Thrombosis Flashcards
Heamostasis and thrombosis involve three components, which are
Endothelium
Platelets
Coagulation Cascade
Discuss the sequence of events in haemostasis
- Vasoconstriction: mediated by neurogenic mechanisms and endothelin
- Primary Haemostasis: exposure of subendothelial ECM causes platelet adherence and activation, release of secretory granules and platelet aggregation
- Secondary Haemostasis: exposure of tissue factor III which combines with factor VII to form thrombin. Thrombin converts fibrinogen to fibrin and a permanent platelet plug is formed. Counter-regulatory mechanisms are also at play.
Endothelial cells usually exhibit procoagulant activities under normal conditions.
True or false
False.
Antiplatelet, anticoagulant, fibrinolytic properties.
Procoagulant activities follow injury or activation
Mention the factors that may activate endothelial cells
- Trauma
- Infectious agents
- Hemodynamic forces
- Plasma mediators
- Cytokines
The balance between anti-thrombotic and prothrombotic activities of the endothelium determines whether propagation or dissolution will occur.
True or false.
True
Mention the antithrombotic properties of the endothelium
A. Antiplatelet Effect
•Intact endothelium
•Prostacyclin PGI2 and nitric oxide
•Adenosine diphosphatase
B. Anticoagulant Effect
•Thrombomodulin
•Tissue factor pathway inhibitor-inhibitors factors VIIa and Xa
•Protein S-cofactor of protein C and TFPI
C. Fibrinolytic Effect
•Tissue-type plasminogen activator
Mention the prothrombotic properties of the endothelium
A. Platelet Effect
•Endothelial Injury-Von Willebrand factor vWF
•Procoagulant effect- Tissue factor
•Antifibrinolytic effects- Inhibitors of plasminogen activator
Genetic disorders of vWF-Von Willebrand disease or it’s receptor- Bernard Soulier syndrome don’t result in bleeding disorders.
True or false. Why?
False.
Platelet adhesion to sub endothelial ECM is mediated by vWF which acts as a bridge between platelet surface receptors and exposed collagen
The secretion that occurs after adhesion of platelets contains?
Calcium-required in the coagulation cascade
ADP-activator of platelet aggregation alongside TxA2
Negatively charged phospholipids-bind calcium and complexes containing coagulation factors
Platelet activation by ADP triggers a conformational change in the platelet GpIIa-IIIb receptors
True or false.
What function does it subserve?
False
GpIIb-IIIa receptors receptors.
They induce binding to fibrinogen that promote platelet aggregation.
Inherited deficiency of GpIIb-IIIa results in?
Glanzmann thrombasthenia
The endothelial damage represents the ___ stage of hemostatic process
1st
The Coagulation cascade represents the 2nd arm of the hemostatic process
True or false
False
3rd arm
What is the most important coagulation factor?
Thrombin, it converts fibrinogen to fibrin
The extrinsic pathway is the most physiologically relevant pathway for coagulation due to vascular damage
True or false
True
The clinical assays used to assess the function of the coagulation pathways are?
- Prothrombin time PT which assess the functions of proteins in the EXTRINSIC pathway
- Partial thromboplastin time PTT which assess the functions of proteins in the INTRINSIC pathway
Mention the endogenous anticoagulants that control clotting
- Antithrombins- antithrombin III inhibits the activities of thrombin and serine proteases-factors IXa, Xa, XIa, and XIIa
- Proteins C and S(Vit K-dependent) proteins that inactivate factors Va and VIIIa
- TFPI inactivates factor VIIa complexes
The three abnormalities that lead to thrombus formation are?
Virchows triad:
- Endothelial Injury
- Stasis/Turbulent flow
- Hypercoagulability of blood
Give settings that could lead to thrombus formation due to endothelial damage
- Endocardial injury/Myocardial infraction
- Ulcerated atherosclerotic plaques
- Vascular injury-inflammatory or traumatic
- Hypertension
- Turbulent blood flow
- Bacterial endotoxins
- Radiation injury
- Metabolic abnormalities/Hypercholesterolemia/Homocysteinemia
- Cigarettes smoke toxins
How does stasis/turbulence contribute to thrombosis?
- Promotes endothelial activation
- Brings platelets in contact with endothelium
- Prevents washout/dilution of clotting factors
Give settings that could lead to thrombus formation due to stasis/turbulence
- Ulcerated atherosclerotic plaques
- Aneurysms
- Myocardial infarctions
- Hyperviscosity e.g Polycythemia Vera
- Sickle cell anemia
Hypercoagulability is any alteration of the coagulation pathways that predisposes to thrombosis.
True or false
True
The most common primary/genetic hypercoagulable states are?
Common:
- Factor V mutation/Leiden
- Prothrombin mutation
- 5,10-methylenetetrahydrofolate reductase
- Increased factors VIII, IX, X, fibrinogen
Rare:
- Antithrombin III deficiency
- Protein C deficiency
- Protein S deficiency
- Smoking
Very Rare:
- Fibrinolysis defect
- Homocystinuria
The most common secondary/acquired hypercoagulable states are?
High risk:
- Immobilization
- Myocardial infraction
- Atrial fibrillation
- Tissue injury
- Cancer
- Prosthetic cardiac valves
Lower risk:
- Cardiomyopathy
- Nephrotic syndrome
- Hyperestrogenic states
- Oral contraceptive use
- Sickle cell anaemia
What is the morphological difference between an arterial thrombi and a venous thrombi?
Arterial thrombi grow retrograde from the point of attachment and venous thrombi extend in the direction of the flow
What are the differences between an antemortem and a postmortem clot?
Antemortem clots:
Dry,
Granular masses,
Well attached to the walls of the vessels
Lines of Zahn are observed microscopically due to alternating RBC and platelet deposits
Postmortem clots:
Jelly like
Easily detachable masses
They have a reddish and yellowish(plasma) portion
Where do mural thrombi occur in the body?
Heart chambers
Aortic lumen
Arterial thrombi are frequently occlusive while venous thrombi, phlebothrombi, is invariably occlusive.
True or false. Why?
True.
Blood moves slower in the veins and tends to contain more enmeshed red cells
Thrombi on the heart valves are known as?
Vegetation
Discuss the fate of the thrombus
- Propagation
- Embolization
- Dissolution
- Organization and recanalization
