Disorders of Haemostasis Flashcards
1
Q
what is haemostasis?
A
the arrest of bleeding and the maintenance of vascular patency
2
Q
what is primary haemostasis?
A
formation of platelet plug
3
Q
what is secondary haemostasis?
A
formation of fibrin clot
4
Q
why does fibrinolysis occur during fibrin clot formation?
A
to maintain vascular patency
5
Q
what cells do platelets come form?
A
megakaryocytes
6
Q
what is the life span of platelets?
A
7-10 dys
7
Q
what is exposed by the endothelium after damage?
A
collagen
8
Q
what factor is released by the endothelium after damage?
A
von willebrand factor
9
Q
what is the function of von willebrand factor?
A
causes platelets to adhere to collagen site of injury
10
Q
why do elderly people tend to bruise more easily?
A
reduced collagen in vessel walls
11
Q
what is the most common inherited bleeding disorder?
A
von willebrand disease
12
Q
what is the main pathology in von willebrand disease?
A
reduced levels of VWF or the VWF doesnt function properly
13
Q
where in the body is purpura most easy to seen?
A
the lower limb
14
Q
does purpura blanch?
A
no
15
Q
which type of epithelium is most susceptible to bleeding when there is a failure of primary haemostasis? (failure of platelet plug)
A
mucosal surfaces
eg epistaxes, GI bleeds, conjuncitval, menorrhagia
16
Q
what are the 3 main components of primary haemostasis? (platelet plug)
A
collagen
VWF
platelts
17
Q
why does the platelet plug have a positively charged surface?
A
platelets released calcium which stick to the surface (calcium is positively charged)
18
Q
why do clotting factors stick to the positively charged membrane of the platelet plug?
A
they have negatively charged carboxyl groups
19
Q
what 2 factors initiate the formation of the fibrin clot?
A
tissue factor and factor VIIa
20
Q
what is the function of tissue factor and factor VIIa?
A
activate factors V and X
21
Q
what is the function of factors Va and Xa?
A
convert prothrombin (clotting factor II) into thrombin (IIa)
22
Q
what is the main function of thrombin?
A
converts soluble fibrinogen (factor I) into insoluble fibrin
23
Q
what factors does thrombin activate in order to amplify the clot process?
A
VIII/IX to VIIIa/IXa
24
Q
what is the function of factors VIIIa and IXa?
A
activate V and X
25
what clotting factor is deficient in haemophilia a?
VIII
26
what clotting factor is deficient in haemophilia b?
IX
27
where are clotting factors made?
the liver
28
what is the function of tissue plasminogen activator? (tPA)
converts plasminogen into plasmin
29
what is the function of plasmin?
breaks down fibrin into FDPs (fibrin degradation products eg D dimers)
30
what is indicated when levels of D-dimers increases?
there has been a blood clot
31
what joints does haemophilia tend to bleed into?
weight bearing eg ankle and knee
| also elbow
32
what are the 2 screening tests for fibrin clot formation disorders? (secondary haemostasis disorders)
```
Prothrombin Time (PT)
Activated Partial Thromboplastin Time (APTT)
```
33
if PT is prolonged, and APTT is normal, which factors are deficienct?
Tissue Factor and Factor VII
34
if APTT is prolonged and PT is normal, which factors are deficient?
Factor VIII and IX (and XI and XII)
35
if both PT and APTT are prolonged which factors could be deficient?
deficiencies on both sides
Tissue Factor and VII
VIII, IX, XII and XII
or
Factor V and X (in the middle)
36
what factors does warfarin affect?
II, VII, IX, X
37
what factors does heparin affect?
X and II
38
when taking bloods to assess clotting factor what top container is used? what does this contain and why?
blue top
| contains citrate to bind to the calcium and therefore stops clot formation
39
what is the function of anti-thrombin III?
inhibits thrombin and Xa
40
what is the function of thrombomodulin?
binds to thrombin and so stimulates proteins C and S,
| these inhibit clotting factors
41
what is a thrombophilia?
a group of disorders with a predisposition for thrombosis
42
what is shock?
the clinical syndrome of tissue hypoperfusion due to circulatory failure
43
what does the mean arterial pressure fall below in shock?
50-60mmHg
44
why does shock cause metabolic acidosis?
anaerobic metabolism occurs leading to lactic acid
45
why does metabolic acidosis reduce cellular performance?
enzymes denature causing reduced function
46
what 3 indicators of shock can you see from the end of the bed?
skin mottling
confusion (reduced GCS)
oliguria (0.5ml/kg/hr)
47
in some cases, shock presents without hypotension- why is this?
physiological compensation
48
what are the 4 key mechanisms of shock?
1. cardiogenic shock
2. obstructive shock
3. hypovolaemic shock
4. distributive shock
49
which types of shock have cold, clammy peripheries and why?
cardiogenic, obstructive, hypovolaemic
| due to compensatory vasoconstriction (to increase systemic vascular resistance to try maintain mean arterial pressure)
50
which types of shock have warm, red peripheries and why?
distributive
| vasodilation
51
how does cardiogenic shock occur?
reduced force of cardiac contraction -->
reduced stroke volume -->
reduced cardiac output -->
reduced mean arterial pressure
52
how does obstructive shock occur?
cardiac output is blocked -->
| reduced mean arterial pressure
53
what happens to the neck veins and JVP in obstructive shock and why?
raised JVP and distended neck veins
| due to venous back pressure
54
how does hypovolaemia shock occur?
