Thrombotic disorders Flashcards
What are the 3 elements of haemostasis?
- Primary haemostasis - Formation of primary platelet plug through primary haemostasis mechanisms
- Blood coagulation - coagulation factor activation leads to fibrin clot deposition. Fibrin cross-linking occurs to form a stable clot. This subsequently triggers the fibrinolytic pathways
- Fibrinolysis - clot degradation
What 3 things happen in the primary haemostasis stage?
- Vasoconstriction - Primary haemostasis is triggered by tissue damage which leads to vasoconstriction at the site of endothelial insult.
- Platelet adhesion - damage to the endothelial lining results in exposure of subendothelial collagen. Platelets bind do this.
- Platelet aggregation - platelets clump together
What happens in Fibrinolysis?
Fibrin is broken down into fibrinogen and fibrin degradation products
- Which enzyme is responsible for breaking down the fibrin network?
- What is the name of the inactive precursor of that enzyme?
- Plasmin
- Plasminogen
What 4 things activate Plasminogen converting it into plasmin?
- Urokinase
- Activation factors:
- FXIIa
- FXIa
- Tissue plamsinogen activator - tPA
Virchow’s triad
- Stasis - bed rest or travel
- Hypercoagulability - pregnancy or trauma
- Vessel wall damage - atherosclerosis
What are the 3 main types of thrombosis?
- Arterial
- Venous
- Microvascular
Examples of arterial thromboembolism
- Coronary thrombosis:
- Myocardial Infarction
- Unstable angina
- Cerebrovascular thromboembolism:
- Stroke
- Transient ischaemia
- Peripheral embolism
- Acute limb ischaemia
Look
Arterial thrombus - platelets and fibrin
Venous thrombus - red cells and fibrin
Risk factors for venous thrombosis
- Age
- Pregnancy
- Surgery
- Obesity
- Systemic disease - cancer, autoimmune disease like IBD or SLE
- Hormonal therapy - combined pill and hormone therapy
- Tissue trauma
- Immonility
- FH
What risk scoring tools are there for DVT? (2)
Wells score
Geneva score
If you have a low probability score which further lab test would you do to completely rule out a serious DVT/clot?
D-dimer - levels will be high if you have serious DVT - d-dimer is a fibrin degradation product which present in the blood after fibrinolysis.
Which imaging is used to look for DVT?
DVT:
- Doppler ultrasound scan - for upper and lower limb veins
- Contrast venography, CT, MRA
PE:
- CT pulmonary angiogram - ‘gold standard’ for PE
- Ventilation perfusion scan (V/Q lung) - mainly used for suspected PE
Aims of management with venous thrombosis
Prevention!!
- Prevent inital clot from propagating
- Prevent clot embolisation
- Prevent clot recurrence in the long term - in high risk patients
Treatment of venothromboembolism
Anticoagulants - act on the coagulation cascade before fibrin generation so prevent inital clot from extending but do not break down the clot:
- LMWH
- Coumarins (Warfarin)
- DOACs - direct oral anti-coagulants
Thrombolysis only in selected cases - these work in the fibrinolytic pathways - used for massive PE
What are some hereditary thrombophilias? (group of conditions where you have an imbalance in naturally occurring blood-clotting proteins, or clotting factors)
Common:
- Factor V Leiden mutation
- Prothrombin G20210A mutation
Rare
- Antithrombin deficiency
- Protein C and S deficiency
Describe the physiology behind the Factor V Leiden mutation seen in hereditary thrombophilia
- In the presence of thrombin, protein C is activated and this is promoted by thrombomodulin.
- Protein C is a natural anti-coagulant
- So in a person without the Factor V Leiden mutation, activation of protein c subsequently inhibits factor 5 and prevents the thrombin formation.
- With the factor V Leiden mutation the actions of activated protein C are blocked and so there is no inhibiting factor on factor 5. Because of this you have an ongoing drive to thrombin generation and fibrin clot formation.
What are protein c, protein s and anti-thrombin?
Naturally occuring anti-coagulants
Microvascular thrombus
- Platelets and/or fibrin involved
- Results in diffuse ischaemia
- Principally in Disseminated Intravascular Coagulation [DIC] - unwell patients
What is disseminated intravascular coagulation?
Diffuse systemic coagulation activation
Seen in very unwell patients such as:
- Sepsis
- Malignancy
- Eclampsia
It causes tissue ischaemia so you can get gangrene and multi-organ failure
- Whilst you are forming your clots there is consumption of platelets and clotting factors which leads to thrombocytopaenia
- Activation of coagulation leading to microvascular thrombosis deposition
- Present with haemorrhagic phenotype and thrombotic phenotype at the same time
