Term
| In terms of coagulation, what happens when a blood vessel ruptures? |
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Definition
| there is a myogenic spasm in the smooth muscle, causing vasoconstriction to limit blood loss; the rough surfaces of the ruptured blood vessel present a clotting area for platelets (as opposed to the smooth surface of unbroken blood vessels) and the blood vessel endothelium upstream of the rupture release NO to prevent clotting before the rupture; the platelets agglutinate and stimulate a fibrin clot to form; fibroblasts are recruited to lay down fibrous tissue and initiate tissue growth |
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Term
| Where are platelets formed? What forms them? How? |
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Definition
1. either in the blood vessels or the marrow
2. megakaryocytes
3. megakaryocytes fracture either in the marrow or in the blood vessels to create platelets |
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Term
| What qualities do platelets have that are similar to full cells? |
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Definition
a, they have contractile proteins (actin, myosin, and thrombosthenin)
b. they have enough ER and Golgi material to synthesize enzymes and prostaglandins
c. they can store significant amounts of calcium in the blood, they contain dense granules of ADP and ATP as well as α-granules with fibrinogen, PDGF, vWF, and fibronectin
d. they release fibrin-stabilizing factor to stabilize the clot
e. and they release VEGF |
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Term
| What is the function of thrombopoietin? Where is it produced? |
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Definition
1. it stimulates the production of more platelets
2. the liver |
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Term
| What is the life-span of platelets? How are they removed from circulation? |
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Definition
1. 8-12 days
2. via macrophages, mostly in the spleen |
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Term
| Why does clotting not occur in non-injured areas of the blood vessels? |
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Definition
| the velocity of the blood flow, the smooth surface of the blood vessels, and the coating on the platelets prevent them from doing so; additionally, thrombin, which catalyzes other steps in clotting, binds to fibrin and becomes deactivated and thrombomodulin specifically prevents spreading of the clot |
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Term
| What is vWF? What is hemostasis? |
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Definition
1. von willebrand factor
2. the process by which the body prevents bleeding, usually by clotting, etc |
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Term
| What are the two biggest activators of platelet activity when a blood vessel is broken? |
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Definition
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Term
| What happens to the platelet when a it becomes activated for a clot? |
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Definition
| its shape becomes irregular, the contractile proteins contract, causing the release of various enzymes and substances, including ADP and thromboxane to activate other platelets; the surface of the platelets also become sticky, assisting with the clotting |
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Term
| When a clot first forms, it is loose and unstable. How does it become stable and secure to avoid falling out of the blood vessel? |
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Definition
| the same thrombin that initiated the polymerization of fibrin to form fibrin fibers also catalyzes the activation of fibrin-stabilizing factor, which causes the fibrin to become bound with covalent bonds and form cross-linkages, reinforcing the clot; additionally, the fibrin fibers will adhere to the damaged vessel surfaces and contractile elements (actin, myosin, and thrombosthenin) in platelets that are bound in the fibrin meshwork will contract and pull the vessel walls together, which will both contribute to hemostasis and the stability of the clot |
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Term
| What is another name for factor I? Factor II? Factor III? Factor IV? Factor X? Factor XIII? |
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Definition
1. fibrinogen
2. prothrombin
3. tissue factor
4. calcium
5. prothrombin activator
6. fibrin-stabilizing factor |
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Term
| When a vessel injury occurs, what is the mechanism of action for the platelets? |
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Definition
a. platelets bind to the subendothelial vWF and collagen via its surface glycoproteins
b. the platelets swell and release platelet agonists from granules and clotting cascades generate thrombin
c. thrombin and platelet agonists activate additional platelets and platelets cross-link
d. contractile elements (actin, myosin, and thrombesthenin) pull fibrin threads, constricting the plug and squeezing serum (plasma without clotting factors) out of the clot)
e. platelets release leukotrienes, thromboxane (causes more granules to be released), thrombospondin (stabilizes platelet-fibrin), PDGF (stimulates smooth muscle proliferation), and ADP (to attract more platelets) |
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Term
| Which kinds of patients are at a greater risk for clotting? |
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Definition
| chemotherapy patients, patients that are immobilized for long periods of time, and patients that lose a large proportion of their blood |
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Term
