Thrombosis
The process leading to thrombus formation
Thrombus’ main constituents
Platelets and fibrin
When can thrombosis be physiological
To prevent bleeding when a vessel wall is breached
What process limits physiological thrombosis and how relate to pathological thrombosis
Fibrinolysis
Thrombosis becomes pathological when it is not controlled by fibrinolysis
What holds a thrombus together
Fibrin
Describe the process of physiological thrombosis
Vessel wall is breached and so circulating platelets aggregate to plug the gap
Platelets release factors which trigger coagulation cascade which converts fibrinogen into insoluble fibrin that wraps together platelets and entrapped RBCs and WBCs
Plasmin
Active enzyme that fragments/degrades fibrin and thus blood clots
Fibrin degradation products (FDPs)
Fragmented bits of fibrin after degradation
Describe the process of normal finrinolysis
Inactive plasminogen in plasma becomes plasmin via plasminogen activators (specifically tissue plasminogen activator t-PA)
When fibrin is formed, plasminogen and t-PA bind to it; t-PA activates nearby plasminogen, leading to fibrin degradation
This controls thrombus size
How might pathological thrombosis occur (simple)
Thrombus grows beyond vessel healing requirements and continues to grow to a size and rate beyond which the fibrolytic system is incapable of controlling the size
D-Dimers and D-Dimer test
D-Dimers are a breakdown product of fibrin mesh, stabilised by factor XIII;
Increased levels may indicate thrombotic events
Factors that predispose thrombus formation (Virchow’s Triad)
Damage to vessel wall (especially endothelium)
Stasis of blood
Change in blood character (especially increases in platelets, RBCs and viscosity)
How is arterial thrombosis most likely to occur
Main predisposing factor is vessel wall damage
How is venous thrombosis most likely to occur
Stasis is the most important factor
How is thrombosis of the heart most likely to occur in the ventricles
Chamber wall damage is the most important factor here
How is thrombosis of the heart most likely to occur in the atria
Stasis of blood is the most important factor
**THINK ATRIAL FIBRILATION
How is thrombosis of the heart valves most likely to occur
Valve surface damage is the most important factor
What may happen to a thrombus in pathological thrombosis
It may be lysed via fibrinolysis (rare)
Occlude the lumen
Extending locally
May undergo organisation & recanalisation
Fragment and detach completely, traveling elsewhere and becoming a thrombo-embolism
What does thrombotic occlusion cause in an artery
This cuts off blood flow and can cause an infarction
What does thrombotic occlusion cause in a vein
It prevents venous drainage of tissues, blood pools that cannot escape –> congestion and often haemorrhagic infarctions
Recanalisation
Re-establishment of blood flow into a formerly occluded region
Organisation & Recanalisation of Thrombus
New vessels grow into the thrombus, vascular granulation tissue develops
Fibroblasts invade and deposit collagen and so fibrovascular granulation tissue develops
This is an organised thrombus; when vessels link up, some degree of recanalisation may occur
Granulation tissue
New connective tissue and microscopic blood vessels that form on the surfaces of a wound during the healing process
Embolism
Transference of abnormal material by blood stream with eventual impaction of material in a vessel distal to origin
Most notable embolised materials
Thrombuses and cancer cells (metastasis)
Thromboembolism
A thrombus breaks off and passes into blood stream to a distal site where they impact and occlude a distal vessel
What would a thromboembolism of lower limb arteries cause
Gangrene of legs
think ischaemia
What might a thrombus in a systemic vein cause
This is likely to embolise to a pulmonary artery branch and cause a pulmonary embolus (economy class syndrome)
Venous Thromboembolism Risk Assessments
Be vaguely aware
Some important risk factors of VTE
Active cancer/cancer treatment Age ?60 Dehydration Obesity Significant medical comorbidities (e.g. heart disease) Personal/Close family history HRT Contraceptives Pregnancy/Post partum
Other materials that can cause embolism
Fat/Marrow
Air
Nitrogen (Decompression sickness)
Amniotic Fluid
