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Questions and Answers
What is one method to prevent blood from clotting when it is removed from a person?
What is one method to prevent blood from clotting when it is removed from a person?
How long does it typically take for the intrinsic pathway to cause clotting?
How long does it typically take for the intrinsic pathway to cause clotting?
Which vitamin is necessary for the liver to form several clotting factors?
Which vitamin is necessary for the liver to form several clotting factors?
What condition can lead to vitamin K deficiency in patients with GI diseases?
What condition can lead to vitamin K deficiency in patients with GI diseases?
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What is the most common factor deficiency in Hemophilia A?
What is the most common factor deficiency in Hemophilia A?
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Why will a woman usually not have hemophilia?
Why will a woman usually not have hemophilia?
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What medical action is taken for surgical patients with liver disease?
What medical action is taken for surgical patients with liver disease?
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Which of these factors is NOT formed by the liver and is crucial for clotting?
Which of these factors is NOT formed by the liver and is crucial for clotting?
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What does the term hemostasis refer to?
What does the term hemostasis refer to?
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Which mechanism is NOT involved in hemostasis?
Which mechanism is NOT involved in hemostasis?
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What initiates vascular constriction immediately after a vessel is cut?
What initiates vascular constriction immediately after a vessel is cut?
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Which substance is released by platelets to enhance vasoconstriction?
Which substance is released by platelets to enhance vasoconstriction?
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How do platelets contribute to the formation of a blood clot?
How do platelets contribute to the formation of a blood clot?
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What is a significant feature of platelets regarding their lifecycle?
What is a significant feature of platelets regarding their lifecycle?
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What is the role of actin and myosin in platelets?
What is the role of actin and myosin in platelets?
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What happens to the size of the vascular spasm as the severity of the vessel trauma increases?
What happens to the size of the vascular spasm as the severity of the vessel trauma increases?
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What usually triggers bleeding in hemophilia?
What usually triggers bleeding in hemophilia?
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Which component is most important in the intrinsic pathway for clotting in classic hemophilia?
Which component is most important in the intrinsic pathway for clotting in classic hemophilia?
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What is the threshold platelet count below which bleeding is likely to occur in thrombocytopenia?
What is the threshold platelet count below which bleeding is likely to occur in thrombocytopenia?
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What condition is characterized by small punctate hemorrhages throughout body tissues?
What condition is characterized by small punctate hemorrhages throughout body tissues?
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What happens to a thrombus if it breaks away from its attachment?
What happens to a thrombus if it breaks away from its attachment?
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Which of the following is a risk associated with blood flow that is very slow?
Which of the following is a risk associated with blood flow that is very slow?
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What is the function of genetically engineered t-PA in thrombosis treatment?
What is the function of genetically engineered t-PA in thrombosis treatment?
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What can cause the initiation of the clotting process due to a roughed endothelial surface?
What can cause the initiation of the clotting process due to a roughed endothelial surface?
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What initiates the intrinsic pathway of blood clotting?
What initiates the intrinsic pathway of blood clotting?
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What does activated Factor XI do in the intrinsic pathway?
What does activated Factor XI do in the intrinsic pathway?
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Which factor is missing in classic hemophilia?
Which factor is missing in classic hemophilia?
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What is the role of ADP in the mechanism of platelet plug formation?
What is the role of ADP in the mechanism of platelet plug formation?
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Which of the following components is secreted by activated platelets to promote further aggregation?
Which of the following components is secreted by activated platelets to promote further aggregation?
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What role does calcium ions play in the intrinsic pathway?
What role does calcium ions play in the intrinsic pathway?
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What is the primary function of the glycoprotein coat on the platelet membrane?
What is the primary function of the glycoprotein coat on the platelet membrane?
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What forms the complex known as prothrombin activator?
What forms the complex known as prothrombin activator?
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What is platelet factor 3, and where is it released from?
What is platelet factor 3, and where is it released from?
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What initiates the activation of platelets upon encountering a damaged vascular surface?
What initiates the activation of platelets upon encountering a damaged vascular surface?
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Which sequence correctly describes the activation of factors in the intrinsic pathway?
Which sequence correctly describes the activation of factors in the intrinsic pathway?
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What is the main structural change that platelets undergo when they interact with damaged vessels?
What is the main structural change that platelets undergo when they interact with damaged vessels?
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What happens when blood trauma occurs in relation to platelets?
What happens when blood trauma occurs in relation to platelets?
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What is the significance of the contractile proteins in platelets during clot formation?
What is the significance of the contractile proteins in platelets during clot formation?
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What is the function of thromboxane A2 in the platelet response?
What is the function of thromboxane A2 in the platelet response?
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What is the primary role of prostaglandins in relation to platelets?
What is the primary role of prostaglandins in relation to platelets?
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What is the primary function of thrombin in the clotting process?
What is the primary function of thrombin in the clotting process?
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What initiates the formation of the prothrombin activator in the extrinsic pathway?
What initiates the formation of the prothrombin activator in the extrinsic pathway?
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What role does calcium ions play in the coagulation process?
What role does calcium ions play in the coagulation process?
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What describes the process of clot retraction?
