Sem1mini2 - Biochemistry – Blood Clotting System

The activated partial thromboplastin time (aPTT) test is used to measure clotting factors in the intrinsic pathway of the coagulation cascade. This pathway is responsible for initiating clot formation within blood vessels. The aPTT test helps evaluate the function of factors such as VIII, IX, XI, and XII, which are involved in this pathway. The test is commonly used to monitor the effectiveness of anticoagulant therapy, diagnose bleeding disorders, and assess the risk of excessive bleeding during surgical procedures.

Thrombin is a protease responsible for converting fibrinogen to fibrin. Fibrinogen is a soluble protein that is converted into insoluble fibrin during blood clotting. Thrombin cleaves fibrinogen at specific sites, leading to the formation of fibrin molecules that polymerize and form a meshwork, which is essential for blood clot formation. Thrombin also has other important roles in the coagulation cascade, including the activation of other clotting factors and platelets.

Factor Xa is not correlated with the inhibition of Factor VII to VIIa. Factor Xa is a key component in the coagulation cascade and plays a crucial role in the activation of prothrombin to thrombin. It is the activated form of Factors X and is involved in the convergence of the extrinsic and intrinsic pathways. However, it does not have a direct correlation with the inhibition of Factor VII to VIIa.

Factor III, also known as Tissue Factor, initiates the extrinsic pathway of the clotting cascade. This pathway is activated when there is damage to the blood vessel wall, and it involves the release of Tissue Factor from the damaged tissue. Tissue Factor then forms a complex with Factor VII, which activates Factor X and leads to the formation of a blood clot. Factors VIII and IX are part of the intrinsic pathway, which is activated by contact between blood and a foreign surface.

Prostacyclin is an inhibitor of platelet adhesion and aggregation. It is a prostaglandin that is produced by endothelial cells and acts to prevent platelets from sticking together and forming clots. Prostacyclin also causes vasodilation, which helps to maintain blood flow and prevent clot formation. Therefore, it is a natural inhibitor of platelet function and plays an important role in maintaining normal blood circulation.

Fibrinogen is soluble, while its precursor fibrin is insoluble. Fibrinogen is a soluble protein found in the blood plasma, and it is converted into fibrin during the clotting process. Fibrin forms a mesh-like structure that helps in the formation of blood clots to stop bleeding. The insolubility of fibrin allows it to form a stable clot, preventing further blood loss.

The extrinsic pathway is a part of the blood clotting process. Lipoprotein associated coagulation inhibitor is a protein that inhibits the activity of the extrinsic pathway. It prevents the formation of blood clots by blocking the activation of factor X, which is a key step in the extrinsic pathway. Therefore, lipoprotein associated coagulation inhibitor inactivates the extrinsic pathway.

Hemophilia A is a disease characterized by the inability to clot blood. It is an X-linked recessive disorder, meaning it is caused by a mutation on the X chromosome. The correct answer is Factor VIII, as this clotting factor is deficient in individuals with Hemophilia A. Factor VIII plays a crucial role in the clotting cascade, helping to form a stable blood clot. Without enough Factor VIII, blood clotting is impaired, leading to prolonged bleeding and easy bruising.

Hemophilia B is a genetic disorder that results from a deficiency of clotting factor IX. This clotting factor is necessary for the formation of blood clots to stop bleeding. Without enough factor IX, individuals with hemophilia B experience prolonged bleeding and have difficulty forming clots. This condition is also known as Christmas disease, named after the first patient diagnosed with it.

Factor II is also known as prothrombin, while Factor IIa is known as thrombin. Prothrombin is an inactive precursor protein that is converted into thrombin through a series of enzymatic reactions. Thrombin is a key enzyme in the coagulation cascade that plays a crucial role in the formation of fibrin, which is the insoluble protein responsible for blood clot formation. Therefore, the correct answer is Prothrombin, thrombin.

All of the options listed in the question are inhibitors of thrombin. Thrombin is a crucial enzyme involved in the blood clotting process, and these inhibitors play a role in regulating its activity. Heparin is a well-known anticoagulant that directly inhibits thrombin. Alpha2-macroglobulin and Alpha1-antitrypsin are both protease inhibitors that can also inhibit thrombin. Heparin cofactor II is a protein that specifically enhances the inhibitory activity of heparin against thrombin. Therefore, none of the options listed are NOT inhibitors of thrombin.

Vitamin K is responsible for the carboxylation of coagulation factors. Carboxylation is a process that adds a carboxyl group to a molecule. In the context of coagulation factors, carboxylation is important for their activation and function in blood clotting. Therefore, the correct answer is K, carboxylation.

