Other - Erythropoiesis, Haemostasis and clotting mechanism

Question 1

What is haemostasis?

Answer 1

Natural mechanism of bleeding arrest

Question 2

What are the steps in haemostasis?

Answer 2

1. vasoconstriction
2. formation of temporary platelet plug (primary haemostasis)
3. Activation of coagulation cascade (Secondary Hemostasis)
4. Formation of fibrin plug
5. Fibrinolysis - dissolve clot and restore function
6. Regeneration and repair

Question 3

How do you test primary haemostasis?

Answer 3

Core factor in primary homeostasis are Platelets:

You look for overall bleed:
Platelet count PC
Bleeding time BT
PLT AGGREGOMETRY

Question 4

Describe the pathology of primary haemostasis and causes?

Answer 4

Disorder of:
Platelet count (thrombocytopenia)
Excess consumption of platelets - DIC
Platelet plug formation,
Premature clot dissolution (fibrinolysis)

Examples: TTP and ITP, Anti-platelet drugs - Aspirin/ clopidogrel, haemolytic uremic syndrome

Other disorder w/ 1+2 hemostasis: DIC, VWF

Question 5

What are these a sign of?

MUCO-CUTANEOUS BLEEDS

Mucosal:
Epistaxis, Menorrhagia, Gum Bleeds, Hematuria, GI Bleed, GU Bleed

Cutaneous
Petechiae, Purpura, Easy Bruising (ecchymoses)

Answer 5

Defective primary hemostasis

Question 6

Describe the pathology of secondary haemostasis and causes?

Answer 6

Disorder of:
Clotting factor deficiency
Clotting factor inhibitors

Causes:
Hemophilia A/B

Other disorder w/ 1+2 hemostasis: DIC, VWF

Question 7

How do you test secondary haemostasis?

Answer 7

Core factor in primary homeostasis are Coagulation factors:
PT - extrinsic pathways
APTT - Intrinsic Pathway

P(e)T - Extrinsic - PT - factor 7
P(i)TT - Intrinsic - APTT - factor 12 11 9 8
Bull

Question 8

Anatomical Deep Tissue Bleeds:

Joints - hemarthroses
Muscle - muscle hematoma
Brain - haemorrhage
Bleeding after tooth extraction
Late rebleeding

Answer 8

Defective secondary haemostasis

Question 9

Question 10

Describe the pathways of the coagulation cascade

Answer 10

Intrinsic (Contact) pathway is activated by exposure to subendothelial collagen

Extrinsic (Tissue factor) pathway is activated by tissue thromboplastin

Question 11

Describe different classes of anti-coagulants and thier MOA

Answer 11

Direct factor XA Inhibitor - Apixaban, Rivaroxaban

Question 12

Which clotting factors are VIT K dependant

Answer 12

1972 WEPT
Clotting factors 10 9 7 and 2
warfarin and PT time

Question 13

What prolongs aPTT

Answer 13

Von willerband disease (severe)
Haemophillia A
Haemophillia B

Question 14

What prolong PT

Answer 14

Liver disease
Vit k def
Warfarin Use

Question 15

MOA of Heparin

Answer 15

Heparin enhances the activity of antithrombin III, which inhibits the activity of thrombin and other clotting factors, thereby preventing the formation of blood clots.

Question 16

MOA of Warfarin

Answer 16

Warfarin inhibits vitamin K epoxide reductase, which reduces the synthesis of clotting factors II, VII, IX, and X. This reduces the ability of the blood to form clots, thereby preventing the formation of new blood clots.

Question 17

MOA of Alteplase

Answer 17

Alteplase converts plasminogen to plasmin, which is a proteolytic enzyme that breaks down fibrin, the major component of blood clots. By promoting fibrinolysis, Alteplase can dissolve existing blood clots.

Question 18

MOA of Clopidogrel

Answer 18

Clopidogrel blocks ADP receptors on platelets, which inhibits platelet activation and aggregation, and reduces the formation of blood clots.

Question 19

MOA of Ticagrelor

Answer 19

Ticagrelor inhibits the P2Y12 receptor on platelets, which prevents platelet activation and aggregation. This reduces the formation of blood clots and improves blood flow in patients with acute coronary syndromes.

Question 20

What is heparin induced thrombocytopenia

Answer 20

Following heparin administration, rarely (5%), antibodies bind to the drug  prothrombotic state
Problem with primary haemostasis

Presentation:
Onset of emboli (PE / DVT / CSVT) following heparin administration
Suspect in any patient on heparin who’s platelets fall >50%
Bloods: platelets low, D-dimer high
Treatment:
Stop heparin
Anticoagulate

Question 21

How are platelets activated?

Answer 21

Platelet activation:
Initial activation:
Collagen binding to GPVI / GPIIbIIIa via vWF

Amplification:
Thromboxane – binds to TPa receptors – NSAIDS inhibit thromboxane formation
ADP binds to P2Y12 / P2Y1 receptors – Clopidogrel / ticagrelor inhibit P2Y12 binding
Other platelets form GPIIb/IIa crossbridges
Thrombin – binds to PAR1 / PAR4 receptors – Dabigatran inhibits thrombin

Effects:
Platelet shape change (pseudopodia, projections increase interlinking with other platelets)
Dense granule release (Contains more ADP for further P2Y12 activation)
Alpha granule release (Inflammatory mediators and clotting factors)