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Y1 - PP > Lecture 9 - Intro To Haemostasis > Flashcards

Lecture 9 - Intro To Haemostasis Flashcards

1
Q

What is haemostasis?

A

Maintenance of fluid status in normal vessels whilst permitting rapid formation of a haemostatic clot at a sit of vascular injury

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2
Q

What are the 3 components of haemostasis?

A

Vascular wall

Platelets

Coagulation cascade:
-Coagulation factors
-Anticoagulant factors

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3
Q

What is the basic aim of normal haemostasis?

A

Stopping bleeding following trauma to blood vessel

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4
Q

What are the 3 general processes of stopping normal bleeding?

A

Vessel wall contracts
Platelet plug forms
Fibrin clot forms to stabilise

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5
Q

How does vessel size relate to bleeding from the vessel?

A

larger vessel = more bleeding

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6
Q

What cells are platelets made from?

A

Megakaryocytes

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7
Q

Where are megakaryocytes/platelets made?

A

In the bone marrow

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8
Q

What is the normal platelet count?

A

150 - 400 x 10^9/L

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9
Q

What 3 stages do platelets go through when a vessel is injured?

A

Adhesion
Activation
Aggregation (Forms platelet clot)

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10
Q

How do platelets adhere to blood vessels?

A

Collagen from tunica adventitia exposed

Von Willebrand factor produced by vascular endothelial cells binds to platelets binding the platelets to the collagen fibres adhering them

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11
Q

When platelets are activated what do they secrete?

A

Granules containg:
-Fibrinogen
-ADP
-Thromboxane
-Some coagulation factors
And more substances to activate other platelets

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12
Q

What is platelet aggregation?

A

When platelets cross link to form a platelet plug

Platelet plug adds some stability but is quite weak

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13
Q

What is the role of collagen in platelets action?

A

Binds platelets to vessel wall

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14
Q

What is the role of Von Willebrand factor?

A

To get platelets to adhere to the collagen

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15
Q

What is the role of ADP and Thromboxane?

A

Cause platelets to interact and form a platelet plug

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16
Q

What is the role of Thrombin?

A

Converts fibrinogen to fibrin

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17
Q

Why is formation of fibrin important?

A

It is insoluble so is what forms the stable clot

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18
Q

What is a zymogen?

A

A proenzyme (enzyme that is not active)

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19
Q

What is the clotting cascade aiming to produce?

What is the point of producing this?

A

Thrombin

Thrombin needed to convert fibrinogen into fibrin

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20
Q

Why does fibrinogen need to be converted into fibrin?

A

Fibrinogen is soluble
Fibrin is insoluble

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21
Q

Why do natural anticoagulants exist?

A

To carefully balanced the clotting cascade to prevent over clotting

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22
Q

What are the 2 pathways of the clotting cascade that lead to the common pathway?

A

Intrinsic pathway (contact activation pathway

Extrinsic pathway (tissue factor pathway)

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23
Q

What do both the intrinsic pathway and the extrinsic pathway produce which is the common insertion point into the common pathway?

A

Factor X (10)

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24
Q

What does Factor X (10) do in the common pathway?

