Thrombotic Disorders Flashcards
What are the elements of haemostasis?
Primary haemostasis
Blood coagulation
Fibrinolysis
What is involved in primary haemostasis?
Tissue damage leading to vasoconstriction
Exposure to sub-endothelial collagen - platelet adhesion
Platelet aggregation
What is involved in coagulation?
Insoluble fibrin formation
Fibrin cross-linking to form a stable clot
How is plasmin formed in fibrinolysis?
By the activation of plasminogen - activated factors 12 + 11, urokinase and TPA
What is the role of plasmin in fibrinolysis?
Breaks down fibrin to fibrinogen + fibrin degradation products
What is a thromboembolism?
Movement of a clot along a vessel
What is included in Virchow’s triad?
Stasis (bed rest + travel), hypercoagulability (pregnancy + trauma) and vessel damage (atherosclerosis)
Describe an arterial thrombus
Results in ischaemia and infarction
Principally secondary to atherosclerosis
Consists of platelets and fibrin - ‘white clot’
What are some examples of arterial thromoembolism?
Coronary thrombosis - MI and unstable angina
cerebrovascular thromboembolism - stroke and transient ischaemia
Peripheral embolism - acute limb ischaemia
What are some of the risk factors of arterial thromboembolism?
Age, smoking, sedentary lifestyle, HTN, diabetes, obesity, FH and hypercholesterolaemia
What is the management for arterial thromboembolism?
Primary prevention - lifestyle modification and treatment of risk factors
Acute presentation - thrombolysis and antiplatelet/ anticoagulant drugs
Secondary prevention
Describe a venous thrombus
Fibrin and red cells - ‘red thrombus’
Results in back pressure
Principally due to stasis and hypercoagulability
What are some examples of venous thromboembolism?
Limb DVT, PE, visceral venous thrombosis, intracranial venous thrombosis and superficial thrombophlebitis
What are the risk factors for venous thromboembolism - stasis/ hypercoagulability?
Increasing age, surgery, pregnancy, obesity, hormonal therapy, systemic disease, tissue trauma, FH and immobility
What systemic disease can cause venous thrombosis?
Cancer
Myeloproliferative neoplasm (MPNs)
Autoimmune disease - IBD, SLE and antiphospholipid syndrome
How is venous thrombosis diagnosed?
Pre-test probability screening - Wells score and Geneva score
Lab testing - D-dimer
Imaging
Doppler US, V/Q scan and CT pulmonary angiogram
What is the aim of treatment in venous thrombosis?
Prevent clot extension, clot embolization and clot recurrence in long term treatment
What is the management for venous thrombosis?
Anticoagulants - LWMH, warfarin and DOACs
Thrombolysis in selected cases - massive PE
What are heritable thrombophilia?
Heritable conditions which increase the individual’s risk of venous thromboembolic events
What are some heritable thrombophilia conditions?
Common - factor V Leiden and prothrombin G20210A
Rare - antithrombin deficiency, protein C deficiency and protein S deficiency
What is the role of protein C and protein S in coagulation?
Activated protein C and S inhibit activated factor 8 and 5
If factor 5 Leiden mutation then actions of activated protein C inhibiting factor 5 are blocked - ongoing drive for thrombin formation
Describe microvascular thrombus
Platelets and/or fibrin
Results in diffuse ischaemia
Principally in disseminated intravascular coagulation
Describe DIC
Diffuse systemic coagulation activation
Causes tissue ischaemia - gangrene and organ failure
Consumption of platelets and clotting factors leading to bleeding
Activation of coagulation leads to microvascular thrombosis
What does DIC occur in?
Septicaemia, malignancy and eclampsia
