1b Haemostasis Flashcards
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 GpIb 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 A2 from arachidonic acid
9
Q
How do platelets aggregate with each other in primary haemostasis?
A
Using the GpIIb / IIIa receptor following activation
10
Q
What happens in secondary haemostasis?
A
Stabilisation of the plug with fibrin
blood coagulation
11
Q
What is the purpose of secondary haemostasis?
A
Stops blood loss
12
Q
What happens during fibrinolysis?
A
Vessel repair and dissolution of clot
Cell migration/proliferation & fibrinolysis
13
Q
What is the purpose of fibrinolysis?
A
Restores vessel integrity
14
Q
What term is used to describe low platelet numbers?
A
Thrombocytopenia
15
Q
What are some causes of thrombocytopenia?
A
Bone marrow failure eg: leukaemia, B12 deficiency
Accelerated clearance eg: immune (ITP), Disseminated Intravascular Coagulation (DIC)
Pooling and destruction in an enlarged spleen
16
Q
What is ITP?
A
Immune Thrombocytopenic Purpura
17
Q
Describe how ITP occurs?
A
- Antiplatelet autoantibodies bind to the sensitized platelet
- The sensitized platelets are then cleared by macrophages in the spleen
18
Q
What is a very common cause of thrombocytopenia?
A
ITP
19
Q
Describe how the function of platelets might be impaired?
A
Hereditary absence of glycoproteins or storage granules
20
Q
What causes of Glanzmann’s syndrome?
A
Absence of GPIIb / IIIa
21
Q
What causes Bernard Soulier Syndrome
A
Absence of GPIb
22
Q
What causes storage pool disease?
A
reduction in the dense granules of platelets
23
Q
Which drugs might cause an acquired impairment to the function of platelets?
A
Aspirin, NSAID’s, Clopidogrel
24
Q
What are the two common antiplatelet drugs?
A
Aspirin and Clopidogrel
25
How does aspirin work?
irreversibly blocks cyclo-oxygenase meaning Thromboxane A2 cannot be produced
26
Why does aspirin not affect prostacyclin synthetase?
Because it can be further generated by the endothelial cells
27
How does clopidogrel work?
Ireversibly blocks the ADP receptor on platelets - P2Y12 on cell membrane
28
What are the two functions of Von Willebrand Factor in primary haemostasis?
Binding to collagen and capturing platelets
Stabilising factor VIII (8)
29
What is the usual inheritance pattern of VWD?
Hereditary = autosomal inheritance pattern
- Deficiency of VWF
- VWF with abnormal function
30
What are the inherited conditions of primary haemostasis related to the vessel wall?
Connective tissue disorders
31
What are the acquire disorders of primary haemostasis related to the vessel wall?
Steroid therapy causes atrophy of the collage fibres which support the blood vessels
Ageing = senile purpura
Vasculitis
Scurvy
32
What is VWD?
Failure of primary haemostasis
Hereditary decrease of quantity +/ function (common)
Acquired due to antibody (rare)
33
What is a key sign of thrombocytopenia?
Petechiae - small red dots on the skin which are less than 3mm in size
34
What causes petechiae and purpura?
Bleeding underneath the skin
35
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
36
What conditions result in purpura on the skin?
Platelet (thrombocytopenic purpura) or vascular disorders
37
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
38
What is the medical term for nose bleeds?
Epistaxis
39
What is the medical term for heavy menstrual bleeding?
Menorrhagia
40
What type of bleeding is seen in Severe VWD?
Haemophillia like bleeding - around joints due to low FVIII
41
What are the visible clinical features of primary haemostasis?
Petechiae
Purpura
Ecchymosis
Senile Purpura
Increased Skin Elasticity
42
What would a coagulation screen (APPT and PT) show in a disorder of primary haemostasis?
Would be normal
43
What tests are done for disorders of primary haemostasis?
Platelet count
Bleeding time
VWF assays
Clinical Observations
44
What range of platelet count would result in no spontaneous bleeding but bleeding with trauma?
40-100 x 10^9 / L
45
What range of platelet count would result in spontaneous bleeding?
10-40 x 10^9 / L
46
What range of platelet count would result in severe spontaneous bleeding?
<10 x 10^9 / L
47
What is the treatment principle for abnormal haemostasis due to immune destruction?
Immunosuppression
Splenectomy for ITP
48
What is the treatment principle for abnormal haemostasis due to failure of production / function?
Replace the missing platelets / factors through prophylactic or therapeutic
Stop drugs like Aspirin
49
What is the treatment principle for abnormal haemostasis due to Increased Consumption?
Treat the cause
Replace as necessary
50
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
51
What are other treatments of abnormal haemostasis?
Tranexamic Acid
Fibrin glue/spray
Hormonal
52
What is secondary haemostasis?
Coagulation
53
What is the role of coagulation?
To generate THROMBIN (IIA) = converts fibrinogen into fibrin
54
What are the three stages of secondary haemostasis?
Initiation
Amplification
Propagation
55
What factor is deficient in patients with Haemophillia A?
Factor 8 deficiency
56
What factor is deficient in patients with Haemophillia B?
Factor 9
57
What are some caused of acquired deficiency of coagulation factor production?
Liver disease
Anti-coagulant drugs - Warfarin and direct oral anti-coagulants
58
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
59
What is the inheritance pattern of Haemophillia?
Sex (X) Linked
60
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
61
What is the hallmark of haemophillia?
Haemarthrosis - spontaneous joint bleeding
62
What specific method of treatment should be avoided in patients with haemophillia?
Intramuscular injections
63
Which clotting factor deficiencies are compatible with life?
Haemophillia
64
Which clotting factor deficiencies are not compatible with life?
prothrombin deficiency
65
What does a factor 12 deficiency result in?
