Thrombotic Disorders Flashcards
What are the 3 components of haemostasis?
- Primary haemostasis
- Blood coagulation
- Fibrinolysis
What is primary haemostasis triggered by?
Triggered by tissue damage causing:
- Vasoconstriction
- Platelet adhesion
- Platelet aggregation
In primary haemostasis, what does tissue damage cause?
- Vasoconstriction
- Platelet adhesion
- Platelet aggregation
What does the coagulation cascade result in?
- Insoluble fibrin formation
- Fibrin cross-linking
What is fibrinolysis?
Plasminogen is converted into plasmin:
- Converted by activation factors XI and XII
What activation factors are required to convert plasminogen into plasmin?
- Converted by activation factors XI and XII
What is plasmin?
This is an enzyme that then converts fibrin into fibrinogen/fibrin degradation products
What is a thrombus?
What is thromboembolism?
Thromboembolism = “movement of clot along a vessel”
Describe the aetiology of thrombosus?
- Virchow’s triad components
- Stasis
- Bed rest
- Travel
- Vessel damage
- Atherosclerosis
- Hypercoagulability
- Pregnancy
- Trauma
- Stasis
What are the 3 components of Virchow’s triad?
Stasis
Vessel damage
Hypercoagulability
What does an arterial thrombus consist of?
- Platelets and fibrin
What are the 3 different kinds of thrombosis?
Describe the aetiology of arterial thrombosis?
- Principally secondary to atherosclerosis
Describe the risk factors for arterial thrombosis?
- Age
- Smoking
- Sedentary lifestyle
- Hypertension
- Diabetes
- Obesity
- Hypercholesterolaemia
What are possible complications of arterial thrombosis?
- Ischaemia and infarction
What are some examples of arterial thrombus disease?
- Coronary thrombosis
- Myocardial infarction
- Unstable angina
- Cerebrovascular thromboembolism
- Stroke
- TIA
- Peripheral embolism
- Acute limb ischamia
Describe the management of arterial thrombosis?
- Primary prevention
- Lifestyle modifications
- Treatment of vascular risk factors
- Acute presentation
- Thrombolysis
- Antiplatelet/anticoagulant drugs
- Secondary prevention
What is a venous thrombus composed of?
- Fibrin and red cells
Describe the aetiology of venous thrombosis?
- Principally due to stasis and hypercoagulability
What are the risk factors for venous thrombosis?
- Increasing age
- Pregnancy
- Hormonal therapy
- COCP/HRT
- Tissue trauma
- Immobility
- Surgery
- Obesity
- Systemic disease
- Cancer
- Myeloproliferative neoplasm (MPNs)
- Autoimmune disease
- Inflammatory bowel disease
- Connective tissue disease such as SLE
- Antiphospholipid syndrome
- Family history
- Heritable thrombophilia
What are examples of heritable thrombophilia?
Describe the pathophysiology of factor V Leiden?
- Normally
- Protein C activated in presence of thrombin
- With protein S, protein C inhibits activated factor VIII and V
- But with factor V mutation
- Action of protein C inhibiting factor V is blocked
- Ongoing drive towards thrombin and clot formation
Describe the pathophysiology of protein C or S deficiency?
- Factors Va and VIIIa not inhibited
Describe the pathophysiology of antithrombin deficiency?
- Thrombin generation continues and fibrin clot formation
Describe complications of venous thrombosus?
- Back pressure
What are some examples of venous thromboembolic disease?
- Limp deep vein thrombosis
- Pulmonary embolism
- Visceral venous thrombosis
- Intracranial venous thrombosis
- Superficial thrombophlebitis
Describe the diagnosis of venous thrombosis?
- Pretest probability scoring
- Wells score
- Geneva score
- Lab tests if pretest probability low
- D-dimer
- Imaging
- Doppler US – for upper and lower limbs
- Ventilation/perfusion scan – for lungs
- CT pulmonary angiogram – for heart and lungs
What probability scoring is used in venous thrombosis?
- Wells score
- Geneva score
What lab investigation can be done for thrombosis?
D-dimer
What imaging is useful for venous thrombosis?
- Doppler US – for upper and lower limbs
- Ventilation/perfusion scan – for lungs
- CT pulmonary angiogram – for heart and lungs
Describe the management of venous thrombosis?
- Aims
- Preventions of clot extension
- Prevent clot embolism
- Prevent clot recurrence in long term treatment
- Drugs
- Anticoagulants – do not break down clot but prevent from extending (workings in clotting cascade)
- LMWH
- Coumarins (warfarin)
- DOACs
- Thrombolysis – breaks down clot
- Anticoagulants – do not break down clot but prevent from extending (workings in clotting cascade)
What is a microvascular thrombus composed of?
- Platelets and/or fibrin
Describe the aetiology of microvascular thrombosis?
- Principally in Disseminated intravascular coagulation (DIC)
- Is diffuse systemic coagulation activation
- Occurs in
- Septicaemia
- Malignancy
- Eclampsia
- Causes tissue ischaemia
- Gangrene
- Organ failure
- Pathophysiology
- Whilst forming clots, consumption of platelets and clotting factors leading to bleeding
- Activation of coagulation leading to microvascular thrombosis deposition
What is a complication of microvascular thrombosis?
Diffuse ischaemia
What does DIC stand for?
Disseminated intravascular coagulation
What conditions does DIC occur in?
- Septicaemia
- Malignancy
- Eclampsia
Describe the pathophysiology of DIC?
- Causes tissue ischaemia
- Gangrene
- Organ failure
- Pathophysiology
- Whilst forming clots, consumption of platelets and clotting factors leading to bleeding
- Activation of coagulation leading to microvascular thrombosis deposition
