Anticoagulation Flashcards
1
Q
Where is tissue factor pathway inhibitor synthesised and what activates it
A
Endothelial cells
Activated by X
2
Q
What does tissue factor pathway inhibitor inhibit
A
TF-VII complex and factor X
3
Q
What activates the protein C pathway
A
Thrombin binding to membrane protein thrombomodulin in normal vessels (low grade thrombin always being made)
4
Q
How does activated protein C affect fibrinolysis
A
It enhances fibrinolysis by inhibiting tissue plasminogen activator inhibitor
5
Q
How does protein C inhibit coagulation
A
Protein C binds to its cofactor protein S and inhibits factor 5 and 8
6
Q
What factors does the protein C pathway inhibit
A
Factor V and VIII
7
Q
What does antithrombin inhibit
A
Thrombin
Factors 9, 10, 11
(12, kallikrein, plasmin)
8
Q
Half life of antithrombin
A
2-3 days
9
Q
What does antithrombin need to work
A
Heparin
Antithrombin and thrombin/factors have binding sites that fit each other but heparin is needed to facilitate binding
10
Q
When does fibrinolysis start
A
A few hours after fibrin cross linking
11
Q
Fibrinolysis components
A
Plasminogen
Tissue plasminogen activator
Plasminogen activator inhibitor 1
12
Q
What does plasmin do
A
Digests fibrinogen, fibrin, factor 5/8
13
Q
What does tissue plasminogen activator do
A
Hydrolyses plasminogen to plasmin (bound/free)
14
Q
Where is urokinase made
A
Urinary tract epithelial cells
Monocytes and macrophages
15
Q
What does urokinase do
A
A minor plasminogen activator
16
Q
When are D dimers found
A
Inflammation
Malignancy
Older age
Recent surgery
Trauma
Childbirth
17
Q
What is the high negative predictive value for D dimers and DVT
A
D dimers will increase in many conditions along with DVT - would be very high if DVT is present along with other factors
A negative D dimmer result means it definitely can’t be DVT
18
Q
Virchows triad for thrombophilia
A
Endothelial injury
Abnormal blood flow
Hypercoagulability
19
Q
Consequences of thrombosis
A
Ischaemia
Embolisation
20
Q
Arterial thrombosis most common cause
A
Rupture of an atherosclerotic plaque
21
Q
General risk factors for arterial thrombosis
A
Diabetes
High BP/cholesterol
Older age
Male
High CRO
Smoking
22
Q
Haemostatic risk factors for arterial thrombosis
A
Heparin induced thrombocytopenia
Antiphospholipid antibodies
23
Q
Consequences of a DVT
A
Pulmonary embolus
Varicose veins
Post thrombotic syndrome
24
Q
Inherited risk factors for DVT/venous thrombosis
A
Antithrombin deficiency
Protein S/C deficiency
Factor V Leiden
Prothrombin mutation
25
Acquired risk factors for DVT
Tissue injury
Immobilisation
Antiphospholid antibodies
Malignancy
Pregnancy
Obesity
HIT
AGE
26
What is factor V Ledien
An inherited thrombophilia (risk factor for DVT)
Mutated factor V resists cleavage by APC to stop coagulation so it just keeps going
27
Tests for Factor V Leiden
APC resistance assay is a screening test to test ability of PrC to prolong APTT from factors 5 and 8 activation
Confirm with genetic testing
28
Prothrombin G20210A
Increased prothrombin levels due to mutation in promoter region
Need genetic testing
29
How more likely are you to get DVT with Factor V Leiden
Hetero - 3x
Homo - 18x
30
How is antithrombin deficiency acquired
Liver disease (less is made)
Consumption from DIC, sepsis, nephrotic syndrome, malignancy, chemo drugs, transfusion reaction, sepsis
31
When does inherited antithrombin deficiency appear
Less than 40 years old
32
Two types of antithrombin deficiency
Type 1: quantitative
Type 2: qualitative so decreased function
33
Antithrombin functional assay (kinda like an enzyme assay) explain the substrate equation
Patient AT sample with thrombin and heparin (to speed it up) to make AT-thrombin complex with residual thrombin
34
Antithrombin deficiency indicator equation
Substrate with residual thrombin from first step
These products are measured for change in absorbance
35
Explain the proportional stuff in antithrombin deficiency assay
Change in absorbance is proportional to residual thrombin which is inversely proportional to antithrombin amounts
36
What factors increase in pregnancy to make it a hypercoagulable state
vWF
Fibrinogen
Factors 5,8,9,10,12
Plasminogen/Dimer
37
What decreases in pregnancy
Factor 11 and protein S (less anticoagulation)
38
What are many miscarriages (15-60%) the result of
Thrombophilia
39
What happens to APTT and PT in pregnancy
Hypercoagulable so shorter times
40
Pregnancy leads to a greater increase in what
DIC
thromboembolism
VTE risk is 100x greater in labour
41
Type 1 HIT
Benign
Recover in couple days
Mild thrombocytopenia (100-150)
42
Type 2 HIT
Heparin induced antibody forms after 7-14 days
Rapid fall in platelets below 100 over 2-5 days
43
Who gets TYPE 2 HIT
Those being treated with UFH
44
Complications of type 2 HIT
MI
Stroke
VTE
45
Test for Type 2 HIT
Platelet aggregation induced by heparin in vivo
46
What must all patients on heparin be monitored for
Thrombocytopenia
47
What are the antiphospholipid antibodies
Antibodies that bind to protein-phospholipid complexes
48
What is antiphospholipid antibodies associated with
Lupus anticoagulant
ACL
APS (antiphospholipid syndrome)
Venous/arterial thrombosis
Recurrent miscarriage
49
Alloimmune antibodies (antiphospholipid)
From infections or drugs
Disappears in less than 12 weeks
Could cause a prolonged APTT not correcting
50
Autoimmune antiphospholipid antibodies
Primary - idiopathic
Secondary to other autoimmune disease like lupus
51
How do antiphospholipid antibodies cause clotting too much
1. Antibodies interact with ECs promoting coagulation and inflammation
2. TF expression increases on ECs and monocytes which promotes WBC activation
3. Antibodies bind to platelet binding proteins on platelets which promotes platelet aggregation
4. Antibodies interfere with coagulation factors inhibiting anti coagulation and fibrinolysis
52
Tests for thrombotic risk
FBC (increase viscosity, marked thrombocytosis)
Protein S/C functional assay of activity
Antithrombin functional assays
HIT SCREEN
53
What is a lupus anticoagulant
An anticoagulant in vitro but prothrombotic in vivo
It blocks thromboplastin in tests leading to high APTT/PT that don’t correct
54
What is needed after a prolonged APTT/TCT in lupus anticoagulant when it doesn’t correct
Phospholipid sensitive functional clotting tests where excess phospholipids will correct the prolonged results - this is phospholipid neutralisation
55
Where does Russell’s viper venom time act
On factor 10
56
How to test for anticardiolipin antibodies
Immunoassays detect antibodies against cardiolipin and beta 2 glycoprotein 1
Ab titre = how much at risk for thrombosis
57
What is cardiolipin and beta 2 glycoprotein 1
Cardiolipin is a component of the inner mitochondrial membrane
B2G1 is an app lipoprotein that binds cardiolipin
58
Lab testing for inherited thrombophilia - how common is it
Not common as results don’t influence patient management
59
When is lab testing for inherited thrombophilia done
People younger than 40 presenting with unprovoked thrombosis and a family history of thrombosis
Children with purpura fulminans (protein C/S deficiency likely)
Pregnant women with previous VTE due to minor provoking factor or relative with one
60
What does unfractioned heparin do
Reduces risk of venous and arterial thromboembolism
Prevents thrombi forming/extending
61
When is UFH given in high doses
Cardiac bypass surgery
Haemodialysis
62
Unfractioned heparin dosage
IV = high dose
Subcutaneous injection = low dose
63
How is unfractionated heparin inactivated/excreted
Inactivated by the liver
Excreted in urine
Half life of 1hr via IV and 2hr via SC
64
Is heparin and warfarin used together
Yes heparin is needed while starting warfarin after a DVT/PE as it can induce a prothrombiotic state
65
What is the therapeutic target for VTE using UFH
APTT should be 1.5-2.5x the baseline or ULM
66
What affects UFH efficacy
People have different anti thrombin levels
Liver and renal issues
Brands
67
What does UFH make a complex with
Anti thrombin
Thrombin
Factor X (9 and 11 lesser)
68
Complications of UFH therapy
Haemorrhage
Osteoporosis
HIT
69
Who is most likely to get haemorrhage using UFH
IV dose
Already have weird coagulation/thrombocytopenia
GI lesions or cerebral bleeding risk
70
What to do if haemorrhage happens on UFH
Stop heparin and give protamine sulphate
This is strongly basic and binds and inactivates heparin
71
Why is low molecular weight heparin better
Reduced bleeding risk
Less anti platelet effect/anti IIa effect
Reduced HIT
No monitoring required unless renal failure then do anti X assay o
Platelet check once a month
72
LMWH vs UFH method
LMWH is smaller so cannot be complexes with as many factors (only works on antithrombin and factor X)
UFH works on thrombin, AT, factor X and 9/11 so more aggressive
73
What does warfarin do
Blocks vitamin K epoxide reductase (VKOR) inhibiting electron transport
So factors 2,5,7,9 are made but can’t bind to platelet phospholipids so can’t function in coagulation
74
Therapeutic range for warfarin
Very narrow
75
How is warfarin given
Orally, absorbed in the GI tract
Mostly bound to protein
76
Half life of warfarin
20-60hrs
Given once a day
77
What effects warfarin metabolism
Other drugs being metabolised by the liver as it can displace warfarin from albumin increasing its effects
Diet
Liver function
78
Protein C affected by warfarin
Protein C has the shortest half life so it falls quickly first leading to an intial procoagulant state
Leads to risk of thrombosis and warfarin induced skin necrosis in the first few days so need to give heparin with it
79
How to monitor warfarin
Using INR
PT is strongly influenced by thromboplasin nature
80
What does PT detect the reduced activity of
Thrombin, factor 7 and 10
81
What does ISI stand for
international sensitivity index
On commercial products standardised against an IRP
82
What is an INR
International normalised ratio
83
INR calculation
(PT time of patient/PT time of mean) ^ ISI
84
Target INR for warfarin treatment of DVT/PE/Afib/APS
2.0-3.0
85
Target INR for warfarin on arterial grafts/prosthetic valves and some APS
2.5 -3.5
86
How long are people on warfarin
3-6 months
Longer for prophylaxis
87
What happens when INR>4
Bleeding risk increases
Stop warfarin and give IV vitamin K
Replace coagulation factors with prothrombinex and FFP
88
Can you take warfarin if pregnant
No
Fetal malformations if used in the first trimester
Use heparin instead
89
How does dabigatran work
Direct thrombin inhibitor
Taken orally
90
What should be monitored with dabigatran
Renal functional
As not metabolised by the liver and kidney excretes it all
Creatinine should be above 30
91
Contradicted dabigatran for who
Patients older than 75 yrs or with renal impairment
92
Half life of dabigatran
13 hrs but longer with renal impairment
93
When is dabigatran used
Prophylaxis for VT post stroke/embolism
Prophylaxis and treatment for DVT and PE
94
Dabigatran lab test
Prolonged APTT/PT
Very high TCT not corrected
ECT, hemoclot thrombin inhibitor assay
95
Antidote for dabigatran
Idarucizumab
96
When is praxabind used
Emergency surgery, uncontrolled bleeding life threatening
97
How does praxabind work
It is a monoclonal antibody fragment which directly inhibits the drug
98
How is fibrinolytic therapy given - local admin
Injected into the occluded coronary artery
Reduced bleeding risk
99
List 3 fibrinolytic agents
Urokinase
Streptokinase
Tissue plasminogen activator
100
What does tissue plasminogen activator do
Recombinant DNA product which converts plasminogen to plasma.
Used to minimise MI size
101
What does streptokinase do
Forms a complex with plasminogen and converts it to plasmin
This is a bacterial product so can’t use often
102
What does urokinase do
A plasminogen activator
