Haemostasis and Thrombosis and Embolism Flashcards Preview

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Flashcards in Haemostasis and Thrombosis and Embolism Deck (59):
1

What exactly is haemostasis

blood stopping process
maintain blood in a fluid state in normal vessels
Balance between:
Clotting (thrombosis) --- Bleeding (Haemorrhage)
Prothrombotic--------------------- Anti-thrombotic

2

What's the difference between a thrombus and clot?

thrombus formed WITHIN the cardiovascular whereas clot formed OUTSIDE or post mortem

3

Order of haemostasis process

Transient vasoconstriction
Primary haemostasis
Secondary haemostasis
Anti-thrombotic counter-regulation

4

What happen at step 1, transient vasoconstriction, in haemostasis?

- reflex vasoconstriction by endothelin from endothelial cells
- temporarily slows bleeding

5

What happen at step 2, primary haemostasis?

- expose thrombogenic subendothelial ECM
- platelets adhere, activate and release granules to recruit more platelet => platelet plug

note: involve vWF, ADP and Thromboxane A2

6

What happen at step 3, secondary haemostasis?

- tissue factor (thromboplastin) released
- tissue factor + factor VII activate coagulation cascade (extrinsic)
- generate thrombin
- thrombin convert fibrinogen to insoluble fibrin => fibrin polymerisation

7

What happen at step 4, anti-thrombotic mechanism, in haemostasis?

- t-PA = fibrinolysis
- thrombomodulin = block coagulation cascade

both t-PA and thrombomodulin limit platelet plug.

8

What are the 3 main ingredients of haemostasis?

1. ENDOTHELIUM (vasoconstriction)
2. PLATELET (platelet plug)
3. COAGULATION (fibrin formation)

9

3 roles of a normal endothelium can do

1. anti-platelet : have prostacyclin, NO and ADPase to prevent adhesion and activation

2. anti-coagulant : anti-thrombin, thrombomodulin, protein C and S, tissue factor inhibitor

3. Fibrinolysis: t-PA

10

What is the normal INTACT endothelium's behaviour?

- anti-thrombotic

11

An injured endothelium promotes____?

thrombosis
- by trauma, cytokines, infectious agents, haemodynamic F, p/m mediators

12

What effects does injured endothelium produce?

- platelet : adhesion via vWF
- pro-coagulant : tissue factor
- anti-fibrinolytic : plasminogen activator inhibitors

13

What are some main things that platelets contain?

glycogen
alpha-granules (fibrinogen, vWF)
dense granules (ATP, ADP, serotonin, adrenaline)
dense tubular system
mitochondria
microtubules

14

What makes platelet adhere to site of injury?

glycoprotein von Willebrand factor (vWF)
(bind to subendothelial collagen)

15

What does platelet secrete?

granules
- dense granules: ADP and serotonin
- alpha granules: vWF, FV, PF4, Fibrinogen

16

What does ACTIVATED platelets secrete more?

Thromboxane A2, vWF
=> activate more platelets

17

What is the aggregation receptor for platelet?

Gp IIb/IIIa : binds to fibrinogen

18

What does Thromboxane A2 (TXA2) do? (4)

- it comes from cyclo-oxygenase pathways
- amplifies aggregation
- activates more platelets
- constricts vessels

19

What can coagulation cascade do?

- enzyme rx occurs on the surface of activated platelets
- to stabilize the platelet plug
- here, RBC, WBC trapped make the plug even bigger

20

What does EXTRINSIC coagulation pathway require?

- Tissue factor
- Factor VII-a

21

What does INTRINSIC coagulation pathway require?

- Hageman factor
- Factor VIII, IX, XI, XII (8,9, 11, 12)

22

What does COMMON coagulation pathway require?

- Factor II (thrombin)
- Factor I (fibrinogen

23

What does it mean by 'stable meshwork' in coagulation?

cross-linked fibrin that stabilize the platelet plug

24

What are ways to investigate coagulation?

Platelet count (~150-400 x 10^9)
Platelet function : PFA, bleeding time
Coagulation studies : APTT, PT/INR

25

What are the 2 main inhibitors of coagulation cascade (physiological)?

- Anti-thrombin : enhance by heparin (endothelium)
- protein C and S : stop cascade! (activated by thrombin & thrombomodulin)
- tissue factor inhibitor : block binding of factor VII-a in extrinsic pathway

26

What is the main inhibitor of fibrin forming (physiological)?

