Haemostasis and Bleeding Disorders Flashcards
(69 cards)
1
Q
- List some pro-coagulant factors in the body.
A
Platelets
Endothelium
vWF
Coagulation cascade
2
Q
- List some anti-coagulant factors in the body.
A
Fibrinolysis
Anti-thrombins
Protein C/S
Tissue factor pathway inhibitor
3
Q
- Which three responses are stimulated by vessel injury?
A
Vasoconstriction Platelet activation (forms primary haemostatic plug) Activation of the coagulation cascade
4
Q
- What are the components of blood clot formation?
A
Vascular endothelium
Platelets
Coagulation factors
White blood cells
5
Q
- What are the two main functions of the endothelium?
A
Synthesis of prostacyclin, vWF, plasminogen activators and thrombomodulin
Maintain barrier between blood and pro-coagulant subendothelial structures
6
Q
- How many platelets are produced by each megakaryocyte?
A
4000
7
Q
- What is the life span of platelets?
A
10 days
NOTE: this is important because it means that the effect of antiplatelet drugs lasts for 10 days after stopping the drug
8
Q
- What are glycoproteins?
A
Cell surface proteins through which platelets can interact with the endothelium, vWF and other platelets
9
Q
- What do dense granules contain?
A
Energy stores (ATP and ADP)
10
Q
- Which features of platelets enable them to massively expand their surface area?
A
Open cannalicular system and microtubules and actomyosin
11
Q
- What are the two ways in which platelets can adhere to sub-endothelial structures?
A
DIRECTLY – via GlpIa
INDIRECTLY – via binding of GlpIb to vWF (this is MORE IMPORTANT)
12
Q
- Which factors, released by platelets after adhesion, promote platelet aggregation?
A
ADP
Thromboxane A2
13
Q
- How do platelets bind to each other?
A
GlpIIb/IIIa
It also binds to fibrinogen via this receptor
14
Q
- Describe the effects of aspirin and other NSAIDs on the arachidonic acid pathway.
A
Aspirin is an irreversible COX inhibitor
Other NSAIDs reversibly inhibit COX
15
Q
- What is the rate-limiting step for fibrin formation?
A
Factor 10a
16
Q
- What are the effects of thrombin?
A
Activates fibrinogen
Activates platelets
Activates profactors (factor 5 and 8)
Activates zymogens (factor 7, 11 and 13)
17
Q
- Name the complex that is responsible for activating prothrombin to thrombin.
A
Prothrombinase complex
18
Q
- Outline the initiation phase of the clotting cascade.
A
Damage to the endothelium results in exposure of tissue factor which binds to factor 7 and activates it to factor 7a
The tissue factor-factor 7a complex then activates factors 9 and 10
Factor 10a binds to factor 5a resulting in the first step of the coagulation cascade
19
Q
- Outline the amplification phase of the clotting cascade.
A
Activated factors 5 and 10 will result in the production of a small amount of thrombin
This thrombin will activate platelets
Thrombin will also activate factor 11 which activates factor 9
Thrombin also activates factor 8 and recruits more factor 5a
Factors 5a, 8a and 9a will bind to the activated platelet
20
Q
- Outline the propagation phase of the clotting cascade.
A
Activated factors 5, 8 and 9 will recruit factor 10a
This results in the generation of a large amount of thrombin (thrombin burst)
This enables the formation of a stable fibrin clot
21
Q
- Why is the prothrombinase complex important?
A
It allows activation of prothrombin at a much faster rate
22
Q
- What is required for adequate production/absorption of vitamin K?
A
Bacteria in the gut produce vitamin K
It is fat-soluble so bile is needed for vitamin K to be absorbed
23
Q
- What is the most common cause of vitamin K deficiency?
A
Warfarin
24
Q
- Name two factors that convert plasminogen to plasmin.
