Haemostasis and Thrombosis Flashcards
What are the components of Virchow’s Triad?
Blood - viscosity
Vessel wall
Blood flow
What are the consequences of thromboembolism?
Death
Recurrence
Thrombophlebitic syndrome
Pulmonary hypertension
What is thrombophlebitic syndrome?
Recurrent pain, swelling and ulcers
What blood properties are relevant in thrombosis?
Viscosity (haematocrit, protein/paraprotein)
Platelet count
Coagulation system
What coagulation factors are regulated by TFPI (tissue factor pathway inhibitor)?
TF/FVIIa actions
What coagulation factors are regulated by Protein C & S?
FXa and FVIIIa
What coagulation factors are regulated by antithrombin?
FXa and Thrombin
What is the role of coagulation regulation proteins?
To regulate the system and stop you making blood clots too easily/inappropriately
What are the procoagulant factors?
V VIII XI IX X II Fibrinogen Platelets
What are the anticoagulant factors?
TFPI Protein C Protein S Thrombomodulin EPCR Antithrombin Fibrinolysis
What is thrombophilia?
A disturbed balance of haemostasis where coagulation occurs more easily
What is Factor V Leiden?
Mutated form of factor V that lacks cleavage site for deactivation by proteins C and S (i.e. increases coagulability)
What is the normal state of the vessel wall?
Antithrombotic
What anticoagulant molecules are expressed by the vessel wall?
Thrombomodulin
Endothelial protein C receptor
Tissue factor pathway inhibitor
Heparans
What antiplatelet factors are secreted by the vessel wall?
Prostacyclin
NO
What is the role of collagen tissue factor?
Triggers coagulation
What stimuli make the vessel wall prothrombotic?
Infection
Malignancy
Vasculitis
Trauma
What happens when vessel wall becomes prothrombotic?
Anticoagulant molecules downregulated TF may be expressed Prostacyclin production decreased Adhesion molecules upregulated Von Willebrand factor release
What do neutrophils do under inflammatory stimuli?
NETosis: release contents of their nucleus
How does blood stasis promote thrombosis?
Accumulation of activated factors
Promotes platelet adhesion
Promotes leukocyte adhesion and transmigration
Hypoxia produces inflammatory effect on endothelium
What are some common causes of stasis?
Immobility
Compression
Viscosity
Congenital
What anticoagulant drugs have immediate action?
Heparin
Direct acting anti-Xa and anti-IIa
What anticoagulant drugs have delayed action?
Vitamin K antagonists e.g. Warfarin
What clotting factors are affected by Warfarin?
II, VII, IX, X
Also protein C and S
How is unfractionated heparin administered?
IV infusion, monitored
How are low molecular weight heparin and pentasaccharide administered?
Subcutaneously, no monitoring
How do heparins work?
Potentiating antithrombin
What are the long term disadvantages of heparins?
Injections
Risk of osteoporosis
Variable renal dependence
Give some examples of anti-Xa direct acting anticoagulants
Rivaroxaban
Apixaban
Edoxaban
Give an example of anti-IIa direct acting anticoagulant
Dabigatran
What are some properties of direct acting anticoagulants?
Oral administration Immediate acting (peak in approx 3-4 hrs) Also useful in long term Short-half life No monitoring
How does warfain work?
Indirect effect by preventing recycling of Vit K
How is warfarin monitored?
INR (international normalised ratio)
Derived from prothrombin time
What interactions occur with warfarin?
Dietary vitamin K
Variable absorption
Interactions with other drugs
Teratogenic
Give examples of mechanical thromboprophylaxis
TED stockings
Intermittent pneumatic compression
What are the patient risk factors for VTE?
Age >60yrs Previous VTE Active cancer Acute or chronic lung disease Chronic heart failure Lower limb paralysis (excluding acute CVA) Acute infection BMI >30
What are the procedure risk factors for VTE?
Hip or knee replacement Hip fracture Other major orthopaedic surgery Surgery >30 mins Plaster cast immobilisation of lower limb
What are the patient risk factors for bleeding?
Bleeding diathesis Platelets <100 Acute CVA in previous month BP >200 systo or 120 dias Severe liver disease Severe renal disease Active bleeding Anticoag or anti-platelet therapy
What are the procedure risk factors for bleeding?
Neuro, spinal or eye surgery
Other with high bleeding risk
Lumbar puncture/spinal/epidural in previous 4 hours
What are the symptoms of thrombophlebitic syndrome?
Recurrent pain
Swelling
Ulcers
What are the possible consequences of thromboembolism?
Death
Recurrence
Thrombophlebitic syndrome
Pulmonary hypertension
What is haemostasis?
Process by which bleeding from an injured vessel is arrested or reduced
What regulates TF and FVIIa?
TFPI
What regulates FVIIIa and FVa
Protein C&S
What regulated FXa and Thrombin?
Antithrombin
