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JMP Y2S1 > Week 31 Haemostasis > Flashcards

Week 31 Haemostasis Flashcards

1
Q

What is Haemostasis?

A

Haemostasis is the process which causes bleeding to stop with the aim of keeping it within a damaged blood vessel.

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2
Q

Opposite of haemostasis?

A

Haemorrhage (escape of blood from circulation)

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3
Q

What kind of response is haemostasis?

A

Positive feedback loop - Platelet activation and coagulation pathways positively re-enforce each other until the breach is sealed.

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4
Q

What is the 3 stages of haemostasis?

A
  1. Vascular spasm –> constriction of damage blood vessel –> blood slowed
  2. Formation of platelet plug –> Platelets bind to collagen at injury site –> stick together and chemicals released to encourage more platelet binding
  3. Blood coagulation –> clotting cascade –> intrinsic and extrinsic pathways occur
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5
Q

What are platelets?

A

basophilic, non-nucleated fragments of megakaryocytes.

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6
Q

How long do platelets last in circulation?

A

7-10 days

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7
Q

What is Thrombopoiesis?

A

Platelet production

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8
Q

What drives the body to produce more platelets?

A

Thrombopoietin (TPO) (produced when platelet numbers are low

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9
Q

Where does Thrombopoietin act?

A

Areas of Megakaryocyte differentiation

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10
Q

Where is Thrombopoietin produced?

A

Liver mainly

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11
Q

What do platelet granules store?

A 
Platelet granules store potent substances involved in inflammation & wound 
healing processes including:
1. Lysosomal enzymes
2. Coagulation factors
3. Immunologic and adhesion molecules
4. Chemokines and growth factors
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12
Q

What is platelet plugging initiated by?

A

Von Willebrand factor (vWF) (found in plasma) Binding to collagen and platelets.

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13
Q

What is the three main steps in platelet action?

A
  1. Adhesion —> Vascular injury exposes collagen for platelet adherence
  2. Aggregation —> more platelets join, release platelet activation mediators (eg ADP and thromboxane A2)
  3. Activation —> when activated platelets produce thrombin which catalysts the initiation of the coagulation cascade, resulting in a mesh-like fibrin deposition to seal the breach.
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14
Q

What are some hormones released by platelets and what are their functions?

A
  1. Platelet derived PDGF —> proliferation of vascular endothelial cells, vascular smooth muscle fibres and fibroblasts (to help repair damaged vessel wall)
    1. ADP —> makes nearby platelets “sticky” (increases platelet deposition into plug)
    2. Thromboxane A2 —> A prostaglandin that strengthens the fibrin clot, also induces vasoconstriction and sustain smooth muscle contraction to decrease blood flow
    3. Serotonin —> induces vasoconstriction and sustain smooth muscle contraction to decrease blood flow
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15
Q

What are the three pathways for blood coagulation?

A
  1. Extrinsic
    1. Intrinsic
    2. Common
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16
Q

What happens in the Extrinsic pathway of blood coagulation?

A
  1. Tissue factor is released (within seconds if trauma is severe)
  2. Numerous reactions with factor VII and X.
  3. Activated factor X (Xa) combines with factor V in the presence of phospholipids and Ca2+ to form prothrombinase which converts prothrombin to thrombin (a serine protease).
  4. Thrombin converts fibrinogen to fibrin.
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17
Q

What happens in the Intrinsic pathway of blood coagulation?

A
  1. Endothelial cell surfaces damaged expose blood to collagen and can activate XII (XIIa).
  2. XIIa activates XI (XIa) which in turn activates factor IX (IXa).
  3. IXa activates X to Xa.
  4. Platelet phospholipids, factors VIII & V Ca2+ and Xa form prothrombinase.
  5. Prothrombinase converts prothrombin to thrombin which converts fibrinogen into fibrin
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18
Q

What happens in the common pathway of blood coagulation?

A
  1. Activation of factor X
  2. Factor X activates thrombin
  3. Thrombin converts fibrinogen to fibrin to stabilise.
  4. Thrombin activates factor XIII which cross links fibrin for clot stabilisation
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19
Q

Where are clotting factors mainly produced?

A

Liver

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20
Q

What is the role of Vitamin K in clotting?

A

Involved in the synthesis of many blood clotting proteins:
1. Prothrombin
2. Factors VII IX and X
Also in production of anticoagulation proteins:
1. Protein C
2. Protein S

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21
Q

What is the Activated Partial Thromboplastin Time (aPTT)?

