Term
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Definition
Pro-coagulation phase
Anti-coagulation phase
Fibrinolysis phase |
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Term
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Definition
| Formation of platelet plug and fibrin clot to stem blood loss |
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Term
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Definition
| Inhibition of the activated factors and their removal to halt clot formation |
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Term
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Definition
Dissolution of fibrin clot once vessel is repaired
Once hole is repaired (by making it part of the blood vessel, we get rid of the clot) |
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Term
| Hemostasis is a system of what? |
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Definition
| Serine protease zymogens; plus non-enzyme cofactors activated and inhibited in a controlled manner. |
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Term
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Definition
| Non-nucleated cells present in the blood |
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Term
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Definition
Form mechanical plugs at site of vessel injury
Secrete chemicals to regulate the clotting and plug forming processes and vessel repair |
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Term
| Actions involved in platelet formation: |
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Definition
1. Adhesion of platelets to exposed subendothelial components (collegen and vWF) become activated:
2. Activation occurs in which certain chemicals are released especially ADP and TXA2 that promote platelet aggregation.
3. Aggregation to form the platelet plug. It is helped by binding fibrinogen |
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Term
| What happens when there is atherosclerosis? |
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Definition
| Rips away, exposes subendothelial surface and turns on hemostatic mechanisms |
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Term
| What happens when you expose collagen and vWF? |
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Definition
| Platelet becomes sticky to endothelial |
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Term
| What happens as platelets aggrigate? |
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Definition
| A plug forms the cut in the blood vessel. |
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Term
| What works with the plug to stem blood loss? |
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Definition
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Term
| What can low-dose asprin be used for? |
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Definition
| Treatment of heart attacks/stroke |
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Term
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Definition
| Inhibit arachiadonic acid -> Cox (irreversible). Inhibits prosteglandins, thromboxanes (TXA2 synthesis) |
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Term
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Definition
| We only want the platelet COX inhibited. Once COX is inactivated you need new platelet to restore activity. |
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Term
| Once COX is inactivated.. |
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Definition
| You need a new platelet to restore activity |
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Term
| If you decrease TXA2 production, what happens? |
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Definition
| Decrease rate of platelet aggrigation |
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Term
| Diagnostic tests for platelet action |
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Definition
Platelet count (normal or low)
Platelet function test (does plug form @ proper rate) |
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Term
| What does platelet function test? |
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Definition
| Does plug form @ proper rate? |
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Term
| When does formation of the stable fibrin clot appear? |
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Definition
| Pro-coagulation phase part 2 |
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Term
| When does formation of the stable fibrin clot appear?? |
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Definition
Pro-coagulation phase part 2
Separate from pplug formation |
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Term
| What makes clot formation possible? |
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Definition
| Enzymes and protein cofactors of the blood coagulation cascade |
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Term
| Where does stable fibrin clot appear? |
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Definition
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Term
| What class of enzymes are the ones found in the blood coagulation cascade? |
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Definition
| Serine proteases w/ one activated by its predecessor. |
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Term
| Non-enzyme protein cofactors |
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Definition
| F5,F8, Protein S, Cofactor Calcium |
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Term
| Where are the clotting factors made? |
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Definition
| Liver. All by factor VIII |
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Term
| Where is factor VIII made? |
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Definition
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Term
| How is factor VIII stabilized ? |
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Definition
| It must bind to circulating vWF in order to be stabilized. |
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Term
| Where do extrinsic path and intrinsic path come together? |
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Definition
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Term
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Definition
| Thrombin via factor Xa w/ Va present |
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Term
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Definition
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Term
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Definition
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Term
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Definition
X
Prothrombin->Thrombin (X, Va)
Fibrinogen->Fibrin (Thrombin)
13A->Stable Clot (fibrin) |
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Term
| Diagnostic blood tests w/ coagulation |
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Definition
PTT (Intrinsic + Common)
PT (Extrinsic + Common) |
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Term
| What tests are most important for platelet function/clotting cascade? |
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Definition
Platelet count
Platelet function
PTT
PT |
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Term
| What triggers activation of cascade? |
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Definition
| Interaction of plasama proteins w/ exposedendothelial @ same time platelets are adhering to collagen &vWF |
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Term
| What initiates coagulation? |
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Definition
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Term
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Definition
1.Injury exposes TF which binds and activates VII (subsequently thrombin will take VII->VIIa immediately)
