Topic 4 Blood coagulation

Question 1

Which 4 processes does the wound healing process consists of?

Answer 1

Hemostasis - inflammation - proliferation/repair phase - maturation/remodeling phase

Question 2

What is hemostasis?

Answer 2

the process which causes bleeding to stop, to maintain blood in the blood vessels and organism

Question 3

Describe the blood vessel anatomy

Answer 3

Vessel wall: epithelial tissue with endothelial cells that have basal lamina, + lots of laminin proteins.
Media: elastin fibers and smooth muscle cells
Outer layer: collagen and elastic fibers and fibroblasts

Question 4

What are the formed elements of blood

Answer 4

Red blood cells, platelets and white blood cells

Question 5

which blood cells do not have a nucleus

Answer 5

Red blood cells and platelets

Question 6

What are platelets

Answer 6

They are not really cells, and have never had a nucleus. Either smooth or spiky (activated). They are formed and excreted by a megakaryocyte. Their cytoplasm contain some cytoplasmic organelles so they can produce proteins.

Question 7

What is inside the platelets

Answer 7

Contains granules, cytoskeletal structures (microtubules), open canal system, typical cytosolic organelles. Myosin so it can contract to some stimuli. The membrane have a lot of receptors to recognize many extracellular proteins.

Question 8

Why are integrins on the platelet surface important?

Answer 8

They can bind to a lot of important blood coagulation factors like vitronectin, von Willibrand factor (VWF). It can also bind to fibrinogen, which can bind to 2 plateltes at a time. With integrins they can bind to pretty much any protein with the RGD sequence.

Question 9

What is a lysosomal granule?

Answer 9

A vesicle including hydroytic enzymes to degrade proteins and other stuff.

Question 10

What does the alpha granules contain?

Answer 10

Platelet specific proteins such as beta-thromboglobulin, thrombin, factor V and factor XIII

Question 11

What does the dense granules contain?

Answer 11

ADP, Calcium and serotonin

Question 12

What can activate platelets?

Answer 12

In contact with collagen, ECM, fibrinogen, VWF, thrombin, soluble molecules,, ADP, thromboxane A2, damaged tissues, proteins absorbed to biomaterial surfaces and anything that is not the healthy endothelial cells (most important)

Question 13

What happens with the platelet when it gets activated?

Answer 13

The Arachiodonic acid metabolic pathway is upregulated, the platelet contracts and thereby secrete granules, increased expression of membrane receptors

Question 14

What is mainly released from the granules?

Answer 14

Platelet activating factors (platelet plug formation) and coagulation factors (fibrin fiber formation!).

Question 15

Briefly what activates and what come out of the Arachidonic Acid pathway?

Answer 15

Activated by Epinephrine, thrombin, platelet activating factor, thromboxane A2, Ca and ADP. The pathway results in prostaglandins, prostacyclin, thromboxane A2, ADP, Ca and serotonin

Question 16

Which of the secreted thing from an activated platelet inhibit vs. activate other platelets activation?

Answer 16

Inhibition by Prostacyclin and Prostaglandin PGD2 and PGE2.

Activation by released Thromboxane A2 and, Prostaglandins PGH2 and PGG2, ADP, Ca and serotonin.

Question 17

Describe the events of platelet plug formation

Answer 17

When endothelial cells get damaged collagen and other molecules in the basal lamina gets exposed. platelets adhere and activates into the irregular shape, contracts and release granule contents. The platelets become sticky, aggregates and this forms a plug. Fibrin is formed to reinforce the plug. local activation of nearby platelets

Question 18

What is the main pathway of fibrin fiber formation from activated platelets?

Answer 18

Thrombin will act on factor V (from a-granule) which in turn activates into factor Va. Factor Va reacts with factor Xa and create prothrombin activator. This + prothrombin becomes thrombin. This can cleave a part of the fibrinogen into fibrin monomers. These monomers can be polymerized in the presence of stabilizing factor 13 which results in fibrin threads. These event need Ca to happen.

Question 19

Which 3 pathways result in blood coagulation?

Answer 19

The extrinsic, intrinsic and the common pathway.

Question 20

Briefly explain the extrinsic pathway

Answer 20

Gets initiated by trauma to the tissue which results in damaged cells that release tissue thromboplastin. Factor VII will bind to this + factor X which will activate factor X to Xa. Then the pathway is the “normal” Xa + Va => prothrombin activator + prothrombin => thrombin => fibrin

Question 21

Briefly explain the intrinsic pathway

Answer 21

Gets initiated when blood comes in contact with foreign surface/not healthy endothelial cell membrane. Factor 12 is activated when it binds to neg. charged surfaces. factor 9 is also involved and can bind to platelet membranes which locally activates factor Xa. then regular fibrin formation pathway…

Question 22

What is the common pathway?

Answer 22

The pathway after factor Xa reacts with some other factor and result in prothrombin activator + prothrombin => thrombin + fibrinogen => fibrin monomer + factor XIIIa => fibrin thread. All in presence of Ca

Question 23

Which blood coagulation factors activate factor X?

Answer 23

Factor VIIa, factor VIIIa, factor IXa or platelet membrane

Question 24

What can be done to prevent blood coagulation?

Answer 24

Bind Ca (EDTA as chelator) as integrin is dependent on this and the whole pathway. Bind thrombin (prevent coagulation) or factor X (no fibrin to stabilize the clot)