Block 2 Biochem Clotting System

The activated partial thromboplastin time (aPTT) test is a laboratory test used to evaluate the clotting factors in the blood. It measures the time it takes for a clot to form in the intrinsic pathway of the coagulation cascade. The intrinsic pathway is one of the two main pathways involved in blood clotting, the other being the extrinsic pathway. The aPTT test specifically assesses the clotting factors in the intrinsic pathway, which includes factors VIII, IX, XI, and XII. Therefore, the correct answer is intrinsic.

Factor Xa is not correlated with the inhibition of Factor VII to VIIa. Factor Xa is a key component in the coagulation cascade and is involved in the activation of prothrombin to thrombin. It is also the activated form of Factors X. However, Factor VII to VIIa is not directly related to Factor Xa. Therefore, the inhibition of Factor VII to VIIa does not correlate with Factor Xa.

Thrombin is a protease responsible for converting fibrinogen to fibrin. It is an enzyme that plays a crucial role in the blood clotting process. Thrombin acts on fibrinogen, a soluble plasma protein, and cleaves it into fibrin monomers. These monomers then polymerize to form a fibrin clot, which helps in the formation of blood clots to prevent excessive bleeding. Thrombin is produced from its precursor, prothrombin, through a series of enzymatic reactions in the coagulation cascade.

Plasmin is primarily responsible for the degradation of fibrin clots. Plasmin is an enzyme that breaks down fibrin, the protein responsible for clot formation. It is derived from plasminogen, which is activated by tissue plasminogen activator (tPA) or urokinase-type plasminogen activator (uPA). Once activated, plasmin cleaves fibrin into smaller fragments, leading to clot dissolution. Thrombin and prothrombin are involved in the clot formation process, while Factor III (also known as tissue factor) is a protein that initiates the clotting cascade.

Prostacyclin is an inhibitor of platelet adhesion and aggregation. It is a potent vasodilator and prevents platelets from sticking together and forming clots. By inhibiting platelet activation, prostacyclin helps to maintain normal blood flow and prevent the formation of harmful blood clots.

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 because in Hemophilia A, there is a deficiency or absence of this clotting factor. Factor VIII plays a crucial role in the clotting cascade, helping to form a stable blood clot. Without enough Factor VIII, individuals with Hemophilia A experience prolonged bleeding and are at risk for excessive bleeding even from minor injuries.

Von Willebrand Disease (vWD) is caused by a deficiency in von Willebrand Factor (vWF). Factor VIII is also affected as a result of this deficiency. Von Willebrand Factor plays a crucial role in stabilizing and protecting Factor VIII in the blood, which is necessary for normal blood clotting. Therefore, a deficiency in vWF leads to a decrease in the levels and function of Factor VIII, contributing to the bleeding tendencies observed in vWD patients.

Thrombomodulin, Protein C, and Protein S all work with thrombin in aiding the degradation of clotting factors. Thrombomodulin is a protein that binds to thrombin and changes its function, leading to the activation of Protein C. Protein C then binds to Protein S, and together they form a complex that degrades clotting factors, such as Factors Va and VIIIa. Therefore, all of the options listed (Thrombomodulin, Protein C, and Protein S) work together in aiding the degradation of clotting factors.

Platelet adhesion, the process of platelets binding to exposed subendothelial tissue after vascular injury, is primarily mediated by Von Willebrand Factor. Von Willebrand Factor is a protein that is released by endothelial cells and binds to platelets, allowing them to adhere to the damaged blood vessel walls. This interaction between Von Willebrand Factor and platelets is crucial for the formation of blood clots and the initiation of the clotting cascade.

Factor III, also known as Tissue Factor, initiates the extrinsic pathway of the clotting cascade. This pathway is activated when there is tissue damage, and Factor III is released from damaged tissue. It then forms a complex with Factor VII, which leads to the activation of Factor X and ultimately the formation of a blood clot. Factors VIII and IX are part of the intrinsic pathway, while Factor X is a common pathway factor that is activated by both the extrinsic and intrinsic pathways.

