41.2 Thrombosis Flashcards
What is thrombosis?
“Haemostasis in the wrong place”
What is a thrombus?
A blood clot that forms in situ within a blood vessel that impedes blood flow.
Compare how arterial and venous thrombi form.
Arterial thrombosis occurs as a result of platelet activation through endothelial damage and abnormal blood flow (atherosclerosis)
Venous thrombosis occurs as a result of stasis and hypercoagulability resulting in blood clot formation NOT platelet activation
What is Virchow’s triad?
3 main factors that promote thrombosis:
* Changes in the intimal surface of the vessel
* Changes in the pattern of blood flow
* Changes in blood constituents
These apply to arterial and venous thrombosis, and atrial fibrillation.
Give examples of changes in the intimal surface of the vessel
- Atherosclerosis
- Trauma
- Inflammation
- Neoplasia
Give examples of changes in the pattern of blood flow
- Changes in speed -> Systemic (e.g. heart failure) or local (e.g. immobilisation)
- Turbulent blood flow -> Atrial aneurysm, atrial fibrillation, myocardial infarction
Give examples of changes in blood constituents
- Increased procoagulant factors
- Decreased anticoagulant factors
- Increased blood viscosity
- Increased platelet numbers and adhesion/aggregation
- Presence of anticardiolipin antibodies (eg in SLE)
- Release of procoagulant factors by tumours
How does endothelial injury contribute to thrombus formation?
Endothelial injury which leads to platelet activation
-exposes vWF and tissue factor
-cytokines downregulate thrombomodulin expression
-activated endothelial cells secrete Plasminogen activator inhibitors (limit fibrinolysis)
What is deep vein thrombosis (DVT)?
The formation of a thrombus in a deep vein, most commonly in the legs or pelvis.
*These thrombi are serious because they are prone to embolise
Where do DVT thrombi end up?
Travel as an embolus to the right side of the heart and block the pulmonary artery which supplies blood to the lungs (pulmonary embolism)
Give examples of vessels in which DVT occurs?
Larger leg veins at or above the knee joint
Popliteal
Femoral
Iliac
What are some risk factors for venous thrombosis?
- Age
- Venous stasis (esp. in the elderly) - immobilisation and bed rest
- Any surgery (esp. orthopaedic and prostate)
- Pregnancy
- Infection
- Malignancy (esp. adenocarcinomas)
- Genetic
- AT-III deficiency
- Protein C Resistance (incl. Factor V Leiden)
What are the effects of ARTERIAL thrombosis?
Stenosis
Ischaemia
Infarction
Embolism
(higher tendency to block vessels whereas venous do not totally occlude)
What are the effects of VENOUS thrombosis?
Embolism
Oedema
Venous leg ulcers
Local congestion and swelling from impaired outflow
Obstruction/Ischaemia (depends on site)
What is stenosis?
the abnormal narrowing of a blood vessel or other tubular organ or structure such as foramina and canals.
How does hypercoagulability contribute to the development of thrombi? Give an example
Defined as an abnormaly high ability of the blood to clot through alterations in coagulation factors
Mutations in factor V (Leiden) which renders it resistant to proteolysis by active protein C (anti-thrombotic counterregulatory mechanism is lost)
How does thrombin regulate the clotting cascade?
Thrombin cleaves fibrinogen to fibrin (pro-coagulation)
Cleaves Factor V to Va which cleaves prothrombin to thrombin
Thrombin binds to thrombodulin (activates protein C which has anti-coagulant activity)
What are venous leg ulcers?
Long-lasting sores in the skin that take more than a month to heal.