A

The time required to generate thrombin and fibrin via the intrinsic and common pathways (Reference range: less than 35 seconds).

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22
Q

What is the Prothrombin Time (PT)?

A

The time for thrombin and fibrin formation via the extrinsic and common pathways (Reference range: 10-13 seconds)

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23
Q

What is the Thrombin time (TT)?

A

The time it takes for a clot to form in the plasma of a blood sample containing anticoagulant, after an excess of thrombin has been added.

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24
Q

What is International normalised ratio (INR)?

A

calculates the standardized PT. INR is based on the ratio of the patient’s PT and the normal mean PT.

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25
Q

What are the main two system branches for physiological anticoagulants?

A
  1. Anticoagulants —> reduces thrombin production/action —> prevention
  2. Fibrinolytic —> degrades fibrin in clots —> removal
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26
Q

What is the main inhibitor of the extrinsic pathway?

A

Tissue factor pathway inhibitor

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27
Q

How is a fibrinogen changed to form a clot in the blood coagulation cascade?

A
  1. Fibrinogen (soluble)
    • Thrombin –> cleaves fibrinogen
  2. Fibrin (Insoluble)
    • Polymerisation –> fibrin is linked
  3. Polymerised Fibrin
    • Factor XIIIa (Transglutaminase)
  4. Cross linked fibrin (CLOT)
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28
Q

What is the term for clotting in an unbroken vessel?

A

Thrombosis

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29
Q

What makes blood clots stay localized to one position?

A

Thrombin is adsorbed by fibrin
Blood flow dilutes active factors too much in circulation
Blow flow also prevents pooling (stasis) of blood –> does not allow accumulation of coagulation factors

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30
Q

What are the two main physiological mechanisms of anticoagulants?

A

Anticoagulants –> for prevention of coagulation –> reduces thrombin production or limits its activity
Fibrinolytic –> for removal of clots –> dissolves formed clots by degrading fibrin

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31
Q

Why is it important that the balance of procoagulants and natural anticoagulants are in balance during the formation of a clot?

A
  1. Aim is for enough clotting to prevent bleeding

2. Not too much clotting that there is a large blood clot that obstructs vein flow of blood

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32
Q

Where is Tissue factor pathway inhibitor (TFPI) located and what does it do?

A

Located on the endothelial cell surface and in plasma –> it is the main inhibitor of the extrinsic pathway.

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33
Q

What is the mechanism of Tissue factor pathway inhibitor? (TFPI)

A

Two mechanisms:
1. Directly inhibits Factor Xa,
2. it complexes with Factor Xa and the complex inhibits TF/FVIIa,
With these mechanisms it impairs the triggering mechanism of the extrinsic pathway.

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34
Q

What are the other main anticoagulants apart from TFPI? (4)

A

Protein S
Protein C
Protein Z
Antithrombin

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35
Q

What is the anticoagulant mechanism of Protein S?

A

Enhances the interaction of TFPI with Factor Xa in the presence of Ca2+ and phospholipid

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36
Q

What is the anticoagulant mechanism of Protein C?

A
  1. Protein C is a vitamin K-dependent plasma glycoprotein.
  2. The thrombin–thrombomodulin–EPCR) complex activated protein C.
  3. Activated protein C (APC) proteolytically deactivates factors Va & VIIIa.
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37
Q

What is the anticoagulant mechanism of Protein Z?

A

Protein Z and Z protease inhibitor induces degradation of the factor Xa

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38
Q

What is the anticoagulant mechanism of Antithrombin?

A

It is a Serine protease inhibitor –> inhibits the protease activities of factor Xa and also thrombin

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39
Q

What is Fibrinolysis?

A

Enzymatic degradation of fibrin

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40
Q

What mediates the fibrinolysis in blood clots?

A

Plasmin –> which is a serine protease activated by the plasminogen activation cascade

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41
Q

What is involved in the fibrinolytic system?

A

Fibrinolysis
Tissue repair
Angiogenesis

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42
Q

What are the two fibrinolytic systems?

A

Cellular –> leukocytes, endothelial, epithelial cells and platelets system
Plasma –> fibrin clot based system

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43
Q

What does the small a next to the number for a factor mean?

A

Activated form

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44
Q

How many clotting factors are there in the coagulation cascade?

