23. Hemostasis Flashcards
What is hemostasis?
Steps taken by the body to limit blood loss
What are the four steps in hemostasis?
- Vascular Spasm
- Formation of a platlet plug
- Formation of a blood clot
- Repair of damage
A platelet is a cell fragment from a megakaryocyte. Production of platelets (thrombocytes) is mainly dependent on?
thrombopoietin(TPO) which is a protein hromone with an amine terminal like erythropoietin (EPO), PRODUCED by liver and kidney
Platelets are made via TPO, which is continually secreted. Thrombopoietin binds Platelet receptor MPL. What transcription factor is used?
JAK2/STAT5
When there is high number of platelets, there is lots of TPO bound to MPL so the platelets internalize TPO and destroy it. What occurs when there is low number of platelets?
Little TPO bound to platelets and not being destroyed so there is alot of TPO free to bind
TPO effects all cell lines including RBCs. What would happen if there was a mutation in the TPO receptor on platelets?
Polycythemia vera, where there is too much TPO d/t not being able to bind platelets and destroy
platelets contain actin and myosin for cell contraction so they are able to empty their vesicles which contain ADP, cyclooxygenase1 which forms thromboxane A2, fibrin stabilizing factor and platelet derived growth factor and serotonin (5HT). What does serotonin do?
A vasoconstrictor which is d/t increase platelet. increased serotonin can cause headaches
What are the three main things platelet cell membranes express?
Glycoproteins (sticky)
Phospholipids including platelet factor 3(activates clotting cascade)
Collagen receptors to bind to damaged endothelium
Vascular spasm occurs when there is damage to a blood vessel, a direct myogenic response to injury. Platelet factors release what (2) to vasoconstrict?
Serotonin and thromboxane A2
What is the other side factor that contributes to vascular spasm but is not neccessary or needed?
a neureal reflex initiated by the mechanical injury and pain
During formation of the platelet plug, when there is damage to the vessel wall, the collagen is exposed and platelets bind to collagen. What is the first step in platelets binding to collagen?
Von willebrand factor (a plasma protein) binds between collagen and the the platelet receptor of the platelet.
Once the von willebrand factor binds to both collagen and platelet receptor, the platelet is activated and what occurs?
The platelet receptor binds to collagen and the platelet is activated causing the platelet to swell and become spikey (podocytes)
When the platelet swells, the ER releases Ca which triggers actin and myosin to contract. The contraction causes granules to leave the platelet. What do the granues do?
ADP serotonin, throboxane A2 cause the platelets to stick to vessel wall and to eachother so more are recruited to the site
Do platelets contribute to the intrinsic or extrinsic pathway for activation of clotting cascade?
The intrinsic pathway due to the damaged surface
Clot retraction gets rid of excess fluid within the clot to solidify it. The platelets are required which do what two things with Calcium?
Bind fibrin polymer together
actin and myosin in platelet cause contraction w Ca2+
platelets have a fibrin receptor which will beind to fibrin polymers and do what?
contract, which brings the fibrins close together and causes coagulation
The final step of hemostasis is to repair the damage, platelets secrete platelet derived growth factor which does what?
Stimulates fibroblasts to grow in the area which are able to differentiate into smooth muscle and other things to close the hole
To get rid of the clot once the tissue is repaired, plasminogen is used. How is plasminogen activated and what releases the molecule that activates it?
Plasminogen is activated by tissue plasminogen activator which is released by damaged tissue. This is inhibited by tPA inhibitor
Since plasminogen has the possiblilty to be activated right away by tissue damage, the inhibitor to the activating factor for plasminogen is supressed unitl the endothelial cell expresses thrombomodulin which binds to thrombin and activates what?
Protein C which inactivates the plasmin inhibitor (tPA inhibitor) so tPA is able to convert plasminogen into plasmin
What does plasmin do once activated by protein C from plasminogen?
Plasmin breaks down fibrin to remove the clot one the endothelium is fixed
The smooth surfaces of the endothelium lining of blood vessels prevents platelets from activating. What membrane proteins also prevent activation?
Glycocalyx which repels platelets and thrombomodulin which makes thrombin into protein C
Why does having atherosclerosis increase the risk for a blood clot?
Plaques of lipids accumulate along the endothelial lining, causing the smooth surface to become rough, activating platelets and initiating the clotting cascade
While activated protein C from thrombumodulin binding thrombin inactivates tPA inhibitor, what else does it inactivate?
Clotting factor 8a (VIIIa) and 5a (Va) which inhibit further fibrin creation
