Week 143 - Haemostasis & Thrombosis Flashcards Preview

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Flashcards in Week 143 - Haemostasis & Thrombosis Deck (52):
1

What factors of the endothelium wall help prevent platelet adhesion?

  • It's negative charge
  • Thrombomodulin and heparin sulphate expression
  • Synthesis of prostacyclin (PGI2) and NO
  • Production of plasminogen activator

2

What vascular response occurs when the vessel is injured?

Reflex vasoconstriction

3

What molecules do platelets adhere to when the endothelium becomes damaged?

Collagen

Bound von Willebrand factor

4

What molecule on the platelet binds to collagen and von Willebrand factor on the endothelium?

Glycoprotein (GP) 1b

5

What molecule is exposed after initial platelet binding to collagen and vWF and what does this molecule bind to?

Glycoprotein IIb/IIIa

Forms a second binding site for vWF

6

What granule type is fibrinogen stored within the platelet and what is the function of this fibrinogen?

It is stored in the α-granules

It forms bridges between adjacent platelets and helps hold them together via the activated GP IIb-IIIb receptor

7

What molecule causes the conformational change in the GP IIb-IIIa receptor?

ADP released from the dense body granules of the platelet

8

How does clopidogrel prevent the production of the platelet plug?

It blocks the ADP receptor on the surface of the platelet preventing its activation and subsequent change in GP IIb-IIIa receptor

9

What is the functions of thromboxane A2?

It is a powerful vasoconstrictor

Lowers cAMP

Initiates the platelet aggregation

10

What molecule opposes the functions of TXA2?

Prostacyclin (PGI2)

11

What is the action of Tissue Factor (TF), once bound to factor VII?

Directly converts factor X to Xa and some IX to IXa

12

What inhibitor blocks the production of factors Xa and IXa, and what is required for its activation?

Tissue factor pathway inhibitor (TFPI)

Activated in the presence of factor Xa

 

13

Apart from TF, what other process can yeild factor IXa?

Factor XIa, which is activated by thrombin

14

What molecule activates factor VIII, and what is the function of factor VIIIa?

Thrombin

It dramatically enhances the activity of factor IXa, which together convert factor X into Xa

15

What molecule activates prothrombin into thrombin, and what molecule enhances its activity?

Factor Xa

Its activity is enhanced by thrombin activated factor Va

16

What molecule does thrombin act upon, and what helps stabilise the products of its activity?

Fibrinogen to produce fibrin

Factor XIII in the presence of calcium ions

17

What factors of the coaguation cascade does antithrombin inhibit?

Factors VIIa

Factor IXa

Factor Xa

Factor XIa

Factors XIIa

Thrombin

18

What factors of the coagulation cascade does activated protein C inhibit?

What molecule enhances its activity?

It inhibits factors V and VIII

Its activity is enhanced by thrombin being bound to thrombomodulin

19

What is the main enzyme of fibrinolysis and what enzyme activates it from its precursor form?

Plasmin

It is activated by tissue plasminogen activator (t-PA)

20

When is D-dimer produced?

When the cross-linked firbin is degraded.

21

What molecule inactivates t-PA?

Plasminogen-activator inhibitor-1 (PAI-1)

22

What coagulation factors are tested by the prothrombin time and what is the normal range?

Factors V, VII and X

Also tests fibrinogen and prothrombin

 

Normal range = 12-16s

(Also called the INR)

23

What coagulation factors are tested by the activated partial thromboplastin time (aPTT) and what is the normal range?

Factors V, VIII, IX, X, XI, XII

Prothrombin and fibrinogen

Normal range = 26-37s

24

Which coagulation factors are Vitamin K-dependent in origin

Prothrombin

Factors VII, IX, and X

Protein C and S

25

What is the normal range of the thrombin time (TT) and what may produce a prolonged time?