What describes the process of clot retraction?
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Which factor is a key component in the activation of factor X in the extrinsic pathway?
Which factor is a key component in the activation of factor X in the extrinsic pathway?
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What happens to the clot within 20 to 60 minutes after it is formed?
What happens to the clot within 20 to 60 minutes after it is formed?
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What is considered the rate-limiting factor in blood coagulation?
What is considered the rate-limiting factor in blood coagulation?
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What substances are activated by thrombin during clot retraction?
What substances are activated by thrombin during clot retraction?
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Study Notes
Hemostasis
- Hemostasis is the prevention of blood loss.
- It's achieved through several mechanisms when a vessel is cut/ruptured.
- Mechanisms include:
- Vascular constriction
- Platelet plug formation
- Blood clot formation (coagulation)
- Fibrous tissue growth into the clot to permanently close the hole in the vessel.
Vascular Constriction
- Immediately after a blood vessel is damaged, the smooth muscle in the vessel wall contracts.
- This reduces blood flow from the ruptured vessel.
- The contraction results from:
- Local myogenic spasm
- Local autacoid factors from traumatized tissues and blood platelets
- Nervous reflexes initiated by pain nerve impulses or other sensory impulses from the traumatized vessel or nearby tissues.
- Increased vasoconstriction in smaller vessels is often caused by platelets releasing thromboxane A2.
Platelet Plug
- A platelet plug seals very small cuts.
- Platelets (thrombocytes) are minute discs (1-4 micrometers in diameter).
- They are formed from megakaryocytes in the bone marrow (150,000 - 300,000 per microliter).
- Platelets do not have nuclei, cannot reproduce, and have a lifespan of 8-12 days, being eliminated by the spleen's tissue macrophage system.
Platelet Cytoplasm
- Platelets contain contractile proteins (actin and myosin and thrombosthenin), which cause contraction.
- They contain residuals of the ER and Golgi apparatus that synthesize enzymes and store calcium ions.
- They also have mitochondria and enzyme systems that form ATP and ADP.
- Platelets synthesise prostaglandins (local hormones affecting blood vessels and tissues).
- They produce fibrin-stabilizing factor and a growth factor to repair damaged vascular walls.
- Platelet membranes have glycoproteins (prevent adherence to normal endothelium) that cause adherence to injured areas (especially injured endothelial cells), and exposed collagen in the vessel wall.
Mechanism of Platelet Plug
- When platelets contact damaged vessel surfaces (especially collagen), they swell, assume an irregular shape, and form numerous radiating pseudopods.
- Their contractile proteins contract strongly.
- Granules are released containing multiple active factors.
- The platelets become sticky.
- They adhere to collagen in the tissues and von Willebrand factor leaking from the plasma.
- The platelets secrete large quantities of ADP and thromboxane A2.
- This activates nearby platelets, causing them to adhere to the original activated platelets, forming a platelet plug.
Blood Coagulation
- The clot develops 15-20 seconds after severe trauma to the vessel wall, and in 1–2 minutes following minor trauma.
- Within 3-6 minutes, if the vessel opening isn't too large, the entire opening is filled with a clot.
- The clot retracts 20 minutes to one hour after formation, closing the vessel further.
Fate of Blood Clot
- Clots can become invaded by fibroblasts which form connective tissue, turning the clot into a small hole of the vessel wall over time within 1-2 weeks.
- Excess blood in a tissue can promote the clot dissolving by enzymes within the clot itself.
Mechanism of Blood Coagulation
- Procoagulants and anticoagulants normally dominate in the bloodstream to prevent blood from clotting.
- However, if a vessel is damaged, the procoagulants from the damaged tissue become activated, overpowering the anticoagulants and causing the clot to develop.
General Mechanism
- Rupture triggers a series of chemical reactions in the blood involving various clotting factors.
- The result is the formation of a complex of activated substances called prothrombin activator.
- Prothrombin activator catalyzes the conversion of prothrombin into thrombin.
- Thrombin acts as an enzyme to convert fibrinogen into fibrin fibers, which trap platelets, blood cells, and plasma to form the clot.
Conversion of Prothrombin to Thrombin
- Prothrombin activator, in the presence of ionic calcium (Ca++), converts prothrombin to thrombin.
- Thrombin causes the polymerization of fibrinogen molecules into fibrin fibers within 10–15 seconds.
- Prothrombin activator formation is usually the rate-limiting factor in blood coagulation.
- Prothrombin on the platelets first attaches to the damaged tissue.
Clot Retraction
- Within minutes of clot formation, it begins to contract, expressing most of the fluid (serum).
- Platelets adhere to fibrin fibers, tying them together.
- Platelets continue releasing fibrin-stabilizing factor, increasing cross-linking bonds.
- Thrombosthenin, actin, and myosin (contractile proteins) activate and contribute to clot retraction
- Thrombin also helps to activate and accelerate clot retraction as well as calcium ions released from calcium stores in the mitochondria, endoplasmic reticulum, and Golgi apparatus.
Initiation of Coagulation
- Prothrombin activator is formed via two pathways:
- Extrinsic pathway—starts with trauma to the vascular wall and surrounding tissues.
