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Adult Patient 1 > Coagulation > Flashcards

Coagulation Flashcards

1
Q

What are the major stages of Haemostasis?

A
  1. Damage to Blood Vessel Wall
  2. Platelet Adhesion to blood vessel wall
  3. Platelet Activation
  4. Platelet Plug Formation
  5. Coagulation Cascade
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2
Q

What is the First Step of the Initiation Phase of the Coagulation Cascade?

What does this step activate?

A

Activation of Factor VII in the presence of tissue factor.

Contributes to the activation of Factors IX and X

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3
Q

Where does vWF act on the Coagulation Cascade?

A

Factor VIIIa

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4
Q

Where does Antithrombin act on the Coagulation Cascade?

A

Factors IXa and Xa and Thrombin (IIa)

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5
Q

Where does Activated Protein C act on the Coagulation Cascade?

What is its mechanism of action?

A

Va and VIIIa

Inhibits amplification phase

Proteolyses peptide binds in FVa and FVIIIa
deactivates them

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6
Q

Where is Calcium required in the Coagulation Cascade?

A

Activation of Factor X and II (prothrombin to thrombin)

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7
Q

What does the Thrombin Burst cause?

A

Positive Feedback
Amplification phase
Activates more Platelets
Activates Factors XI, VIII and V

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8
Q

What factor causes a loose mesh to become a stable clot?

A

Factor XIIIa

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9
Q

How to Platelets stick to Exposed Collagen?

A

Glycoprotein Ia

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10
Q

How to vWF and Fibrinogen promote platelet aggregation?

A

Glycoprotein IIb and IIIa

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11
Q

What are the 3 aims of clot regulation?

A
  1. prevent clot formation in normal vessels
  2. restrict clot to damaged area
  3. remove clot as tissue repair is completed
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12
Q

What is the role of the Liver in clotting?

A

Synthesises clotting factors by synthesising bile salts

Bile salts released into the GI tract in bile
Allows absorption of vitamin K (with pancreatic juices)
Post-translational modification produces clotting factors in blood

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13
Q

How is a clot broken down?

A

Plasminogen in incorporated into a clot
This is activated into plasmin
Plasmin causes the breakdown of fibrin into fibrin degradation products (FDPS)
FDPs are soluble forms of fibrin

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14
Q

What activates plasminogen?

A

tPA - tissue plasminogen activator

urokinase/streptokinase - fibrinolytic drugs

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15
Q

What activates fibrinogen?

A

Thrombin

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16
Q

What is the role of the endothelium in preventing clot formation and propagation?

A

Separates tissue factor and circulating FVII
Cover vWF - prevent platelet adhesion
Collagen not exposed
Glycocalyx - prevents platelet adhesion
Prostacyclin and Nitric Oxide - prevent platelet adhesion and aggregation
CD39 - metabolises ADP released by activated platelets
tPA - involved in clot breakdown
Thrombomodulin - activates protein C, absorbs excess thrombin
Heparin sulfate - cofactor for antithrombin

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17
Q

What is Purpura and what are the different types?

A

Collective term for bleeding into the skin or mucous membranes

Petechia - small haemorrhages up to pin head size
Ecchymoses - larger haemorrhages

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18
Q

What is thrombocytopenia?

How does it present?

A

Low blood platelet count

Petechiae in skin and other tissues

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19
Q

What are the indications for Anticoagulant Therapy? (3)

A

Prophylaxis
Post-Thromboembolic event
During therapeutic procedures

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20
Q

How do anticoagulant drugs work, generally?

What are the different types of anticoagulant drugs?

A

Prevent or reduce coagulation of blood
Prolong clotting time
Do not stop the formation of a platelet plug
Act on the clotting cascade to prevent fibrin production

Heparin
Warfarin
DOACs

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21
Q

What are the two types of heparin?

A

Unfractioned heparin

Low molecular weight heparin

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22
Q

What is the mechanism of action of Heparin?

A

Increases effectiveness of antithrombin-III

Inactivates thrombin and Factors VIII, IX, X, XI, XII

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23
Q

How is unfractioned Heparin administered?

A

Subcutaneously or Intravenously

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24
Q

What is used to monitor unfractioned heparin?

A

APTT activated partial thromboplastin time

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25
Q

What is the problem with unfractioned heparin?

A

absorbed by endothelial cells
unpredictable half life
normally half an hour but can increase up to 2-3 hours when the endothelium becomes saturated and the renal excretion is relied upon

26
Q

What are some drug options for LMWH?