A
Tissue plasminogen activator
Urokinase
25
25. Name a factor that inhibits the factors mentioned in question 24.
Plasminogen activator inhibitor 1 and 2
26
26. Name two factors that directly inhibit plasmin.
Alpha-2 antiplasmin
| Alpha-2 macroglobulin
27
27. What is the role of thrombin-activatable fibrinolysis inhibitor (TAFI)?
Inhibitor of fibrin breakdown
28
28. Describe the action of antithrombins.
Bind to thrombin in a 1:1 ratio and this complex is excreted in the urine
29
29. How many types of antithrombin are there?
Five (antithrombin-III is the most active)
30
30. What is the most thrombogenic hereditary condition?
Antithrombin deficiency
31
31. Outline the role of protein C and protein S.
Trace amounts of thrombin generated at the start of the clotting cascade activate thrombomodulin
This allows protein C to bind to thrombomodulin through the endothelial protein C receptor
Protein C is then fully activated in the presence of protein S
Fully activated protein C will inactivate factors 5a and 8a
32
32. Why does Factor V Leiden cause a prothrombotic state?
The factor 5a will be resistant to breakdown by protein C
33
33. State two causes of activated protein C resistance.
Mutated factor 5 (e.g. factor V Leiden)
| High levels of factor 8
34
34. What is the role of tissue factor pathway inhibitor?
TFPI neutralises the tissue factor-factor 7a complex once it has initiated the clotting cascade
35
35. List some genetic defects that cause excessive bleeding.
Platelet abnormalities
Vessel wall abnormalities
Clotting factor deficiencies
Excess clot breakdown
36
36. List some acquired defects that cause excessive bleeding.
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Liver disease
Vitamin K deficiency
Autoimmune diseases (platelet destruction)
Trauma
Anti-coagulants/anti-platelets
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37
37. List some genetic defects that cause excessive thrombosis.
Clotting factor inhibitor deficiencies
| Decreased fibrinolysis
38
38. List the types of disorders of haemostasis.
Vascular disorders (e.g. scurvy)
Platelet disorders
Coagulation disorders
Mixed disorders (e.g. DIC)
39
39. What is the difference between immediate and delayed bleeding with regards to the underlying pathological process?
Immediate – issue with the primary haemostatic plug (platelets, endothelium, vWF)
Delayed – issue with the coagulation cascade
40
40. Describe the key clinical differences between platelet disorders and coagulation factor disorders.
Platelet disorders
• Bleeding from skin and mucous membranes
• Petechiae
• Small, superficial ecchymoses
• Bleeding after cuts and scratches
• Bleeding immediately after surgery/trauma
• Usually mild
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Coagulation factor disorders
• Bleeding into soft tissues, joints and muscles
• No Petechiae
• Large, deep ecchymoses
• Haemarthroses
• No bleeding from cuts and scratches
• Delayed bleeding from surgery or trauma
• Often SEVERE
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41
41. When is treatment for platelet disorders required?
Platelet count < 30 x 109/L (this is associated with spontaneous haemorrhage)
42
42. Why is it important to look at platelets under the microscope in thrombocytopaenia?
To check whether it is pseudothrombocytopaenia (platelets clump together giving an erroneously low result)
Also allows identification of other abnormalities (e.g. Grey platelet syndrome – large platelets)
43
43. What can cause a decrease in platelet number?
Decreased production
Decreased survival (ITP)
Increased consumption (DIC)
Dilution
44
44. What can cause defective platelet function?
Acquired (e.g. aspirin)
Congenital (e.g. thrombasthenia)
Cardiopulmonary bypass
45
45. What can cause immune-mediated thrombocytopaenia?
```
Idiopathic
Drug-induced (e.g. quinine, rifampicin)
Connective tissue disorder (e.g. SLE)
Lymphoproliferative disease
Sarcoidosis
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46
46. List two non-immune mediated conditions that cause thrombocytopaenia.
DIC
| MAHA
47
47. Describe the pathophysiology of ITP.
Autoantibodies are generated against platelets
| Platelets are tagged by autoantibodies and then destroyed by the reticuloendothelial system (liver, spleen, bone marrow)