| What are the types of COX enzymes and what are their functions? |
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Definition
a. COX I - normal production of prostaglandins and thromboxanes
b. COX II - pathological inflammation
c. COX III - its function was not mentioned |
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Term
| Where is fibrinogen made? |
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Definition
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Term
| What is the function of α2-antiplasmin? |
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Definition
| it binds to plasmin to prevent it from working until it is needed |
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Term
| What is the rate-limiting step in coagulation? |
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Definition
| the formation of factor Xa |
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Term
| What vitamin is required for the formation of prothrombin? |
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Definition
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Term
| What is the function of anti-thrombin? Where is it found? |
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Definition
1. it works in conjunction with heparin to degrade thrombin
2. it is present in many organs, especially in the heart and lungs |
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Term
| What is the function of a calcium chelator? Give examples. Which is the preferred chelator and why? |
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Definition
1. it absorbs excess calcium and can be used to prevent the clotting cascade
2. citrate and oxalate
3. citrate is preferred because it is easily processed and is not involved in kidney stone precipitation |
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Term
| How are fibroblasts attracted to the area of injury? |
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Definition
| PdGF and fibronectin act as chemotaxic agents for fibroblasts |
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Term
| What are the types of anti-platelet agents, how do they work, and what pathway do they affect? |
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Definition
a. aspirin - irreveribly inhibits COX enzymes; affect ADP, collagen, and thromboxane 2 pathways
b. NSAID - reversibly inhibits COX enzymes; affects ADP, collagen, and thromboxane 2 pathways
c. glycoprotein IIb-IIIa receptor antagonist; affects ADP, collagen, thrombin, epinephrine, serotonin, and thromboxane 2 pathways |
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Term
| What initiates the intrinsic clotting pathway? How quickly does it act? The extrinsic clotting pathway? How quickly does it act? |
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Definition
1. surface contact with broken blood vessels surfaces/collagen
2. in a few minutes
3. tissue damage releases tissue factor, which initiates the pathways
4. immediately |
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Term
| Why don't interstitial fluids usually coagulate? Why do they coagulate in some pathological conditions? |
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Definition
1. fibrinogen is required for the clotting cascades and it is too large to leak into the IF normally
2. when membrane permeability is pathologically increased, fibrinogen can leak into the IF and IF can clot |
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Term
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Definition
| 1. plasma without clotting factors |
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Term
| List the steps in the extrinsic clotting pathway. |
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Definition
a. tissue trauma causes the formation of tissue factor, which activates factor VII
b. factor VIIa and Ca2+ activate factor X
c. factor Xa, factor V, and tissue phospholipids combine in the presence of Ca2+ to make prothrombin activator, which, along with platelet phospholipids and Ca2+, cleave prothrombin into thrombin |
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Term
| List the steps of the intrinsic clotting pathway. |
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Definition
a. blood trauma or contact with collagen causes activation of factor XII; the trauma also releases platelet phospholipids (aka platelet factor 3)
b. factor XIIa activates factor XI
c. factor XIa activates factor IX (in the presence of Ca2+) and thrombin activates VIII
d. factors VIIIa and IXa along with platelet phospholipids and Ca2+ activate factor X
e. thrombin activates factor V and factor Va and factor Xa combine with platelet phospholipids in the presence of Ca2+ to make prothrombin activator
f. prothrombin activator and platelet phospholipids in the presence of Ca2+ cleaves prothrombin into thrombin |
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Term
| What is heparin? What is its function? What cells release it? |
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Definition
1. a powerful anticoagulant
2. physiologically, it works with antithrombin III to prevent the activity of thrombin; it is also used at supraphysiological levels to prevent clotting
3. mast cells and basophils (small quantities) in the lungs and liver |
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Term
| What is the function of plasmin? |
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Definition
| it digests fibrin fibers and other coagulants, lysing the clot fibers and dissolving the clot; a lot of plasminogen is trapped in a clot and is activated by tissue plasminogen activator (t-PA), which is very slowly released from the injured tissues and vascular endothelium |
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Term
| Where does the common pathway (between intrinsic and extrinsic clotting) for clotting begin? |
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Definition