A

Factors 1-5 and 7-13 (there are 12 because the numbering skips 6)

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45
Q

What is factor I and where does it come from?

A

Fibrinogen –> comes from the liver

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46
Q

What is factor II and where does it come from?

A

Prothrombin –> comes from the liver

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47
Q

What is factor III and where does it come from?

A

Tissue factor (Thromboplastin) –> comes from the endothelium/platelets

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48
Q

What is factor IV and where does it come from?

A

Calcium –> comes from bone and GIT

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49
Q

What is the other name for factor X (10)?

A

Stuart factor

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50
Q

What is factor XIII?

A

Fibrin stabilising factor

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51
Q

What is the origin for most of the coagulation factors?

A

They are from the liver

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52
Q

What initiates the extrinsic pathway?

A
  1. Tissue trauma –> endothelium/vascular damage

2. causes release of TISSUE FACTOR (Thromboplastin)

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53
Q

What does tissue factor do?

A

Extrinsic pathway component (factor III) –> converts factor VII –> VIIa (active)

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54
Q

What does factor VIIa do in the extrinsic pathway?

A

Combines with Tissue factor and Ca2+ to cause the conversion of factor X (10) to its active form –> Xa –> in the presence of factor V and Ca2+

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55
Q

What initiates the intrinsic pathway?

A

Trauma to the blood cells or exposure of blood/platelets to collagen –> Causes factor XII (12) activation –> XIIa

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56
Q

What is the flow of the intrinsic pathway of coagulation?

A
  1. XII –> XIIa in presence of trauma or collagen
  2. XIIa converts factor XI (11) into its active form XIa
  3. Xia (11) converts factor IX (9) into its active form Ixa
  4. Factor 9 in combination with factor 8 and Ca2+ activates factor X –> Xa
  5. Xa in combination with Ca2+ and factor V(5) forms the prothrombin activator
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57
Q

What initiates the common pathway of the coagulation cascade?

A

Prothrombin activator (or active factor 10 depends how they ask)

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58
Q

What is the steps in the common pathway?

A
  1. Prothrombin activator converts prothrombin to thrombin
  2. Thrombin –> acts on fibrinogen to form fibrin monomers
  3. Fribrin stabilising factor XIII (13) stabilises the fibrin monomers to form fibrin polymers
  4. Fibrin polymers –> form a fibrin mesh
  5. Fibrin mesh –> attracts platelets and phospholipids
  6. Stable blood clot –> haemostasis
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59
Q

What do both the intrinsic and extrinsic pathway lead to?

A

prothrombin activator –> which is a complex of coagulation factors

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60
Q

What does activated coagulation factor X do?

A

In the presence of Ca2+ it converts Prothrombin into Thrombin

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61
Q

What does Thrombin do?

A

Converts fibrinogen –> Fibrin monomers

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62
Q

What factor is responsible for converting fibrin monomers into polymers?

A

Factor XIII (13) –> fibrin stabilising factor

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63
Q

What is the Tunica of blood vessels?

A 
3 layers:
Tunica Intima (inner)
Tunica Media (middle)
Tunica Externa (outer)
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64
Q

What is the tunica intima composed of?

A

Single layer of endothelial cells in contact with the blood supported by an internal elastic lamina

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65
Q

What is the tunica media composed of?

A

Smooth muscle cells and elastic tissue

66
Q

What is the tunica externa composed of?

A

Mainly collagen —> to anchor to surrounding organs

67
Q

Average adult blood volumes?

A
  1. 5L for males

4. 5L for females

68
Q

How much blood is in reservoirs at any one time in the body?

A

About 64% in the veins.

69
Q

What organs are blood reservoirs?

A

Liver

Spleen

70
Q

What is haemostasis?

A

The stopping of blood flow

Haemostasis: is the process which causes bleeding to stop with the aim of keeping it within a damaged blood vessel.

71
Q

What are the type of shock can be aligned closely with issues in haemostasis?

A

Acute Hypovolemic shock

Obstructive shock

72
Q

What are the two phases in response to hypovolemic shock?

A

Rapid

Sustained

73
Q

What happens in the rapid response to hypovolemic shock?

A

EXCLUSIVELY Neural response:
Sympathetic nervous system activity:
Adrenergic release of adrenalin and noradrenalin –> drives peripheral vasoconstriction and increased cardiac activity

74
Q

What happens in the sustained response to hypovolemic shock?

