Haemostasis Flashcards
What is haemostasis?
The arrest of bleeding with the maintenance of vascular patency
What are the requirements for well functioning haemostasis?
Permanent state of readiness
Prompt response
Localised response
Protection against unwanted thrombosis
What is primary haemostasis?
Formation of platelet plug
What is secondary haemostasis?
Formation of fibrin clot
What are the components of normal haemostasis?
Primary haemostasis; platelet plug
Secondary haemostasis; fibrin clot
Fibrinolysis
Anticoagulant defences
How are platelets formed?
Budding of megakaryocytes in bone marrow
What is the life span of a platelet?
7-10 days
Do platelets have a nucleus?
No
How does platelet adhesion occur?
Endothelial damage exposes collagen and releases von Willebrand factor (VWF) which results in platelet adhesion at the site of injury
How do platelets know where the site of injury is?
Once initial platelet adhesion has occurred, degranulation occurs leading to aggregation of platelets
What can cause failure of platelet plug formation?
Vascular; scurvy, old age
Thrombocytopenia
Reduced function; antiplatelets
VWF
What are the consequences of failure of primary haemostasis?
Spontaneous bruising and purpura
Mucosal bleeding; epistaxis, GI, conjunctival, MENORRHAGIA
Severe; intracranial haemorrhage, retinal haemorrhage
What is the screening test for primary haemostasis?
Platelet count
In VWF; there will be decreased platelets and a low factor 8 (prolonged APTT)
Descibe the mechanism of fibrin clot formation
Tissue Factor binds with factor 7a (initiation)
This leads to the activation of factors 5 and 10a.
Factors 5 and 10a will result in the cleavage of prothrombin (2) to thrombin (2a)
Thrombin results in the cleavage of fibrinogen to fibrin
Thrombin will also act to activate factors 8 and 9 (amplification)
Which will act to further increase factors 5 and 10a (propagation) to increase thrombin levels
Formation of a stable fibrin clot
What is initiation in fibrin clot formation?
Activation of tissue factor and clotting factor 7a
What is amplification in fibrin clot formation?
Thrombin acts to activate clotting factors 8 and 9
What is propagation in fibrin clot formation?
Activated clotting factors 8 and 9 act on 5 and 10a to increase thrombin levels via cleavage of prothrombin
What can cause failure of fibrin clot formation?
Single clotting factor deficiency; haemophilia
Multiple clotting factor deficiencies; DIC
Increased fibrinolysis
What is haemophilia A (more common)?
Deficiency of clotting factor 8
What is haemophilia B?
Deficiency of clotting factor 9a
Describe fibrinolysis
Plasmin is formed from plasminogen via tPA
Plasmin will act on fibrin to break it down into FDPs
How are FDPs measured?
D-dimer
Indication of excess fibrinolysis; DIC and DVT/PE
Is there a clinical syndrome for failure of secondary haemostasis?
No
If haemophilia; bleeding into joints (haemarthrosis) and muscles
What are the screening tests for fibrin clot formation?
Prothrombin time
Activated Partial Thromboplastin Time (APTT)
What does prothrombin time assess?
Extrinsic Pathway
Add tissue factor and phospholipid thromboplastin) to patients serum to activate factor 7a
Measures factor 7a, 5, 10a and prothrombin
What does APTT assess?
Intrinsic Pathway
Clotting factors 8 and 9a
And 5, 10a and prothrombin
What will increase prothrombin time?
Deficiency in factor 7
What will increased APTT time?
Deficiency in factors 8 or 9a (haemophilia)
What will increase both prothrombin and APTT?
Deficiency in 5, 10a, prothrombin, fibrinogen or both 8/9a and 7
Multiple clotting factor deficiency or the main pathway that links both (5, 10a, prothrombin, fibrinogen)
What is the clinical approach to bleeding disorders?
History; bleeding, bruising, duration(? life-long)
Previous surgery/ dental extractions
Drug hx
FMHx
Exam; fundal haemorrhages, mouth, purpura (primary haemostasis), muscles and joints (secondary haemostasis), splenomegaly
What is the action of anti-thrombin?
Serine protease inhibitor
Naturally occuring anti-coag
Deactivates TF/7a, 5/10a and 8/9a along with thrombin inactivation
What drug acts to increase anti-thrombin action?
Heparin
What is the action of protein C and S?
Act to deactivate 5/10a and 8/9a
Thrombin will also bind to thrombomodulin to have a positive feedback to increase levels of protein C and S
What is thrombophilia?
Deficiency of naturally occuring anticoagulants
Tendency to develop DVT/ PE
In primary haemostasis; what will activated platelets release and what is the result of that?
Thromboxane A2 (TXA2) Acts to release serotonin and ADP which will result in platelet aggregation and vasoconstriction
What component of the platelet cell membrane allows for adhesion?
Pseudopodia
What role does ADP specifically have in primary haemostasis?
Aggregation to form soft plug
Expose acidic phospholipids on platelet surface to initiate coagulation and solid clot formation
What is virchows triad?
Injury to vessel wall
Abnormal blood flow
Increased coagulability of blood
Describe an arterial thrombus
White; mainly platelets in a fibrin mesh
Forms an embolus
ANTIPLATELET THERAPY
Describe a venous thrombus?
White head, jelly like red tail, fibrin rich
ANTICOAG THERAPY
