Topic 4 Blood coagulation Flashcards
Which 4 processes does the wound healing process consists of?
Hemostasis - inflammation - proliferation/repair phase - maturation/remodeling phase
What is hemostasis?
the process which causes bleeding to stop, to maintain blood in the blood vessels and organism
Describe the blood vessel anatomy
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
What are the formed elements of blood
Red blood cells, platelets and white blood cells
which blood cells do not have a nucleus
Red blood cells and platelets, though platelets aren’t technically cells
What are platelets
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.
What is inside the platelets
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.
Why are integrins on the platelet surface important?
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.
What is a lysosomal granule?
A vesicle including hydroytic enzymes to degrade proteins and other stuff.
What does the alpha granules contain?
Platelet specific proteins such as beta-thromboglobulin, thrombin, factor V and factor XIII
What does the dense granules contain?
ADP, Calcium and serotonin
What can activate platelets?
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)
What happens with the platelet when it gets activated?
The Arachiodonic acid metabolic pathway is upregulated, the platelet contracts and thereby secrete granules, increased expression of membrane receptors
What is mainly released from the granules?
Platelet activating factors (platelet plug formation) and coagulation factors (fibrin fiber formation!).
Briefly what activates and what come out of the Arachidonic Acid pathway?
Activated by Epinephrine, thrombin, platelet activating factor, thromboxane A2, Ca and ADP. The pathway results in prostaglandins, prostacyclin, thromboxane A2, ADP, Ca and serotonin
Which of the secreted thing from an activated platelet inhibit vs. activate other platelets activation?
Inhibition by Prostacyclin and Prostaglandin PGD2 and PGE2.
Activation by released Thromboxane A2 and, Prostaglandins PGH2 and PGG2, ADP, Ca and serotonin.
Describe the events of platelet plug formation
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
What is the main pathway of fibrin fiber formation from activated platelets?
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.
Which 3 pathways result in blood coagulation?
The extrinsic, intrinsic and the common pathway.
Briefly explain the extrinsic pathway
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
Briefly explain the intrinsic pathway
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…
What is the common pathway?
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
Which blood coagulation factors activate factor X?
Factor VIIa, factor VIIIa, factor IXa or platelet membrane
What can be done to prevent blood coagulation?
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)
