blood

Question 1

Q: What are the two categories of blood-contacting medical devices based on duration of use?

Answer 1

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.

Question 2

Q: What are the main types of drugs used to manage medical device thrombosis, and how do they work?

Answer 2

A:

Anticoagulants (e.g., Heparin, Warfarin): Inhibit coagulation and fibrin formation.
Antiplatelets (e.g., Aspirin, Clopidogrel): Inhibit platelet binding or activation.

Question 3

Q: Define thrombosis and name its main components.

Answer 3

A:

Thrombosis: The process of blood clot formation.
Main components:
Cellular: Platelets, leukocytes.
Protein: Fibrin, formed from fibrinogen.

Question 4

Q: Compare haemostasis and pathological thrombosis.

Answer 4

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.

Question 5

Q: What is thrombogenicity?

Answer 5

A: Thrombogenicity is the tendency of a material to cause thrombosis. High thrombogenicity indicates a material is more likely to cause blood clot formation.

Question 6

Q: Name the primary components and pathways involved in material thrombosis.

Answer 6

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.

Question 7

Q: How does protein conformational change affect thrombosis on material surfaces?

Answer 7

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.

Question 8

Q: Describe how platelets are activated during thrombosis on material surfaces.

Answer 8

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.

Question 9

Q: What are the effects of rough vs. smooth surfaces on thrombogenicity?

Answer 9

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.

Question 10

Q: How does surface wettability affect thrombogenicity?

Answer 10

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.

Question 11

Q: Explain the role of leukocytes in material thrombosis.

Answer 11

A:

Leukocytes (e.g., neutrophils, monocytes) bind to fibrinogen and vWF on thrombi.
Once activated, they release coagulation factors and fibrinogen, contributing to thromboinflammation.

Question 12

Q: What is the role of the complement pathway in thrombosis?

Answer 12

A:
The complement pathway activates enzymes like C3b, which recruits immune cells (monocytes and neutrophils), stimulating the immune response and promoting thromboinflammation.

Question 13

Q: What material properties contribute to increased thrombogenicity?

Answer 13

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.

Question 14

Q: Why are systemic blood thinners problematic in managing device thrombosis?

Answer 14

A: They increase the risk of bleeding complications, such as hemorrhagic stroke or gastrointestinal bleeds.

Question 15

Q: You are designing a new stent for long-term implantation. What material properties would you prioritize to reduce thrombogenicity, and why?

Answer 15

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.

Question 16

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?

Answer 16

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.

Question 17

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?

Answer 17

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.

Question 18

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?

Answer 18

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.

Question 19

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?

Answer 19

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.

Question 20

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?

Answer 20

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.

Question 21

Q: In a patient with high blood flow conditions, what type of material properties would be essential for a blood-contacting implant, and why?

Answer 21

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.

Question 22

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?

Answer 22

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.

Question 23

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?

Answer 23

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.

Question 24

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?

Answer 24

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.

Question 25

Q: You are tasked with reducing the risk of thrombosis in a blood-handling machine (e.g., a dialysis machine). What properties of the tubing material would you optimize, and how would these changes impact thrombogenicity?

Answer 25

A:

Optimize hydrophilicity: A hydrophilic surface would reduce protein denaturation and platelet adhesion.
Ensure the material has a smooth surface to minimize the accumulation of coagulation factors.
Adding an anti-thrombogenic coating would further reduce clot formation by minimizing interaction with blood components.

Question 26

Q: A patient with a long-term stent develops thrombosis despite being on antiplatelet medication. Upon investigation, you find the stent surface is slightly rough. How would this contribute to thrombosis, and what could be done to improve the stent design?

Answer 26

A:

Contribution to thrombosis: The rough surface increases thrombogenicity by trapping platelets and coagulation factors, which facilitates clot formation. Additionally, roughness may promote air bubble trapping, which is thrombogenic.
Solution: The stent could be redesigned with a smoother surface to reduce platelet and protein adhesion. Applying a hydrophilic coating or using materials with anti-thrombogenic properties (e.g., polyethylene glycol) could further decrease clot formation.

Question 27

Q: A dialysis patient frequently experiences clot formation in the blood tubing, even though anticoagulants are being used. You discover the tubing is made from a hydrophobic polymer. How does this material property increase thrombosis, and what changes would you recommend?

Answer 27

A:

Explanation: The hydrophobic polymer surface likely causes denaturation of fibrinogen, exposing binding sites for platelets, thus promoting clot formation.
Recommendation: Use a hydrophilic material that repels protein adsorption and reduces platelet activation. Additionally, you could consider a coating with anti-thrombogenic agents like heparin to minimize clot formation.

Question 28

Scenario 3
Q: A patient with a ventricular assist device (VAD) presents with recurrent thrombosis, even though the flow rates through the device are high. What could be causing the thrombosis, and how would you address the material and flow conditions?