2. FVIIa cleaves FX->FXa to complete extrinsic path.
3. FVII a also turns on intrinsic path why IX->IXa(which is another serine protease which turns X->Xa) |
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Term
| Are intrinsic/extrinsic essential for clotting? |
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Definition
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Term
| Is factor VII always necessary for clotting? |
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Definition
| No. Deficient people have been found to exhibit no bleeding problems. |
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Term
| Localized clot formation is considered what? |
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Definition
| An "amplification cascade" |
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Term
Fibrinogen->Fibrin
Solubility? How? |
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Definition
Soluble->Insoluble
Thrombin Cleaving off fibrinopeptides FpA; FpB |
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Term
| What is fibrinogen made of? |
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Definition
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Term
| What happens when fibrnogen is clipped @ FpA and FpB(substance wise)? |
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Definition
| Becomds insoluble and aggregates |
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Term
| What is the charge on fibrinopeptides A/B? why? |
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Definition
Negative
Due to ASP(Coo-);GLU(Coo-); Tyrosine Sulfate (protonated in the blood) |
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Term
| What happens when FpA/B clipped (charge-wise)? |
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Definition
| Negative charge repulsion is relieved. |
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Term
| What is the monomer formed when FpA/B are clipped? |
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Definition
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Term
| What does the fibrin monomer form? |
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Definition
| "soft clot" (it's unstable) around platelet plug |
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Term
| Final crosslinking reaction in the common pathway involves what side chains? |
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Definition
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Term
| Final crosslinking reaction in the common pathway is catalyzed by what? |
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Definition
| FXIIIa (transglutaminase) |
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Term
| Final crosslinking reaction in the common pathway does what? |
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Definition
| Forms stable, functional "hard clot" |
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Term
| What do hemophelia's arise from? |
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Definition
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Term
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Definition
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Term
| What do the presence of GLA residues involve? |
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Definition
| Role of Vitamin K in blood clotting |
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Term
| What factors contain GLA Domains? |
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Definition
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Term
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Definition
| Synthesized by gut bacteria |
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Term
| What form of vitamin K is useful for what reaction? |
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Definition
KH2, reduced form.
Glutamate carboxylation reaction |
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Term
| What catalyzes the glutamate carboxylation reaction? |
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Definition
| Vitamin K dependent carboxylase |
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Term
| Formation of gla side chains in the factors by carboxylation of glu does what? |
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Definition
| Turns the Glu into excellent Calcium chelators by adding 2nd carboxyl group |
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Term
| Vitamin K deficiency states |
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Definition
*Newborns need vitamin K b/c their guts are sterile
*After prolonged antibiotic use
*Problems w/ fat absorption |
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Term
| Why do newborns need vitamin K? |
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Definition
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Term
| Why are you in a vitamin K deficient state after prolonged anti-biotic use? |
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Definition
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Term
| Why can problems w/ fat absorption lead to a vitamin K deficiency? |
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Definition
Because K=fat soluble
Ex.Gallstones inhibit bile production
Cystic fibrosis=decrease in bile transport |
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Term
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Definition
Extra strong binding. Making a little compartment.
