1b Haemostasis Flashcards
(96 cards)
1
Q
What is haemostasis?
A
the cellular and biological processes that enable both the specific and regulated cessation of bleeding in response to vascular insult
2
Q
What is haemostasis for?
A
Prevention of blood loss from intact vessels
Arrest bleeding from injured vessels
Enable tissue repair
3
Q
What is the response to injury to endothelial cell lining?
A
Vessel constriction - vascular smooth muscle cells contract locally which limits blood flow to the injured vessel
4
Q
What does primary haemostasis involve?
A
Formation of an unstable platelet plug - platelet adhesion and platelet aggregation
5
Q
What is the purpose of primary haemostasis?
A
Limits blood loss and provides a surface for coagulation
6
Q
How do platelets bind directly to the exposed collagen?
A
The platelets bind to the GpIa receptor = binds directly to the exposed collage
7
Q
How do platelets bind to Von Willebrand Factor?
A
Using the Gp1b receptor
8
Q
What happens to the platelets after they bind and adhere to the endothelial lining?
A
Release of their granular contents = ADP and thromboxane
9
Q
How do platelets aggregate with each other in primary haemostasis?
A
Using the GpIIb / IIIa receptor
10
Q
What term is used to describe low platelet numbers?
A
Thrombocytopenia
11
Q
What are some causes of thrombocytopenia?
A
- Bone marrow failure
- Accelerated clearance
- Pooling and destruction in an enlarged spleen
12
Q
What conditions might cause bone marrow failure
A
leukemia, B12 deficiency, BM infiltration
13
Q
What conditions might cause accelerated clearance of platelets?
A
Immune (ITP), Disseminated Intravascular Coagulation (DIC)
14
Q
What is ITP?
A
Immune Thrombocytopenic Purpura
15
Q
Describe how ITP occurs?
A
- Antiplatelet autoantibodies bind to the sensitized platelet
- The sensitized platelets are then cleared by macrophages in the spleen
16
Q
What is a very common cause of thrombocytopenia?
A
ITP
17
Q
Describe how the function of platelets might be impaired?
A
- Hereditary absence of glycoproteins or storage granules
- Acquired due to drugs
18
Q
What causes of Glanzmann’s syndrome?
A
Absence of GPIIb / IIIa
19
Q
What causes Bernard Soulier Syndrome
A
Absence of GPIb
20
Q
What causes storage pool disease?
A
reduction in the dense granules of platelets
21
Q
Which drugs might cause an acquired impairment to the function of platelets?
A
Aspirin, NSAID’s, Clopidogrel
22
Q
What are the two common antiplatelet drugs?
A
Aspirin and Clopidogrel
23
Q
How does aspirin work?
A
irreversibly blocks cyclo-oxygenase meaning Thromboxane A2 cannot be produced
24
Q
Why does aspirin not affect prostacyclin synthetase?
A
Because it can be further generated by the endothelial cells
25
How does clopidogrel work?
Ireversibly blocks the ADP receptor on platelets - P2Y12 on cell membrane
26
What are the two functions of Von Willebrand Factor in primary haemostasis?
Binding to collagen and capturing platelets
Stabilising factor VIII (8)
27
What is the usual inheritance pattern of VWD?
Hereditary = autosomal inheritance pattern
- Deficiency of VWF
- VWF with abnormal function
28
What are the inherited conditions of primary haemostasis related to the vessel wall?
- Hereditary haemorrhagic telangiectasia
- Ehlers-Danlos syndrome
- Other connective tissue disorders
29
What are the acquired disorders of primary haemostasis related to the vessel wall?
Steroid therapy causes atrophy of the collage fibres which support the blood vessels
Ageing = senile purpure
Vasculitis
Scurvy
30
What is VWD a failure of?
Failure of primary haemostasis
31
What is a key sign of thrombocytopenia?
Petechiae - small red dots on the skin which are less than 3mm in size
32
What causes petechiae and purpura?
Bleeding underneath the skin
33
What is the difference between petechiae and purpura
Petechiae = < 3mm and Blanch when pressure is applied
Purpura = 3-10mm and do not blanch when pressure is applied
34
What conditions result in purpura on the skin?
Platelet (thrombocytopenic purpura) or vascular disorders
35
What are the typical bleeding features of primary haemostasis?
Immediate bleeding
Prolonged bleeding from cuts
Nose / gum / Heavy menstrual bleeding
Prolonged bleeding after trauma / surgery
Bruising
36
What is the medical term for nose bleeds?
Epistaxis
37
What is the medical term for heavy menstrual bleeding?
Menorrhagia
38
What type of bleeding is seen in Severe VWD?
Haemophillia like bleeding - around joints
39
What are the visible clinical features of primary haemostasis?
Petechiae
Purpura
Ecchymosis
Senile Purpura
Increased Skin Elasticity
40
What would a coagulation screen (APPT and PT) show in a disorder of primary haemostasis?
Would be normal
41
What tests are done for disorders of primary haemostasis?
Platelet count
Bleeding time
VWF assays
Clinical Observations
42
What range of platelet count would result in no spontaneous bleeding but bleeding with trauma?
40-100 x 10^9 / L
43
What range of platelet count would result in spontaneous bleeding?
10-40 x 10^9 / L
44
What range of platelet count would result in severe spontaneous bleeding?
<10 x 10^9 / L
45
What is the treatment principle for abnormal haemostasis due to immune destruction?
Immunosuppression
Splenectomy for ITP
46
What is the treatment principle for abnormal haemostasis due to failure of production / function?
Replace the missing platelets / factors
Stop drugs like Aspirin
47
What is the treatment principle for abnormal haemostasis due to Increased Consumption?
