Hemostasis Flashcards
(20 cards)
1
Q
vessel injury/stages of clotting
A
- Vascular constriction – often time there will be a histamine release and vasodilation initially that serves to wash out the wound and then after that there is vasoconstriction to limit blood loss
- Platelet plug – to fill the hole while the fibrin clot is forming (Forms loose first and then retracts, Clamps down and then restricts, The proteins involved in the clot have some contractility to them)
- Fibrin clot
- Clot retraction/vessel repair
- Clot dissolution
2
Q
vascular constriction
A
- Mostly from myogenic response to injury – whenever you traumatize a smooth muscle it will respond by contracting (It’s also thought that the constriction response is proportional to the damage done)
- Response proportional to damage
- In small vessels, thromboxane A2 – this can cause vasoconstriction in the small vessels preventing blood loss
3
Q
platelet lineage
A
- Pieces of membrane slough off from the megakaryocyte and then become surrounded by membranes -> these are what make platelets
- Megakaryocyte never leaves the bone marrow
4
Q
platelets
A
- NOT cells – they have no cellular apparatus or metabolic machinery at all (They do have surface proteins made by the megakaryocytes)
- Fragments of cells, megakaryocytes
- Binding to injured vessel wall or tunica media (collagen) through surface proteins
- Half-life of 8-12 days
5
Q
platelet receptors
A
- GPIb/IX – glycoprotein adhesion molecule (binds subendothelium through vWF) (vWF is an important part of platelet adhesion whenever the vessel wall is injured)
- GIIb/IIIa – fibrinogen binding protein
- Clotting factor/Ca++ complex (Xa/Va complex limits activation of thrombin to site of injury) (Multiple clotting factors require Ca to be activated)
6
Q
platelet “plugging”
A
- Exposure to tissues beyond intima causes platelet activation (The response of the platelet involved swelling up and forming foot processes that allow the platelet to move around)
- Contraction causes release of factors
- Adherence to von Willebrand factor
- Thromboxane A2 formation activating others (Formed by platelets)
- All of this makes the platelets sticky and causes them to aggregate
7
Q
clotting
A
- Depends on balance between blood factors – when they are in balance, we are stable and we aren’t throwing thrombi everywhere
- Process begins with formation of complex called prothrombin activator
- PA converts prothrombin (much bound to platelets) to thrombin – find that on the platelets (they have a receptor that binds the prothrombin moleculte)
- Prothrombin made by liver (requires Vit K) – this is one of the ways warfarin inhibits clot formation
- Thrombin removes fibrin proteins from fibrinogen (made in liver)
- Long fibrin fibers form reticulum of clot – self assemble on vessel wall to form fibrin fibers that trap blood cells and other circulating elements to forma firm clot
8
Q
fibrinogen
A
- Very big molecule so it stays in the blood stream and doesn’t really leak out to the interstitial fluid
- Alpha and beta are the two subunits necessary for clotting (Thrombin hydrolyzes the disulfide bonds that connect the alpha and beta subunits to form 4 subunits)
9
Q
A and B peptides
A
- Fibrinopeptides A & B are charged – prevent aggregation – keeps them from self aggregating and allows enzyme to penetrate to where the disulfide bridges are to liberate them
- Thrombin catalyzes removal creating monomers of fibrin which aggregate spontaneously when they are not attached to the larger molecule
10
Q
fibrin reticulum
A
-Meshwork traps RBCs and maybe monocytes or platelets
11
Q
early clot
A
- Unstable because only bonding is hydrogen
- Fibrin stabilizing factor activated by thrombin (Causes covalent bonds and cross linking to form, This makes the clot more stable and solid)
12
Q
blood clotting cascade in humans
A
- This diagram shows you where the calcium dependent processes are
