Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Haematology > Coagulation > Flashcards

Coagulation Flashcards

1
Q

What is haemostasis?

A

process to prevent and stop bleeding, to keep blood within a damaged blood vessel which involves coagulation, blood changing from a liquid to a solid (gel) which has three steps: vasoconstriction, temporary blockage by platelet plug and blood coagulation (= formation of a fibrin clot). These seal the hole until tissues are repaired.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are endothelial cells?

A

Simple squamous cells (endothelial cells) lining the interior surface of blood vessels and lymphatic vessels forming a barrier between intravascular volume in the lumen and the rest of the vessel wall

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are the roles of endothelial cells in clotting?

A
  • Produce thrombomodulin
  • Produce heparin sulphate (activate anti-thrombin to inhibit IIa production)
  • Release enzymes degrading platelet granule-derived molecules (reduced TXA2 to reduce platelet aggregation)
  • Produce NO and Prostacyclin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

List 4 substances produced by endothelial cells to prevent clotting.

A
  • Produce thrombomodulin
  • Produce heparin sulphate (activate anti-thrombin to inhibit IIa production)
  • Release enzymes degrading platelet granule-derived molecules (reduced TXA2 to reduce platelet aggregation)
  • Produce NO and Prostacyclin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are platelets?

A

circulating, nuclear fragment of a bone marrow megakaryocytic which functions to maintain integrity of vasculature by producing a platelet plug in the second phase of clotting when attracted by lowered prostacyclin and collagen fragments; TXA2 + serotonin from platelets ≈ vasoconstriction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is platelet production stimulated by? In what organ does this occur?

A

Thrombopoetin (TPO) - liver derived

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

How long do platelets circulate for?

A

Platelets circulate for 5-10 days with 30% stored in the spleen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

How are platelets produced and involved in a breach of endothelium?

A

a) Platelets in circulation 

1) Megakaryocytes produced in bone marrow 

2) Pseudopods form from megakaryocytes in endothelium 

3) Platelets bud off of megakaryocytic mixing with RBCs and WBCs in circulation

b) Intrinsic vessel wall damage, exposure of collagen 6, binding GP IIa-IIb + platelet plug
4) Breach in endothelium wall ≈ exposes subendothelium
5) Prostacyclin levels lower subendothelium cf endothelium + collagen + subendothelial molecules ≈ platelet sticking ≈platelet plug
6) Platelets bind glycoprotein receptor (Gp Ib-Ix) via von Willebrand Factor (vWF) located in association with type VI collagen microfibrils in subendothelium
7) TXA2 + serotonin released from ‘activated platelets’ ≈ vasoconstriction ≈ reduce vessel lumen ≈reduced blood flow ≈ reduced blood loss
8) Increase platelets adhere to site @ GP IIa-IIb platelet receptor in combination with plasma protein fibrinogen
9) Platelets reduced from aggregation + extension along endothelium by in-tact endothelium ≈ endothelial cells produce prostacyclin
10) Platelets changed shape ≈release a granules from platelet cytoplasm ≈ irreversible aggregation

c) Coagulation plug
11) ADP, thrombin, thromboxane A2 released ≈ recruit more platelets

12) Thrombin catalyses conversion of soluble fibrinogen to fibrin ≈ stabilise platelet plug
13) Platelet factor 4 and ß-thromboglobulin promote clotting by neutralising heparin + heparin-like substances

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

How are platelets stored?

A

Platelets present in circulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

How are platelets destroyed?

A

Antibody-coated platelets recognised by macrophages primarily in the spleen ≈ phagocytosis ≈ destruction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is the coagulation cascade?

A

Clotting factors present in circulation as inactive proteins (zymogens) which are triggered by local damage from an intrinsic or extrinsic event leading to activation of other clotting factors to partake in coagulation reaction. Cascade triggered by local damage ≈ coagulation factors in contact with negatively charged phospholipid surfaces + non-endothelial surfaces. The coagulation cascade has two main components: coagulation (blood clot production) + fibrinolysis (dissolving clot).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are the two pathways in the coagulation cascade?

A

Intrinsic pathway: Initiated on exposure to negatively charged non-endothelial surface e.g. collagen ≈ results in XII —> XIIa —> XIa —> IXa —> Xa production of Factor Xa

Extrinsic pathway: Initiated by tissue factor (TF; Factor III) and involves serine protease factor VII in plasma ≈ results in production of Xa from X

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is the common pathway?

A

Prothrombin (II) —> thrombin (IIa) (Common pathway)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is the end-stage of clot production?

