secondary hemostasis Flashcards
secondary hemostasis events
Coagulation cascade
Fibrin clot formation
Healing
Fibrinolysis
TF
tissue factor
PL
Platelet membrane phospholipid
XIII
fibrin stabilizing factor, transglutaminase
VII
stable factor, serine protease
IX
Christmas factor, serine protease
XI
plasma thromboplastin
XII
hangman factor, serine protease
factor I
fibrinogen
Factor II
prothrombin
Factor III
Tissue factor/ tissue thromboplastin
factor IV
ionized calcium
Factor V
labile factor (proaccelerin)
Factor VI
not assigned
Factor VII
stable factor
Factor VIII
anti hemophilic factor, factor VIII:C
Factor X
stuart power factor
factor XI
plasma thromboplastin antecedent
Factor XII
Hageman factor
Factor XIII
fibrin stabilizing factor (plasma transglutaminase)
HMWK or HK
high molecular weight kininogen (Fitzgerald factor)
PK
Prekallikerin factor
Extrinsic pathway activation
some substance has to enter the blood stream
injury to endothelium - tissue factor from damaged tissue
Intrinsic pathway activation
substances are in the blood stream
certain inactivated factors come in contact with exposed sub endothelium or collagen and are activated
Both extrinsic (TF) and Intrinsic (contact activation)
come together to the common pathway by activation of Factor X.
factors of extrinsic pathway
VII, TF (III)
First in the coagulation cascade to occur.
injury to vessel causes vessel wall to secrete Tissue Factor (III) (Tissue Thromboplastin)
Tissue Factor activates and complexes with Factor VII (stable factor)
= TF:VIIa
TF:VIIa
This serine protease complex of extrinsic pathway acts on factor X (Stuart Power Factor) starting the common pathway.
Extrinsic pathway measured by
PT
TF doesn’t originate in
the blood
Extrinsic pathway study strategy
3+7 =
10 ! Factor X = common pathway
Intrinsic pathway factors
XII
XI
IX
VIII
all factors of the intrinsic pathway originate from
the blood
surface contact - intrinsic pathway
negatively charged
Phospholipids on platelet membrane - or collagen from sub endothelium
Intrinsic pathway measured by
APTT
Factor VIII - Intrinsic Pathway
Largest protein in coag. cascade.
(anti-hemophilic factor)
activated by thrombin in the common pathway
Factor VIII =
vWF + VIII:c + antigenic portion
vWF -
von willebrand factor
carrier protein of VIII:c
VIII:c
coagulant portion of factor VIII
Order of factors in intrinsic pathway
think TENET
XII
XI
IX
VIII
X
PF3
platelet thromboplastin
XIIa –> HMWK
PK –> K –> K
common pathway starts with
Factor X
activated from either intrinsic pathway or the extrinsic pathway
both extrinsic and intrinsic pathway requires a “tenase” complex that includes
calcium, ca2+
tense for intrinsic
IXa + Ca2+ PF3 + VIII:c
tense for extrinsic
TF:VIIa + Ca2+
Factors of the common pathway
X
V
II
I
XIII
common pathway is measured by
PT, APTT, TT
IIa (II = prothrombin)
thrombin
Ia (I = fibrinogen)
fibrin
Common pathway - Prothombinase complex
Xa + Va + PF3 + Ca2+
enzymatically converts prothrombin into thrombin
assembles on the surface of activated platelets
Activation of thrombin is slow, but once generated, it further amplifies coagulation
Common pathway - thrombin
converts fibrinogen (I) into fibrin (Ia)
Activates factor XIII
Activation of cofactors V and VIII
induces platelet aggregation and secretion
Thrombin splits
fibrinogen into fibrino-peptide A and B from main molecule producing fibrin monomer and fibrin peptides
fibrin monomers line up end to end and side to side to produce fibrin polymers
soluble fibrin polymers become cross linked and stable through the action of FXIIIa and Ca2+
A stable fibrin clot is formed
Thrombin splits
fibrinogen into fibrino-peptide A and B from main molecule producing fibrin monomer and fibrin peptides
fibrin monomers line up end to end and side to side to produce fibrin polymers
soluble fibrin polymers become cross linked and stable through the action of FXIIIa and Ca2+
A stable fibrin clot is formed
substrate
I
cofactors
Proteins that accelerate enzymatic reactions
III
V
VII:c
HMWK
serine proteases
II
VII
IX
X
XI
XII
PK
transaminase
XIII
Contact proteins
XI
XII
PK
HMWK
prothrombin proteins
II
VII
IX
X
fibrinogen groups
I
V
VIII
XIII
substrate acted on to produce product
I - Fibrinogen –> fibrin
enzymes
catalyze biochemical reactions
serine protease - cleaves peptide bond ( IIa, VIIa, Xa, XIa, XIIa, prekallikrein)
transaminases - transfers amino groups
transaminase example
transfers amino groups
XIII, crosslink between fibrin monomers to form stable fibrin clot
consumed
yes/no
yes = all used up
no = found in serum
stable
yes/no
yes = can be found in stored plasma
no= requires fresh sample
vitamin k dependent?