A
  1. Decreased renal blood flow and sympathetic nervous system activity:
    Release of renin, angiotensin and aldosterone
    –>Arterial vasoconstriction
  2. Pituitary releases –> ACTH and AVP
    Increases in cortisol and Na+/water retention –> prevents further volume loss to urine
75
Q

What activates platelets?

A
  1. Endothelial damage –> plateletscome into contact with exposed collagen and von Willebrand factor, becomingactivated.
  2. Thrombin
76
Q

How does turbulence of blood affect coagulation?

A
  • Increased stress of endothelium

- increase contact between platelets and the vascular walls

77
Q

How does stasis affect coagulation?

A
  • Stasis of blood can increase contact between platelets and the vascular wall
  • allows localized imbalances in pro- and anti-coagulant factors within the plasma.
78
Q

How does viscosity affect coagulation?

A

Increases coagulability

79
Q

How does blood pressure affect coagulation?

A

Increased pressure –> increases coagulation

80
Q

In what kind of vessel injuries is haemostasis primarily responsible for cessation of blood flow?

A

Small vessel injuries –> medium and large vessels require surgery

81
Q

What is the first step of thrombus formation post injury?

A

Blood vessel spasm (Vasoconstriction)

82
Q

How does vasoconstriction assist in haemostasis?

A
  • Increases vascular resistance and decreases the flow of blood.
  • Allows for the collection of coagulation factors
83
Q

What are some antiplatelet effects of normal endothelium to regulate blood clotting and blood flow?

A

Antiplatelet effects:
- Endothelial prostacyclin (PGl2) and NO release inhibit platelet aggregation

  • ADPase –> degrades ADP –> ADP an important signal for platelet aggregation
84
Q

What are some anticoagulant effects by normal endothelium?

A
  • Heparin-like cofactor –> mediates antithrombin III inactivation of thrombin
  • Thrombomodulin –> binds and CONVERTS thrombin to an anticoagulant enzyme
85
Q

What are some Fibrinolytic effects of endothelium?

A

Tissue plasminogen activator (tPA) –> activates plasmin

Plasmin promotes lysis of clots (through fibrin degradation)

86
Q

What is the normal way endothelium cells induce the antithrombosis effect vascular smooth muscle relaxation (Vasodilation)?

A

Nitric oxide (NO) release

87
Q

How does the prothrombic affect of vasoconstriction happen in endothelial cells?

A
  • Activated platelets release Ca2+ during thrombus formation

- Increased amounts of Ca2+ enter the smooth muscle cells to induce stronger contraction

88
Q

How can drugs modify the coagulation cascade?

A
  • Defect in coagulation

- Stop unwanted coagulation

89
Q

What does heparins affect?

A

Coagulation

90
Q

What is the mechanism of heparins?

A
  1. Heparin binds and activates antithrombin 3 and simultaneously binds coagulation factor 2a (prothrombin) (to limit its availability)
  2. Heparin can also limit availability of coagulation factor 10a as 10a binds to antithrombin 3 –> heparin does not bind directly to 10a
91
Q

What are some drugs and their forms that affect coagulation through direct thrombin inhibition?

A

Bivalirudin –> synthetic 20mer peptide –> binds to active site and exosite of thrombin to inhibit activity

Dabigatran –> pro-drug metabolised to active species –> binds competitively to thrombin active site –> inhibits thrombin activity

92
Q

What is the antidote to Dabigatran?

A

Idarucizumab –> humanised monoclonal antibody –> binds to dabigatran –> stable complex reverses anticoagulant effect of dabigatran

93
Q

What are some drugs that are factor Xa (10) inhibitors?

A

Fondaparinux

Apixaban and rivaroxaban

94
Q

What is the mechanism of Fondaparinux?

A
  1. Binds anti thrombin 3
  2. Induces conformational change
  3. New form can conjugate to factor Xa and stop it’s affect initiating coagulation
95
Q

What is the mechanism of apixaban and rivaroxaban?

A

Inhibits factor Xa (10) by binding to its enzymatic active site –> the drug works through competitive binding to active site

96
Q

What is the mechanism of Warfarin?

A

Vitamin K reductase antagonist –> stops production of Vitamin K
Vitamin K is important for carboxylation of factors 2, 7, 9 and 10

97
Q

What is the antidote for a Warfarin overdose?

A

Vitamin K

98
Q

How is warfarin monitored?

