Fichas
Platelets and coagulation, bleeding and thrombotic disorders
Fichas del conjunto (110)
- 1What is haemostasis?The prevention of blood loss from the circulatory system.
- 2What are the four main systems involved in the prevention and arrest of blood loss?The vascular system, platelets, the coagulation system, and the fibrinolytic system.
- 3What does haemostasis provide a balance between?A pro-coagulant and an anti-coagulant environment.
- 4Starting with the vascular endothelium, list the layers of a blood vessel towards the outer aspect.Vascular endothelium, tunica intima, internal elastic lamina, tunica media, external elastic lamina, and tunica adventitia.
- 5When exposed in the tunica media, what protein can activate haemostatic processes?Collagen.
- 6Under normal circumstances, what negative properties does blood have that are removed with damage?Anticoagulant properties.
- 7Under normal circumstances, what negative properties does blood have that are removed with damage?Anticoagulant properties.
- 8What are thrombocytes?The second numerous blood cell after erythrocytes, they are cytoplasmic fragments of megakaryocytes in the bone marrow.
- 9What is the range of thrombocytes per litre of blood found in humans?150 - 400 x 10^9/L
- 10What number of thrombocytes per litre of blood can exist without spontaneous bleeding?50 x 10^9/L
- 11What number of thrombocytes per litre of blood would be expected for spontaneous bleeding?20 x 10^9/L
- 12List the three zones of a platelet.The outer zone, the cytosol gel zone and the platelet organelles.
- 13What does the outer zone of a platelet consist of and what is it's role?It consists of a mucopolysaccharide surface coat, submembranous filaments, and open and closed membrane systems which provide phospholipid for participation in the coagulation cascade. The outer zone has a role in platelet adhesion and aggregation.
- 14What does the cytosol gel zone of a platelet consist of and what is its role?It contains contractile proteins, microfilaments and microtubules. The contents contribute to the platelet's shape change (inside out), as well as to adhesion, aggregation, and the 'release action' of their granule contents which potentiates aggregation.
- 15What do the platelet organelles consist of?Electron-dense bodies, ADP, serotonin and calcium for release action, and alpha-granules containing growth factors, fibrinogen and other procoagulants, and also lysosomes and mitochondria.
- 16Where does thrombopoiesis occur?In the bone marrow.
- 17What do megakaryocytes, large cells in the bone marrow of 5000um3 in volume, not undergo?Cell division.
- 18What is endomitosis and what does it produce?Endomitosis is when the nucleus of a cell divides but the cytoplasm does not, producing a polyploid nucleus.
- 19How many thrombocytes can be produced per megakaryocyte?Thousands!
- 20What chemical modulates thrombopoiesis and where is it produced?Thrombopoietin, produced in the liver and kidneys.
- 21The concentration of thrombopoietin in the blood is always the same. What is this concentration?100 picograms thrombopoietin/ mL of blood.
- 22What does thrombopoietin do?Thrombopoietin triggers maturation of thrombocytes and their release from the bone marrow.
- 23How does thrombopoietin act and how does it feed back to the liver and kidneys?Thrombopoietin binds to receptors on platelets and megakaryocytes to trigger maturation and release from the bone marrow. If there are few platelets in the circulation, more thrombopoietin will make it back to the bone marrow and trigger the maturation and release, whereas if platelets are plentiful in the circulation, the thrombopoietin will bind to their receptors and less will make it back to the bone marrow to have an effect.
- 24What do the platelet's alpha-granules contain?Factors to assist cohesion, factors to promote the chemotaxis of fibroblasts, platelet-derived growth factor, and coagulation factors V, IX, and XIII.
- 25What effect does serotonin have on blood vessels and why is it significant that it is present in platelet electron-dense granules?Serotonin is a vasoconstrictor which is significant in the function of platelets which is to arrest blood loss. Thrombosis is made possible by blood vessels being constricted and disallowing much blood to reach a damaged area to be lost.
- 26What activates the open canalicular system of platelets?Collagen and other extravascular components exposed after blood vessel damage.
- 27What does the open canalicular system allow platelets to do?It allows them to turn themselves inside out so that their granules are exterior. This means that they have a larger surface area to attach to blood vessels and/or each other in thrombosis.
- 28In what situation is the coagulation system activated?If thrombocytes alone are not enough to achieve haemostasis, for example if a large blood vessel is damaged, the coagulation system is activated to form a secondary plug on top of the primary thrombocyte plug.
- 29What composes the coagulation system?A series of functionally specific plasma proteins.
- 30What does the coagulation system 'aim' to produce?Fibrin, which forms a stable 'plug' on top of the primary thrombocyte plug.
- 31The coagulation cascade is a sequence in which......a series of enzymes act on substrates to cleave them, in turn activating their enzymatic function.
