4- Thrombosis Flashcards
1- Learnign outcomes of thrombosis
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1- Defintion 2- Predisposing factors 3- Effects 4- Outcomes 5- Common clinical examples
2- What is the defintion of thrombosis?
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Thrombosis is the formation of a solid mass of blood within the circulatory system.
Clot: a solid mass of blood constituents occuring outside the vascular tree
Thrombosis (pathological):
a solid mass of blood constituents (thrombus) formed within the vascular lumen during life
3- Explain the relationship between hemostasis and thrombosis
(5)
Arterial thrombosis is primarily an exaggerated hemostatic responses at sites of vascular injury.
4- What are the main differences between Hemostasis and Thrombosis?
(5)
1- Relative localiztion in th vessel wall
- arterial thrombi form exclusively within the vessel lumen
hemostatic plugs primarily form in the vessel wall and extracellular space
2- The blood flow conditions operating around forming thrombi and hemostatic plugs are quite distinct
3- The time frame of formation
- Hemostatic plugs form within minutes of vascular injury to quickly stop bleeding
- Arterial thrombi can form over hours or days
5- Why does thrombosis occur?
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Virchow’s Triad
1- Abnormalities of the vessel wall (endothelial Injury) - Atheroma - Direct injury - Inflammation 2- Abnormalities of blood flow - Stagnation - Turbulence 3- Abnormalities of blood components (hypercoagulability of the blood)
6- What does endothelial Injury cause?
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1- Physical loss of endothelium (ECM exposure)
- adhesion of platelets
- release of tissue factor
- local depletion of PGI2 (vasodilator) and plasminogen activators
7- What are the consequences of endothelial injury?
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Causes thrombus fromation in the heart or the arterial circualtion, where the normally high flow rates might otherwise impede clotting by preventing platelet adhesion and washing out activated coagulation factors.
Heart: within cardiac chambers (e.g. after endocardial injury due to myocardial infarction)
Arterial circualtion:
atherosclerotic arteries
sites of traumatic or inflammatory vascular injury (vasculitis)
8- What induces endothelial dysfunction?
1- Hypertension 2- Turbulent blood flow 3- Bacterial endotoxins 4- Radiation injury 5- Metabolic abnormalities (hypercholesterolemia) 6- Toxins absorbed from cigarette smoke 7- Increase in procoagulant factors ( platelet adhesion molecules, tissue factor, PAIs) 8- Decrease in antocoagulant effectors (thrombomodulin, NO, PGI2, t-PA)
9- Relationship between inflammation and endotheial dysfunction
(12)
1- Endothelial Damage or Dysfunction causes inflammation 2- Inflammation induces 1. Increase in adhesive molecules 2. Increase in monocytes 3. increase in lymphocytes 4. increase in inflammatory markers 5. decrease in nitric oxide 6. increase in endothelin 7. increase Activated platelet 8. Increasae in the actiavtion of the clotting system 9. Decrease in the fibrinolytic system
10- Relationship between alteration in normal blood flow with thrombosis
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1- Normal bood flow is laminar such that the platelets (and other bood cellular elements) flow centrally in the vessel lumen, separated from endothelium by a slower moving layer of plasma
2- Turbulence (bifurcation points and areas of severe stenosis) contributes to arterial and cardiac throbosis by causing endithelial injury or dysfunction,as well as by forming
- countercurrentes ( artherial and venous thrombi)
- Stasis ( major contributor in the deevelopment of venous thrombi)
3- Both conditions alter normal laminar blood flow ( leukocytes in the central part og the vessel ) and:
1, Promte endothelial activation (increased procoagulant activity and leukocyte adhesion)
2. Disrupt laminar flow and bring platelets into contact with the endothelium
3. Alterated plasmatic concentrations of coagulation factors and inhibitors.
11- What are the relevance of turbulence and stasis in a clinical setting?
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1- Turbulence/countercurrents:
1. Ulcerated atherosclerotic plaques
2- Stasis:
- Aneurysms (aortic and arterial dilations)
- Acute myocardial infarctions ( areas of noncontractile myocardium)
- Rheumatic mitral valve stenosis
- Hyperviscosity
12- Describe Hypercoagulability
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1- Less frequent contributor of thrombotic states
2- Defintion: any alteration of the coagulation pathways that predisposes to thrombosis
3- Hypercoagulable states
- Primary ( genetic)
- Secondary (Acquired)
13- Explain the primary coagulable states
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1) Common
1- Factor V mutation (factor V laiden)
- single-nucleotide mutationo in factor V
- present in 22 to 15 % of caucasions
-renders factor V resistant to protein C cleavage
2- Prothrombin mutation
- SIngle nucleotide change in the 3UTR of the prothrombin gene
-Associated with elevated prothrombin levels
2) Rare
1- Antithrombin III deficiency
2- Protein C deficiency
3- Protein S deficiency
3) Very Rare
1- Fibrinolysis defects
2- Homozygous homocystinuria ( deficiency of cystathion B-synthetase)
14- Explain the secondary hypercoagulable state
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High-Risk-for-Thrombosis
- Prolonged bed rest of)immobilization
- Myocardial)infarction
- Atrial)fibrillation
- Tissue)injury)(surgery,)fracture,)burn)
- Cancer
- Prosthetic)cardiac)valves
- Disseminated)intravascular)coagulation
- HeparinBinduced)thrombocytopenia
- Antiphospholipid)antibody)syndrome
Lower-Risk-for-Thrombosis
- Cardiomyopathy
- Nephrotic)syndrome
- Hyperestrogenic)states)(pregnancy)and)postpartum)
- Oral)contraceptive)use
- Sickle)cell)anemia
- Smoking
15- Types of thrombi
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1- Occlusive thrombi
result in necrosis of the part sevred (infarction)
2- Mural thrombus
release fragments (emboli) which can travel in the bloodstream to block distal vessels
3- Vegatative thrombus
on heart valves due to infection can also embolise