A

Fibrinogen (I) —> Fibrin (Ia): by Thrombin (IIa)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

List the physiological coagulation inhibitors involved in the clotting cascade.

A

1) Protein C: Reduce Factor Va production ≈reduce IIa production) + reduce Factor VIIIa production (≈ reduce Xa production) 
- activated by thrombomodulin-thrombin complex
2) Thrombomodulin: reactant with Protein C and Protein S to form Active Protein C to inhibit VIIIa production
3) Co-factor, Factor S: Produce active protein C≈ Decreased Va and VIIa (+ reduced production)
4) Antithrombin: inhibits production of Xa and IIa (thrombin IIa + Xa production from X)
5) Heparin cofactor II: inhibits IIa
6) Heparin: stimulates antithrombin + heparin cofactor II

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is the fibrinolytic system?

A

System responsible for breaking down clot after clot served purpose in haemostasis which is coordinated by a series of enzymatic reactions

  • Plasminogen —> Plasmin (tissue plasminogen activator - tPA) from endothelial cells
  • Fibrin —> fibrin degradation products e.g. D-dimers
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What protein is the key player in the fibrinolytic system?

A

Plasmin is the key player which is formed from plasminogen which is covered through tissue plasminogen activator (tPA) from endothelial cells to plasmin ≈ fibrin degradation ≈ release of fibrin degradation products (FDPs)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Why would a D-dimer assay be better than FDP assay?

A

D-dimer assay shows in-vivo lysis of fibrin cf FDP assay would show in-vivo degradation of fibrin OR fibrinogen ≈ less specific

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What therapeutic uses are there which utilise the fibrinolytic system?

A

Streptokinase or tPA for clot busting in acute myocardial infarction or thrombotic stroke ≈ thrombolysis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What intervention utilises therapeutics involved in the fibrinolytic system and radiology?

A

Thrombolysis, combines interventional radiology/cardiology and fibrinolytic system therapeutics, which must be delivered < 3-4 hours with a risk of bleeding after

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Give 4 measures of coagulation.

A
  1. FBC: platelet count/size/granules
  2. PT: Plasma + Ca++ + Brain Thromboplastin (tissue factor) ≈ 12-15 clotting
    - -> Extrinsic Pathway
  3. APPT: Plasma + Ca++ + Kaolin and Phospholipids (contact factor) ≈ 25-36 seconds
  4. TCT: Plasma + Ca++ + Thrombin
  5. Correction tests: Repeat PT or APTT with 50:50 blood and see if corrected
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Which of the following tests can be used to monitor Warfarin therapy?

A. FBC

B. APTT

C. PT

D. TCT

A

C. PT

23
Q

Which of the following tests can be used to monitor Heparin therapy?

A. FBC

B. APTT

C. PT

D. TCT

A

B. APTT

24
Q

Which of the following tests involved addition of brain thromboplastin?

A. FBC

B. APTT

C. PT

D. TCT

A

C. PT

25
Q

Which of the following tests involved addition of kaolin and phospholipids?

A. FBC

B. APTT

C. PT

D. TCT

A

B. APTT

26
Q

Which of the following tests usually takes 12-15s to complete?

A. FBC

B. APTT

C. PT

D. TCT

A

C. PT

27
Q

Which of the following tests usually takes 25-36s to complete?

A. FBC

B. APTT

C. PT

D. TCT

A

B. APTT

28
Q

Which of the following tests measures the common pathway?

A. FBC

B. APTT

C. PT

D. TCT

A

D. TCT

29
Q

Which of the following tests measures the extrinsic pathway?

A. FBC

B. APTT

C. PT

D. TCT

A

C. PT

30
Q

Which of the following tests measures the intrinsic pathway?

A. FBC

B. APTT

C. PT

D. TCT

A

B. APTT

31
Q

List the clotting factors produced in the liver.

A

Factors 2, 7, 9 and 10

32
Q

Which of the following tests is the best measure of DIC?

A. FBC

B. APTT

C. PT

D. TCT

A

D. TCT

33
Q

Which of the following tests is an additional test using another individual as a comparison?

A. Correction Test

B. Activated Partial Thromboplastin Test

C. Prothrombin Time

D. Thrombin Clotting Time

A

A. Correction Test

34
Q

Give a drug to help blood clot.

A
  1. FFP: Normal proportions given in 15ml/kg with 200ml plasma from blood
  2. CryPpt: Frozen concentration of I, VIII and vWF
35
Q

What are the components of Cryoprecipitate?

A

vWF, factor I and factor VIII at 4ºC

36
Q

Give 3 examples of drugs that can prevent clotting.