- 32What is the first tissue factor to be activated in the coagulation system in both the intrinsic and the extrinsic pathways?Tissue factor VII.
- 33What are the second tissue factors activated in the intrinsic and extrinsic pathways of the coagulation system?In the intrinsic pathway, factor VII activates factor X, whereas in the extrinsic pathway it activates factor IX.
- 34What is TFPI and what does it do?Tissue Factor Pathway Inhibitor inhibits both the intrinsic and extrinsic pathways relatively early in the coagulation cascade by inhibiting both factor X and factor IX.
- 35Which tissue factor is produced in the extrinsic pathway?Factor VIII, von Willebrand's factor.
- 36What does factor VIII, along with PL and Ca2+, activate in the intrinsic pathway of the coagulation cascade?Factor X to factor Xa (a = activated).
- 37Along with PL and Ca2+, what does factor Xa activate?Prothrombin to thrombin.
- 38In what three ways can thrombin increase its own production earlier on in the coagulation cascade once a small amount has been produced?It can help to activate prothrombin, along with Xa, PL and Ca2+; it can activate factor VIII which in turn activates factor X which activates prothrombin; and it can activate XI which activates VIII - then X - then prothrombin to thrombin.
- 39What does thrombin catalyse the conversion of?Fibrinogen to a fibrin monomer.
- 40Once the fibrin monomers have joined to form a polymer, what happens?Thrombin activates factor XIII and this stabilises the fibrin polymer into a clot.
- 41What does the coagulation cascade occur on top of?On top of platelets and fibrinogen. The fibrinogen is present in the circulating blood and aggregates with platelets on an area of damage to form a platelet-fibrinogen complex, then the coagulation cascade reactions to form a stable fibrin clot occur on top of this.
- 42Thrombin feeding back to increase its own production, can amplify the thrombin concentration by how many times?200,000.
- 43What are the two main roles of thrombocytes in haemostasis?Contraction of the secondary haemostatic plug (which is the function of the submembranous filaments, the cytoplasmic contractile elements) to reduce the endothelial gap and facilitate tissue re-growth, and release of growth promoters (primarily platelet-derived growth factor which is a fibroblast mitogen that is chemotactic for fibroblasts, neutrophils and smooth muscle cells).
- 44If the vascular endothelium is damaged or missing, what is exposed that results in platelet activation and induces the formation of a primary haemostatic plug?The subendothelium, containing collagen and fibronectin.
- 45What type of charge is lost if the vascular endothelium is missing or damaged?The negative coating charge.
- 46What are the two main chemicals produced by the vascular endothelium in balance when it is healthy/not damaged?Von Willebrand's factor and thrombomodulin.
- 47What is von Willebrand's factor?It is a procoagulant as its function is to carry factor 8 to prevent it from being broken down. Factor 8 is a crucial part of the coagulation cascade that activates factor X, the second step in the cascade.
- 48What is the function of thrombomodulin?Thrombomodulin is a chemical produced when the vascular endothelium is intact. It is an anticoagulant produced in balance with von Willebrand's factor. It is a negative regulator that binds thrombin to the vascular endothelium to inactivate it, preventing it from converting/clotting fibrinogen to fibrin. The thrombomodulin-thrombin complex also activates protein C, which stimulates fibrinolysis.
- 49What is the major function of the fibrinolytic system?The degradation and dissolution of formed fibrin within the circulation.
- 50What is the key proteolytic enzyme in the fibrinolytic system?Plasmin!
- 51Outline the steps/factors in the fibrinolytic system.When intact, the vascular endothelium produces tissue plasminogen activator (T-PA), which activates the protein plasminogen. Once plasminogen is activated it is converted to plasmin, which breaks down fibrin.
- 52What happens to the products of the degradation of fibrin by the fibrinolytic pathway?They are removed from the circulation and further degraded by macrophages and eosinophils.
- 53List the three most important chemicals produced by the intact vascular endothelium that promote an anticoagulant environment and explain what they do.Tissue factor pathway inhibitor (TFPI) binds to/inhibits X so that it cannot be activated to Xa, and the resulting complex inactivates VIIa. Prostacyclin (PGI2) inhibits platelet aggregation and induces vasodilation. Tissue plasminogen activator (T-PA) activates plasminogen to plasmin which induces the lysis of fibrin/fibrinogen.
- 54If intact, what is the overall effect of the factors produced and inhibited by the vascular endothelium?Inhibition of platelets/coagulation reactions and limitation of haemostatic activity.
- 55Disorders of haemostasis and coagulation are a result of one of two things. What are these?Quantitative defects, the platelets are functional but present in low numbers, or qualitative defects, the platelets are present but not functional.
- 56What four things may disorders of haemostasis and coagulation involve?Coagulation proteins, platelets, inhibitors, and the vascular endothelium.
