr virus