A

Prothrombin time (PT) –> INR

99
Q

How is heparin monitored?

A

APTT (activated partial thromboplastin time)

100
Q

What coagulation pathway is important for heparin and heparin monitoring?

A

Intrinsic pathway

101
Q

How is warfarin administered?

A

Oral administration

102
Q

How fast is it absorbed and how is it transported in blood?

A

Rapid absorption

Transported bound to albumin

103
Q

What enzyme metabolises warfarin in the liver?

A

CYP2C9

104
Q

What are some factors that can increase the effect of warfarin?

A
  1. Liver disease –> less clotting factors synthesised
  2. Drugs:
    - Inhibit hepatic metabolism
    - Inhibit platelet activation
    - Displace warfarin from albumin
    - Inhibit reduction of Vit K or reduce its availability
105
Q

What are some factors that may cause a decrease in warfarin’s effects?

A
  1. Inducers of hepatic cytochrome P450 enzymes (active warfarin is inactivated faster
  2. Drugs that reduce absorption
  3. Increased levels of Vit K
106
Q

What does administration of Vitamin K do to reinstate the clotting ability of blood?

A

Clotting factors become carboxylated and functional

107
Q

What are the drugs that affect platelet adhesion and activation?

A
  • Cyclooxygenase (COX) inhibitors –> aspirin
  • Phosphodiesterase inhibitors
  • P2Y12 receptor antagonists
  • GPIIb-IIIa receptor antagonists
108
Q

How does COX inhibitors like aspirin affect platelet adhesion and activation?

A
  1. Blocks COX1 and COX2
  2. COX1 and COX2 can no longer process arachidonic acid
  3. Reduces formation of prostacyclin and thromboxane (also protaglandins)
  4. Thromboxane inhibition –> reduces granule release and reduces platelet aggregation
109
Q

What is the main difference between Aspirin and other NSAIDS?

A
  1. Aspirin is irreversible–> destroys enzymes in platelets for thrombus formation –> then as they have no nucleus they are effectively deactivated
  2. Others are reversible
110
Q

Does platelets have a nucleus?

A

No

111
Q

How does Phosphodiesterase inhibitors like dipyridamole affect platelet adhesion and activation?

A
  1. Inhibits platelet phosphodiesterase
  2. Phosphodiesterase can no longer destroy cAMP
  3. Increase in cAMP
  4. Activates PKA
  5. PKA regulates thrombin receptor by deactivating it
  6. Response from thrombin no longer happens so no adhesion
112
Q

What is the other bonus mechanisms of phosphodiesterase inhibitors like dipyridamole?

A
  1. Blocks adenosine uptake –> adenosine has receptors to encourage adhesion/activation–> so reduces its effect
  2. Inhibits TXA2 (thromboxane) synthesis
113
Q

Why is dipyridamole rarely used along and is instead part of a combination therapy?

A

Phosphodiesterase is everywhere –> lots of potential off target effects

114
Q

What is some examples of P2Y12 receptor antagonists?

A

Clopidogrel and prasugrel

115
Q

What is the mechanism of P2Y12 receptor antagonists?

A
  1. Pro-drugs –> activated in the liver by CYP isozymes
  2. Inhibits the P2Y12(ADP) receptor on the platelets
  3. Increases adenylate cyclase activity
  4. Adenylate cyclase increases cAMP
  5. More cAMP –> more PKA –> reduces platelet aggregation
116
Q

What is the GPIIb-IIIa receptorand what does it do?

A

It is areceptorfor fibrinogen and von Willebrand factor and aids platelet activation.

117
Q

What is an examples of a GPIIb-IIIa receptor antagonists and what form do they take?

A

Abciximab –> chimeric mouse-human monoclonal antibody
Eptifibatide –> cyclic peptide with common sequence to GPIIb-IIIa receptor ligands
Tirofiban –> synthetic non-peptide small

118
Q

What kind of drug is tranexamic acid?

A

Anti-fibrinolytic drug

119
Q

What does tranexamic acid do?

A

Stops excessive bleeding from fibrinolytics –> promotes clotting

120
Q

How does tranexamic acid work?

A
  1. It is a lysine analogue
  2. Bind lysine binding sites on plasminogen and plasmin
  3. Its binding prevents plasmin and plasminogen binding to fibrin
  4. Promotes haemostasis in areas fibrinolysis contributes to bleeding
121
Q

When can tranexamic acid be used?