- 57What are the two, opposing, possible results of a haemostatic/coagulant disorder?Excessive bleeding (a haemorrhagic disorder), or inappropriate/excess clotting (a thrombotic disorder).
- 58Can haemostatic/coagulation disorders be congenital or acquired?Both.
- 59What must therapy for haemostatic/coagulant disorders try to do?Correct the cause of the disease, as opposed to only treating the symptoms.
- 60List 4 systemic diseases that affect haemostasis.Liver disease (as thrombopoietin is produced in the liver), disseminated intravascular coagulation (DIC), leukaemia, and septacaemia (widespread damage to vessels).
- 61Name two congenital haemorrhagic disorders of platelets and give a brief explanation of each of them.Bernard-Soulier disease is a deficiency of glycoproteins which prevents platelet adhesion to collagen. It is a fairly rare qualitative condition in which the platelets are often very large. Thrombasthenia is another qualitative disorder that is the opposite of Bernard-Soulier disease, in which normal vascular adhesion is permitted but not the aggregation of platelets.
- 62List three inherited coagulopathies.Haemophilia A (factor VIII deficiency), haemophilia B (factor IX deficiency), and von Willebrand's disease (pseudohaemophilia).
- 63Which of the haemophilias is more common?Haemophilia A.
- 64Two which chromosome are haemophilias A and B linked?The X chromosome, which is why those affected are predominately male while females are carriers of the disease.
- 65What are the two pathologies of haemophilia A?Markedly reduced factor VIII (0.5-5% of the normal concentration), or a functional defect with normal or near-normal levels of factor VIII.
- 66What is likely to be the most striking clinical presentation of haemophilia A?Large haemorrhages following minor trauma as a result of haemostasis being impaired.
- 67What is the correct term for haemorrhages around joints?Haemarthritis.
- 68What is the actual result of haemophilia A (factor VIII deficiency)?Very little factor X is activated and so the rest of the coagulation cascade in which eventually activated thrombin converts fibrinogen to fibrin cannot occur.
- 69What is the treatment for haemophilia A in the event of trauma, which patients may also choose to administer prophylactically?Factor VIII administration.
- 70Can haemophilia B be distinguished from haemophilia A by clinical presentation?No, both present with spontaneous and painful bleeding into the muscles and joints (depending on the severity of the factor VIII or IX deficiency).
- 71What proportions of people with haemophilia B lack factor IX entirely or have a functionally defective protein?85% of patients lack factor IX and a smaller proportion have a functionally defective protein.
- 72What is the treatment for haemophilia B?As with haemophilia A, treatment is by administering factor IX either when it is needed i.e. in the event of trauma, or prophylactically.
- 73What is the result of the deficiency of von Willebrand's factor in pseudohaemophilia?The lack of von Willebrand's factor means that factor 8 is degraded and thrombocyte aggregation is impeded.
- 74Generally, what do pseudohaemophilia patients present with as opposed to the haemarthritis seen in haemophilia?Mild, episodic bleeding from mucous membranes (superficial).
- 75What are pseudohaemophilia patients treated with in the event of episodic bleeding, trauma-induced life-threatening haemorrhage, or spontaneous bleeds?Factor VIII protein, as with haemophilia A.
- 76Name two acquired coagulopathies.Disseminated intravascular coagulation (DIC) and vitamin K deficiency.
- 77What does 'petechiae' refer to?Bruising.
- 78What does 'purpura' refer to?Bleeds.
- 79Why is disseminated intravascular coagulation (DIC) a coagulopathy rather than a thrombotic disorder?Because it has a haemorrhagic effect, despite having a thrombotic cause.
- 80Why is there a high risk of spontaneous bleeding in disseminated intravascular coagulation (DIC)?Microthrombi form in DIC, causing all the clotting factors to be used up. Deposits of fibrin and vascular injuries lead to both damage to and high usage of platelets which depletes thrombocytes and leads to a high risk of spontaneous bleeding. Hence DIC has a thrombotic cause but a haemorrhagic effect.
- 81In disseminated intravascular coagulation (DIC), thrombosis of small vessels is widespread. List four areas that frequently become populated with microinfarcts.The kidneys, central nervous system, adrenal glands and myocardium frequently become populated with microinfarcts.
- 82Name two conditions that DIC is often associated with.Leukaemia (and other malignant blood disorders) and complications in pregnancy/childbirth.
- 83Which blood clotting factors require vitamin K for their synthesis?Factors 2, 7, 9 and 10.
- 84What is the result of the deficiency of blood clotting factors resulting from vitamin K deficiency?The inability to form a secondary fibrin clot.
- 85Name two things that might result in vitamin K malabsorption.Bowel cancer, or removal of some bowel in bariatric surgery.
- 86Name two situations which may cause malnutrition and resulting vitamin K deficiency.A strict diet, or famine.
