Haemostasis and Coagulation Flashcards
Thrombosis
Disorder of clotting
Formation of unwanted clots
Causation : venous - clots form in veins due to stasis of blood, Amy travel to lungs to give pulmonary embolism
atrial fibrillation: risk of Transient Ischaemic Attack or stroke
Pathways of clotting mechanisms
Intrinsic
Extrinsic
Intrinsic pathway
exposed collagen from injured blood vessel wall, test tube
Extrinsic pathway
damaged tissue releases thromboplastin
Clotting cascade
Thromboplastin and clotting factors cause inactive factor X to become active
This causes prothrombin to become thrombin
Which chops fibrinogen to form fibrin
Fibrin becomes stable due to factor XIII
Forms scaffold and clot
Atrial fibrillation
Tachycardia
Arrhythmia
SA node not pacemaker, but many sites on atria
Leads to uncoordinated contraction of atria
Heart looks like it’s wriggling
What is AF a risk factor for?
Cardioembolic stroke/TIA if clots form in left side
What is fibrinogen a risk factor for?
Cardiovascular disease
What are platelets
Non-nuclear cellular fragments
Form mechanical plugs during damage to blood vessels
Steps of platelet action
- Adhesion
- Aggregation
- Platelet mass
Adhesion
Platelets adhere to sub-endothelial surface on damage/disease due to binding to Von Willebrand’s factor
Adhesion causes release reaction
Aggregation
Release reaction : activated platelets release ADP and thromboxane
Promoting platelet aggregation
Platelets activated by ADP and release glycoprotein IIb-IIIa
This crosslinks platelets with fibrinogen and vWF, therefore sticks and scaffold
Platelet mass
to plug area of endothelial damage
promotes coagulation reaction: -vely charged phospholipids on activated platelets which have adhered to site of damage localize fibrin formation
Lab tests
Bleeding time
Prothrombin time
Activated partial thromboplastin time
Bleeding time
Incision in forearm with venous cuff
Time taken for bleeding to stop
Increased in platelet dysfunction/thrombocytopenia
Prothrombin time
International normalised ratio (INR)
Time for coagulation following addition of thromboplastin
Prolonged due to liver disease or warfarin
Arterial thrombosis
Platelet aggregation at atherosclerotic sites, leading to arterial blockage
Heart attack and stroke
Blood doesn’t perfuse down stream leading to myocardial infarction
Is venous/arterial thrombosis more of a coagulation/platelet event
Venous - coagulation (DVT)
Arterial - platelet (MIs and ischaemic strokes)
Haemophilia A
Genetic - defect on X chromosome, males affected, females carries
Low/lack factor VIII
Haemorrhage and prolonged bleeding when there is slight tissue trauma
How to treat haemophilia a
- Factor VIII from blood donors or analogue of vasopressin (ADH)
- Emicizumab - monoclonal antibody, monthly subcutaneous injections
Bispecific, binds to activated factor IX and X
Haemophilia b
Christmas disease
Christmas factor (coagulating) affected
Deficiency of factor IX
How to treat haemophilia b?
Prophylactic factor IX
Von willebrand’s disease
Hereditary lack/defect in vWF
increased bruising, nose bleeds, mucosal bleeding
How to treat Von Willebrand’s disease?
Analogue of ADH , factor VIII or vWF
Liver disease
Reduced synthesis of clotting factors
Leads to increased bleeding (increased prothrombin time)
Thrombocytopenia
Reduced platelet number
Spontaneous skin bleeding
Causes: idiopathic, viral, drug-induced, toxins
Drug-induced thrombocytopenia
Immune mechanisms
Eg. Cytotoxic anti cancer drugs may induce due to bone marrow depression
How to treat drug-induced thrombocytopenia
- Stop drug
- Treat with steroids, suppress immune response
- Remove spleen
DIC
Disseminated Intravascular Coagulation
What is DIC
Large amounts of fibrin generated by procoagulant material like amniotic fluid
Vast consumption of clotting factors and platelets therefore none left
Widespread haemorrhage and may also be thrombosis
How to treat DIC
Give platelets and fresh frozen plasma
What is factor V Leiden mutation?
Abnormal factor V
Single nucleotide polymorphism (protein has single different AA)
therefore less susceptible to deactivation
What does factor v Leiden mutation cause?
Increases risk of venous thrombosis
