Haemostasis Flashcards
Define haemostasis
Stopping of bleeding
Define thrombosis
Formation of solid mass of blood with circulatory system
What does the haemostatic system consist of
Many proteins which interact with platelets and blood vessel endothelial cells
What are the 5 stages of the haemostatic mechanism
Vascular phase (vasoconstriction)
Platelet plug formation
Clot formation
Clot retraction
Fibrinolysis
What happens in the vascular phase
Constrictor to limit blood loss and slow flow
Vascular smooth muscle contracts when vessels are damaged
First response
What are platelets attracted to
Exposed extracellular matrix at the damaged site
What do platelets adhere to
Vessel wall and each other
What do activated platelets release
Thromboxane A2 and thrombin
How do platelets work
Adhere to connective tissue via platelet receptor that recognises glycoproteins on connective tissue
Assisted by von willebrand factor which binds collagen
ADP, thromboxane A2 and thrombin are released recruiting more platelets
What is fibrinolysis
Dissolving clot after bleeding has stopped
What is the clotting cascade
A series of reactions where inactive proteins are converted into active proteins
What are the 2 clotting cascade pathways
Intrinsic and extrinsic
What is the intrinsic pathway
Required factors are in blood
Activated by blood exposure to sub endothelial surfaces
Negatively charged surfaces exposed by endothelial damage
Prekallikrein converted to kallikrein setting off a cascade of protease reactions
What is the extrinsic pathway
Initiating factor outside the blood
Activated by tissue factor released after cellular injury and binds to factor VII
TF is a protein found on sub endothelial cells
Cascade starts as thrombin activates factor VII
What forms the clot in the clotting cascade
Fibrin polymers
What does warfarin do the the clotting cascade
It is a competitive antagonist of vitamin K inhibiting the synthesis of vitamin K dependent clotting factors (II, VII, IX and X)
Increasing warfarin increases slow clotting therefore low vitamin K leads to reduced production of some clotting factors
What does a lack of factor VIII lead to
Failure of intrinsic pathway
What are 4 symptoms of haemophilia A
Frequent, severe bleeding
Bleeding into joints
Intracranial bleeding
Prolonged aPTT in screening, confirmed with factor VIII assay
What are treatment options there for haemophilia A
Replacement factor VIII
But the body can generate antibodies to this after time
Ideal would be gene therapy
What is haemophilia B
Much rarer than A
X linked recessive
Defect in gene for factor IX
Intrinsic pathway compromised and similar manifestations as A, treatment is the replace factor IX
What is von willebrands disease
Most common hereditary blood clotting disorder
Autosomal dominant
Lack of vWF so compromised platelet adhesion
Excessive brushing and bleeding gums
What is the blood flow risk factors of thrombosis
Stagnation
Long surgery, long periods of inactivity
What is the endothelial or vessel wall injury risk factors of thrombosis
Vessel damage
Hypertension
Foreign bodies from injury or implant, bacteria
Inflammation
What is the coagulation risk factors of thrombosis
Post operative
Postpartum
Deficiency of various anticoagulation factors - hypercoagulability
Cigarette smoking, oral contraceptives
What does aspirin do to the blood
Prevents platelet plug formation by inhibiting COX enzymes which make thromboxane A2
