18 Questions
What is the role of thrombin in the stabilization of the fibrin clot?
Thrombin activates factor XIII, which then cross-links the fibrin into polymers that stabilize the clot.
Which of the following is NOT a mechanism by which natural anticoagulants prevent clot extension?
Protein S directly inhibits the activity of thrombin.
What is the role of calcium ions (Ca$^{2+}$) in the coagulation cascade?
Ca$^{2+}$ is only required for the activation of the amplification phase in the intrinsic pathway.
How do endothelial cells and platelets prevent clot extension?
Endothelial cells secrete prostacyclin and nitric oxide, which promote vasodilation and inhibit platelet activation.
What is the role of protein S in the regulation of the coagulation cascade?
Protein S acts as a cofactor for activated protein C, which then inhibits the activity of factors Va and VIIIa.
Why does blood not clot in healthy blood vessels?
The endothelial cells lining the blood vessels secrete prostacyclin and nitric oxide, which inhibit platelet activation.
What is the primary function of the Fibrinolytic Phase in haemostasis?
Break down the fibrin clot
Which enzyme catalyzes the decarboxylation of factor II, VII, IX, and X in the Coagulation Cascade?
Vitamin K
During the BLOOD COAGULATION PHASE, what do Coagulation Factors primarily circulate as?
Inactive proteolytic enzyme precursors
What is the main role of Thrombin in the Coagulation Cascade?
Convert soluble fibrinogen into insoluble fibrin
Which cells are responsible for synthesizing Factor XIII in the Coagulation Cascade?
Endothelial cells
What is the purpose of the IMMEDIATE CONSTRICTION PHASE in haemostasis?
Induce vasoconstriction
Which of the following is NOT one of the factors that help keep blood in a fluid, un-clotted state in healthy blood vessels?
The healthy endothelial lining of blood vessels is smooth and positively charged to repel negatively charged surfaces.
Which of the following is the primary mechanism by which the liver removes activated clotting factors from circulation?
The liver directly degrades and metabolizes the activated clotting factors.
Which of the following is the primary way that the speed of blood flow helps prevent unnecessary clot formation?
The fast flow prevents the clotting factors from coming into contact with tissue factor (TF), which can activate the extrinsic pathway of coagulation.
Which of the following is the primary mechanism by which the glycoprotein coat on circulating platelets helps prevent unnecessary clot formation?
The glycoprotein coat creates repulsive forces that prevent the platelets from adhering to the healthy endothelium.
What is the primary role of the fibrinolytic system in preventing the propagation of blood clots?
The fibrinolytic system, through the action of tissue plasminogen activator (t-PA), converts plasminogen into plasmin, which can digest and lyse the fibrin clot.
Which of the following is the primary way that antithrombin III, a natural anticoagulant in plasma, helps prevent unnecessary clot formation?
Antithrombin III binds to and inactivates thrombin, a key enzyme in the coagulation cascade, preventing further clot formation.
Study Notes
Blood Coagulation and Fibrin Clot Formation
- Thrombin, in the presence of Ca, activates factor XIII, which cross-links fibrin into polymers, stabilizing the fibrin clot.
- Platelets retract within the fibrin clot.
- Ca ions play a crucial role in the activation of most coagulation phases, except for the first two steps in the intrinsic pathway.
Factors Preventing Clot Extension
- Natural anticoagulants:
- Antithrombin III, a non-Vit K dependent plasma protein that inhibits factors IIa, Xa, and other coagulation factors.
- Heparin, a natural anticoagulant that enhances antithrombin III activity.
- Protein C, a natural anticoagulant that inhibits factors V and VIII activity.
- Protein S, a cofactor that activates protein C and increases plasmin formation.
- Autocrine-paracrine mediators:
- Prostacyclin, which promotes vasodilation and inhibits platelet activation.
- Nitric oxide, which inhibits platelet adhesion and aggregation in response to thrombin.
- Tissue-Factor Pathway Inhibitor (TFPI), an anticoagulant that inhibits the extrinsic Tenase complex.
Why Blood Doesn't Clot in Healthy Vessels
- Clotting factors circulate in an inactive form and are activated only upon injury.
- The liver removes activated factors regularly.
- The speed of blood flow prevents activation of clotting factors and contact with tissue factor (TF).
- The healthy endothelial lining of blood vessels is smooth and negatively charged, repelling negatively charged surfaces that can activate the intrinsic pathway.
- Endothelial cells secrete mediators with anticoagulant action, such as NO and PGI2.
- Circulating platelets have a glycoprotein coat that creates repulsion forces, preventing them from sticking to healthy endothelium.
- Plasma contains natural anticoagulants, such as anti-thrombin III and heparin, that antagonize coagulation.
- Plasma contains a tightly regulated fibrinolytic system that prevents uncontrolled extension of thrombus.
Fate of a Blood Clot
- The fibrinolytic phase breaks down the fibrin clot once it becomes unnecessary, preventing uncontrolled extension of thrombus or embolization.
- The process is meant to regain patency of blood vessels during repair.
Haemostasis Process
- Immediate constriction phase:
- Brief reflexive contraction regulated by local myogenic spasm, nervous reflex, and released vasoconstrictors from platelets and endothelium.
- Blood coagulation phase:
- Involves sequential activation reactions of coagulation factors to convert soluble fibrinogen into an insoluble fibrin fiber.
- Most coagulation factors belong to plasma proteins and circulate as inactive proteolytic enzyme precursors.
- Coagulation factors are synthesized mainly by the liver, with the exception of factor XIII, which is synthesized by endothelial cells.
Test your knowledge on the factors involved in keeping blood in a fluid, un-clotted state within healthy blood vessels. Learn about how these factors prevent unnecessary clot formation and thrombosis.
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