NO bleeding at all
66
What does a factor 11 deficiency result in?
Bleeding after trauma but not spontaenouslt
67
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
68
What is disseminated intravascular coagulation?
Generalised activation of coagulation due to tissue factor which therefore consumes and depletes coagulation factors, resulting in thrombocytopenia
69
What dimer is raised in DIC?
D dimer - breakdown product of fibrin due to increased fibrinolysis
70
Why do superficial cuts not bleed in coagulation disorders?
The unstable platelet plug is sufficient to stop small vessel bleeds
71
What are the clinical features of coagulation disorders?
Bruising is common, nose bleeds are rare
Spontaneous bleeding into the muscles and joints
Delayed spontaneous bleeding after trauma, and bleeding frequently restarts after stopping
72
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
73
What does APTT measure?
The intrinsic pathway (12 11 9 8)
74
What does PT measure?
The extrinsic pathway (3+7 - 10 5 2)
75
What four conditions could cause a normal PT time but elevated APTT time?
Haemophillia A / B
factor 8 / 9 deficiency
76
What condition could cause a normal APTT time but abnormal (elevated) PT time?
Factor 7 defiency
77
What conditions could cause both APTT and PT to be raised?
Liver disease
Anticoagulant drugs
DIC
Dilution following RBC transfer
78
What is used to replace all the coagulation factors?
Fresh Frozen Plasma
79
What does cyroprecipitate contain?
Fibrinogen, Factor 8, VWF and factor 13
80
What are recombinant forms of Factor 8 and 10 used for?
Used on demand to treat bleeds
81
What are factor concentrates?
Concentrates available for all factors except factor V.
Prothrombin complex concentrates (PCCs) Factors II, VII, IX, X
82
What are some of the novel treatments for haemophillia?
Gene therapy
Bispecific antibodies
RNA silencing
83
Which drugs are increase fibrinolytic factors?
tPA and Heparin
84
What are the signs of pulmonary embolism?
Tachycardia - palpitations
hypoxia
Shortness of breath
Chest Pain
haemoptysis
sudden death
85
What are the signs of Deep vein Thrombosis/
Painful leg
Swelling
Redness
Warmth
May embolise to the lungs
86
What do most people with disorders of thrombosis die of?
haemostatic end point
87
What is a thrombosis?
It is an intravascular coagulation, can be venous or arterial (more commonly venous) which obstructs flow
88
What are the three contributory factors to Virchow's triad?
Blood
Vessel Wall
Blood Flow
89
Which factor in Virchow's triad is dominant in venous thrombosis?
Blood
90
Which factor in Virchow's triad is dominant in arterial thrombosis?
Vessel wall
91
Which factor in Virchow's triad contributes to both arterial and venous thrombosis?
Blood flow
92
What is thrombophillia?
Increased risk of venous thrombosis
93
What are anti-coagulant proteins?
Anti-thrombin
Protein C and Protein S
94
What change to anti-coagulant proteins might lead to venous thrombosis?
Decreased anticoagulant proteins
95
What might increase in order for a thrombosis to occur?
Coagulant factors
Platelets - in myeloproliferative disorders
96
How does the risk of venous thrombosis change with age?
Increases with age
97
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
98
What is stasis and what can cause it?
reduced blood flow
Surgery, long haul flights, surgery, pregnancy
99
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
100
What is the treatment of venous thrombosis?
Assess and prevent risks
Prophylactic anti-coagulation therapy
Reduce risk of recurrance - lower procoagulant factors,(warfarin/DOACs) or increase anti-coagulant activity (Heparin)
101
What are some indications for anticoagulation?
Venous thrombosis
Atrial fibrillation to reduce risk of embolic stroke
Preventative following surgery or hospital admssion
102
What is heparin, how is it produced and what are the two ways it can be administered?
Naturally occurring glycosaminoglycan
Produced by mast cells of most speciesLong chains - Unfractionated (UFH) – intravenous administration, short half life
- Low molecular weight (LMWH) – subcutaneous administration
103
What are the actions of unfractionated heparin?
Enhancement of Antithrombin
Inactivation of thrombin (Hep binds AT + Thrombin)
Inactivation of FXa (Hep binds AT only)
(Inactivation of FIXa, FXIa, FXIIa)
104
What are the actions of LMWH?
Contain pentasaccharide sequence for binding anti thrombin
No need to monitor as it is predictable
105
How does warfarin work?
Blocks recycling of Vitamin K
Reduces production of coagulation factors
Induces antocoagulated state slowly
Reversible slowly by Vitamin K administration or rapidly by infusion of coag factors (ffp or pcc)
106
What are some side effects of warfarin?
Bleeding
Skin necrosis
Purple toe syndrome - (Disrupted atheromatous plaques bleed
Cholesterol emboli lodge in extremities)
Embryopathy Chondrodysplasia punctata - (Early fusion of epiphyses
Warfarin teratogenic in 1st trimester)
107
Equation for INR and what does it mean and what is the normal/target?
108
What might cause resistance to warfarin?
Lack of compliance
Diet - increased vit k intake
Increased metabolism Cyt P450 (CYP2C9)
Reduced binding (VKORC1)
109
What are DOACs?
Direct Oral Anticoagulants
110
What are some DOACs and where do they work?
Rivaroxaban, apixaban, edoxabanaffects fator Xa in propagation
Dabigatran affect Factor IIa in fibrin formation
111
What are the differences between Warfarin and DOACs
112
For which condition are DOACs ineffective?
Mechanical prothetic heart valve (Warfarin) and not safe for preganacy (LMWH)
113
In which conditions can you use DOACs or LMWH?
Surgery and initial treatment for clot or embolism (then can switch to DOAC or warfarin)
114
In which conditions can you use DOAC or warfarin?
Long term conditions and to reduce risk of embolic stroke
