Blood Coagulation Flashcards
Give an overview of the blood clotting process
- The injured vessel initially contracts, restricting the flow of blood
- Platelets aggregate at the site, forming a primary hemostatic plug
- Clotting cascade occurs, and a fibrin network is formed
- A fibrin clot forms
- Clot retraction occurs
Trauma causes smooth muscle in vessel wall to contract via local myogenic spasm, autacoid factors from tissues and platelets, and nervous reflexes. Vasoconstriction is enhanced (esp. in small vessels) by TxA2.
How do platelets activate the clotting cascade?
Upon injury, they bind to collagen and vWF (von Willebrand Factor) and stimulate structural changes in the platelets, and causes them to release factors (TxA2 and ADP) that recruit more platelets.
(https://www.jci.org/articles/view/20986/figure/1)
Platelets are also known at ___________.
thrombocytes
Explain the process of forming the hemostatic plug
Prothrombin (Factor II) forms into thrombin, which then activates fibrinogen (Factor I) to form fibrin.
(http://www.vce.bioninja.com.au/aos-2-detecting-and-respond/defence-against-disease/second-line-of-defence.html)
What is Factor IV? What does it do?
Calcium, it helps the clot stick
Explain and draw out the coagulation cascade
There are two branches; the intrinsic (contact factor) pathway, and the extrinsic (tissue factor) pathways. They converge at factor X and the final common pathway. The pathways function simultaneously and are interdependent.
What activates the intrinsic pathway?
Exposure to highly (-) charged surfaces, including collagen and glass
What activates the extrinsic pathway?
Releasing of tissue factor (III) by injured tissue
Where are most coagulation factors produced? Are they active when released?
Most are produced in the liver, and all are released as zymogens to the serum (so they are not active)
What steps of the coagulation process involve Gla proteins, and require Ca2+ and phospholipids?
What can Abx cause a deficiency of?
Vitamin K
What is a normal platelet count?
Normally 150,000-400,000 cells/mL
What is prothrombin time?
Measures rate of clotting by the extrinsic and common pathways, and is determined mainly by the amount of prothrombinin the plasma. Oxalated blood is treated with excess Ca+2and tissue factor, and the clotting time is measured. Normally 10-14 seconds.
What is the partial thromboplastin time (PTT)?
Measures rate of clotting by the intrinsic and common pathway. Oxalated blood is treated with excess Ca+2, phospholipid, and a nucleating surface such as kaolin. The clotting time is measured. Normally 30-42 seconds.
What factors does thrombin activate?
Thrombin activates Factors V, VII, VIII and XI, thereby accelerating the rate of clot formation. It also stimulates platelet aggregation, thus further promoting secondary clot formation.
How does feedback inhibition regulate the cascade?
Endothelial cells express thrombomodulinon their surface. Thrombin has a high binding affinity for thrombomodulin and fibrin fibers, and is thus removed from the plasma. The thrombomodulin:thrombincomplex activates protein C, which forms an active complex with protein S to cleave FVaand FVIIIa, thus slowing the clotting cascade.
How do serpins regulate the cascade?
The serpins (serine protease inhibitors) are a group of naturally occurring inhibitory proteins. At least 8 serpinshave been identified, and inhibit either coagulation or fibrinolysis.
Antithrombin III is a key serpin. It irreversibly inactivates thrombin, as well as a few other clotting factors.
How does heparin affect antithrombin III/thrombin interaction?
The activity of antithrombin III toward thrombin is enhanced ~10,000X in the presence of heparin. Heparin is normally present in very small amounts in the plasma, and is used clinically as an anticoagulant.
Describe the process of fibrinolysis
Once healing is underway, and the fibrin clot is no longer needed, the clot will be dissolved in a process called fibrinolysis.
- Plasminogen, a plasma protein, has a high affinity for fibrin and is incorporated into the fibrin clot during coagulation.
- Proteolysis of plasminogen by tissue plasminogen activator (tPA) or urokinase (U-PA) produces plasmin, a protease that cleaves fibrin, as well as several clotting factors.
Where is tPA and urokinase produced, and how are they regulated?
tPAis synthesized by vascular endothelial cells, and urokinase is produced by most tissues.
Physical stress, hypoxia, and a number of small molecule regulators increase the synthesis and release of tPAand urokinase.
Factor III
Tissue factor, released in the extrinsic pathway by injured tissue
vWF
Binds to Factor VIII in serum, and stabilizes it (Intrinsic pathway). It also acts as a platelet activator.