Treat the cause
Replace as necessary
48
What is desmopressin and how can it help in disorders of primary haemostasis?
2-5 fold increase in VWF and Factor 8 - releases endogenous stores so only useful in mild disorders
49
What is secondary haemostasis?
Coagulation
50
What is the role of coagulation?
To generate THROMBIN (IIA) = converts fibrinogen into fibrin
51
What are the three stages of secondary haemostasis?
Initiation
Amplification
Propagation
52
What factor is deficient in patients with Haemophillia A?
Factor 8 deficiency
53
What factor is deficient in patients with Haemophillia B?
Factor 9
54
What are some causes of acquired deficiency of coagulation factor production?
Liver disease
Anti-coagulant drugs - Warfarin and direct oral anti-coagulants
55
What is dilution and how does it cause a coagulation disorder?
Inadequate plasma replacement following blood transfusion, as only RBC's are given, not plasma therefore more dilute
56
What is the inheritance pattern of Haemophillia?
Sex (X) Linked
57
What is haemophillia?
Lack of clotting factors results in a failure to generate fibrin to stabilise a platelet plug, therefore it becomes unstable, falls apart and bleeds
58
What is the hallmark of haemophillia?
Haemarthrosis - spontaneous joint bleeding
59
What specific method of treatment should be avoided in patients with haemophillia?
Intramuscular injections
60
Which clotting factor deficiencies are compatible with life?
Haemophillia
61
Which clotting factor deficiencies are not compatible with life?
prothrombin deficiency
62
What does a factor 12 deficiency result in?
NO bleeding at all
63
What does a factor 11 deficiency result in?
Bleeding after trauma but not spontaneously
64
Why might liver failure case an acquired coagulation disorder?
Most of the clotting factors are synthesised in the liver - except VWF which is made in the endothelial cells of blood vessels
65
What is disseminated intravascular coagulation?
Generalised activation of coagulation due to tissue factor which therefore consumes and depletes coagulation factors, resulting in thrombocytopenia
66
What dimer is raised in DIC?
D dimer - breakdown product of fibrin due to increased fibrinolysis
67
Why do superficial cuts not bleed in coagulation disorders?
The unstable platelet plug is sufficient to stop small vessel bleeds
68
What are the clinical features of coagulation disorders?
* Superficial cuts do not bleed
* Bruising is common, nose bleeds are rare
* Spontaneous bleeding into the muscles and joints
* Bleeding after trauma may be delayed and is prolonged
* Bleeding frequently restarts after stopping
69
What are the two main clinical distinctions between bleeding due to platelet and coagulation defects?
Platelet = Bleeding is subcutaenous, mucosal membranes, and immediate after injury
Coagulation = bleeding is deeper (in muscle and joints) and is delayed after injury, but prolonged
70
What does APTT measure?
The intrinsic pathway (12 11 9 8)
71
What does PT measure?
The extrinsic pathway (3+7 - 10 5 2)
72
What found conditions could cause a normal PT time but elevated APTT time?
Haemophillia A / B
factor 8 / 9 deficiency
73
What condition could cause a normal APTT time but abnormal (elevated) PT time?
Factor 7 defiency
74
What conditions could cause both APTT and PT to be raised?
Liver disease
Anticoagulant drugs
DIC
Dilution following RBC transfer
75
What is used to replace all the coagulation factors?
Fresh Frozen Plasma
76
What does cyroprecipitate contain?
Fibrinogen, Factor 8, VWF and factor 13
77
What are recombinant forms of Factor 8 used for?
Used on demand to treat bleeds
78
What are some of the novel treatments for haemophillia?
Gene therapy
Bispecific antibodies
RNA silencing
79
Which drugs are increase fibrinolytic factors?
tPA and Heparin
80
What are the signs of pulmonary embolism?
Tachycardia - palpitations
hypoxia
Shortness of breath
Chest Pain
81
What are the signs of Deep vein Thrombosis/
Painful leg
Swelling
Redness
Warmth
May embolise to the lungs
82
What do most people with disorders of thrombosis die of?
haemostatic end point
83
What is a thrombosis?
It is an intravascular coagulation, can be venous or arterial (more commonly venous) which obstructs flow
84
What are the three contributory factors to Virchow's triad?
Blood
Vessel Wall
Blood Flow
85
Which factor in Virchow's triad is dominant in venous thrombosis?
Blood
86
Which factor in Virchow's triad is dominant in arterial thrombosis?
Vessel wall
87
Which factor in Virchow's triad contributes to both arterial and venous thrombosis?
Blood flow
88
What is thrombophillia?
Increased risk of venous thrombosis
89
What are anti-coagulant proteins?
Anti-thrombin
Protein C and Protein S
90
What change to anti-coagulant proteins might lead to venous thrombosis?
Decreased anticoagulant proteins
91
What might increase in order for a thrombosis to occur?
Coagulant factors
Platelets - in myeloproliferative disorders
92
How does the risk of venous thrombosis change with age?
Increases with age
93
How does inflammation relate to arterial thrombosis?
Many proteins active in coagulation are expressed on the surface of the endothelial cels and their expression is altered in inflammation
94
What is stasis and what can cause it?
reduced blood flow
Surgery, long haul flights, surgery, pregnancy
95
What is the cause of venous thrombosis?
Multi-causal = arises from interacting genetic and acquired risk factors, results in a cumulative risk which is over the thrombotic threshold
96
What is the treatment of venous thrombosis?
Assess and prevent risks
Prophylactic anti-coagulation therapy
Reduce risk of recurrance - lower procoagulant factors, or increase anti-coagulant activity
