Thrombotic disorders Flashcards
What are the 3 main elements of haemostasis?
Primary haemostasis
Blood coagulation
Fibrinolysis
Primary haemostasis is triggered by tissue damage and involves what processes?
Vasoconstriction (mediated mainly by NO?)
Platelet adhesion
Platelet aggregation
Basically - involves diverting blood flow elsewhere through vasoconstriction and plugging the exposed collagen bit with platelets
Coagulation occurs following primary haemostasis and involves which processes>
Insoluble fibrin formation
Fibrin cross-linking
Fibrinolysis occurs when plasminogen in converted to plasmin by the actions of what molecules?
Factors XIa and XIIa
Tissue plasminogen activator (t-PA)
Urokinase plasminogen activator (u-PA)
What is Virchow’s triad?
Stasis
Hypercoagulability
Vessel damage
If one or more of these occurs then it leads to the formation of a thrombus - an unwanted thrombosis
Considering virchows triad - what might cause each of these thingies to occur?
Stasis = bed rest, travel
Vessel damage = atherosclerosis
Hypercoagulability = pregnancy, trauma and lots of others
What are the 3 main types of thrombosis?
Arterial
Venous
Microvascular
What are the features of an arterial thrombus?
Arterial thrombi are called ‘white clots’
Clot is made up of Platelets and fibrin
They tend to be secondary to atheroscleroses and cause ischaemia and infarction downstream
Give examples of arterial thrombotic disease
Coronary thrombosis:
- MI
- unstable angina
Cerebrovascular thromboembolism:
- Stroke
- TIA
Peripheral embolisms:
- acute limb ischaemia
What are risk factors for arterial thromboembolic disease
Age
Smoking
Sedentary lifestyle
Hypertension
Diabetes mellitus
Obesity
Hypercholesterolaemia
Describe the management for arterial thromboembolic disease
Primary prevention:
- modify lifestyle factors
- treatment of vascular risk factors eg atheros
Acute presentation:
- thrombolysis
- antiplatelets/anticoagulant therapy
Secondary prevention
What are the features of a venous thrombus?
‘Red thrombus’
Made up of fibrin and red cells
Results in clogging up and increasing pressure upstream
Principally due to stasis and hypercoagulability
What are the main types of venous thromboembolic disease
Limb deep vein thrombosis
Pulmonary embolism
visceral venous thrombosis
intracranial venous thrombosis
superficial thrombophlebitis
Venous thrombus formation generally occurs due to stasis and hypercoagulability
What are the risk factors for venous thrombus formation?
Increasing age, Immobility
Pregnancy
Surgery or trauma
Obesity
Family history
Systemic disease
Hormonal therapy - COCP, HRT
What systemic diseases are risk factors for venous thrombosis?
Cancer
Myeloproliferative Neoplasm (MPNs)
Autoimmune disease:
- Inflammatory bowel disease
- Connective tissue disease e.g SLE
- Antiphospholipid syndrome: arterial and venous thrombosis
How is a diagnosis of venous thrombosis and VTE made?
Pretest probability scoring (Geneva or Wells score) followed by either:
1) Lab testing - if probability score low
2) Imaging - if high
What modalities of imaging are used for diagnosing VT and VTE?
Suspected Upper and lower limb VT:
- Doppler US
Suspected pulmonary embolism:
- CT pulmonary angiogram (CTPA) - gold standard
- V/Q scan
What are the aims of management for Venous thrombosis?
Prevent clot extension (growing)
Prevent embolisation
Prevent recurrence in long term management
What drugs are used to treat venous thromboembolism?
Anticoagulants - to prevent extension of clot:
- DOACs - apixaban/rivaroxaban
- LMWH - dalteparin
- warfarin
For massive PE - thrombolysis eg Streptokinase, alteplase etc
Heritable thrombophilia conditions predispose individuals to VT and VTE
What are the heritable thrombophilias?
Factor V Leiden
Prothrombin G20210A
Antithrombin deficiency
Protein S deficiency
Protein C deficiency
Describe how Factor V leiden predisposes an individual to VT
Protein C and Protein S normally inhibit Factor IIIa which blocks the coagulation cascade (when we dont need it)
Factor V Leiden gene mutation means that there is Protein C resistance so its inhibition is far less effective and coagulation happens more readily
Under what circumstances is thrombophilia screened for?
Screening is limited to high risk heritiable thrombophilia - such as antithrombin deficiency
What are the main features of microvascular thrombi?
Made up of platelets and/or fibrin
Reults in diffuse ischaemia
Principally occurs in DIC
What is DIC?
What can precipitate DIC?
Disseminated intravascular coagulation
basically clots form absolutely everywhere - its really not good
Can be caused by:
- septicaemia (esp Meningitis)
- malignancy
- eclampsia
