Other - Erythropoiesis, Haemostasis and clotting mechanism Flashcards
What is haemostasis?
Natural mechanism of bleeding arrest
What are the steps in haemostasis?
- vasoconstriction
- formation of temporary platelet plug (primary haemostasis)
- Activation of coagulation cascade (Secondary Hemostasis)
- Formation of fibrin plug
- Fibrinolysis - dissolve clot and restore function
- Regeneration and repair
How do you test primary haemostasis?
Core factor in primary homeostasis are Platelets:
You look for overall bleed:
Platelet count PC
Bleeding time BT
PLT AGGREGOMETRY
Describe the pathology of primary haemostasis and causes?
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
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)
Defective primary hemostasis
Describe the pathology of secondary haemostasis and causes?
Disorder of:
Clotting factor deficiency
Clotting factor inhibitors
Causes:
Hemophilia A/B
Other disorder w/ 1+2 hemostasis: DIC, VWF
How do you test secondary haemostasis?
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
Anatomical Deep Tissue Bleeds:
Joints - hemarthroses
Muscle - muscle hematoma
Brain - haemorrhage
Bleeding after tooth extraction
Late rebleeding
Defective secondary haemostasis
Describe the pathways of the coagulation cascade
Intrinsic (Contact) pathway is activated by exposure to subendothelial collagen
Extrinsic (Tissue factor) pathway is activated by tissue thromboplastin
Describe different classes of anti-coagulants and thier MOA
Direct factor XA Inhibitor - Apixaban, Rivaroxaban
Which clotting factors are VIT K dependant
1972 WEPT
Clotting factors 10 9 7 and 2
warfarin and PT time
What prolongs aPTT
Von willerband disease (severe)
Haemophillia A
Haemophillia B
What prolong PT
Liver disease
Vit k def
Warfarin Use
MOA of Heparin
Heparin enhances the activity of antithrombin III, which inhibits the activity of thrombin and other clotting factors, thereby preventing the formation of blood clots.
MOA of Warfarin
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.
MOA of Alteplase
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.
MOA of Clopidogrel
Clopidogrel blocks ADP receptors on platelets, which inhibits platelet activation and aggregation, and reduces the formation of blood clots.
MOA of Ticagrelor
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.
What is heparin induced thrombocytopenia
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
How are platelets activated?
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)