- 87Why might chronic ingestion of oral antibiotics result in vitamin K deficiency?Because the antibiotics will deplete the E. coli populations in the large intestine, and these produce the majority of an individual's vitamin K and exchange it for the energy provided by food passing through the gut.
- 88What condition to do with the liver/gallbladder can cause vitamin K deficiency, as well as the deficiency of other fat-soluble vitamins?Obstructive jaundice - bile is required to emulsify fats for absorption so that they, and anything dissolved in them, can be absorbed. If the bile is blocked then the fat consumed in an individual's diet cannot be effectively absorbed, along with the fat-soluble vitamins.
- 89In thrombotic disorders, what kind of environment is an individual's blood/circulatory system?A procoagulant environment.
- 90What is thrombocytosis?A normal, reactive increase in platelet number in response to tissue damage.
- 91What is thrombocythaemia?A thrombotic disorder, the cause of which is idiopathic (not known), in which there is an abnormally increased number of platelets and an increased risk of haemorrhage and thrombosis.
- 92What conditions might thrombocythaemia be associated with?Myeloproliferative disorders, such as chronic myeloid leukaemia (as platelets result from a myeloid progenitor).
- 93What is thrombocytopenia?An abnormally reduced number of platelets.
- 94What happens in idiopathic thrombocytopenic purpura (ITP)?There is increased removal of platelets from the circulation by antibodies, which results in depleted platelet numbers and increased bleeding. Although ITP could be seen as haemorrhagic disorder because of the pathological bleeding, the abnormality is actually to do with the production, sequestration or removal of platelets.
- 95What can thrombocytopenia be caused by?Generalised bone marrow failure (e.g. by cytotoxic drugs), bone marrow replacement by malignant cells or fibrosis, selectively impaired platelet production (e.g. in rubella), or metabolic impairment of megakaryocyte production (e.g. vitamin B12 or folic acid deficiencies).
- 96What is thrombotic thrombocytopenic purpura (TTP) characterised by?Thombi in small vessels, decreased numbers of platelets, and haemolysis. Vascular injury is followed by damage and destruction of thrombocytes and erythrocytes.
- 97What is the difference between idiopathic thrombocytopenic purpura (ITP) and thrombotic thrombocytopenic purpura (TTP)?In ITP, platelets are removed from the circulation by antibodies (prematurely/incorrectly sequestered) which results in thrombocytopenia and haemorrhage, whereas in TTP the platelets are removed from the circulation by forming thrombi which results in thrombocytopenia and haemorrhage.
- 98What is thrombophilia?The increased tendency to form blood clots.
- 99What can inherited thrombophilia be a result of?Inherited deficiencies of coagulation inhibitors such as protein C (and its cofactor proteins) and anti-thrombi III.
- 100What is the function of anti-thrombin III?It inactivates thrombin by joining a complex of thrombin and a cofactor.
- 101Why would lack of anti-thrombin III result in thrombophilia?Thrombin is required, along with fibrinogen, to form fibrin clots. If anti-thrombin III is deficienct then there is reduced inhibition of thrombin and, provided there is a ready supply of fibrinogen, fibrin clots can form without any vascular damage.
- 102What is it called when thrombi travel and lodge?Thromboemboli.
- 103Why would protein C deficiency result in thrombophilia?Protein C destroys coagulation factors 5 and 7 when activated, so its deficiency results in reduced inhibition of factors 5 and 7 and therefore more fibrin being produced.
- 104What is there a high risk of if fibrin production is not inhibited?Venous thromboembolism.
- 105What is venous thromboembolism?The occlusion of a blood vessel by a thrombus which originated in a larger blood vessel and has been carried by the circulatory system away from its original site.
- 106What does venous thromboembolism commonly occur after?After surgical operations followed by prolonged bed rest, as a result of reduced blood flow and also the postoperative hypercoagulable state.
- 107Even if the fibrinolytic system is activated, how might venous thromboemboli still occur?Fragments of a clot may break off and form emboli before dissolution by the fibrinolytic system.
- 108How does a pulmonary embolism result from a venous thromboembolism?Venous thromboemboli can pass through the vena cava and the right chambers of the heart but lodge in the pulmonary circulation, resulting in a pulmonary embolism.
- 109What is the result of a pulmonary embolism and what are the common clinical symptoms?Pulmonary embolism results in reduced perfusion of blood in the lungs, varying in severity depending on the site and size of the occluded vessel(s). Common symptoms include chest pain, and haemoptysis (coughing up bloody sputum).
- 110Give some examples of acquired thrombophilia.Post-operative thrombophilia, and arterial/venous thrombosis caused by: increasing age, obesity, immobility, high saturated fat/low fibre diet, stress, smoking etc.
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- (Biology of Disease) Fichas sobre Platelets and coagulation, bleeding and thrombotic disorders, creado por sophietevans el 02/08/2013.
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