Haemostasis Flashcards
What are the 3 key components to haemostasis?
- platelets
- VWF
- clotting proteins
Define haemostasis
Bleeding through a lesion/defect in the vascular wall
What is primary haemostasis?
- platelets adhere to the margins of the lesion
- platelets aggregate forming a primary platelet plug
What are the properties of platelets?
- non-nucleated
- derived from bone marrow megakaryocytes
- 1 to 4 micrometer diameter
What is the normal volume of platelets in blood?
140 to 400-450 x 10^9 L
What is the lifespan of platelets?
8-14 days
Then removed from circulation by reticuloendothelial system
What are the features of the platelet cell membrane?
- glycoproteins
- phospholipids
What is the role of glycoproteins in the platelet cell membrane?
- receptors for agonists, adhesive proteins, coagulation factors, other platelets
What are the most abundant glycoproteins in the platelet cell membrane?
- GpIIb/IIIa
- GPIb
What is the role of the phospholipids in the platelet cell membrane?
- prostaglandin synthesis
- calcium mobilisation
- localisation of coagulant activity to platelet surface
What organelles do platelets contain?
- dense osmophillic granules (nucleotides - ADP)
- alpha granules (series of different proteins)
What is the role of VWF?
- forms a bridge linking the exposed collagen and platelet
- also directly links 2 platelets
Serious inherited platelet disorder where you lack Gp1b?
Bernard Soulier Syndrome
Serious inherited platelet disorder where you lack GpIIb/IIIa?
Glanzmann’s
What is the treatment for Bernard Soulier and Glanzmann’s?
Platelets or novoseven
Steps of initial adhesion?
- vessel wall injury
- platelets contact with and adhere to collagen and subendothelial bound VWF via GpIb
- Gp IIb/IIIa exposed
- forms second binding site for VWF so fibrinogen can bind promoting platelet aggregation
Features of VWD
- autosomal inheritance
- deficient or defective VWF
- type 1 = mild to moderate deficiency
- type 2 = protein present but defective
- type 3 = total absent protein
- treat with DDAVP if mild
- also treat with tranexamic acid and VWF containing concentrate
What is TF?
- present on subendothelial tissue
- expressed by cells which are normally not exposed to flowing blood
- physical injury exposes TF to flowing blood
- necessary for coagulation initiation
- forms via factor VII
Steps of secondary haemostasis
- TF activates coagulation factors in blood at site of injury
- coagulation factors adhere to platelet surfaces and form catalytic complexes
- complexes cause formation of thrombin
- thrombin converts fibrinogen to fibrin
- fibrin polymers form long chains between platelets in the platelet plug, cross linked, form stable clot
Difference between haemophilia A and B
A = fVIII deficiency B = fix deficiency
Differences between severe, moderate and mild haemophillia
Severe < 1%
Moderate 2-5%
Mild 5-40%
(severe bleed spontaneously and potentially fatal)
Sites of severe haemophilia
Soft tissue Joints (knees, ankles, elbows) Psoas Intracranial Operative sites
Prophylaxis for severe haemophillia
- self administer factor concentrate
- moderate fVIII levels
Treatment for mild and moderate haemophilia
Mild A = DDAVP Factor concentrate (often can't self admin)
What is antithrombin?
- major inhibitor of thrombin and Xa
- also inhibits VII, IX, XI
- member of the SERine Protease INhibitor family
What is protein C?
- activated by thrombin
- activation increased with thrombomodulin
- inactivates Va and VIIIa
- is a serine protease
What is protein S?
- cofactor for activated protein C
Fibrinolytic Pathway
Plasminogen breaks down into plasmin by tPA, plasmin convers fibrin into fibrin degradation products which are soluble
