section 5 - coag cascade 1 Flashcards
name the three major portions of the coag cascade and how they’re related
- intrisic
- extrinsic
- common: where intrinsic and extrinsic combine
describe the extrinsic tenase complex
- constituents and action
- TFIII and Ca activate VII
- FVII, TFIII and Ca = tenase complex
- Tenase complex activates factor 10
describe the intrinsic tenase complex
- constituents and action
- contains FIXa, PF3, Ca, FVIIIa
- activates FX
what is the meaning behind a lowercase a by roman numerals ex: VIIa
activated factors - more efficient
describe the prothrombinase complex
- constituents and action
- contains: Xa, PF3, Ca and Va
- converts prothrombin (II) to thrombin (IIa)
list the actions of thrombin
- activates fibrinogen to fibrin
- activates V, VIII, XI and XIII
what are the final steps of the coag cascade
fibrinogen -(thrombin)-> fibrin -(XIIIa)-> cross linked fibrin polymer (stable)
name the ‘magic four’ factors
vitamin K dependent: II, VII, IX and X
-> under warfarin forms incomplete factors
true or false
thrombin (factor IIa) is the only substance necessary to convert fibrinogen (FI) to fibrin (Ia)
true
describe the intrinsic pathway activation steps
- vascular injury exposes collagen
- collagen contact activates FXII
- FXIIa activates both XI and pre-kallikren
define and describe HMWK
high molecular weight kininogen
- made in the liver
- contact factor
- cofactor for FXIIa to activate XI
-deficiency leads to thrombosis
what is the role of HMWK in the intrinsic pathway
in two separate complexes with FXI and PK
facilitates rxns for XI activation and kallikren activation
what is the role of FXIa in the intrinsic pathway
activates FIX to participate in tenase complex
describe the action of HMWK/PK in the intrinsic pathway
- part of clot breakdown and XIIa activation
- activated to kallikrein via XIIa and activates further XIIa
describe the role of kallikrein in the intrinsic pathway
- activates further XII
- using XIIa activates plasminogen to plasmin
- converts HMWK to bradykinins (part of healing process)
describe the alternate pathway
extrinsic tenase complex activates IX to take place in intrinsic pathway
describe labile factors V and VIII
- only factors that are not enzymes -> co-factors
- can participate in inactive forms
- activated by thrombin
- targets of protein C
describe Thrombin (IIa) activity on fibrinogen
- splits fibrinopeptide’s A and B from end of two polypeptide chains of fibrinogen
- forms fibrin monomer
- fibrin monomers attach end to end to form fibrin polymer
- thrombin + Ca = activated XIII to stabilize clot
describe fibrinogen (FI)
- made in liver
- absorbed in platelets alpha granules
- acute phase reactant
- increased in pregnancy and smoking
describe tissue factor III
found in all tissues -> esp brain, liver, lung and placenta
- released when injured
- cofactor for activation of FVII
- part of extrinsic tenase complex
describe calcium (FIV)
- mediator of platelet activation
- low lvls not a problem in vivo
- in screening tests must add Ca to overcome anticoag
describe FV
- activity decreases at room temp
- attaches to receptor on activated platelets
- thrombin modified
- inactivated by protein C
describe FVIII - vWF complex
- produced mostly liver (and other tissues)
- heat labile
- works with intrinsic tenase complex
- inactivated by Protein C
- deficiency = hemophilia A
describe FIX (christmas factor)
- activated by XIa or VIIa
- works in intrinsic tenase complex
- deficiency = hemophilia B
describe FX
- part of prothombinase complex
- magic 4 - vit K depndent
describe FXI
- contact factor
- complex with HMWK to amplify function
- activated by XII or thrombin
- deficiency = hemophilia C
decribe FXII
- contact factor with collagen
- activated with contact to subendothelial tissue
- deficiency does not mean bleeding
- defiencey = thrombosis due to lack of clot breakdown
describe FXIII
- fibrin stabilizing factor
- activated by thrombin and Ca
- forms covalent bonds between D domains in polymerized fibrin
- deficiency found in urea clot lysis test
describe PK (prekallikrein)
- contact factor
- activates more XII, plasminogen to plasmin, HMWK to Bradykinins for Kini system initiation
- deficiency = thrombosis due to lack of clot breakdown
describe the role of Bradykinins
- increase vascular permeability
- contract smooth muscle
- dilate blood vessels
- induce pain/inflammation
- release prostaglandins from tissue
what is the role of PF3 in coagulation
- phospholipids on the surface provide binding sites for Vit K-dependent factors
- membranes of activated platelets supply the phospholipids
what is the role of DDAVP
stimulates release of vWF from endothelial cells