Adding an additional -1 charge makes a better spot for Ca2+ |
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Term
| What does the presence of Gla residues permit? |
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Definition
| Rapid, efficient activation of gla-containing clotting factors by their activating proteases located on the surface of platelets aggregated to the cut. |
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Term
| Two proteolytic cleavages activates what cofactor? |
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Definition
| Protrhombin->Thrombin by factor 10a |
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Term
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Definition
| Monomer w/ intrachain disulfide bond |
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Term
| Where does prothombin bind? |
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Definition
| To negative charges on platelet membrane surface via gla-Calcium bridge |
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Term
| Process of activating prothrombin |
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Definition
Prothrombin binds to Gla/Ca bridge
Interaction brings prothrombin into complex w/ Xa,Va
Prothrombin cleaved by Xa->
Active thrombin w/ inter-chain disulfide bonds |
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Term
| What happens to the N-terminal amine and gla residues after prothrombin is activated? |
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Definition
| They are eventually degraded |
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Term
| Where is prothrombin activated? |
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Definition
| The surface membrane that the gla/ca bridge is attached to is the platelet membrane. (near the cut) |
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Term
| How do vitamin K antagonists/deficiency hinder blood clotting? |
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Definition
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Term
| Examples of vitamin K antagonists |
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Definition
| Coumadin, Warfarin, Dicoumerol |
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Term
| What are warfarin and dicoumerol? |
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Definition
Vitamin KO analogs (KO is oxidized form)
They are competative inhibitors of the K reductases (which keeps KH2 from being formed)
This keeps gla residues from being formed, preventing factors from being formed. |
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Term
| What are coumadin and dicoumerol used for? |
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Definition
| Prophylactic treatment of people at risk of thrombosis (unwanted blood clots) that can lead to heart attack and stroke |
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Term
| There is a fine line between hemorrhage and what? |
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Definition
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Term
| Why does factor activation in the anti-coagulation step form at such an explosive rate? |
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Definition
| Due to thrombin's autocatalytic role (activate factors before it) and increased platelet concentration |
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Term
| What can slow the clotting process? |
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Definition
| Dilution of clotting factors (depends on [enzyme]) |
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Term
| What happens when factors V and VIII are in complex w/ it's own protein cofactor,S? |
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Definition
| They are degraded by a specific serum protease, thrombin activated protein C. |
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Term
| Steps of anti-coagulation phase |
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Definition
1. factor activation occurs @ explosive
2. Dilution
3.Active non-enzyme protein cofactors
4.Protein-inhibitor complexes
5. Use of HMWH and LMWH |
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Term
| What enhances protein-inhibitor complexes in the anti-coagulation phase? |
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Definition
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Term
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Definition
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Term
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Definition
| Turns off thrombin and certain other cofactors. |
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Term
| Key proteins involved in heparin? |
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Definition
Serpin (serine protease inhibitor)
AT3 (Anti-thrombin 3, sometimes acts as an irreversible suicide inhibitor) |
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Term
| What are the most highly sulfated GAGs? |
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Definition
| Heparins, enhances their inhibition |
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Term
| What was first used to inhibit clotting in the hospital? |
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Definition
| LMWH and HMWH isolated mix |
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Term
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Definition
Heparin induced thrombocytopenia)
Major clinical complication. Unpredictable. |
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Term
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Definition
Antibodies are generated in response to HMWH platelet complex
Binding of antibodies activates platelets
Excessive thrombi are produced throughout the body
Result: Drop in platelets + Multi-organ failure from blood inhibition by thrombosis. |
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Term
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Definition
| LMWH, can be given outpatient. Saves $ |
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Term
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Definition
High molecular weight heparin
N=23 (46 sugar units) |
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Term
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Definition
Low molecular weight heparin
N<9 |
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Term
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Definition
Yes, negatively.
Most density of - charge b/c - @ physiological pH |
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Term
| Fibrinolysis phase of hemostasis |
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Definition
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Term
| Once the vessel has undergone tissue repair, what happens, specific |
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Definition
| The active serine protease plasmin cleaves fibrin clot into soluble peptide fragments. |
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Term
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Definition
| Plasminogen by tPA (Tissue plasminogen activator) |
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Term
| How is cloned human tPA used clinically? |
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Definition
Impatiet. To enhance disolution of thromboses
ex. coranary arteries during HA. |
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