Factor II is known as prothrombin, while Factor IIa is known as thrombin. Prothrombin is an inactive precursor protein that is converted into active thrombin through a series of enzymatic reactions. Thrombin plays a crucial role in the coagulation cascade by converting fibrinogen into fibrin, which forms a clot to stop bleeding. Therefore, the correct answer is Prothrombin, thrombin.

The lipoprotein associated coagulation inhibitor is the correct answer because it is known to inactivate the extrinsic pathway of coagulation. This inhibitor plays a crucial role in regulating blood clotting by inhibiting the activity of tissue factor pathway inhibitor (TFPI), which is involved in the extrinsic pathway. By inhibiting TFPI, the lipoprotein associated coagulation inhibitor prevents the activation of factor X and subsequent clot formation through the extrinsic pathway.

Hemophilia B is a genetic disorder that occurs due to a deficiency of a specific clotting factor. In this case, the correct answer is Factor IX. This clotting factor plays a crucial role in the blood clotting process, specifically in the formation of fibrin, which helps in stopping bleeding. A deficiency of Factor IX leads to impaired blood clotting and excessive bleeding, which is characteristic of Hemophilia B.

Vitamin K is responsible for the carboxylation of coagulation factors. Carboxylation is a process that adds a carboxyl group to a molecule, and in this case, it is necessary for the activation of coagulation factors. Vitamin K plays a crucial role in blood clotting by helping to convert inactive coagulation factors into their active forms.

Fibrin is insoluble, while its precursor Fibrinogen is soluble. Fibrinogen is a soluble protein that circulates in the blood plasma, and it is converted into insoluble fibrin during the blood clotting process. Fibrin forms a mesh-like structure that helps in the formation of blood clots to prevent excessive bleeding. This conversion from soluble fibrinogen to insoluble fibrin is a crucial step in the clotting cascade.

factor 13a forms covalent crosslinks between fibrin dimers

All of the options listed in the question are inhibitors of thrombin. Heparin is a widely used anticoagulant that inhibits thrombin by binding to antithrombin III and enhancing its activity. Alpha2-macroglobulin is a protease inhibitor that can also inhibit thrombin. Alpha1-antitrypsin is a serine protease inhibitor that can inhibit thrombin as well. Heparin cofactor II is a protein that specifically inhibits thrombin by binding to it and preventing its activity. Therefore, the correct answer is that all of the options listed are inhibitors of thrombin.

Warfarin acts by competitively inhibiting Vitamin K, which is essential for the activation of clotting factors in the body. By inhibiting Vitamin K, warfarin reduces the production of active clotting factors, thus preventing the formation of blood clots. This mode of action makes warfarin an effective anticoagulant medication.

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 lack of this anticoagulant, leading to an increased risk of blood clot formation. Heparin is commonly used to prevent and treat blood clots in individuals with antithrombin deficiency.

Calcium is the trivial name for Factor IV.

The tenase complex is a key component of the coagulation cascade and is responsible for activating 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 tissue factor-factor VIIa complex. Therefore, factor VIIa is not part of the tenase complex.

Prothrombin is cleaved to form a 2-chain active thrombin molecule, with one long chain and one short chain. The short chain of the active thrombin molecule is referred to as the A chain.

The prothrombin time test is used to measure clotting factors found in the extrinsic pathway besides the common pathway. The extrinsic pathway is one of the two pathways involved in blood clotting, the other being the intrinsic pathway. The extrinsic pathway is activated by tissue factor (TF) released from damaged blood vessels, while the intrinsic pathway is activated by factors within the blood. Therefore, the prothrombin time test specifically measures the clotting factors in the extrinsic pathway to assess the overall clotting function of an individual.

Heparin is a medication that inhibits blood clotting. It works by preventing the formation of fibrin, a protein that forms the mesh-like structure of blood clots. Therefore, heparin does not inhibit fibrin, making it the correct answer in this case. Factors XIIa, XIa, IXa, and Xa are all enzymes involved in the blood clotting cascade, and heparin can inhibit their activity. Thrombin is also inhibited by heparin, as it plays a crucial role in converting fibrinogen to fibrin.