Answer 28

A:

Cause: High flow rates can lead to shear-induced platelet activation, especially if the material surface is rough or thrombogenic. Additionally, some materials may cause protein unfolding and platelet aggregation under high shear stress.
Solution: Ensure the VAD has a smooth, non-thrombogenic surface (e.g., hydrophilic or biomimetic coatings). You may also need to adjust the flow dynamics to reduce shear stress on the blood components.

Question 29

Q: A new vascular graft shows signs of thrombosis during initial clinical trials. It is made from a polymer known to activate Factor XII (FXII). How does FXII activation lead to thrombosis, and what changes to the material would mitigate this issue?

Answer 29

A:

FXII activation: When FXII is activated by contact with the graft material, it triggers the coagulation cascade, leading to thrombin and fibrin formation, which ultimately causes a thrombus.
Material modification: Switch to a less reactive material, such as a hydrophilic, neutral polymer that does not activate FXII. Consider applying a surface coating with anticoagulant properties (e.g., heparin).

Question 30

Q: A surgeon notices significant thrombus formation around a temporary catheter used for extracorporeal circulation. The catheter surface is designed to be smooth but highly hydrophobic. Why is this problematic, and how can the material be adjusted to reduce thrombosis?

Answer 30

A:

Problem: The hydrophobic surface promotes protein denaturation, particularly of fibrinogen, which leads to platelet adhesion and thrombus formation.
Adjustment: Replace the hydrophobic material with a hydrophilic surface, which is less likely to cause protein denaturation and platelet activation. Alternatively, coat the catheter with a biocompatible, anti-thrombogenic substance like PEG or heparin.

Question 31

Q: A patient with an artificial heart valve develops thromboembolism despite anticoagulation therapy. The valve is made of a smooth metal alloy. What could be the cause, and how could you improve the design of the heart valve?

Answer 31

A:

Cause: Even though the metal alloy is smooth, metals can trigger the coagulation cascade and platelet activation through surface chemistry interactions. Additionally, high blood flow through the valve may induce platelet activation due to shear stress.
Improvement: Coat the metal with a biomimetic or hydrophilic layer to reduce thrombogenicity. The design could also be modified to optimize flow dynamics and reduce shear forces that activate platelets.

Question 32

Q: In a study of new bioresorbable stents, it was found that as the material begins to degrade, the rate of thrombosis increases. What factors could explain this, and what could be done to address the issue?

Answer 32

A:

Explanation: As the material degrades, it may expose rough or uneven surfaces, which can trap platelets and coagulation factors, increasing thrombosis risk. Degradation products might also be thrombogenic.
Solution: Optimize the degradation profile so that the material maintains a smooth, non-thrombogenic surface during the entire resorption process. Additionally, apply a surface coating that remains intact until the material fully resorbs, or adjust the material’s chemistry to make degradation products less thrombogenic.

Question 33

Q: A medical device manufacturer develops a new synthetic polymer for use in heart valves. Early tests show significant leukocyte adhesion to the polymer surface. What are the implications of this finding, and how could the polymer be modified to prevent this?

Answer 33

A:

Implications: Leukocyte adhesion indicates that the material may be triggering an inflammatory response, leading to thromboinflammation, which could result in clot formation.
Modification: Reduce surface reactivity by making the polymer more hydrophilic or by adding a biomimetic coating that mimics endothelial cells, which are naturally non-thrombogenic and reduce immune cell adhesion.

Question 34

Q: A bioengineer is developing a biodegradable scaffold for vascular repair. However, clot formation occurs around the scaffold within days after implantation. What are the possible reasons for this, and what steps can be taken to reduce thrombosis?

Answer 34

A:

Possible reasons: The scaffold material might be rough or hydrophobic, leading to protein and platelet adhesion. Degradation by-products may also promote thrombosis.
Steps to reduce thrombosis: Use a smoother, hydrophilic material for the scaffold to reduce platelet adhesion. Ensure the scaffold degrades slowly and in a controlled manner, releasing non-thrombogenic by-products. You could also add a coating that inhibits coagulation or modifies surface properties to be less thrombogenic.

Question 35

Q: A researcher tests a new material for an extracorporeal oxygenator. The material is highly thrombogenic despite being coated with a hydrophilic polymer. What could be causing the thrombosis, and what further modifications could be made?

Answer 35

A:

Cause: The coating may be incomplete or uneven, exposing thrombogenic regions of the base material. Additionally, the hydrophilic coating might still denature certain proteins, triggering thrombosis.
Modifications: Ensure a uniform and durable application of the hydrophilic coating. Consider using an anti-thrombogenic additive or improving the chemical composition of the base material to make it less thrombogenic even if small areas are exposed.