Plasmin is primarily responsible for the degradation of fibrin clots. Plasmin is an enzyme that is derived from its inactive precursor, plasminogen. When plasminogen is activated, it converts fibrin, the protein responsible for clot formation, into soluble fragments, resulting in the breakdown of the clot. Thrombin and prothrombin are involved in the clotting process, while Factor III is not directly involved in clot degradation.

Platelet adhesion is the process of platelets binding to exposed subendothelial tissue after vascular injury. This process is primarily mediated by Von Willebrand Factor (VWF). VWF is a large multimeric glycoprotein that is secreted by endothelial cells and circulates in the blood plasma. It plays a crucial role in platelet adhesion by binding to both platelets and exposed subendothelial collagen. This interaction facilitates the initial attachment of platelets to the site of injury, leading to the formation of a platelet plug and initiation of the clotting cascade.

Thrombin plays a crucial role in the clotting process, but it also needs assistance in breaking down clotting factors to prevent excessive clot formation. Thrombomodulin is a protein that binds to thrombin and activates protein C. Activated protein C, in turn, helps degrade clotting factors. Protein S works in conjunction with protein C to enhance its anticoagulant activity. Therefore, all of the above options (thrombomodulin, protein C, and protein S) work together with thrombin to aid in the degradation of clotting factors.

During vascular injury, the subendothelial cells are exposed, which contain collagen. Collagen is a protein that acts as a binding site for platelets. When platelets come into contact with exposed collagen, they bind to it and initiate the formation of a blood clot to stop bleeding. Therefore, subendothelial cells containing exposed collagen are the site where platelets bind during vascular injury.

Thrombin combines with thrombomodulin present on endothelial cell surfaces forming a complex that converts protein C to protein Ca. Thrombomodulin is a glycoprotein that is expressed on the surface of endothelial cells. When thrombin binds to thrombomodulin, it changes its substrate specificity and instead of promoting clot formation, it activates protein C. Activated protein C then inhibits factors Va and VIIIa, which are necessary for the formation of blood clots, thereby preventing excessive clotting and maintaining blood flow.

Warfarin works by competitively inhibiting the action of vitamin K, which is necessary for the production of clotting factors in the body. By blocking the action of vitamin K, warfarin reduces the production of clotting factors and slows down the clotting process. This helps to prevent the formation of blood clots and is why warfarin is commonly used as an anticoagulant.

The prothrombin time test measures clotting factors in the extrinsic pathway. This pathway is activated when tissue factor is released from damaged blood vessels, leading to the production of thrombin and ultimately the formation of a blood clot. The test is commonly used to monitor the effectiveness of anticoagulant medications and to diagnose clotting disorders.

Von Willebrand Disease (vWD) is a condition caused by a deficiency in von Willebrand Factor (vWF). This deficiency affects the clotting factor known as Factor VIII. Therefore, as a result of the deficiency of vWF, Factor VIII is also affected.

Heparin treatment is most correlated to antithrombin deficiency. Heparin is a medication that works by enhancing the activity of antithrombin, a natural anticoagulant in the body. Antithrombin deficiency is a condition where there is a decreased level or impaired function of antithrombin, leading to an increased risk of blood clot formation. Heparin is commonly used to prevent or treat blood clots in individuals with antithrombin deficiency.

The short chain of the active thrombin molecule is the A chain.

Hemophilia A is characterized by easy bruising and prolonged bleeding. This is because it is a genetic disorder that affects the blood's ability to clot properly. It is caused by a deficiency in clotting factor VIII, which is necessary for the formation of blood clots. Without enough factor VIII, the blood cannot clot effectively, leading to excessive bleeding and easy bruising.

Calcium is the trivial name for Factor IV.

Xa is the point where extrinsic and intrinsic pathways converge. This is because Xa is the activated form of factor X, which is a key component in both pathways. In the extrinsic pathway, factor X is activated by factor VIIa, while in the intrinsic pathway, factor X is activated by factor IXa. Therefore, Xa serves as the common point where these two pathways come together.

Heparin inhibits the coagulation cascade by binding to antithrombin III and enhancing its activity. This leads to the inhibition of several factors involved in the coagulation process, including factor XIIa, factor XIa, factor IXa, factor Xa, and thrombin. However, heparin does not directly inhibit the formation of fibrin, which is the end product of the coagulation cascade. Fibrin is formed when thrombin cleaves fibrinogen, leading to the formation of fibrin monomers that polymerize to form a stable clot.

