Test 3 Study Guide Part 3 Flashcards
Von Willebrand’s factor:
Von Willebrand’s factor which are bound to collagen, they then bind thrombocytes and anchor them so blood flow does not move them away.
What is within the granules of thrombocytes?
When is it released?
Serotonin
Thromboxane A2 (promotes binding/clotting of thrombocytes)
ADP (promotes binding/clotting of thrombocytes)
Platelet release reaction
The release of Thromboxane A2, ADP, and Seratonin is called what?
A platelet release reaction.
Describe the complete arc of platelet plug formation, starting from the normal state.
endothelial cells produce: NO-, prostacyclin. (which act as vasodilators and inhibit clotting)
Endothelial cells also have CD39 on their plasma membrane surface, which ADP -> AMP (ADP promotes clotting so this is important)
Wounding exposes the collagen of the tissue behind the endothelium, which results in clotting. Thrombocytes bind to Von Willebrands factor, which in turn binds to collagen.
There are two signalling changes which have occurred. Death of endothelium has likely resulted in decreased production of prostacyclin two, and decreased production of NO (and a little less CD39 activity). Additionally a platelet release reaction has occurred, and the platelets have released granules of ADP, thrombaxane A2, and serotonin.
The platelet plug will form, and can stop bleeding, but requires fibrin reinforcement to be able to hold.
Platelets also help produce what change in fibrinogen?
It converts it fibrin, which is insoluble, and helps form the clot.
What does the color of a clot tell you?
Fibrin forms a mesh which traps other cells within it, if it traps a great deal of RBCs, it will form a red clot. If it is in an artery, it will not trap as many and the clot will be white.
Clot retraction can occur because:
Contractile actin myosin system, as is seen elsewhere in the body.
- Step called clot retraction
Serum redefined:
Plasma without fibrinogen (as it has been used in clot formation)
Extrinsic pathway:
Tissue Factor (thromboplastin, factor III) -> factor VII -> VII complex (tissue factor, factor VII, and Ca2+) -> Common Pathway (factor X)
Intrinsic Pathway:
Activator (collagen) -> Factor XII -> Factor XI -> Factor IX -> VIII complex (factor IX activated, factor VIII, Ca2+)
Common Pathway:
X -> V complex (factor five V, X activated, Ca2+) -> factor II (Prothrombin) which becomes thrombin -> fibrinogen -> fibrin
How is the clotting pathway stopped in plasma tubes?
Ca2+ is chelated, which stops it from participating in clotting complexes
Aim of coagulation:
Create fibrin from fibrinogen (factor 1)
Fibrin stabilizing factor (factor VIII)
Common Pathway pneumonic:
1 * 2 * 5 = 10
Factor ten forms complex five (X activated, factor V, Ca2+) activates prothrombin into thrombin (thrombin/prothrombin is factor II) -> fibrinogen (factor I) -> fibrin
Extrinsic pathway pneumonic:
3 + 7 = 10 factor III (tissue factor, thromboplastin), complexes with factor VII, and Ca2+
Intrinsic pathway pneumonic:
Factors 12 to 8 are involved in the intrinsic pathway, excluding factor X which is the common.
XII -> XI -> IX -> VIII complex (VIII, IX, Ca2+)
(plasminogen is the inactive precursor) Plasmin:
Decays blood clots (like fibrin)
How is the extrinsic pathway started?
Tissue is damaged, and cell innards are revealed, including thromboplastin (Factor III), which can now bind with factor 7, calcium and phospholipids to start activate factor 10
Which pathway generates thrombin and fiber the most quickly? Which is predominant in vivo?
The extrinsic pathway
The extrinsic pathway
What role does phosphatidylserine play in blood clotting?
It anchors clotting factor VIII and V on the platelet surface, and greatly increases thrombin production.
What is the main role of the intrinsic pathway supposedly?
Amplification of the clotting cascade, after it has been initiated by the extrinsic pathway.
What activates plasmonigen into plasmin?
Kallikrein
What does Kallikrein stand for?
What does the kallikrein do?
Sweet = Kalli, Flesh = Krein
It activates plasminogen -> plasmin which eats away clots
What does plasmin digestion produce?
Split products (fibrin degradation products)
What are potential activators for plasminogen?
Kallikrein
Tissue plasminogen activator (TPA)
Urokinase
Streptokinase
How does plasminogen get into the clots?
It is incorporated into them as the clots are formed.
Where does tissue plasminogen activator come from?
It is released slowly by damaged epithelium.
Thrombus:
a blood clot which obstructs a vessel. (a coagulation of your blood within your body)
Where does tissue urokinase and streptokinase come from?
Bacteria
Factor V Leiden:
Inherited defect. Uncontrolled and vigorous factor V activation of clotting.
Atherosclerosis:
Build up of a fatty plaque under the endothelial cells of the vein. Causes the vein to shrink. Can eat its way into the interior of the vein, causes collagen to activate thrombus formation
Varicose Vein:
Caused by weakened one way valves in the legs
What causes an increased chance of clot formation?
Bed ridden (there is less blood flow in legs, and thrombus form)
Factor V leiden (a defect in factor V, which resists inactivation)
Atherosclerosis
Varicose Veins.
Inflamed Veins (phlebitis)
Infection
Swelling is proinflamatory, and damage can expose collagen promoting clot formation
Phlebitis:
Where are you most likely to form clots?
In the veins of your legs, because this is where the blood flows the slowest.
What is an embolus:
Any mass of undissolved material carried away within the blood.
What is a common cause of pulmonary embolism?
A thrombus in the leg, which breaks off a piece, which travels to the lungs, and causes loss of blood flow somewhere there.
Cerebral infarction (infarction is a region of tissue deprived of blood):
Is often caused by an embolus which originates in the left side of your heart. Thrombus formation here could be caused by damaged tissue from a heart attack.
Anticoagulants (list them):
Aspirin (interferes with thromboxane A2 formation): EDTA (chelates Ca2+): Sodium Citrate (chelates Ca2+): Heparin (inhibits thrombin): Warfarin:
Aspirin:
Inhibits thromboxane A2 formation (and other prostaglandins) which stops platelets from releasing Thromboxane A2 in their coagulation formation
Permanently inactivates platelets so that they cannot clump
Bleeding time test (prolonged by taking aspirin)
Sodium Citrate (chelates Ca2+) metobolism:
Chelates Ca2+
This is metabolized within the bloodstream to deactivate it.
What does EDTA stand for?
Ethylenediaminetetraacetic acid
Heparin:
activates Antithrombin III which inactivates thrombin (resulting in no new fibrin formation). Antithrombin III: Inactivates thrombin, factor IX and factor X
Warfarin:
Stops cellular activation of vitamin K.
Details of the pathway which warfarin interrupts
Gamma-glutamyl carboxylase (uses vitamin K) adds a carboxyl group factor II (prothrombin), factor VII, IX, and X.
Addition of carboxyl group oxidizes vitamin K
Another enzyme Vitamin K epoxide reductase reduces vitamin K.
Warfarin blocks Vitamin K epoxide reductase
Which factors are vitamin K dependent?
Factor II, IIV, IX, and X
Why isn’t Warfarin (coumadin) used immediately?
Why is heparin used immediately?
Warfarin: prevents factor II, IIV, IX and X synthesis (but does not remove current levels of these)
Heparin:
Activates Antithrombin III which inactivates thrombin (immediate effect)