Factor III, also known as tissue factor, is NOT calcium dependent. Tissue factor is a transmembrane protein that initiates the extrinsic pathway of blood coagulation. Unlike other clotting factors, Factor III does not require calcium ions for its activation. Instead, it forms a complex with Factor VIIa, which then activates Factor X to start the coagulation cascade.

Thrombomodulin is the correct answer because it is the protein present on endothelial cell surfaces that forms a complex with thrombin. This complex then converts protein C to protein Ca. Protein S, Factor Va, Factor VIIa, and Protein C are not directly involved in this process.

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

During vascular injury, the inner lining of blood vessels, called endothelial cells, gets damaged, exposing the underlying layer of cells known as subendothelial cells. These subendothelial cells contain exposed collagen, which acts as a binding site for platelets. Platelets bind to the exposed collagen to form a plug and initiate the clotting process to prevent excessive bleeding. Therefore, subendothelial cells are the correct answer as they contain exposed collagen to which platelets bind during vascular injury.

Factor XIII is the correct answer because it is involved in the transglutaminase reaction. Transglutaminase is an enzyme that catalyzes the formation of covalent bonds between proteins. Factor XIII is a clotting factor in the blood that plays a role in stabilizing blood clots by cross-linking fibrin. This cross-linking process is mediated by the transglutaminase activity of Factor XIII.

Factor VIIIa is not found in the prothrombinase complex. The prothrombinase complex is composed of factor Xa, factor Va, and phospholipids, which work together to convert prothrombin to thrombin. Factor VIIIa, on the other hand, is part of the intrinsic pathway of the coagulation cascade and is not directly involved in the formation of the prothrombinase complex.

Xa is the point where the extrinsic and intrinsic pathways converge. Xa is formed through the activation of factor X in both pathways, with the extrinsic pathway being triggered by tissue factor and the intrinsic pathway being triggered by factors within the blood. Once Xa is formed, it goes on to activate factor II (prothrombin) to form thrombin, which then leads to the formation of a blood clot. Therefore, Xa is the common point where both pathways merge and initiate the clotting cascade.

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 involved in blood clotting. This disorder can result in prolonged bleeding and easy bruising. Hemophilia A and Hemophilia 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 all other types of bleeding disorders, but they are not as commonly inherited as Von Willebrand Disease.

Antithrombin III is the correct answer because it is a natural anticoagulant that inhibits the activity of thrombin as well as several other clotting factors including Factors IXa, Xa, XIa, and XIIa. It works by binding to these factors and preventing their activation, thereby preventing the formation of blood clots. Heparin, another option, also inhibits thrombin and some of these clotting factors, but it does so indirectly by enhancing the activity of antithrombin III. Thrombomodulin is a protein that helps activate protein C, which in turn inhibits thrombin. Calcium, on the other hand, is not directly involved in inhibiting these clotting factors.

Women on oral contraceptives may also experience disorders of fibrinogen and factor XIII. This is because oral contraceptives can alter the levels of certain clotting factors in the blood, including fibrinogen and factor XIII. These alterations can increase the risk of abnormal blood clotting or bleeding disorders in some women.

Factor XI deficiency is a common disorder in Ashkenazic Jews. This is a hereditary bleeding disorder that affects the blood's ability to clot properly. Contact activation refers to the process by which the blood clotting cascade is initiated, and factor XI plays a crucial role in this process. Therefore, it is common for Ashkenazic Jews to have a deficiency in factor XI and abnormal contact activation, leading to a higher risk of bleeding and clotting disorders.

Warfarin, a coumarin-type drug, inhibits the enzyme Epoxide reductase. This enzyme is responsible for the conversion of vitamin K epoxide back to its active form, vitamin K hydroquinone, which is essential for the synthesis of clotting factors. By inhibiting epoxide reductase, warfarin interferes with the recycling of vitamin K and disrupts the normal clotting process, leading to internal hemorrhaging and ultimately death.

Hemophilia B is characterized by prolonged coagulation time. Hemophilia B is a genetic disorder caused by a deficiency in clotting factor IX, which is necessary for the blood to clot properly. Without enough factor IX, the coagulation process is impaired, leading to prolonged bleeding.