Haemostasis intro Flashcards
What is primary haemostasis?
Platelets and vasoconstriction for platelet plug
What cells do platelets develop from
Megakaryocytes
Diameter of platelets?
1-4um
Define thrombocytopenia
Low platelet count
<150*10^9
Normal platelet count?
150-400*10^9
Define thrombocytosis
> 450*10^9
Function of the various proteins found inside platelets
Surface proteins: help platelets stick to breaks in vessel wall and to eachother
Granule proteins: help make plug
Contained proteins: Allow platelet to change shape
What causes platelet migration initially?
The collagen that is exposed when blood vessel breaks causes platelet migration and structural change
Describe structural changes that occur when platelets form initial clot
Originally flat (look like plates) Then extend long filaments and filaments from different platelets interlock to make a clot
What is secondary haemostasis
The use of fibrin to stabilise platelet clot
What is the first thing to trigger coagulation cascade
Tissue factor
Where is tissue factor found?
Outside of endothelium
When does extrinsic pathway of coagulation cascade occur?
When a vessel is injured
Describe the extrinsic pathway (excluding common pathway)
- Factor VII is converted to VIIa via tissue factor
- VIIa converts factor X to factor Xa complex (complex including factor Xa, calcium and more)
Describe the common pathway of coagulation cascade?
- Factor Xa converts prothrombin to thrombin
- Thrombin converts fibrinogen to fibrin
- Fibrin forms stable clot
What is the rate limiting step in extrinsic pathway
X->Xa
What measurment is used to test extrinsic and common pathways?
Prothrombin time
When does the intrinsic pathway of coagulation cascade occur?
occurs without injury to vessels
Describe the instrinsic pathway exclusing the common pathway
Factor XII–> Factor XIIa
XIIa converts XI to XIa
XIa converts IX to IXa
IXa converts X to Xa
What tests the intrinsic and common pathway
Activated partial prothrombin time
Describe bleeding time test
Shallow incision made on underside of forearm
Time taken for bleeding to fully stop in measured
Normal is 3-10 minutes
What is INR?
Derived from prothrombin time
Healthy is 0.8-1.2
What is the INR to aim for in patients taking warfarin and heparin
2.0-3.0
What type of feedback loop regulates thrombin production
Positive feedback
What activates the positive feedback loop
Release of tissue factor causes small amount of thrombin to be produced
Thrombin activates feedback loop
What three factors does the thrombin made by tissue factor activate in the amplification phase?
Va
VIIIa
XIa
How does factors Va, VIIa and XIa produce more thrombin
VIIa and XIa combine to increase conversion of X to Xa
Va increases efficiency of Xa
Therefore more thrombin made by coagulation cascade
How does fibrin make the clot more stable
Polymerases inside the clot.
How does factor XIIIa increase clot stability
Increased crosslinking
What is the main enzyme responsible for clot removal
plasmin
How does plasmin circulate in the blood
Plasminogen
What keeps plasminogen inactive within the clot
Alpha-2 antiplasmin
What enzyme catalyses plasminogen–> plasmin
Tissue plasminogen activator
Describe process by which tpa causes clot breakdown
Tpa production is suppressed at injury site
Once healed tpa is released
this converts plasminogen to plasmin
clot breakdown
What product of clot breakdown can be measured to test for people with DVT?
D-dimer
Deficiency of which factor causes haemophillia A?
Factor VIII
Describe haemophillia A
Factor VIII levels low
Reduces effectiveness of positive feedback loop manufactoring thrombin
Deficiency of which factor causes haemophillia b?
Factor IX
Describe haemophillia B?
Deficiency of factor IX
IXa is essential component o tenase complex which converts X to Xa
What is released by platelets to aid vasoconstriction in formation of primary haemostatic plug
Serotonin
What is released by platelets to cause aggregation
TXA2
ADP
Arer there more erythrocytes or platelets in a clot
Erythrocytes
What does tissue plasminogen activator prevent?
Clot extending too far along blood vessel into health tissue