Pathological Processes > PP 5 Intro To Haemostasis > Flashcards

PP 5 Intro To Haemostasis Flashcards

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1
Q

What is haemostasis?

A

Stopping of blood flow

Maintains fluid stasis in vessels whilst permitting rapid clot formation

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2
Q

What are the 3 components of haemostasis?

A

Intact vascular wall
Platelets
Coagulation cascade - (anti)coagulation factors

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3
Q

Aim of haemostasis

A

Stop bleeding after trauma to blood vessel

  1. Make clot
  2. Control clotting
  3. Breakdown clot
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4
Q

Process of haemostasis

A

1- contraction of vessel wall
2- formation of platelet plug at site
3- formation of fibrin clot to stabilise

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5
Q

Vessel wall structure

A

Tunica intima - endothelium
Tunica media - smooth muscles
Tunica adventitia - comprised of fibroblasts + collagen

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6
Q

What happens to the vessel wall in haemostasis

A
  • vasoconstriction- increased blood flow
  • production of vWF
  • exposure of collagen + tissue - initiates activation of clotting factor
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7
Q

What is vWF?

A

Von Willebrand factor

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8
Q

Von Willebran factor function

A

Platelet adherence
Carries + protects factor VIII

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9
Q

What are platelets made from?

A

Cytoplasm of megakaryocyte in bone marrow

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10
Q

Platelet life span

A

7-10 days

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11
Q

Describe platelets

A

Disc shaped
Anucleated

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12
Q

Platelet action at injury

A

Adhesion
Activation/secretion
Aggregation

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13
Q

Describe platelet adhesion

A
  • After vessel wall damage - exposure of underlying tissues
  • Platelets adhere to collagen via vWF
  • vWF acts as a bridge between platelets + collagen
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14
Q

Describe platelet activation/secretion

A
  • Platelets secrete granules containing ADP, thoromboxane etc..
  • Granules get activated + activate other platelets
  • Activation of clotting cascade
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15
Q

Describe platelet aggregation

A
  • Cross linking of platelets to form platelet plug
  • Provides some stability but friable
  • Need to form clot - more stable
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16
Q

List mediating factors of platelet action + their functions

A
  • fibrinogen- links platelets
  • collagen- binds platelets
  • ADP + thromboxane- causes interaction of platelets to make plug
  • thrombin- converts fibrinogen to fibrin
  • von Willebran factor- platelet adherence
  • platelet receptors- glycoproteins complexes e.g. GP1, GPIIa/Ia - binding site for fibrinogen
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17
Q

Fibrinogen function in clotting cascade

A

Links platelets to from platelet plug

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18
Q

Collagen function in clotting cascade

A

Binds platelets

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19
Q

ADP + thromboxane function in clotting cascade

A

Cause interaction of platelets to make plug

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20
Q

Thrombin function in clotting cascade

A

Converts fibrinogen to fibrin

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21
Q

Von Willebrand factor function in clotting cascade

A

Platelet adherence
Carries factor VIII

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22
Q

What are tests for clotting defects performed on?

A

Platelet poor plasma

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23
Q

Test for clotting defects

A

APTT activated partial thromboplastin time
PT prothrombin time
TT thrombin time

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24
Q

What does APTT test?

A

Activated partial thromboplastin time
Intrinsic pathways
Factors VIII, IX, XI, VIII

