blood Flashcards
Q: What are the two categories of blood-contacting medical devices based on duration of use?
A:
Short-Term (< 30 days): ECMO (lung machine), oxygenator, dialysis catheter, dialyser.
Long-Term (> 30 days): Stents, heart valves, ventricular assist devices (heart pumps), grafts.
Q: What are the main types of drugs used to manage medical device thrombosis, and how do they work?
A:
Anticoagulants (e.g., Heparin, Warfarin): Inhibit coagulation and fibrin formation.
Antiplatelets (e.g., Aspirin, Clopidogrel): Inhibit platelet binding or activation.
Q: Define thrombosis and name its main components.
A:
Thrombosis: The process of blood clot formation.
Main components:
Cellular: Platelets, leukocytes.
Protein: Fibrin, formed from fibrinogen.
Q: Compare haemostasis and pathological thrombosis.
A:
Haemostasis: Normal process stopping bleeding after vessel injury, involving vasoconstriction, platelet adhesion, and fibrin formation.
Pathological Thrombosis: Occurs in diseased vessels, causing blockage due to platelet and fibrin activation at constricted sites.
Q: What is thrombogenicity?
A: Thrombogenicity is the tendency of a material to cause thrombosis. High thrombogenicity indicates a material is more likely to cause blood clot formation.
Q: Name the primary components and pathways involved in material thrombosis.
A:
Proteins: Fibrinogen, von Willebrand factor (vWF).
Cells: Platelets, leukocytes.
Pathways:
Coagulation Pathway: Involves activation of Factor XII (FXII), leading to thrombin and fibrin formation.
Complement Pathway: Recruits immune cells, linking thrombosis to inflammation.
Q: How does protein conformational change affect thrombosis on material surfaces?
A: When proteins unfold or denature on material surfaces, they expose cell-binding sites, leading to the activation of enzymes (e.g., FXII), and initiating thrombosis.
Q: Describe how platelets are activated during thrombosis on material surfaces.
A:
Platelets bind to unfolded fibrinogen and vWF via integrins.
Once activated, they spread, release pro-thrombotic factors, and upregulate receptors to bind more platelets and leukocytes.
Q: What are the effects of rough vs. smooth surfaces on thrombogenicity?
A:
Rough surfaces: Accumulate coagulation factors, trap cells and air (which is thrombogenic).
Smooth surfaces: Traditionally less thrombogenic, but surface topography manipulation can reduce thrombosis further.
Q: How does surface wettability affect thrombogenicity?
A:
Hydrophilic surfaces: Generally less thrombogenic, repelling proteins and water.
Hydrophobic surfaces: Tend to absorb proteins, such as fibrinogen, which leads to platelet activation and increased thrombosis.
Q: Explain the role of leukocytes in material thrombosis.
A:
Leukocytes (e.g., neutrophils, monocytes) bind to fibrinogen and vWF on thrombi.
Once activated, they release coagulation factors and fibrinogen, contributing to thromboinflammation.
Q: What is the role of the complement pathway in thrombosis?
A:
The complement pathway activates enzymes like C3b, which recruits immune cells (monocytes and neutrophils), stimulating the immune response and promoting thromboinflammation.
Q: What material properties contribute to increased thrombogenicity?
A:
Surface roughness: Traps coagulation factors and cells.
Hydrophobicity: Leads to protein adhesion and platelet activation.
Surface charge: Negatively charged surfaces (e.g., ceramics) can activate coagulation pathways.
Q: Why are systemic blood thinners problematic in managing device thrombosis?
A: They increase the risk of bleeding complications, such as hemorrhagic stroke or gastrointestinal bleeds.
Q: You are designing a new stent for long-term implantation. What material properties would you prioritize to reduce thrombogenicity, and why?
A:
Prioritize smooth, hydrophilic surfaces to reduce protein adhesion and platelet activation.
Avoid rough or hydrophobic surfaces, as they increase the risk of trapping coagulation factors and activating the thrombosis pathway.
Consider materials with anti-thrombogenic coatings like PEG or natural polymers (e.g., perlecan) to reduce blood clot formation.