A
  1. Minor surgery
  2. Heavy menstral bleeding
  3. Traumatic hyphaema (blood in eye)
  4. Cardiac surgery
  5. Knee or hip arthroplasty
122
Q

What is the drug that reverses action of heparins?

A

Protamine

123
Q

What is the mechanism of protamine?

A
  1. Chemical antagonist
  2. Binds onto heparin molecules –> forms a stable complex
  3. Negates effect of heparin
124
Q

What is the mechanism of the thrombolytic drug plasminogen?

A
  1. Plasminogen deposited on fibrin strands within a thrombus
  2. Plasminogen is a zymogen (It is an inactive enzyme that when cleaved by another enzyme changes to active form)
  3. Active form is a plasmin –> plasmin’s cleave fibrin
  4. Fibrin degradation –> stops coagulation/clotting
125
Q

What is fibrinogen and what turns it into insoluble fibrin within a coagulation site?

A

Fibrinogen is a soluble peptide –> action by prothrombin –> fibrin results

126
Q

What is the role of plasmin?

A

Digests proteins (trypsin like):

1. Fibrin
2. Fibrinogen
3. Factors II, VIII
127
Q

What is some features of Tissue plasminogen activator?

A

Activates plasminogen to form plasmin for fibrin degradation:
Activates fibrin bound plasminogen 100X more effectively than plasminogen in circulation.

128
Q

What are some examples of tissue plasminogen activators?

A

Alteplase
Reteplase
Tenecteplase

129
Q

What do Recombinant tissue plasminogen activators do?

A

Increased activity on fibrin-bound plasminogen –> makes them clot selective

130
Q

What is the difference of Urokinase compared to other tissue plasminogen activators?

A

It is not selective for clot-bound plasminogen
Binds equally to fibrin bound plasminogen and plasma plasminogen
Causes significant fibrinolysis in clots and also systemically

131
Q

What are some risks of thrombolytic drugs?

A
  1. Bleeding

2. Systemic fibrinolysis especially with Urokinase

132
Q

What are the triage categories in the emergency departments?

A

1-5 –> 1 being most serious
Category 1 –> immediate life threatening condition –> seen immediately
Category 2 –> seen within 10mins
Category 3 –> seen within 30mins
Category 4 –> seen within 60mins
Category 5 –> chronic or minor condition–> seen within 2 hours

133
Q

What is diverticular disease?

A

A condition where small budges or pockets form in the wall of the large intestine (called diverticula) –> they often cause no symptoms.
–> they have been linked with low fibre diets and more common with age

134
Q

What is diverticulitis?

A

Inflammation of the diverticula pouches that can form in the large intestine

135
Q

What are some causes of GI bleeding?

A
  1. Haemorrhoids
  2. Peptic ulcers
  3. Tears or inflammation of the oesophagus
  4. Diverticulitis
  5. Ulcerative colitis
  6. Crohn’s disease
  7. Colonic polyps
  8. Cancer –> of oesophagus, stomach or colon
136
Q

What are some causes of constipation?

A
  1. Low water or low fibre in diet
  2. Low activity
  3. Stress
  4. Medications –> eg antidepressants, iron supplements
  5. IBS
  6. Pregnancy
  7. Colon cancer
  8. Neurological conditions like parkinsons or MS
  9. Hypothyroidism
137
Q

What are some causes of diarrhoea?

A
  1. Allergies
  2. Intestinal disease –> crohn’s and ulcerative colitis
  3. Bacterial infection
  4. Laxative abuse
  5. Medications
  6. Hyperthyroidism
  7. Malabsorption –> osmotic affect of lack of absorption
138
Q

How does the kidney regulate urine production?

A
  1. ADH –> decreases urine production through recapture of solutes and water follows
  2. Diuretics –> increase urine production through interfering with solute recapturing
  3. Natriuretic hormones –> inhibit aldosterone release –> therefore inhibits Na+ recovery –> Na+ remains in forming urine –> water follows to increase volume
139
Q

What are some blood vessel abnormalities that can predispose someone to abnormal bleeding?

A
  1. Friability –> if blood vessels are more fragile than normal can lead to bleeding
  2. AV malformation –> abnormalconection between artieries and veins (bypasses the capillary system). This connectionputs extreme pressure on the walls of the affected arteries and veins, causing them to become thin or weak. -> increases chance of bleed
140
Q

What are the commonly inherited haemophilia’s?

