Heart failure and von Willebrand's disease

Question 1

What are the effects of congestive heart failure?

Answer 1

1) Failure of heart to pump blood
2) Lung congestion: shortness of breath on exertion
3) Less blood flow to the kidney: blood fluid retention
4) Edema (swelling) on extremities

Question 2

What are the diagnostic features of a failing heart?

Answer 2

Perform echocardiogram to use sound to look at the heart and take snapshots to assess changes in area of left ventricle (LV)

Use LV in order to assess ejection fraction (should be sending >55% of blood to aorta)

Question 3

List 3 examples of etiological treatment for heart failure.

Answer 3

1) Artificial heart: different hydrodynamics from biological heart. Prosthetic material can result in blood clotting problems. Risk of failure
2) Heart transplant: limited supply, potential for organ rejection, surgical risk
3) Regenerate cardiac tissue

Question 4

Describe 4 cell types that can be used for cardiac cell transplantation therapy.

Answer 4

1) Cardiac progenitor cells (CPCs): Multipotent. SCA1 and c-KIT positive. Been some controversy around whether these are actually real.
2) Embryonic stem cells: ESC derived cardiomyocytes (activin A and BMP4 treatment). Potential teratoma formation and ethical issues.
3) Induced pluripotent stem cells: Fibroblasts + Yamanaka factors. Avoids ethical issues, tumorigenicity concerns, challenges in cost efficiency.
4) Bone marrow derived stem cells: Most will become blood cells, but some will become cardiac cells. Easiest to get ahold of.

Question 5

Describe the components of hemostasis.

Answer 5

Vascular injury leads to the following:
1) Vascoconstriction

2) Platelet activation: forms platelet plug that contributes to blood clot formation.
3) Coagulation cascade: fibrinogen is converted into fibrin by thrombin. This contributes to the formation of a blood clot.

Question 6

What are the intrinsic and the extrinsic pathways of blood coagulation?

Answer 6

Intrinsic: Contact activation pathway. Comes from things like pathogens/damaged surfaces inside bleeding.

Extrinsic: Tissue factor pathway. Trauma and cells are being damaged (for example, cutting of tissue) and intracellular stuff is leaking into tissue as tissue factor that activates that pathway.

Two pathways converge together to convert fibrinogen to fibrin.

Question 7

What is the pharmacological mechanism of action of desmopressin?

Answer 7

1) Initiates cAMP signaling.

2) Induces exocytosis of vWF in endothelial cell storages

Question 8

von Willebrand Disease (vWD)

Answer 8

Bleeding disorder. When a blood vessel is injured and bleeding occurs, VWF helps cells in the blood, called platelets, mesh together and form a clot to stop the bleeding. People with VWD do not have enough VWF, or it does not work the way it should.

Question 9

T/F: CPCs have the highest tumorigenicity concerns.

Answer 9

False

Question 10

T/F: ESCs have ethical issues.

Answer 10

True

Question 11

T/F: iPSCs are the most feasible in terms of cell harvest and preparation.

Answer 11

False, bone marrow derived stem cells.

Question 12

T/F: BMSCs have the potential to show the best improvement in terms of
clinical cardiac functions.

Answer 12

False, these cells are not the same cell type as heart, but future research may be able to fix this.

Question 13

Hemostasis

Answer 13

The stopping of blood flow

Question 14

Hemophilia cs vWD

Answer 14

Both are bleeding disorders.

Hemophilia has a distinct inheritance pattern (X-linked recessive) and is the result of problem with clotting Factor VIII (A) or Factor IX (B). VWD is the result of an issue with VWF. Symptoms from VWD also tend to be milder than hemophilia.

Question 15

Thrombin

Answer 15

Activates fibrinogen by converting fibrinogen to fibrin.

Thrombin comes from prothrombin.

Question 16

Describe 3 clinical tests of hemostasis.

Answer 16

1) Prothrombin time (PT): Add tissue factor (III) to plasma and measure the clotting time. Evaluates extrinsic and common pathway.
2) Partial thromboplastin time (PTT or aPTT): Add surface activator and measure the clotting time. Evaluates intrinsic and common pathway.
3) Bleeding time: Evaluates platelet function

Question 17

What are the 2 major roles of vWF?

Answer 17

1) Binds and carries Factor VIII

2) Binds and activates platelets

Question 18

What would PTT, PT and bleeding time be for Hemophilia A?

Answer 18

Increased PTT

Normal PT

Normal bleeding time

Question 19

Hemophilia A treatment

Answer 19

Desmopressin (DDAVP) in mild cases

Factor VIII transfusion

Question 20

Desmopressin

Answer 20

Vasopressin 2 receptor agonist that Initiates cAMP signaling

Induces exocytosis of vWF in endothelial cell storages

Used to treat mild cases of vWD and Hemophilia A

Question 21

Prothrombin time (PT)

Answer 21

Add tissue factor (III) to plasma and measure the clotting time.

Evaluates extrinsic and common pathway.

Question 22

Partial thromboplastin time (PTT or aPTT)

Answer 22

Add surface activator and measure the clotting time.

Evaluates intrinsic and common pathway.

Question 23

What triggers the intrinsic pathway?

Answer 23

Initiated by contact with an abnormal/foreign surface

Question 24

What triggers the extrinsic pathway?

Answer 24

Initiated by exposure to tissue factors

Question 25

T/F: In von Willebrand’s disease, bleeding time increases while aPTT is normal.

Answer 25

False

Question 26

T/F: In Hemophilia A, aPTT increases while PT is normal

Answer 26

True

Question 27

T/F: Desmopressin induces the secretion of factor VII from endothelial cells.

Answer 27

False

Question 28

T/F: Desmopressin is used to treat Hemophilia A.

Answer 28

True