12-14s

Prolonged in fibrinogen deficiency, or if inhibitors such as heparin are taken

26

By what mode of inheritence is hereditary haemorrhagic telangectasia passed on?

Autosomal dominant inheritence

27

What genes have been associated with hereditary haemorrhagic telangectasia?

ENG

ALK1

SMAD4

28

What are the symptoms of hereditary haemorrhagic telangectasia?

Dilated capillaries and arterioles producing small red branching spots, particularly around the nose and GIT

Recurrent epitaxis

Chronic GI bleeding → chronic iron deficiency anaemia

Vascular malformations may also be present

29

What is the common age range of immune thrombocytopenic purpura (ITP) in children?

Between 2 and 6

30

What is the typical history of a child presenting with ITP?

Acute onset of mucocutaneous bleeding with a previous history of a recent viral infection, including varicella zoster or measles.

31

Why is there a low platelet count in ITP?

There are auto-antibodies against the platelets and are thus destroyed by macrophages etc.

32

What common symptoms are seen in ITP?

Easy bruising

Purpura

Epistaxis

Menorrhagia

33

What coagulation factor is missing in haemophilia A?

Factor VIII

34

What mode of inheritence is haemophilia A and how prevelant is the disease?

X-linked recessive inheritence pattern

Affects about 1 in 5000 men

35

What findings are seen in laboratory tests in haemophilia A?

Reduced level of factor VIII

Prolonged aPTT

Normal PT, bleeding time and vWF levels

36

What are the 3 grades of haemophilia A and what are the symptoms of each?

Severe haemophilia A ( Factor 8 < 1IU/dL):

  • Spontaneous bleeding from birth, typically joints and muscle

Moderate haemophilia A (F VIII 1-5IU/dL):

  • Severe bleeding following injury and occasional spontaneous bleeding

Mild haemophilia A (F VIII >5IU/dL):

  • Bleeding only after injury or surgery, diagnosed late in life

37

What drug can be given to patients with haemophilia A

Desmopressin

38

What coagulation factor is missing in haemophilia B and what is another name for this condition?

Factor IX

Christmas disease

39

Which disease is more common, haemophilia A or B?

Haemophilia A

(Haemophilia B affects around 1 in 30,000, but mode of inheritence is the same)

40

What are the test results commonly seen in von Willebrand's disease?

Prolonged bleeding time

Normal PT

Normal/ or raised aPTT

Decreased levels of VIII and vWF

41

What is the cause of Factor V Leiden?

There is a mutation in V, which means it is less likely to be inactivated by protein C, therefore leading to thrombosis

42

By what mode of inheritence is antithrombin deficiency passed on?

Autosomal dominant

43

What are some conditions that can cause an increased risk of thrombosis?

Factor V Leiden

Prothrombin varient

Antithrombin deficiency

Protein C and S deficiencies

Homocysteine

44

What enzyme does aspirin inhibit within the platelet?

COX, resulting in a decrease in the production of TXA2

45

What molecule does streptokinase act upon and what is it used for?

It acts on plasminogen activating it to plasmin

Used for thrombolysis

46

What molecule does heparin bind to ?

Antithrombin, leadining to a conformational change increasing antithrombins inhibitory effects

47

What coagulation factor does Fondaparinux and LMWH inhibit?

Factor Xa

48

What is the mechanism of action of warfarin?

It lowers the ability of the patient to form a blood clot by interfering with vitamin K metabolism and therefore reducing the vitamin K-dependent coagulation factors

49

What are the contraindications of giving warfarin?

  • Severe uncontrolled hypertension
  • Non-thromboembolic strokes
  • Peptic ulceration
  • Severe liver and renal disease
  • Pre-existing haemostatic disease
  • Non-compliance

50

Why should warfarin be avoided in pregnancy?

It is teratogenic in the first trimester

It can also cause foetal haemorrhage in later pregnancy

51

What class of drug are rivaroxaban and apixaban?

Xa inhibitors

52