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25
What does PT test?
Prothrombin time Tests extrinsic pathway **PET**
26
What does TT test?
Thrombin time Tests conversion of fibrinogen to fibrin by thrombin
27
What converts fibrinogen to fibrin?
Thrombin
28
What factors are in the common pathway? What do deficiencies in them do?
**Factors of 10** Factor V Factor X Prothrombin II Fibrinogen I Prolong APTT + PT
29
What do deficiencies in factors V, X thrombin + fibrinogen prolong? Why?
APTT and PT In the common pathway
30
Functions of natural anticoagulants
Stop over clotting Breakdown clot
31
Natural anticoagulant examples
Antibthromin Protein C + S
32
Function of anttithrombin
Inhibits action of thrombin
33
Explain the action of antithromin
- Activated by heparin on surface of endothelial cells - Prevent spread of a clot by rapidly inactivating clotting factors - carried away in blood
34
Explain how protein C is activated
- thrombin binds to thrombomodulin - this complex activates protein C - activated protein C **inactivates factor VIIIa + Va** >> **prevents prothrombin > thrombin** - protein S is a cofactor for APC
35
Function of activated protein C
Prevents prothrombin > thrombin
36
Function of tissue factor (extrinsic) pathway inhibitor
Opposes clot formation Inhibits ability to generate Xa
37
What are the two pathways of the clotting cascade?
Contact activation (intrinsic) pathway Tissue factor (extrinsic) pathway
38
What converts prothrombin to thrombin?
Factor Xa + Va
39
What is the intrinsic pathway measured by?
Activated partial thromboplastin time
40
What is the extrinsic pathway measured by?
Prothrombin time
41
Factors in the intrinsic pathway of the clotting cascade
**IN**trinsic - 12**IN**ch sub XII > XIIa XI > XIa IX > IXa VIII X > Xa
42
Factors in extrinsic pathway of clotting cascade
**E**xtrinsic - s**E**v**E**n VII > VIIa X > Xa
43
What triggers the intrinsic pathway of the clotting cascade?
Exposure of collagen after blood vessel is damaged
44
What triggers the extrinsic pathway of the clotting cascade?
Trauma
45
Do natural anticoagulants destroy clots? If not, what do they do?
No They oppose production of fibrin to control clotting cascade
46
When does tissue factor pathway inhibitor act?
Initiation phase of clotting
47
What breaks down fibrin ?
Plasmin
48
Function of plasmin
Breaks down fibrin Dissolves thrombus
49
What does fibrin get broken down into?
D-dimers + other fibrin degradation products
50
What can be tested in the blood for clotting?
D-dimers
51
What converts plasminogen to plasmin?
Tissue plasminogen activator (tPA)
52
How can tPA be used therapeutically?
Dissolving thrombin and thromboembolisms
53
Side effect of tPA usage therapeutically
Undesired bleeding
54
What are bleeding disorders due to?
Abnormalities in vessel wall, platelets or coagulation factors
55
What is thrombocytopenia?
Deficiency of platelets
56
Presentation of thrombocytopenia
Puparia Petechiae Mucosal bleeding Epistaxis Menorrhagia
57
What is purpura?
Red/purple blemishes/bruises
58
What is petechiae?
Small round spots on skin from bleeding
59
What is epistaxis?
Nose bleeds
60
What is menorrhagia?
Heavy periods
61
What is the condition where you have low platelet count with the absence of a cause?
Immune thrombocytopenia purpura
62
What is immune thrombocytopenia purpura?
Low platelets With absence of cause Immune disease
63
What is thrombotic thrombocytopenia purpura?
- Blood clots form in small vessels - Increased consumption of platelets + RBCs due to breakdown Immune disease
64
What is haemolytic uraemic syndrome?
Low RBC + platelets Acute kidney injury Associated with E. coli In children more than adults Non immune
65
Signs + symptoms of haemolytic uraemic syndrome
Fever Vomiting Weakness Kidney failure Low platelts Bloody diarrhoea
66
What is hypersplenism?
Enlargement of spleen Decreased circulating blood cells Proliferation response in bone marrow Non immune disease
67
Treatment of Hypersplenism
Splenectomy
68
List congenital coagulation factor disorders
Haemophilia A Haemophilia B Von Willebrand’s disease
69
List acquired coagulation factor disorders
Disseminated Intravascular coagulation Liver disease Vitamin K deficiency Anticoagulants
70
Presentation of haemophilia
Muscle haematomas Joint pain + deformities Recurrent haemarthroses Prolonged bleeding post dental extraction Life threatening post-op + trauma bleeding Intracerebral haemorrhage Spontaneous bleeding
71
Where does spontaneous bleeding occur in haemophilia?
In sites subject to trauma e.g. *joints*
72
What causes haemophilia A?
Factor VIII deficiency ‘**A**te’
73
Treatment of haemophilia A
Recombinant factor VIII
74
Clotting test in haemophilia A
Factor VIII in intrinsic pathway Prolonged APTT Normal PT
75
What type of genetic condition is haemophilia?
X linked recessive
76
Who do X linked recessive conditions effect?
All males Homozygous for mutation females
77
What causes haemophilia B?
Factor IX deficiency ‘Benign’ - **B** **nine**
78
Clotting tests in haemophilia B
Factor IX in intrinsic pathway Prolonged APTT Normal PT
79
Treatment of haemophilia B
Recombinant factor IX
80
Which haemophilia has a increased risk of bruising and mucosal bleeds?
B
81
What type of genetic condition is Von Willebrand disease?
Autosomal dominant
82
Cause of Von Willebrand disease
Several genetic defects
83
vWF function and how is it effected in Von Willebrand disease?
- **Carries factor VIII** - decreased factor VIII + activity - **Mediates platelet adhesion** - abnormal platelet adhesion to vessel
84
Presentation of Von Willebrand disease
Epistaxis Excessive wound bleeding Menorrhagia Prolonged bleeding time with normal platelet count
85
Platelets in haemophilia
Platelets unaffected Low clotting factors > less fibrin made
86
What type of anaemia is DIC? Describe how it causes anaemia
- **Microangiopathic haemolytic anaemia** - Many microthrombi formed in circulation > increased consumption of clotting factors + platelets
87
What is DIC?
Disseminated intravascular coagulopathy
88
Clotting tests in DIC
Raised PT Raised APTT Low fibrinogen Raised D dimers
89
Causes of DIC
**must always be a trigger** Malignancy Massive tissue injury e.g. *burns* Infection Massive haemorrhage Amniotic fluid embolism Pre-eclampsia Placental abruption
90
Complications of anticoagulants and what to do dependent on the drug used
**Bleeding** - **if warfarin** - stop - give vitamin K - if emergency > prothrombin complex concentrate - **if heparin** - stop - give protamine sulphate if needed
91
Where is prothrombin made?
Liver
92
What is prothrombin?
Protein Clotting factor
93
What are the vitamin K dependent clotting factors?
II - prothrombin VII IX X Anticoagulants - Protein C + S
94
What do DOACs do?
Inhibit thrombin + factor Xa
95
Examples of DOACs
*Dabigatran Rivaroxaban Apixaban*
96
Causes of thrombophilias
- **Congential** - deficiency in natural anticoagulants - abnormal factor V > factor V Leiden - **Acquired** - antiphospholipid syndrome
97
What are thrombophilias?
Abnormality in blood coagulation that increases the risk of thrombosis
98
Presentation of vessel wall abnormalities
Bruises easily Spontaneous bleeding from small vessels Purpura Petechiae

Pathological Processes (14 decks)

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