Week 3 - Haemostasis and Thrombosis Flashcards
(28 cards)
What is Haemostasis?
involves the prevention and cessation of bleeding from blood vessels by formation of blood clots
Haemostatic interventions are effective for small vessels but not so much for large vessels
How does Endothelium relate to blood?
- it contains and secretes anti-coagulant proteins (thrombmodulin and prostacyclin) -> maintains blood in fluid phase
- also prevents contact between blood components and subendothelium
How does Subendothelium relate to blood?
- it contains collagen and von Willebrand factor, ligands for platelet surface receptors -> platelet adhesion and activation
Features of Coagulation
- has to pass a certain threshold of injury
- restricted to the site of the injury
- limited only until injury is healed
What are the Mechanisms of Haemostasis?
- Vascular spasm -> constriction of blood vessel
- Exposure of subendothelium -> activation of platelets
- Platelet aggregation -> platelet plug formation
- Activation of blood protein coagulation cascade -> fibrin clot formed
- Dissolution of clot
What type of cells does Haemostasis occur at?
- platelet
- endothelial surface
- monocytes
What are the pathways to make a fibrin clot?
Intrinsic and Extrinsic pathway
Describe the cell-based model of Coagulation? (3 steps)
Initiation Step in a Tissue Factor Bearing Cell:
- cell exposed to tissue factor 7 -> becomes 7a
- 10 -> becomes 10a
- 10a and 5a converts prothrombin to thrombin
- 9 -> also becomes 9a
Priming Step in Platelet and Activated Platelet:
- Thrombin activates platelet
- Platelets secrete and convert 5 to 5a
- 8 -> becomes 8a
- factor 8a and 5a go to activated platelet
Propagation Step in Activated Platelet:
- 9a comes across
- lot more 10 to 10a
- lot more prothrombin to thrombin
What is the role of Thrombin in Haemostasis?
- Turns fibrinogen to fibrin
- Activates platelets via PARs
- Activates 11a and intrinsic cascade
How can fibrin form a fibrin clot
- needs to be activated and cross-linked with factor 13a
- cross-linked clot has exposed lysine residues -> t-PA & plasminogen attaches to the lysine residues
- plasminogen forms plasmin by t-PA -> plasmin dissolves the clot
How is Patient History important regarding bleeding?
- is bleeding fully unexpected?
- Any haemostatic defects?
- On any medications? (antiplatelet? anticoagulents?)
Platelet (Purpuric) and Coagulation Disorders summarised
What are some common bleeding disorders?
Hereditary:
- Haemophilia
- Von Willebrand Disease
- Factor deficiency
- Platelet Disorders (platelet receptors not functioning normally)
Acquired:
- Liver disease
- Vit K deficiency
- DIC
- Excessive anticoagulation
- ITP
What is Von Willebrand disease?
= Heterogenous hemorrhagic disorder caused by deficiency or dysfunction of von Willebrand factor
- can be inherited or acquired
What are the functions of von Willebrand protein?
- vWF mediates platelet adhesion at site of injury
- stabilises FVIII in circulation
- brings fVII (factor 8) to site of injury
What is likely to happen at high and low levels of von Willebrand protein?
What is the treatment of von Willebrand disease?
Desmopressin:
- releases fVIII & vWFAg from storage sites
Replacement Therapy:
- fVIII and cWFAg
Antifibrinolytic - Tranexamic acid
Fibrin glue
What is Haemophilia A? what are clinical manifestations?
= deficiency in factor VIII
Clinical manifestations:
- Hemarthrosis
- Subcutaneous and intramuscular haemotomas
- Psoas and retroperitoneal haematomas
- Traumatic bleeding
What are treatments for Haemophilia A?
- Purified or Recombinant factor VIII therapy
- Tranexamic acid
- Topical thrombin
- Role of FFP
What are dosing guidelines for Haemophilia A?
What are platelet disorders?
= disorders of either number or function of platelets
What is Thrombocytopenia?
Increased destruction or decreased production of thrombocytes
What do you do when there’s platelet dysfunction?
Stop Antiplatelet agents before surgery
- use aspirin
- NSAID
- Clopidgrel
What is Tranexamic acid?
- anti-fibrinolysis