Flashcard 2
Q: A patient with a ventricular assist device (VAD) has been experiencing frequent clot formation despite being on anticoagulants. What could be the material-related causes, and how would you address them?
A:
Material-related causes: Rough surface of the VAD, hydrophobic nature of the material (e.g., PTFE), or denatured proteins like fibrinogen binding to the device.
Solution: Modify the VAD with a smooth, hydrophilic coating to prevent platelet adhesion or switch to materials that repel protein adhesion. You could also explore using biomimetic surfaces to mimic non-thrombogenic natural surfaces like endothelial cells.
Q: A new dialysis catheter material is being tested for use. However, it is found that FXII (Factor XII) activation occurs when the catheter is exposed to blood. What does this indicate about the material’s properties, and how could the design be improved?
A:
FXII activation suggests that the material is likely negatively charged or hydrophobic, both of which are known to trigger the coagulation cascade.
To improve the design, use a hydrophilic and neutral-charged material, or consider adding anti-coagulant coatings to minimize FXII activation.
Q: You are tasked with choosing a material for a heart valve that will contact blood long-term. The primary concern is preventing thrombosis while maintaining durability. What properties would you select and why?
A:
Choose a smooth, durable material like metal or synthetic polymer with an anti-thrombogenic surface coating (e.g., PEG).
Ensure the material is hydrophilic to prevent protein denaturation and reduce platelet activation.
Durability is critical, so the material should be resistant to mechanical wear without compromising its non-thrombogenic properties.
Q: A clinical trial is evaluating a new blood-handling device that is highly hydrophobic. Patients using this device experience increased platelet aggregation. How can this be explained based on the material’s thrombogenicity, and what change could reduce this issue?
A:
The hydrophobic nature of the material likely causes protein denaturation, particularly fibrinogen, which can bind platelets and activate them.
Switching to a hydrophilic surface would reduce protein denaturation and lower platelet aggregation. Incorporating a coating that repels protein and platelet adhesion (e.g., PEG) could further reduce thrombogenicity.
Q: A new study shows that a stent made from a rough material causes more thrombus formation than a smooth stent. What is the reason behind this, and how could the surface be modified to reduce thrombosis?
A:
Rough surfaces trap coagulation factors, platelets, and air bubbles, leading to increased thrombus formation.
Solution: Modify the surface to be smoother and possibly apply anti-thrombogenic coatings to further prevent clot formation by repelling protein and platelet adhesion.
Q: In a patient with high blood flow conditions, what type of material properties would be essential for a blood-contacting implant, and why?
A:
In high-flow conditions, choose a material with smooth and non-thrombogenic properties to avoid platelet activation, which can be triggered by high shear stress.
A hydrophilic surface would be beneficial as it repels protein adhesion and prevents platelet aggregation under high-shear conditions.
Q: A research team is developing a biodegradable vascular graft for short-term use in arterial repairs. What factors should they consider to balance the need for biodegradability with minimizing thrombosis?
A:
The material should be smooth and hydrophilic to minimize thrombosis during its functional period.
The rate of degradation should match the healing time of the vessel to avoid early thrombosis or excessive degradation that might expose rough or thrombogenic surfaces too soon.
Q: During a surgical procedure, air is accidentally introduced into a blood-contacting device. Why is this dangerous, and what properties of the material could exacerbate this issue?
A:
Air can act as a nucleation site for thrombus formation, trapping coagulation factors and platelets.
A material with a rough surface can exacerbate this by trapping air, increasing the risk of thrombosis. The use of smooth, non-porous materials would reduce the likelihood of air-related clot formation.
Q: A new artificial heart valve material shows excellent mechanical properties but a tendency to cause leukocyte adhesion. What are the implications of this, and how could the material be modified to address the issue?
A:
Leukocyte adhesion suggests that the material may trigger thromboinflammation, leading to clot formation and inflammation.
Modifying the surface to be less thrombogenic, such as by adding biomimetic coatings that repel immune cells (e.g., coatings mimicking endothelial cells), could help reduce leukocyte adhesion.