- t-PA : activate plasminogen to break down fibrin

27

What is the process of fibrinolysis (counter mechanism)?

t-PA (tissue plasminogen activator)
- started by the activation of coagulation cascade
- plasminogen cleaved to plasmin
- plasmin breaks down fibrin : D-dimers

28

What pharmaceutical products block platelet R binding?

- monoclonal aB
- clopidogrel

29

What pharmaceutical product inhibit TXA2 product?

Aspirin

30

What pharmaceutical products 'block' coagulation cascade?

heparin
warfarin
clexane
dabigatran

31

What pharmaceutical products 'block' the cleaving of plasminogen to plasmin?

streptokinase

32

What are the main problems with bleeding disorder?

- fragile endothelium or blood vessels
- defective/deficient platelet
- defective/deficient coagulation factors

33

Common causes of blood vessel wall abnormalities?

- petechiae < purpura < ecchymoses in skin and mucous membrane

34

What are causes of abnormal blood vessel wall?

Infection (DIC)
Drug Rx (immune)
Vitamin C deficiency

35

What is thrombocytopenia?

Bleeding disorder
Deficient platelet = 'Low platelet count'

36

What are the causes of thrombocytopenia? (4)

- Reduced platelet function : bone marrow failure and liver disease (reduce thrombopoietin)
- Reduced platelet survivals
- Sequestration in hyper-splenism
- Dilution

37

What makes platelet function defects?

- inherited defects of adhesion, aggregation or secretion
- acquired cause (uremia, drugs and food)

38

What are the inherited cause of abnormal clotting/coagulation factor? (2)

von Willebrand disease
haemophilia A and B

39

What is von Willebrand disaese

Bleeding disorder that reduce platelet function
familial defective vWF (autosomal dominant)

40

What are the consequences of vWD?

prolonged bleeding time
bruising tendency
menorrhagia
female bias

41

What is haemophilia A and B?

Bleeding disorder at joints and m/s with causative mutation
- Haemoph A : factor VIII deficiency
- Haemoph B : factor IX deficiency

42

How to treat haemophilia A and B?

IV clotting factor
- usually as prophylaxis regularly
- before surgery or dental treatment

43

What are the acquired causes of abnormal clotting factors, thus result in bleeding?

- vitamin K deficiency
- warfarin/heparin
- DIC
- Severe liver disease

44

What is Warfarin?

Vitamin K antagonist
- inhibit carboxylation of clotting factors II, VII, IX and X
- to reduce risk of thrombosis

45

What is vitamin K?

It's a biological redox reagent to regulate coagulation factor

46

What does Vitamin K-deficiency result in?

- decrease carboxylation of Vit.K
- thus coagulation factors (2, 7, 9, 10) is non-functional

47

What can Vit K limited to?

new born infants (as no transfer across placenta)
intestinal malabsorption (lack of bile salts)

48

What is haemorrhage?

leakage of blood from vessels into extravascular space
- result in external bleeding or accumulation of blood within tissue (hematoma)

49

What are 3 ranges of haematoma?

- petechia : dot hemorrhage
- purpura : small hemorrhage (2-5mm)
- ecchymoses : bruises (1-2cm and larger)

50

What haematoma associated with thrombocytopenia, defective platelet function and increased intravascular pressure?

- petechiae
- purpura (also increase vascular fragility, inflammation and trauma)

51

What is the process of ecchymoses?

RBCs leaked and being phagocytosed by Mø

Hb (red-blue) ---> bilirubin (green-yellow) ---> hemosiderin (yellow brown)

52

What is Virchow's triad?

Pathogenesis of Thrombosis
- Endothelial injury
- Abnormal blood flow
- Hyper-coagulability

53

What are the 4 possible outcomes after a thrombus formed

- resolution : fibrinolysis
- embolisation to lungs : cause PE
- organisation and recanalisation : reestablish blood flow
- propagation : thrombus occluded vessels (to heart)

54

What is thromboemolism?

thrombus travel through the blood and lodge in narrow vessels.
result in vascular occlusion

55

What is pulmonary embolism (PE)?

Thrombi from deep leg veins (DVT) travel to Right side of heart then block at pulmonary trunk.

56

Where does ARTERIAL thromboemboli originate from?

intracardiac mural thrombi
- aortic aneurysms
- ulcerated atheroscelrotic plaques
- valvular vegetations

57

What does arterial emboli result in?

infarction

58

What is another name of large emboli that occlude in the pulmonary trunk centre?

Saddle embolus in PE

59

What is the 'sad' consequence of PE?

sudden death
- due to obstruction of blood flow to lungs as acute right sided heart failure, called 'acute cor pulmonale'