A

Haemophilia A and Haemophilia B

141
Q

What is the mechanism in Haemophilia A that causes dysfunction in haemostasis?

A

X-linked recessive disorder:

In the disorder there is a deficiency of functional plasma clotting factor VIII (8) (8 comes from the liver)

142
Q

What is the mechanism in Haemophilia B that causes dysfunction in haemostasis?

A

X-linked recessive disorder
In the disorder there is antibodies produced against self clotting factor IX (9) –> destroys the clotting factor and reduces haemostasis

143
Q

What coagulation pathway does Haemophilia B interfere?

A

Intrinsic pathway –> conversion of 10 to 10a X–> Xa

144
Q

What are the common ways clotting factor dysfunction can be acquired (not genetic)?

A
  1. Liver disease –> reduces production
  2. Vitamin K deficiency –> factor needed to activate clotting factors
  3. External factors such as drugs (anticoagulants)
145
Q

What are the common causes of platelet dysfunction?

A
  1. Von Willebrand disease –> inherited platelet disorder
  2. Aspirin and other NSAIDS –> can impact platelet function
  3. Antiplatelet drugs such as clopidogrel
  4. Cirrhosis/liver disease
  5. Bone marrow disorder
  6. Multiple myeloma
  7. Kidney disease
  8. Systemic lupus
146
Q

What are some clinical signs of bleeding disorders from platelet issues which are not normally found in deficiencies of coagulation factors?

A
  1. Petechiae –> red, purple spots under the skin, mouth, eyelids –> bleeding under the skin
  2. Profuse bleeding from cuts and scratches
147
Q

What are some clinical signs of coagulation factor deficiency which are not found in platelet issues?

A
  1. Deep dissecting haematosis
  2. Joint bleeding
  3. Family history is commonly present
148
Q

How long does it take to bleed after trauma with platelet vs coagulation factor issues?

A

Platelet –> immediate bleeding after trauma

Coagulation factors –> minutes to hours after trauma

149
Q

What are the most common inherited thrombophilia’s and how do they disrupt haemostasis?

A
  1. Factor V (5) Leiden –> abnormally shaped clotting factor 5 –> does not get broken down normally and remains in the blood for longer –> increasing clotting chance
  2. Prothrombin G20210A mutation –> more prothrombin is produced as consequence of the mutation –> more clotting potential with more prothrombin
150
Q

What aspects of coagulation is PT measuring and how is it measured?

A

PT measures the speed of clotting by means of the extrinsic pathway and common pathway of coagulation

151
Q

What coagulation factors are important for the extrinsic pathway?

A
  1. Tissue factor (III)
  2. Factor VII
  3. VIIa Calcium and tissue factor combine to cause conversion of X –> Xa
152
Q

What aspects of coagulation is APPT measuring and how is it measured?

A

Speed at which the blood clots during two biochemical reactions –> measuring the INTRINSIC pathway and the common pathway of coagulation

153
Q

What coagulation factors are important for the intrinsic pathway?

A
  1. Factor XII
  2. Factor XII
  3. Factor 9 + Factor 8 causes conversion of X–> Xa
154
Q

What is INR and what is it measuring?

A

INR is the international normalised ratio (INR) and is calculated from a PT result

155
Q

What are some indications for blood transfusions?

A
  1. Symptomatic anaemia
  2. Sickle cell crisis
  3. Acute blood loss (more than 30% blood volume)
156
Q

What does “group and save” mean?

A

It is the sampling process of an antibody screen to determine a patients blood grouping for future transfusion

157
Q

What does cross match mean?

A

A check to see if the donor blood is compatible for the patient needing transfusion

158
Q

What is massive transfusion protocol?

A

Massive transfusion is defined:
- Adults, as replacement of >1 blood volume in 24 hours or >50% of blood volume in 4 hours (adult blood volume is approximately 70 mL/kg).

  • Children, it is defined as transfusion of >40 mL/kg (blood volume in children over 1 month old is approximately 80 mL/kg).
159
Q

When is massive transfusion protocol indicated?

A

Critically bleeding patients anticipated to require a massive transfusion

160
Q

What are some risks of blood transfusions?

A
  1. Allergic reaction –> hives, itching and fever
  2. Bloodborne infections –> HIV, Hep B, C
  3. Acute immune haemolytic reaction

JMP Y2S1 (24 decks)

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