A
  1. Tranexamic Acid
  2. Warfarin
  3. Heparin
  4. DOACs
37
Q

Give an example of an anti-fibrinolytic drug.

A

Tranexamic acid

Inhibits tPA thus reduced conversion of plasminogen to plasmin and reduced clot busting

38
Q

Outline the mechanism of action of Warfarin.

Suggest 3 benefits and 3 drawbacks.

A
  1. Warfarin: Competitive inhibitor of vitamin K epoxide + Vitamin K reductase ≈ reduced reduced vitamin K ≈ reduce production of II, VII, IX and X

+ Established

+ Cheap

+ Easy measurable effect 

+ Reversible: vitamin K or factor concentrate (y-cardboxyglutamate of factors II, VII, IX, X)

- Drug interactions: increase or decrease warfarin exposure 

- Slow onset 
- several days 

- Unpredictable dose need 

- Regular blood testing: PT 

- Haemorrhage risk
39
Q

Give 3 factors which increase exposure to Warfarin.

A
  • Reducing vitamin K (Amoxicillin)
  • Enzyme inhibition (Statins, Alcohol, Erythromycin)
  • Platelet function change (Aspirin, Clopidogrel, NSAIDs)
40
Q

Give 3 factors which decrease exposure to Warfarin.

A
  • Enzyme reduction (Rifampicin, Carbamazepine, Phenytoin, Chronic alcohol intake)
  • High levels of vitamin K
  • Cranberry juice
41
Q

Give the decision-making algorithm and its factors used to decide Stroke Risk.

A

Scoring: CHADSVASc ≈ increase score = increased association with stroke risk 

- CHF (or LV systolic dysfunction)

- HTN (HTN ≈ 140/90mmHg or treated HTN on medication)

- Age (Age > 75) = 2 

- DM 
- Stroke (TIA or thromboembolism) 

- Vascular disease (PAD, MI, aortic plaque) 

- Age (65-74)

- Sex category

42
Q

Give an example of a DOAC which inhibits Factor II

A

Dabigatran

43
Q

Give an example of a DOAC

A

Apixaban

Rivaroxaban

Dabigatran

44
Q

Give 3 benefits of using DOACs

A
  • Lower bleeding risk
  • Effective in stroke prevention
  • Shorter half life
45
Q

Give one major drawback of DOACs

A

No reversal agent

Cost

46
Q

Give the mechanism of action of heparin.

Outline its size effects.

Suggest how it can be monitored.

A
  1. Heparin: Anti-coagulant binding to anti-thrombin to reduce Xa and thrombin generation

MOA: Binds and activates anti-thrombin ≈ reduce Xa + increase antithrombin (≈ reduced Xa and IIa) ≈ reduced thrombin generation

Forms: Unfractioned or LMWG

SEs

  • Pain at site
  • GI bleeding
  • OP
  • Thrombocytopenia (5-10 days into Rx)

Monitoring:
1. APTT

  1. Fixed dose prophylaxis
    - check with Anti-Xa levels
47
Q

Give an example of an anti-platelet drug.

A
  1. Aspirin

2. Clopidogrel

48
Q

Outline the MOA of aspirin.

Give its dose and administration.

A

Aspirin≈ Irreversible, non-selective COX-1 inhibitor ≈ competitively inhibits arachidonic acid at PGH2 synthase cyclooxygenase active site ≈reduce formation of PGH2, PGE2 and TXA2 ≈less platelet aggregation at endothelial surface 
-

Administration: Orally or IV 
-

Dose: 75mg-150mg/day

49
Q

Give the MOA of clopidogrel.

Give its dose and administration.

A

Clopidogrel ≈ inhibit ADP-induced platelet aggregation ≈ anti-platelet drug


  • MOA: inhibit ADP-induced platelet aggregation 

  • Used with aspirin ≈ X recurrent MI

Administration: Orally

Dose: 75-300mg

50
Q

What is the reversal agent for aspirin?

A

None, effects last for platelet lifespan of 5-10 days

51
Q

What is the reversal agent for clopidogrel?

A

No reversal agents so effects last for platelet lifespan ≈5-10 days

52
Q

Give an example of a clot-busting drug.

Outline its MOA.

How can its function be measured?

A

Streptokinase/Alteplase

tPA activation ≈ plasminogen to plasmin ≈ breakdown fibrin cross-linked clot to FDPs or D-dimers

Measured: D-dimer assay or FDP assay

53
Q

Give the reversal agent of heparin.

A

Protamine sulphate

54
Q

Give the reversal agent of warfarin.

A

Vitamin K concentrate + FFP or CryoPPt

Haematology (2 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions