Haem: Thrombosis Aetiology and Management Flashcards
Why is thrombosis important?
- Prevalant cause of morbidity and mortality especially in hospital patients
- Significant sequelae (death is rapid)
- Preventable (thromboprophylaxis)
- May be an indicator of underlying disease (cancer)
What is an important risk factor for VTE?
Age - risk of VTE doubles every decade. There is a greater risk for PE than DVT.
What are 4 main consequences of thromboembolism?
- Death - mortality rate is 5%
- Recurrence - 20% in first 2 years and 4% pa thereafter
- Thrombophlebitic syndrome (recurrent pain, swelling and ulcers) - Severe TPS in 23% at 2 years
- Pulmonary hypertension - 4% at 2 years
What is thrombophlebitic syndrome characterized by?
Thrombophlebetic syndrome:
- Swelling
- Painful
- Eventual ulcers
What is a serious complication of thromboembolism?
Chronic thromboembolic pulmonary hypertension - extremely debilitating and often fatal disorder
What is Virchow’s triad?
There are three contributory factors to thrombosis:
Blood
Vessel wall
Blood flow
What determines the viscosity of blood?
Haematocrit - more RBCs and less plasma means more likely to thrombose
Protein/Paraprotein content - in the plasma this increases viscosity. This may be related to multiple myeloma.
What 3 factors of the blood may effect risk of thrombosis?
- Viscosity - haematocrit, protein/paraprotein
- Platelet count
- Coagulation system - triggered by tissue factor, generates thrombin, thrombin converts fibrinogen to fibrin
Draw out the extrinsic and common pathway of the coagulation cascade.
Give a list of procoagulant factors.
- V
- VIII
- XI
- IX
- X
- II
- Fibrinogen
- Platelets
Draw the coagulation cascade with the addition of regulators of coagulation.
- TFPI
- Protein C and S
- Antithrombin
These are the main regulators of coagulation
Give a list of anticoagulant factors.
- TFPI
- Protein C
- Protein S
- Thrombomodulin
- EPCR
- Antithrombin
- Fibrinolysis
Give examples of thrombophilic traits and their severity.
In order of severity:
- Protein S deficiency
- Protein C deficiency
- Antithrombin deficiency
- Factor V Leiden
Over 50-60 years, most people with protein C and S deficiency are getting thrombosis. Rate of thrombosis is about 1% per annum for these people.
What percent of thrombotic events are precipitated in people with thrombophilic traits?
50% of these thrombotic events are precipitated - partly attributed to the deficiency of an anticoagulant, but this is not the whole story. There will be other factors e.g. pregnancy, cancer, broken leg, surgery etc.
In what ways it the vessel wall normally antithrombotic?
- Expresses anticoagulant molecules
- Thrombomodulin
- Endothelial protein C receptor
- Tissue factor pathway inhibitor
- Heparans
- Does not express tissue factor
- Secretes antiplatelet factors
- Prostacyclin
- NO
What may cause the vessel wall to become prothrombotic?
Stimulus:
- Infection
- Malignancy
- Vasculitis
- Trauma
How does the vessel wall become prothrombotic?
- Anticoagulant molecules (eg TM) are down regulated
- Adhesion molecules upregulated
- TF may be expressed
- Prostacyclin production decreased
If you have a metastatic disease, what is the chance of thrombosis?
4% - this is much higher than the background rate in the population
How does stasis of blood flow promote thrombosis?
- Accumulation of activated factors
- Promotes platelet adhesion
- Promotes leukocyte adhesion and transmigration
- Hypoxia produces inflammatory effect on endothelium
What are causes of blood stasis?
- Immobility
- Surgery, Paraparesis, Travel
- Compression
- Tumour, pregnancy
- Viscosity
- Polycythaemia, Paraprotein
- Congenital
- Vascular abnormalities
Thrombotic risk factors often ______ to produce thrombosis. Thrombotic factors may have power _____ that are unpredictable.
Thrombotic risk factors often combine to produce thrombosis. Thrombotic factors may have powerful interactions that are unpredictable.
Describe the combining mechanisms that increase risk of thrombosis in:
- Pregnancy
- Malignancy
- Surgery
- Pregnancy:
- increases VIII, Fibrinogen
- decreases Protein S
- reduces flow
- Malignancy:
- increases TF expression on tumour cells
- Inflammation
- Obstructs blood flow
- Surgery:
- Trauma
- Inflammation
- Reduced flow
What are the 2 main uses of anticoagulation therapy?
- Therapeutic dose (high dose) - used on the wards for people who have had thrombosis. The whole coagulation system is very active so needs to stop.
- Prophylactic (low dose) - when anticipating entering a risky period or if somebody is a high-risk patient and entering a high risk circumstance we give a low dose as prophylaxis.