A

Clexane, Dolteparin, Nadroparin

27
Q

What are the benefits of LMWH over unfractioned heparin?

A

more predictable, binds with low affinity to endothelium
longer duration of action
greater effect on factor X than thrombin so reduced risk of bleeding
only needs to be monitored during pregnancy and renal failure

28
Q

How is LMWH monitored?

A

anti-Xa assay

29
Q

What anticoagulant is first line for DVT/PE and for prophylaxis after surgery?

A

Low Molecular Weight Heparin

30
Q

How is LMWH administered?

A

Subcutaneously

31
Q

What are the side effects of heparin?

A

Haemorrhage - exacerbated by alcohol
Osteoporosis - only unfractioned heparin - if used for a few weeks
Thrombocytopaenia - can occur after 7-10 days of therapy - heparin induced antiplatelet antibodies
Hyperkalaemia - due to inhibition of aldosterone secretion
Hypersensitivity

32
Q

What will prevent the action and reverse the effect of unfractioned heparin?

A

Protamine Sulphate

33
Q

In simple terms, What is Warfarin?

A

Vitamin K antagonist

34
Q

Which clotting factors are dependent on vitamin K?

A

Factors II, VII, IX and X

Proteins C and S

35
Q

What is the specific antidote to warfarin and how should it be administered?

A

Vitamin K

Orally or intravenously

36
Q

What is the mechanism of action Warfarin?

A

Binds to vitamin K reductase enzyme on liver cells
Decreases production of reduced form of vitK
Suppresses production of clotting factors that contain the Gla proteins (Factors II, VII, IX, X; protein C and protein S)
Decreased prothrombin levels and amount of thrombin produced

37
Q

How is Warfarin Administered?

A

Orally

38
Q

What is the effect of LMWH on prothrombin time?

A

normal

39
Q

What is the effect of unfractioned heparin on prothrombin time?

A

mildly prolonged

40
Q

What is the effect of warfarin on prothrombin time?

A

prolonged - PT aka INR

41
Q

What is the effect of LMWH on APTT? (activated partial thromboplastin time)

A

mildly prolonged, not used for monitoring

42
Q

What is the effect of unfractioned heparin on APTT?(activated partial thromboplastin time)

A

prolonged - used for monitoring

43
Q

What is the effect of warfarin on APTT?(activated partial thromboplastin time)

A

prolonged

44
Q

What is the effect of LMWH on thrombin time?

A

mildly prolonged at therapeutic level

45
Q

What is the effect of unfractioned heparin on thrombin time?

A

prolonged

46
Q

What is the effect of Warfarin on thrombin time?

A

normal

47
Q

what is prothrombin time?

A

blood test
used to see how long it takes for blood to clot
INR

48
Q

What are the normal values for thrombin time?

A

12-14 seconds

49
Q

In simple terms, what are DOACs?

A

Factor Xa inhibitors

50
Q

What is the mechanism of action of DOACs?

A

inhibit prothrombinase complex-bound and clot-asscoaited factor Xa
resulting in reduced thrombin burst
Do not inhibit platelet aggregation but decrease clot formation induced by thrombin

51
Q

What are some examples of DOACs?

A

Rivaroxaban, Apixaban, Edoxaban, Betrixaban

52
Q

When are fibrinolytic/thrombolytic drugs used?

A

Myocardial Infarction
Cerebrovascular Accident
Venous Thromboembolism
Pulmonary Embolism

53
Q

What do fibrinolytic/thrombolytic drugs do and how?

A

Restore blood flow to an area that has been occluded

Dissolve clots by activating plasminogen into plasmin

54
Q

What are some examples of fibrinolytic/thrombolytic drugs?

A

Streptokinase
Urokinase
Tissue Plasminogen Activator

55
Q

What is the mechanism of action of streptokinase?

A

Complexes with and activates plasminogen

56
Q

What is the mechanism of acton of urokinase?

A

Direct acting plasminogen activator

57
Q

What is the mechanism of action of tPA?

A

Activates plasminogen

58
Q

What do antiplatelet drugs do?

A

decrease platelet aggregation and prevent thrombus formation

59
Q

what are some examples of anti platelet drugs?

A

Aspirin and Clopidogrel

60
Q

What is Clopidogrel?

When is it used?

A

Antiplatelet
Prodrug - activated by CYP450
Used in atherosclerotic disease to reduce morbid events

61
Q

What is Desmopressin?

When is it used?

A

Stimulates release of vWF from endothelial cells
More form and complex with factor VIII
ADH analogue
Haemophilia A and Von Willebrand Disease

Adult Patient 1 (4 decks)

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