| with activating/activated factor X |
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Term
| What is the function of antithrombin III? |
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Definition
| it combines with thrombin and inactivates it |
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Term
| List the intravascular anticoagulants. Mention their activity. |
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Definition
| endothelial cells (smooth surfaces and glycocalyces prevernt coagulation), fibrin (absorbs thrombin to the fibers, prevernting its catalytic activity), antithrombin III (absorbs free-floating thrombin), and heparin (combines with antithrombin to increase its effectiveness) |
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Term
| Which enzymes can activate plasminogen? Which can inhibit it? |
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Definition
1. tissue plasminogen activator, urokinase, and streptokinase
2. plasminogen activator inhibitor (inhibits TPA), alpha2-antiplasmin (blocks binding plasminogen to fibrin) |
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Term
| What are possible defects that can prevent coagulation? How do they do so? |
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Definition
a. vitamin C deficiency - lack of stable collagen, meaning a reduction in clotting
b. hepatic failure - reduced liver production of clotting factors
c. vitamin K deficiency - vitamin K is required for factors II, VII, IX, X, and protein C; may be due to fat malabsorption due to a lack of bile secretion
d. hemophilia - a lack of factor VIII or factor IX
e. thrombocytopenia - a low number of platelets means less clotting; may cause bleeding in small capillaries and blood vessels
f. disseminated intravascular clotting - abnormal bleeding and clot formation eventually uses up all the clotting factors, making clotting impossible |
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Term
| What is a use of exogenous TPA? |
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Definition
| it can be administered to a patient who has gotten a heart attack in order to dissolve the clot and prevent additional clotting |
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Term
| What are the types of hemophilia? Which is more common? What to they involve? How are they treated? |
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Definition
1. hemophilia A and hemophilia B
2. hemophilia A (80-85% of cases)
3. A involves a mutation in factor VIII |
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Term
| How common is hemophilia? How is hemophilia A transmitted? How about hemophilia B? |
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Definition
1. 1/10,000 males
2. X-linked
3. X-linked |
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Term
| What are the types of vWD diseases? What do they involve? Which is most common? |
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Definition
1. von Willebrand diseases
a. type I - 5-35% reduction in vWF; most common
b. type II - mild decrease in vWF, causing a large decrease in platelet adhesion; this looks like thrombocytopenia because vWF that is present binds to platelets and clears them from the plasma
c. type III - large decrease in vWF and factor VIII; this resembles hemophilia |
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Term
| How are vWDs acquired? How are they treated? |
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Definition
1. type I and III are autosomal recessive; not sure about II
2. desmopressin, which mimics the vasoactive effects of ADH, triggers more prothrombin and can ameliorate from of the bleeding |
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Term
| What is thrombocytosis? What are the types? What do they involve? |
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Definition
1. an excessive of platelets
2. a. essential thrombocytosis - a stem cell disorder that often shows up after a patient is 50 years old; it can cause an enlarged spleen, vasoocclusion, and hemorrhaging (the latter due to unneeded clotting using up all the clotting factors)
b. DIC (disseminated intravascular coagulation) - dysfunction in secondary hemostasis; associated with large amounts of TNF-α, IL-1, IL-6, and huge amounts of tissue factor; it causes a thrombus, causing increased thrombin, causing increased TPA, producing plasmin, which disables other clotting factors |
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Term
| What situations can DIC be associated with? |
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Definition
| generally large amounts of traumatized or damaged tissue; known situations involved include septicemia, cancer, severe trauma, severe burns, blood transfusion reactions, problems in pregnancy (amniotic fluid eruption or placental ablation) |
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Term
| What is thrombocytopenia? What does it involve? How is it diagnosed? How is it treated? |
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Definition
1. a deficiency of platelets (under 50,000 platelets/μL
2. usually a lot of bleeding from small blood vessels
3. small system-wide bleedings result in small purplish blotches in the skin; platelet counts will be low and the patient's blood will not retract (because platelets are required for the contraction in clots)
4. transfusion of large amounts of platelets can treat the problem and removal of the spleen can often cause an almost complete cure, since large numbers of platelets are removed from circulation in the spleen |
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Term
| What measures do physicians take to ensure that patients on dialysis do not experience blood clots? |
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Definition
| heparin or siliconized tubing and calcium chelators are used to prevent clotting |