48
48. What are the main differences between acute and chronic ITP?
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Acute
• Mainly children
• Usually there is a preceding infection
• Abrupt onset of symptoms
• Lasts 2-6 weeks
• Spontaneously resolves
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Chronic
• Mainly occurs in adults
• More common in females
• Can be abrupt or indolent
• Does not resolve spontaneously
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49
49. How is ITP treated?
Mainly with steroids and IVIG based on the platelet count
50
50. Give some examples of causes of thrombocytopaenia that can be diagnosed by blood film.
Vitamin B12 deficiency
| Acute leukaemia
51
51. What clotting study abnormality would be seen in Haemophilia?
Prolonged APTT (A normal PT with an abnormal aPTT means that the defect lies within the intrinsic pathway)
52
52. Outline the clinical features of haemophilia.
Haemarthroses (MOST COMMON)
Soft tissue haematomas (e.g. shortened tendons, muscle atrophy)
Prolonged bleeding after surgery/dental extractions
NOTE: haemophilia A and B are clinically indistinguishable
53
53. What is a typical lesion seen in coagulation factor disorders?
Ecchymoses
54
54. What is the most common coagulation disorder? What is its inheritance pattern?
Von Willebrand disease
Autosomal dominant – type 1 and 2
Autosomal recessive – type 3
Type 1 – partial quantitative deficiency
Type 2 – qualitative deficiency
Type 3 – complete quantitative deficiency
55
55. What is the main clinical feature in von Willebrand disease?
Mucocutaneous bleeding
56
56. Outline the classification of von Willebrand disease.
Type 1 – partial quantitative deficiency
Type 2 – qualitative deficiency
Type 3 – complete quantitative deficiency
57
57. Describe the relationship between vWF and factor 8.
Binding of factor 8 to vWF protects factor 8 from being destroyed
NOTE: type 3 vWD has a very similar phenotype to haemophilia A (because absent vWF leads to low factor 8)
58
58. Describe the expected laboratory test results for the three types of von Willebrand disease.
Type 1 – low antigen, low activity, normal multimer
Type 2 – normal antigen, low activity, normal multimer
Type 3 – very low antigen, very low activity, absent multimer
59
59. Name a source of vitamin K.
Green vegetables
| Vitamin K is synthesised by intestinal flora
60
60. What is vitamin K required for?
Synthesis of factors 2, 7, 9 and 10
| Synthesis of protein C, S and Z
61
61. List some causes of vitamin K deficiency.
Malnutrition
Biliary obstruction
Malabsorption
Antibiotic therapy
62
62. Outline the pathophysiology of DIC.
Release of thromboplastic material into the circulation causes widespread activation of coagulation and fibrinolysis
This results in increased vascular deposition of fibrin, which leads to thrombosis of small and mid-size vessels with organ failure
Depletion of platelets and coagulation factors leads to bleeding
63
63. List some causes of DIC.
Sepsis (MOST COMMON)
Trauma (e.g. fat embolism)
Obstetric complications (e.g. amniotic fluid embolism)
Malignancy
Vascular disorders
Reaction to toxin
Immunological (e.g. transplant rejection)
64
64. Describe the typical clotting study results in DIC.
Prolonged APTT (intrinsic pathway) and PT (extrinsic pathway)
Prolonged TT
Decreased fibrinogen
Increased FDP
Decreased platelets
Schistocytes (due to shearing of red blood cells as it passes through a fibrin mesh)
65
65. Outline the treatment of DIC.
```
Treat underlying disorder
Anticoagulation with heparin
Platelet transfusion
FFP
Coagulation inhibitor concentrate
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66
66. Describe how liver disease leads to bleeding disorders.
Decreased synthesis of clotting factors 2, 7, 9, 10, 11 and fibrinogen
Dietary vitamin K deficiency
Dysfibrogenaemia
Enhanced haemolysis (decreased alpha-2 antiplasmin)
DIC
Thrombocytopaenia due to hypersplenism
67
67. Outline the treatment of:
a. Prolonged PT/APTT
b. Low fibrinogen
c. DIC
a. Oral vitamin K
FFP infusion
b. Cryoprecipitate
c. Replacement therapy
68
68. What is the management of vitamin K deficiency due to warfarin overdose based on?
INR
| NOTE: warfarin is reversed by giving vitamin K (oral or IV). If severe, FFP or PCC could be given
69
69. What is PCC?
Prothrombin complex concentrate (contains vitamin K-dependent clotting factors)