- Does not show where the vitamin K dependent processes are: All of the vit K dependent factors require Ca and phospholipids as part of their activation
- Start from the bottom of the chart with formation of thrombin
- Thrombin liberates fibrin from fibrinogen
- Extrinsic pathway: factor 3 (tissue factor, or thromboplastin), comes from elements outside of the blood stream (expose blood to tissue components from cells that were damaged)
- Intrinsic pathway: comes from trauma from within the vessel itself: Vessel trauma or anything inside the vessel, If you have enough trauma to the blood vessel to expose it to the outside, you activate both pathways
- Factor 12 is sensitive to the presence of collagen – if blood vessel is exposed to the blood, then factor 12 is sensitive to that and will trigger the start of the cascade – causes a conformational change in factor 12
- 12a can jump across to extrinsic pathway and collaborate in the activation of factor 10
13
Q
vitamin K
A
- Liver carboxylates factors using vit K making factors able to bind Calcium: 2, 7, 9, 10 all use vit K as cofactor in carboxylation – makes clotting factors capable of binding to Ca
- Warfarin is a structural analog: Analog of vitamin K that can bind its receptors but doesn’t act like vit K
14
Q
intrinsic and extrinsic pathways
A
- Extrinsic: In tissues – exposure to tissue proteins and molecules
- Intrinsic: In vasculature – the initiation comes from exposure within the blood vessel
15
Q
control/clot dissolution
A
- Antithrombin III – always circulates as control: Acts as an enzyme that irreversibly binds to thrombin
- Inactivates thrombin by irreversible binding – makes it so that you cannot clot
- Heparin binds and concentrates antithrombin III, increases activity – and so it accentuates the natural process of antithrombin 3: Both heparin and warfarin prevent formation of additional clots – one by blocking vit K dependent factors and the other by inactivating thrombin so it cant break down fibrinogen
- Protein C – activated by binding to excess thrombin
- Activity of Activated Protein C enhanced by binding to protein S, inactivates factor Va (part of the final common pathway)
- S/APC complex binds plasmin activator to allow clotting, activated complex cleaves creating tPA (plasminogen activator) which dissolves clots
- Plasmin causes fibrinolysis which breaks down clots – the protein S/APC binds to this compound so it prevents breakdown of clot: Controls timing of clot formation and dissolution
16
Q
disorders
A
- Failure to clot - bleed
- Inappropriate clotting – you will throw emboli, deny tissues of O2, cause ischemia, etc.
17
Q
testing
A
- PTT (aPTT) – activate partial thrombopastin time: Measures intrinsic system, Used to monitor heparin tx
- Factors XII, XI, IX, VIII (these are on the intrinsic side of the clotting cascade): X tested by PT and aPTT
- Heparin therapy – get PTT
- Warfarin therapy – get PT
- PT – Prothrombin time and INR (normalizes results from one lab to the next: Extrinsic pathway, Factors I, II, V, VII, X, Used to monitor, adjust coumadin tx
- Thrombin time (activated factor II): Tests abnormality affecting conversion of fibrinogen to fibrin
- Fibrinogen: Can be measured chemically
18
Q
drugs
A
- Antiplatelet: Aspirin, Clopidogrel/Ticlopidine, Abciximab
- Anticoagulants: Heparin, Warfarin/coumadin
- Thrombolytics – break down existing clots: tPA, Streptokinase, urokinase, alteplase
19
Q
DIC
A
- disseminated intravascular coagulation
- Presence of D-dimer and FBP (fibrinogen breakdown product) elevation confirm DIC
- Prolonged PT
- Prolonged PTT
- Prolonged TT
- These all seem counterintuitive – this is because the clotting factors are being taken up in other places
- Hypofibrinogenemia
- Thrombocytopenia – the platelets are being used up in the widespread clotting that’s happening
20
Q
platelet function
A
- Platelet count
- Peripheral smear
- Bleeding time – cut someone and watch for how long it takes them to stop bleeding
- Clot retraction – put tube of blood on the counter and wait for it to clot