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Term
| What is a DVT? How can it be dangerous? |
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Definition
1. a deep vein thrombosis
2. if the thrombosis becomes large it can use up a lot of clotting factors and produce a clotting problem; even more insidious, if it becomes dislodged, it could quickly go to the heart and could likely become a pulmonary embolism |
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Term
| What is coumarin? Describe it as much as you can. |
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Definition
| 1. a class of drugs that compete with vitamin K, causing a decrease in prothrombin and factors VII, IX, and X, in 2-4 days of treatment; its effects wear off after 1-3 days; the most common drug in this class is warfarin (aka coumadin) |
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Term
| What is a normal platelet count? What is a thrombocytopenic level of platelets? |
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Definition
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Term
| What is PT timing? How is it used in diagnosis? Describe the test to measure it. |
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Definition
1. prothrombin time; this is the time it takes for the extrinsic pathway to work
2. increased PT time can be indicative of deficiencies in factors V, X, or VII; liver problems can cause this to occur and PT time will vary with other factors like vitamin K and warfarin
3. plasma, thromboplastin, and calcium are mixed and the time is measured until the blood clots |
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Term
| What is aPTT time? How is it used in diagnosis? Describe the test to measure it. |
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Definition
1. activated partial thromboplastin time; the amount of time for the intrinsic pathway to be activated
2. increased aPTT time may indicate a deficiency in factors XII, XI, IX, or VIII; if there is increased time and the patient bleeds more easily, there is a deficiency in one of the factors XI, IX, or VIII; if there is increased time and the patient does not bleed more easily, there is a deficiency in factor VII
3. plasma, phospholipids, and calcium are mixed and the time is measured until they clot |
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Term
| What is an autoantibody in term of clotting? |
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Definition
| an antibody either against plasma phospholipid or a clotting factor |
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Term
| What test would a physician do if a patient has increased PT time and normal aPTT time? What might this test show? |
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Definition
1. the physician would mix a 50:50 mixture of normal clotting plasma and the patient's plasma
2. if the problem resolves itself, the patient had a factor deficiency (V, VII, or X); if not, an autoantibody may be present in the patient's blood |
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Term
| What test would a physician do if a patient has increased aPPT time and normal PT time? What might this test show? |
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Definition
1. the physician would mix a 50:50 mixture of normal clotting plasma and the patient's plasma
2. if the problem resolves itself, that means the patient has a factor deficiency (IX, XI, or VIII); if not, the patient has an autoantibody against IX, XI, VIII or phospolipid (probably phospholipid 3) |
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Term
| What test would a physician do if a patient has increased PT time and an increase aPTT time? What might this test show? |
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Definition
1. the physician would mix a 50:50 mixture of normal clotting plasma and the patient's plasma
2. if the problem resolves itself, there may be a deficiency in factor V, X, prothrombin, or fibrinogen; if not, there may be autoantibodies for any of them or phospholipid |
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Term
| What is massive pulmonary embolism? |
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Definition
| when a thrombus grow so large that it can occlude both pulmonary arteries simulataneously |
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Term
| How quickly does blood normally clot outside the body? |
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Definition
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Term
| What is INR? What does it indicate? What is a normal INR range? How is INR measured? |
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Definition
1. international normalized ratio
2. it compared the clotting value of a patient's blood to that of a standardized sample
3. 0.9-1.3
4. INR = [(PT test time)/(PT normal time)]^ISI |
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Term
| What is ISI? What does it indicate? What is a normal ISI range? |
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Definition
1. international sensitivity index
2. it indicates the activity of the tissue factor in a standardized sample; the tissue factor is used to determine the PT test time
3. 1.0-2.0 |
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Term
| In an INR calculation, there is a PT test time and a PT normal time. How is the PT test time determined? How is the PT normal time determined? |
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Definition
1. a sample of the patients blood is taken and mixed with oxalate to remove the calcium and prevent clotting; then a large excess of tissue factor and calcium is mixed in to nullify the oxalate effects and the clotting is timed
2. it is predetermined by testing. The normal value is about 12 seconds |
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