- Intrinsic pathway—starts with trauma to the blood itself or exposure to collagen from a damaged vessel wall.
Clotting Factors
- Detailed list of clotting factors and their synonyms provided.
Extrinsic Pathway
- Tissue damage releases tissue factor (a complex of several factors).
- Tissue factor complexes with Factor VII, then with Factor X.
- Calcium ions catalyze the conversion of Factor X to activated Factor X (Xa).
- Activated Factor X combines quickly with tissue phospholipids from tissue factor or platelet phospholipids to initiate the prothrombin activator complex.
- Calcium ions split prothrombin into thrombin.
Intrinsic Pathway
- Blood trauma or contact with collagen activates factor XII to form activated factor XII (XIa).
- Activated factor XII acts on factor XI to activate factor XI.
- Activated factor XI activates factor IX.
- Activated factor IX, activated factor VIII, platelet phospholipids, and platelet factor 3 activate Factor X.
- Factor X forms the prothrombin activator complex.
Role of Calcium
- Crucial for all clotting reactions except the first two steps in the intrinsic pathway.
- Calcium ion concentration rarely becomes so low as a to significantly affect clotting in a healthy body.
- Blood can be prevented from clotting by lowering the calcium ion concentration (using substances like oxalate ion).
Interaction Between Pathways
- The extrinsic pathway is relatively fast, often only taking 15 seconds.
- The intrinsic pathway is much slower, usually taking 1-6 minutes.
Bleeding Disorders
- Almost all bleeding disorders involve factors created by the liver
- Vitamin K is important for liver function and the formation of several clotting factors.
- Vitamin K deficiency occurs rarely in healthy adults as it is produced by intestinal bacteria.
- Bleeding disorders can occur due to problems with GI absorption of fats, liver disease, or obstruction of the bile ducts.
- Bleeding disorders in newborns before their gut bacteria produce Vitamin K
Hemophilia
- Hemophilia is a bleeding disorder occurring almost exclusively in men.
- Hemophilia A (classic hemophilia) is due to the deficiency of Factor VIII.
- Hemophilia B affects Factor IX.
Hemophilia (cont.)
- Females are often carriers of hemophilia genes.
- A female carrier will pass on hemophilia to half of her male offspring.
- A female will not have hemophilia if she has at least one X chromosome containing the normal gene for a clotting factor.
Thrombocytopenia
- Bleeding usually happens from small venules and capillaries in thrombocytopenia.
- Small purplish spots (thrombocytopenic purpura) often develop on the skin due to small hemorrhages.
- Bleeding does not start until the platelet count drops below 50,000/µl.
Thrombocytopenia (cont.)
- Clot retraction test can be performed.
- Idiopathic thrombocytopenia is an autoimmune condition.
- Treatment may involve corticosteroids or splenectomy
Thrombi and Emboli
- A thrombus is an abnormal blood clot that forms inside a blood vessel.
- An embolus is a thrombus that dislodges and travels through the bloodstream.
- Emboli can block blood flow in major arteries or the pulmonary arteries.
- In the case of pulmonary emboli, this may cause massive pulmonary embolism
Thromboembolic Conditions
- Conditions that may cause blood clots include:
- Roughened/damaged endothelial surfaces (e.g., from arteriosclerosis, infections, trauma.)
- Slow blood flow (where small quantities of thrombin and other procoagulants are always being formed).
Use of tPA
- tPA (tissue plasminogen activator) is a genetically engineered enzyme.
- tPA is delivered directly to a thrombosed area through a catheter.
- tPA activates plasminogen into plasmin.
- Plasmin dissolves intravascular clots.
- Effective if administered within the first hour or so of a coronary artery occlusion.
Thrombosis and Embolism
- Blood clots often occur in individuals confined to bed due to limited blood flow in the lower extremities.
- Blood clots can dislodge from their initial site, traveling to other parts of the body as emboli.
- Large emboli may block major arteries.
- Pulmonary emboli can lead to massive pulmonary blockage.
Disseminated Intravascular Coagulation
- Widespread activation of clotting mechanisms occurs in widespread areas of the circulation due to the presence of large amounts of traumatized/dying tissue, releasing a large amount of tissue factor.
- Resulting small clots lead to decreased oxygen and nutrient delivery.
- Can result in circulatory shock and/or bleeding due to the consumption of clotting factors.
Anticoagulants - Heparin
- Commercial heparin is derived from animal tissues and purified.
- Heparin injection increases clotting time from a normal 6 minutes to 30 minutes or more.
- Immediate prevention or slowing of further thromboembolic conditions is possible.
- The effects of heparin last 1.5-4 hours, broken down by the enzyme known as heparinase in the blood.
Summary of Hemostasis Test Values
- Bleeding time: 1–6 minutes
- Clotting time: 6–10 minutes
- Prothrombin time: 12 seconds
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Description
Explore the vital processes involved in hemostasis, the prevention of blood loss. This quiz covers the mechanisms like vascular constriction, platelet plug formation, and blood clotting. Learn how these mechanisms interact to heal damaged blood vessels effectively.