PBL 3 - Von Willebrand Disease Flashcards

1
Q

List the three stages of response that normally occur to arrest bleeding after vascular injury and briefly outline their role in haemostasis. (3 marks) `

A

a) Vascular response (1/2 mark) vasoconstriction leading to reduced blood flow (1/2 mark)
b) Platelet response (1/2 mark) the platelets adhere to the edge of the damaged vessel and then
aggregate to form a platelet plug (1/2 mark)
c) The coagulation pathway (cascade) (1/2 mark)
tissue factor expressed on damaged cells initiates the cascade by binding to activated factor VII (1/2
mark)

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2
Q

Explain briefly the activation and role of tissue factor (factor III) in the coagulation pathway (3 marks)

A

Tissue factor (TF) is a protein found inside endothelium (in the subendothelial tissue) (1/2 mark).
Damage to endothelial cells exposes tissue factor to the circulating blood (1/2 mark). Factor VII is
converted by the exposed tissue factor to VIIa (1/2 mark) and the complex of TF with factor VIIa
catalyzes the conversion of factor X (the common pathway) to Xa (1/2 mark). Xa combines with
activated factor V (1/2 mark) converts prothrombin to thrombin, which in turn converts fibrinogen
to fibrin (1/2 mark).

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3
Q
Outline the steps involved in the removal of blood clots from blood vessels after the damage has
been repaired (2 marks)
A

Tissue plasminogen activator (t-PA) (1/2 mark) is released from the repaired endothelium (1/2
mark). t-PA converts the inactive precursor protein plasminogen (1/2 mark) into plasmin. Plasmin is
a protease enzyme (1/2 mark ) that dissolves clots by breaking down fibrin (1/2 mark). (any four
half marks)

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4
Q

What parts of the coagulation pathway does the activated partial thromboplastin time (APTT)
measure (1 mark)?

A

APTT measures the efficiency of the intrinsic (1/2 mark) and common pathways (1/2 mark)

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5
Q

How does haemophilia B differ from haemophilia A? (1 mark)

A

Deficiency in different clotting factors Haemophilia B - deficiency of Factor IX (1/2 mark)
Haemophilia A - deficiency of Factor VIII (1/2 mark)

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6
Q

What is the normal bleeding time? (1)

A

2-9 mins

it tests platelet plug formation

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7
Q

How does the data in the table point towards von willebrand disease (2)

A

Normal factor 9 (not Hb B)
Haemophilia A as reduction in factor 8 however it is X-linked recessive so unlikely as mother has it (in males)
Factor 8 reduced
Long bleeding time - problem in aggregation and plug formation ( VWF assists in platelet adherence)

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8
Q

What is the function of VWF? (2)

A

Prevents the breakdown of factor 8 by binding factor VIII, a key clotting protein, and platelets in blood vessel walls, which help form a platelet plug during the clotting process.

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9
Q

What is the inheritance of von willebrand disease (2)

A

Chromosome 12
Type 1 + 2 - autosomal dominant
Type 3 - Autosomal recessive
Acquired - autoimmune

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10
Q

What are the different types of Vwd, what are the differences between them? (4)

A

Type 1 - Mild deficiency (60-80%) - mild bruising, menorrhagia, epistaxis (nosebleed)
Type 2 - Abnormal VWF (20-30%) - mild to moderate depending on subtype (2A,2B, 2M, 2N)
Type 3 - Severe deficiency of VWF - severe haemarthroses, spontaneous bleeding

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11
Q

Why should sharon be careful about her alcohol intake? (2)

A
  • Liver cirrhosis – interferes with liver’s ability to produce coagulation factors
  • VWD – avoid damaging liver as more vulnerable,
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12
Q

What is the action of desmopressin and tranexamic acid? (2)

A

Desmopressin - synthetic version of vasopressin, stimulates endothelial cells to release Vwf – also increases factor 8

Tranexamic acid- preventing blood clots from breaking down too quickly

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13
Q

What drugs should patients with VWD avoid? (1)

A

Aspirin as blocks thromboxane

use paracetamol

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14
Q

Side effect of desmopressin

A

Hyponatraemia

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15
Q

Management of VW disease

A

Desmopressin
Tranexamic acid
Factor 8 IV infusion or VWF concentrate
Oral contraceptives if heavy periods

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16
Q

What type of VWD does the patient have

A

type 1

17
Q

How do you carry out the Prothrombin Time and what does it measure

A

Tissue thromboplastin from brain –>incubated with citric acid –> recalcified –> time required for formation is measured –>INR generated
= Extrinsic and common pathway

18
Q

How do you carry out the Activated Partial Thromboplastin Time and what does it measure

A

= Intrinsic and common

Surface activator phospholipid/Kaolin) –> incubated with citrate –> recalcified –> time taken for formation measured.

19
Q

What does thrombin time test

A

Common pathway
tests fibrinogen action
uses bovine thrombin

20
Q

Extrinsic pathway

A

(Activated by damage) - Tissue Factor (factor 3) reacts with factor 7 to activate it to factor 7a. 7a converts factor 10 into 10a using Calcium.
–> Initial burst of thrombin

21
Q

Extrinsic pathway

A

Without tissue injury- e.g. blood stasis) – Factor 12a activates factor 11 to factor 11a which activates 9 to 9a which is combined with factor 8 to activate 10 to 10a.

22
Q

Common pathway

A

Prothrombinase (factor V, X and calcium and serine) converts prothrombin –> thrombin
thrombin (and Ca2+) will turn fibrinogen to fibrin.

23
Q

What factors does thrombin activate

A

5,7,8,11,13
Creates a positive feedback to the intrinsic pathway
= Amplification

24
Q

What is the function of factor 13

A

Causes crosslinks to be formed on the fibrin

25
Q

What is vitamin K needed for

A

Factor 2,7,9,10

Protein C and S

26
Q

What does antithrombin do

A

Inhibits 10a, thrombin

and plasminogen to plasmin

27
Q

What is the platelet plug formation

A

Platelets secrete ADP and 5HT + arachidonic acid + thromboxane A2
–> adhesion via vwf –> temporary plug

28
Q

What is coagulation

A

the process by which fibrin strands create a mesh that binds blood
components together to form a blood clot