A

Convert prothrombin to thrombin

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25
Where are most the coagulation factors made?
The Liver
26
What are the 3 coagulation tests for clotting defects?
APTT (Activated partial Thromboplastin time) PT (Prothromin time) TT (Thrombin time)
27
What pathways does PT (prothrombin time) measure?
Extrinsic pathway
28
The function of what clotting factor is assed by PT (extrinsic pathway)?
Factor VII
29
What pathway is the (Activated partial thromboplastin time) APTT measuring the functioning of?
Intrinsic pathway
30
What does increased/abnormal APTT and PT indicate?
Problem in common pathway (From factor X downwards) Usually deficient Factor V, X, thrombin an fibrinogen
31
What does Thrombin clotting time measure?
Conversion of fibrinogen to fibrin via action of thrombin
32
If somebody has Haemophilia A or B what anticoagulation test is abnormal?
APTT (activated partial thromboplastin)
33
What happens to the vessel wall when damaged?
Vasoconstriction (Reduce blood flow/bleeding) Producing Von Willebrand factor (so platelets stick to the collagen) Exposure of platen and tissue factor initiates activation of clotting factors
34
What is the goal of haemostasis?
Make a clot Control clotting Break down clot
35
What 3 natural anticoagulants?
Protein C Proteins S Antithrombin
36
What Factors does Protein C inactivate?
Factor VIIIa Factor Va
37
How is protein S related to Protein C?
Proteins S is a cofactor for protein C Protein S must be activated in order for Protein C to be activated
38
What vitamin is the synthesis of Protein C and Protein S dependant on?
Vitamin K dependant
39
What does Antithrombin inactivate?
Thrombin Other clotting factors
40
What activates Antithrombin?
Heparin
41
What is the function of Antithrombin on the body as a whole ?
Prevents spread of clot (rapidly inactivates travelling clotting factors)
42
Where does Tissue Factor Pathway Inhibitor act?
Start of Extrinsic pathway inhibiting Factor VII Extrinsic pathway = tissue factor activation pathway
43
What is Fibrinolysis?
Break down of the final clot
44
What takes place in fibrinolysis?
Plasminogen converted to plasmin Plasmin breaks down clot forming D-Dimers
45
What is the clinical significance of measuring D-Dimers in the blood?
Indicates clotting is taking place
46
What causes bleeding disorders?
Abnormalities in: -Vessel wall -Platelets -Coagulation factors
47
What is Thrombocytopenia?
Deficiency of platelets in the blood resulting in bleeding into the tissues, bruising and slow blood clotting after injury
48
What are the signs of Thrombocytopenia?
Purpura Petechiae Mucosal bleeding Epistaxis Menorrhagia
49
What are the signs of Thrombocytopenia?
Purpura Petechiae Mucosal bleeding Epistaxis Menorrhagia
50
What is Purpura?
Haemorrhages in skin
51
What is petechiae?
Red dots/rash on skin
52
What is epistaxis?
Nose bleeds
53
What is menorrhagia?
Heavy menstrual periods
54
On a basic level, how does Thrombocytopenia happen?
Decreased production Increased consumption
55
What are some causes of decreased production of platelets?
Marrow aplasia Megaloblastic anaemia Sepsis
56
What are some immun causes of thrombocytopenia?
Immune Thrombocytopenic Purpura Thrombotic Thrombocytopenic Purpura
57
What is Immune Thrombocytopenic Purpura?
Low platelet count with a normal bone marrow and any other cause of low platelets has been ruled out
58
What is Thrombotic Thrombocytopenic Purpura?
Many small blood clots forming in small vessels are ounce the body Leads to platelets and RBCs being used up and consumed
59
What are some non immune causes of thrombocytopenia?
Haemolytic-uraemic syndrome (HUS) Hypersplenism Disseminated Intravascular Coagulation
60
What’s characteristic of Haemoytic-uraemia syndrome (HUS)?
Low RBCs Acute kidney injury Low platelets
61
Who often get Haemoytic-uraemia syndrome?
Children more than adults Associated with E.Coli infection
62
What are the symptoms of Haemoytic-uraemia syndrome?
Bloody diarrhoea Fever Vommiting Weakness Kidney failure Low platelets
63
How does Hypersplenism cause Thrombocytopenia?
Enlarged overactive spleen removes too many platelets from blood (Bone marrow tries to proliferate more to compensate)
64
What are the 3 most common congenital Coagulation factor disorders?
Haemophilia A Haemophilia B Von Willebrand’s disease
64
What are the 3 most common congenital Coagulation factor disorders?
Haemophilia A Haemophilia B Von Willebrand’s disease
65
What type of genetic inheritance are both forms of Haemophilia?
X linked recessive
66
What Factor is lacking in Haemophilia A?
Factor VIII
67
Why in Haemophilia A is APTT longer but PT normal?
Factor VIII is normally present in intrinsic pathway which is measured by APTT PT measures the extrinsic pathway (factor VII)
68
How is Haemohillia A treated?
Recombinant Factor VIII
69
What Factor is deficient in Haemophilia B?
Factor IX
70
Why is APTT prolonged but PT normal with Haemophilia B?
Factor IX involved in intrinsic pathway
71
What is the only way to distinguish between Haemophilia A and B and why?
Presence of Factor VIII or IX Both have same results of prolonged APTT and normal PT
72
How does Haemophilia present?
Prolonged bleeding post dental extraction Muscle haematomas Life threatening post operative an post traumatic bleeding Easy bruising Mass haaemorrhaging
73
What type of disease is Von WIllebrand disease?
Autosomal dominant
74
What is reduced in Von Willebrand disease?
Reduced platelet adhesion to vessel walls Reduced Factor VIII
75
How does Von Willebrand Disease present?
Spontaneous nose bleeds Excessive wound bleeding Menorrhagia
76
What do vessel wall abnormalities usually lead to?
Easy bruising SPontaeous small vessel bleeds Mainly from skin but can be mucous membranes
77
What are 2 examples of vessel wall abnormalities?
Ehlers Danlos (connective tissue disorders) Scurvy
78
What is Disseminated Intravascular coagulation (DIC)?
Lots of small blood thrombi form and get broken down Platelets and clotting factors get consumed When actually need to form clots (Haemostasis) you can so you haemorrhage
79
What would the levels of fibrinogen and D dimers be in someone with DIC and why?
Low fibrinogen High D dimers Lots of fibrinogen converted to fibrin due to overactive clotting Lots of fibrolysis happening so high D-Dimers
80
There is always a trigger to cause DIC, what are some?
Malignancy Massive tissue injury (burns) Infections (gram - sepsis) Massive haemorrhage Obstetric cause (amniotic fluid embolism, preeclampsia)
81
What are Thrombophilias?
Congenital or acquired defects of haemostasis which can increase a patients risk of thrombosis
82
What is a congenital cause of thrombophilia?
Deficient in anticoagulants
83
What is more likely to happen in antiphospholipid syndrome? Who is more likely to get this defect?
Clot development A thrombophilia Afro-Caribbean’s, Hispanics, Asians and Native Americans
84
What are some Anticoagulant drugs?
Vitamin K inhibitors (Warfarin) Direct oral anticoagulants Heparin
85
What are some Direct oral anticoagulants? How do they work?
Dabigatran Rivaroxaban Apixaban Rivaroxaban and Apixaban inhibit Factor X, this means that less prothrombin is converted to thrombin so less fibrinogen to fibrin
86
Why is warfarin being moved away from as an anticoagulant?
Needs constant patient monitoring
87
What are 2 anti platelet drugs?
Aspirin Clopidogrel
88
How does Aspirin act as an anti platelet drug?
Blocks formation of Thromboxane Therefore preventing formation of platelet plug
89
How does Clopidogrel act as an anti platelet drug?
Blocks ADP produced by platelets Preventing the formation of the platelet plug
90
What is the main risk of anticoagulants?
BLEEDING
91
What is the most common Inherited Thrombophilia in Caucasians? What type of inheritance?
Factor V Leiden Autosomal dominant

Y1 - PP (20 decks)

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