Von Willebrand Disease is the most commonly inherited bleeding disorder in humans. It is caused by a deficiency or dysfunction of von Willebrand factor (VWF), a protein that plays a crucial role in blood clotting. This disorder can result in prolonged bleeding, easy bruising, and other symptoms related to abnormal clotting. Hemophilia A and B are also inherited bleeding disorders, but they are less common than Von Willebrand Disease. Disorders of Fibrinogen and Factor XIII, Factor XI and Contact Activation, and Antithrombin deficiency are less commonly inherited bleeding disorders.

Antithrombin III is the correct answer because it is a natural anticoagulant that inhibits the activity of several clotting factors, including thrombin, Factors IXa, Xa, XIa, and XIIa. It works by binding to these factors and preventing their interaction with other molecules involved in the clotting cascade. This inhibition helps regulate and prevent excessive blood clotting, reducing the risk of thrombosis. Heparin, another option listed, also inhibits these clotting factors but primarily works by enhancing the activity of antithrombin III. Thrombomodulin and calcium do not directly inhibit these clotting factors.

Factor III, also known as tissue factor, is not calcium dependent. Tissue factor is a protein that plays a crucial role in initiating the coagulation cascade. Unlike other clotting factors, it does not require calcium ions for its activity. Calcium ions are essential for the activation of other clotting factors such as Factor II, VII, IX, and X. Therefore, Factor III is the correct answer as it is the only factor in the given options that is not calcium dependent.

Factor XIII is the correct answer because it is the only factor listed that involves the transglutaminase reaction. Transglutaminase is an enzyme that cross-links proteins by forming covalent bonds between glutamine and lysine residues. Factor XIII is a blood clotting factor that plays a crucial role in stabilizing blood clots by cross-linking fibrin strands, which is achieved through the transglutaminase activity of Factor XIII.

Factor XI and Contact Activation are common in Ashkenazic Jews. This is because Ashkenazic Jews have a higher prevalence of certain genetic mutations that lead to factor XI deficiency, a clotting disorder. Contact activation is a process that triggers blood clotting, and factor XI is involved in this process. Therefore, Ashkenazic Jews are more likely to have abnormalities in factor XI and contact activation, leading to an increased risk of bleeding disorders.

The tenase complex is a key component of the coagulation cascade and is responsible for the activation of factor X. It consists of factor VIIIa, factor IXa, and calcium ions (Ca2+). Factor VIIa, on the other hand, is part of the extrinsic pathway and forms the initiation complex, not the tenase complex. Therefore, factor VIIa is not part of the tenase complex.

Hemophilia B is characterized by prolonged coagulation time. Hemophilia B is a genetic disorder caused by a deficiency or dysfunction of clotting factor IX. This deficiency leads to impaired blood clotting and prolonged bleeding time.

Women on oral contraceptives may also experience disorders of fibrinogen and factor XIII. Oral contraceptives can affect the levels of various coagulation factors in the blood, including fibrinogen and factor XIII. Fibrinogen is a protein necessary for blood clot formation, and factor XIII is an enzyme that stabilizes the clot. Changes in the levels or function of these factors can lead to abnormal clotting or bleeding. Therefore, women on oral contraceptives may be at an increased risk of developing disorders related to fibrinogen and factor XIII.

Factor VIIIa is not found in the prothrombinase complex. The prothrombinase complex is a complex of enzymes and cofactors that converts prothrombin to thrombin during the coagulation cascade. It consists of factor Xa, factor Va, calcium ions, and phospholipids. Factor VIIIa, on the other hand, is not directly involved in the prothrombinase complex but plays a role in the intrinsic pathway of coagulation.

Warfarin, a coumarin-type drug, inhibits the enzyme epoxide reductase. Epoxide reductase is responsible for converting vitamin K epoxide back to its active form, vitamin K hydroquinone. By inhibiting this enzyme, warfarin prevents the recycling of vitamin K and ultimately disrupts the production of clotting factors in the liver. This leads to a decrease in blood clotting ability and can result in internal hemorrhaging, ultimately causing death.

Factor VIIIa is primarily responsible for the formation of fibrin polymers. Factor VIIIa is a cofactor that works together with Factor IXa to activate Factor Xa, which then converts prothrombin to thrombin. Thrombin then acts on fibrinogen, converting it into fibrin monomers. These fibrin monomers then polymerize to form fibrin polymers, which are the main component of blood clots. Therefore, Factor VIIIa plays a crucial role in the formation of fibrin polymers.