Blood Coagulation, Haemostasis and it Investigations Flashcards Preview

CLINICAL PATHOLOGY > Blood Coagulation, Haemostasis and it Investigations > Flashcards

Flashcards in Blood Coagulation, Haemostasis and it Investigations Deck (25)
Loading flashcards...
1

What is haemostasis? 

Life preserving process to maintain blood flow 

  • Respond to tissue injury 
  • Curtail blood loss 
  • Restore vascular integrity + promote healing 
  • Limit infection 

2

What is the effect of haemostasis in infections? 

Give an example of an infection where coagulation plays an important role. 

Infection is an important initiator of haemostasis. Coagulation can also acts as a mechanism against infection. 

This occurs in meningococcal septicaemia which initiates haemostasis resulting the formation of excessive clots which will occlude blood vessels = disseminated intravascular coagulation 

3

What are the key components of haemostasis? 

  • Endothelium 
  • Coagulation 
  • Platelet 
  • Fibrinolysis

4

Provide a summary of the phases that occur in haemostasis. 

  1. Primary haemostasis 
    • Vasoconstriction 
    • Platelet adhesion 
    • Platelet aggregation and contraction 
  2. Secondary haemostasis 
    •  Activation of coagulation factors (within seconds) 
    • Formation of fibrin (within minutes) 
  3. Fibrinolysis 
    1. Activation of fibrinolysis (within minutes) 
    2. Lysis of the plug (within hours) 

5

Describe the steps in primary haemostasis 

  1. Blood vessel recognises there is damage when various signalling molecules become exposed e.g tissue factor and collagen (both in sub-endothelium) 
  2. Specific mediators will cause the blood vessels to constrict in diameter (vasoconstriction) = vascular spasm → less blood flow (less blood loss) 
  3. vWF (normally a globular structure) in the endothelium will unwind and form a straight molecule with sticky ends which will attach to collagen in subendothelium and cover up injury site 
    • vWF will also carry factor 8 of coagulation cascade
  4. vWF will act as an anchor for platelets, (vWF will bind to glycoprotein 1b-IX-V receptors on platelets) this will activate them causing them to become flatter for a larger SA
  5. Glycoprotein 2b-IIIa will also go a confirmational change and bind platelets to eachother and bind fibrinogen
  6. Initial activated platelets will release cytoplasmic granules (contain ADP, serotonin and thromboxane A2) this will result in aggregation and adhesion = platelet plug formation = primary haemostasis 

6

What is the function of wWF? 

  • Attaches to collagen in the subendothelium and acts as an anchor for platelets to attach to it (glycoprotein 1b) and form a platelet plug 
  • This will prevent excessive blood loss at injury site 

 

7

What is secondary haemostasis? 

Formation of the fibrin clot 

  • Activation of coagulation factors (within seconds) 
  • Formation of fibrin (within minutes) 

8

What is the role of platelets? 

  • Platelets will recognise the injured area 
  • They will form complexes with fibrin, collagen and wWF with glycoproteins on their surface
  • ADHESION = wWF will bind to extracellular collagen and Gp1b-IX-V complex
  • ACTIVATION = Gp2b-3b will undergo confirmational changes and bind to eachother 
  • Exposure of negatively charged phospholipids will provide a pro-coagulant surface

9

Where are the clotting factors made? 

 

Clotting factors are made in the LIVER 

  • Hence why people with liver problems will often have bleeding disorders due to deficiencies in clotting factors 

10

What are the three coagulation pathways? 

  • Intrinsic (Surface contact) 
  • Extrinsic (tissue factor) 
  • Common 

11

What is important to note about the classical concept of the coagulation pathway? 

  • The concept of the distinct intrinsic, extrinsic then common pathway is not physiologically correct
    • But useful in interpreting a routine coagulation screen
      • However, it does FAIL to explain why
        • FXII deficient patients do not bleed
        • FXI deficiency only usually a mild disorder
        • FVIII/IX deficiency causes severe bleeding disorder but should be bypassed by FVII activity
          • Thrombin generation has a lag phase then rapid production

12

More accurate explanation for the process of coagulation 

  1. Initiation = tissue factor in sub-endothelium will form a complex with FVIIa (TF-Vlla) when there is bleeding 
  2. Complex binds small amounts of FX and FV to the exposed endothelial surface producing small amounts quantities of thrombin 
  3. Thrombin will activate platelets which are attracted to the site of injury and recruits other plasma-borne clotting factors 
  4. Amplification: activated factors (including FIXa and FVIIIa) enable binding of FXa and FVa to surface of platelets 
  5. Propagation: Thrombin burst necessary for large-scale production of fibrin and subsequently an effective clot 

13

What does thrombin do? 

Convert fibrinogen to fibrin 

14

How does fibrinolysis occur? 

  • Dissolution of a clot 
    • Clot limiting mechanism 
      • Activation of fibrinolysis (minutes) 
      • Lysis of plug (within hours) 

15

Describe how fibrinolysis occurs. 

  1. Plasminogen will be converted to the active form plasmin via t-PA and urokinase plasminogen activator 
  2. Plasmin will break down fibrin clots 

16

What are D-dimers? 

  • These are products generated when cross-linked fibrin becomes degraded 
    • D-dimer levels are used clinically to detect for clots 

 

17

What can cause thrombosis? 

What can it lead to? 

  • High coagulation factors and platelets 
  • Low fibrinolytic factors and antioagulant proteins 

 

Can lead to chronic venous insufficiency 

  • Atrophic changes 
  • Hyperpigmentation 
  • Ulceration 
  • Infection 

 

18

What is the main principle of clotting tests? 

  • Incubate plasma with reagents 
  • Reagents below are added 
    • Phospholipid, co-factors 
    • Trigger or activator 
    • Calcium 
  • Measure time taken to form fibrin clot 

19

How is blood anti-coagulated in haemostasis testing? 

Identify some pre-analytical errors in haemostasis testing

Blood is anticoagulated with 3.2% Sodium Citrate (removes Ca2+ because calcium is a cofactor for coagulation keeping it unclotted)

20

What is the prothrombin time? 

Measures the activity of pro-thrombin in the blood - measures the extrinsic coagulation pathway 

 

21

What does the activated partial thromboplastin time measure? 

Measures the intrinsic coagulation pathway 

22

What does thrombin time measure? 

Detects the defects in conversion of fibrin to fibrinogen 

23

Why do we carry out mixing studies? 

  • If there is an unexlained prolongation in any of the three screening tests a correction test is carried out 
  • This is where equal amounts of plasma and control plasma are mixed to produce 50:50 mixed plasma 

24

What information can we get from mixing studies? 

There are two possibilities 

  1. Deficient in clotting factor 
  2. Something is interfering with the coagulation cascade usually an antibody or a anticoagulant (e.g heparin) 

To determine what is wrong we test the plasma by mixing it with a control. If the test plasma has a clotting factor deficiency the clotting factors will be replaced by those in control plasma. The final tube should contain a 50:50 mix of plasma. 

If the patient has antibodies interfering with conagulation the antibodies will inhibit the added coagulation factors = clotting time is still prolonged (50:50 mix will only correct deficiency but doesnt correct clotting time when ABs are in plasma) 

25

D-dimer testing 

  • A measure of the D-dimer, a fibrin degradation product
  • Found elevated in the situation of enhanced fibrinolysis (Thrombosis, DIC)
  • Not specific for thrombosis also elevated as an acute phase reactant
  • A negative result is useful if clinical suspicion of VTE is low

Decks in CLINICAL PATHOLOGY Class (52):