```
reduced blood volume -->
reduced venous return -->
reduced force of cardiac contraction -->
reduce stroke volume and cardiac output
--> reduced mean arterial pressure
```
55
what is the main cause of non-septic distributive shock?
spinal shock
56
how does spinal shock occur?
blockage of sympathetic output to blood vessels- vasodilation
57
what is becks triad of cardiac tamponade?
distended neck veins
hypotension
diminished heart sounds
58
what are the main two causes of hypovolaemia?
haemorrhage
| dehydration
59
how does henloch-schonlein purpura cause failure of the platelet plug? (primary haemostasis)
immune-complex deposition causes the vessel walls to be leaky (a vascular abnormality)
60
how does scurvy cause failure of the platelet plus?
lack of vitamin C (needed for collagen synthesis- a vascular abnormality)
61
what 3 areas in the body should you especially look for bleeding in?
lower limbs
mouth
eyes
62
what is the pathophysiology of immune thrombocytopenic purpura? (ITP)
IgG antibodies stick to platelets, cause the spleen to remove these platelets
63
why can renal failure cause platelet functional defects?
uremia can interfere with platelets
64
is vWF more likely to be acquired or hereditary?
hereditary
65
if inherited, what type of inheritance is vWF?
autosomal dominant
66
what causes the release of tissue factor?
damaged tissue
67
what are the 2 main reasons why liver failure can cause bleeding problems?
1. portal hypertension leading to splenomegaly (reduced platelets)
2. clotting factors are made in the liver, so decreased production
68
what clotting factors are vitamin K dependent?
II, VII, IX, X
69
what is the function of vitamin K in the production of clotting factors?
carboxylates them, giving them a negative charge so they want to bind to the positive surface of the platelet plug
70
what are the 2 main sources of vitamin K?
dietary (leafy green vegetables)
| intestinal bacterial synthesis
71
where is vitamin K absorbed in the gut?
upper intestine
72
why can obstructive jaundice cause vitamin K deficiency?
vitamin K requires bile slats for absorption
73
why are newborn given a vitamin K injection?
to prevent against haemorrhagic disease of the newborn
74
why are newborns prone to bleeding? (haemorrhagic disease of the newborn)
no bacteria in gut to make vitamin K
| diet may not have much vit K
75
what are the 5 main causes of vitamin K deficiency?
- poor dietary intake
- malabsorption
- obstructive jaundice
- haemorrhagic disease of the newborn
- vitamin K antagonists (Warfarin
76
what is disseminated intravascular coagulatioon?
excessive and inappropriate activation of the haemostatic system
leading to clotting factor consumption and severe bleeding
77
what will the platelet count, D-dimers, PT and APTT be like in DIC?
low platelet count
high D dimers
prolonged PT and APTT
78
what are the 4 main causes of DIC?
sepsis
obstetric emergencies
malignany
hypovolaemic shock
79
why are obstetric emergencies prone to lead to DIC?
placenta is very rich in tissue factor
80
what is the treatment of DIC?
```
treat underlying cause
replacement therapy (platelets, plasma, fibrinogen)
```
81
what is the inheritance of haemophila?
X linked recessive
82
which is more common- haemophilia A or B?
haemophilia A
83
in haemophilia, why do you get at target joint?
bleed into a certain joint -->
iron deposition causes new abnormal blood vessel formation -->
bleed easier from these abnormal blood vessels --> same joint always affected
84
is haemophilia an abnormality with primary or secondary haemostasis?
secondary haemostasis
85
in haemophilia, which is prolonged- PT or APTT?
APTT
86
how do you treat haemophilia?
life long replaement therapy of factor concentrates
87
in atherosclerosis, what is the plaque made of?
cholesterol
88
is arterial thrombosis associated with primary or secondary haemostasis?
primary haemostasis (platelets)
89
is venous thrombosis associated with primary or secondary haemostasis?
secondary haemostasis (fibrin clot)
90
in deep vein thrombosis do you get pitting or non-pitting oedema?
pitting
91
what is seen on ECG in a PE?
S1 Q3 T3
(deep S wave in lead 1
Q wave in lead 3
inverted T wave in lead 3)
92
what is virchows triad?
stasis
vessel wall
hypercoaguability
93
what is factor V leiden deficiency and what does is predispose to?
a thrombophilia where factor V cannot be switched off as easily by protein C and S, predisposes to thrombosis
94
what is the most common acquired thrombophilia?
antiphosphlipid syndrome
95
which is a stronger risk factor for thombosis- hereditary thrombophilias or acquired thrombophilias? (eg APS)
acquired thrombophilias
96
does antiphospholipid syndrome affect arteries or veins?
both
97
in addition to recurrent thromboses, what is a characteristic feature of antiphospholipid syndrome?
recurrent fetal loss
98
what is the pathogenesis of antiphospholipid syndrome?
autoantibodies bind to B2 glycoprotein 1 which leads to activation of primary and secondary haemostasis
99
what are the autoantibodies in antiphospholipid syndrome known as?
lupus anticoagulants
100
what happens to the APTT in antiphospholipid syndrome?
prolonged
| -despite being a thrombophilia (an in vitro finding)
101
what is the treatment of antiphospholipid syndrome?
none if no symptoms
if arterial thrombosis- antiplatelet (eg aspirin)
if venous thrombosis- anticoagulant (eg warfarin)
if both- both antiplatelet and anticoagulant
102
what are the 3 main indications for anticoagulant drugs?
atrial fibrillation
venous thrombosis
valve replacement
103
what conditon is the use of anticoagulants in AF is to prevent?
stroke
104
how does heparin work?
potentiates the effect of antithrombin
105
how long does heparin take to work?
minutes
106
how is heparin administered?
IV or SC
107
what are the 2 forms of heparin?
unfractioned heparin
| low molecular weight heparin
108
compare unfractioned hepatin and LMWH in terms of their affect on different clotting factors?
unfractioned- potentiates the antithrombin-thrombin complex most
LMWH- potentiates the antithrombin-Xa complex most
109
how do you monitor heparin?
measure APTT for unfractioned heparin
Anti-Xa assay for LMWH (usually no monitoring required)
110
why is no monitoring required for LMWH when is is needed for unfractioned heparin?
as LMWH affects factor X the most it is more predictable in it's response
111
what autoimmune condition can occur with heparin?
heparin induced thrombocytopaenia (with thrombosis) HITT
112
when does heparin induced thrombocytopaenia (with thrombosis) tend to occur?
first 5-10 days of starting heparin
113
what is the pathogenesis of heparin induced thrombocytopaenia (with thrombosis?
autoantibodies to the heparin-platelet complex is formed causing platelets to stick together
platetes get consumed (thrombocytopaenia) and aggregate formin a clot (thrombosis)
114
how can you tell whether someone is potentially getting heparin-induced thromocytopaenia (with thrombosis)?
monitor RBC
| and look for falling platelet count
115
if you stop heparin, how long does it take to get out of your system?
half an hour
116
if you want to reverse the effect of heparin very fast (ie in severe bleeding), what drug can be given?
protamine sulphate
117
why does starting warfarin put you into a prothrombotic state initially?
protein C and S are also vitamin K dependent, their half lives are very short so are affected first
118
in order to balance out the initial pro-thrombotic state of warfarin, what is usually done?
patient is additionally put on heparin for a week
119
what enzyme metabolises warfarin?
cytochrome P50
120
how does alcohol interfere with warfarin and knock the dose out of the therapeutic window?
alcohol is also metabolised by the cytochrome P50 enzyme
121
does warfarin affect PT or APTT mainly?
PT
122
what INR do we want for the prevention of stroke or venous thrombosis?
2/3
| ie PT roughly prolonged by 2/3 x
123
if you stop warfarin, how long will it take for the INR to come down?
2/3 days
124
if you want the INR to come down quicker than it would with just stopping warfarin, what can you do?
administer PO vit K
| admister clotting factor concentrates
125
how long does administering PO vit K take to work?
6 hours
126
how long does administering clotting factors take to work?
immediatelyy
127
new oral anticoagulants target which 2 clotting factors?
- direct thrombin inhibitors eg dabigatran
| - direct Xa inhibitors eg rivaroxiban
128
what is the 2 main benefits of new oral anticoagulants over heparin and warfarin?
oral (warfarin is also oral)
| no drug monitoring required
129
what is the main downside of new oral anticoagulants?
currently no specific antidoes
130
what is the current main use of oral anticoagulants?
prophylaxis in elective hip/knee replacements (instead of LMWH)
131
compare the use of protamine sulphate in unfractioned heparin and LMWH?
unfractioned- complete reversal
| LMWH- partial reversal
132
how do thromboses form from atherosclerotic plaques?
if plaque is unstable, it can rupture
| platelets are recruited and a thrombus is formed
133
what 4 main factors cause damage to the endothelium and so increase risk of arterial thrombosis?
- hypertension
- smoking
- high cholesterol
- diabetes mellitus
134
once adhered to the site of injury, platelets secrete which chemicals and why?
ADP
thromboxane A2
to cause platelet aggregation
135
platelets bind to the subendothelial collagen via what?
von willebrand factor
| glycoprotein 1b
136
platelets aggregate to each other via what?
glycoprotein 2b3a
| fibrinogen
137
how does aspirin work?
inhibits COX 1 to prevent production of thromboxane A2 and so less aggregation of platelets
138
what are the main 3 side effects of aspirin?
1. bleeding
2. GI ulceration
3. bronchospasm
139
why does aspirin cause GI ulceration and bronchospasm?
effect of inhibiting prostaglandins
140
aspirin is contraindicated in patients with which respiratory condition?
asthma
141
how does clopidogrel work?
ADP receptor antagonist (P2Y12)
| so reduced aggregation of platelets
142
how many days before elective operations should you stop antiplatelets
7 days