yes = affected by Vitamin K deficiency or Warfarin/Coumadin
no = not affected
contact proteins - chart
Found in initial phase of intrinsic pathway
NOT consumed
Fairly stable - can be present in stored plasma
NOT vitamin K dependent
Prothrombin proteins - chart
Found in ALL pathways
NOT consumed, except II !!!!
Stable
VITAMIN K DEPENDENT
attracted to surface of activated platelets
Only one that is vitamin K dependent
Prothrombin proteins
Fibrinogen group chart
Found in intrinsic and common pathway
ARE consumed - NOT present in serum
V and VIII are least stable/very labile
NOT VITAMIN K DEPENDENT
stable groups
contact proteins
prothrombin proteins
consumed groups
fibrinogen group
prothrombin
complexes are assembled on
anionic (neg-charged) phospholipid surface
Ca2+ Required.
Extrinsic tenase
Enzyme: VIIa
Cofactor: TF
Substrate: X
Intrinsic tenase
Enzyme: IXa
Cofactor: VIIIa
Substrate: X
Prothrombinase tenase
Enzyme: Xa
Cofactor: Va
Substrate: II
protein C complex
Enzyme: IIa
Cofactor: Thrombomodulin Protein S
Substrate: Protein C
Factor decreased reasons
Decreased synthesis
Synthesis of dysfunctional factor molecule
Excessive destruction of factors through acquired disorders
Inactivation of factors through circulating inhibitors
Consequences of factor decreased
Coagulation will not proceed at normal rate
initiation of next subsequent reaction delayed
time required for clot to form prolonged
bleeding from the injured vessel continues for a longer time
PT test
Reagent contains Thromboplastin (TF)
- Extrinsic and common
- Factors: VII, X, V, II, I
detects vitamin K deficiency (II,VII, X)
used to monitor Warfarin (Coumadin) - removes vitamin K
involves INR
Normal range PT test
11-13 seconds
INR
varies in TF conc.
- helps compare between different laboratories
INR = PTpatient/PTcontrol ^ISI
Normal range APTT
25-38 seconds
APTT test
reagent contains phospholipids mimicking activated platelets; lacks tissue factor –> partial thromboplastin
Intrinsic and Common Pathway
deficiency in any of these factors will result in a prolonged test
(XII,XI,IX,VIII,X,V,II,I,PK,HMWK)
what test is used for monitoring heparin treatment
APTT
TT test
Reagent contains thrombin
measures conversion of fibrinogen into fibrin
- bypasses extrinsic + intrinsic pathway
Prolonged TT test
Hypofibrinogenemia/Dysfibrinogenemia
Treatment w/ heparin
FDP - circulating degradation products
Pathologic circulating anticoagulants
APTT abnormal
PT abnormal
TT normal
Vitamin K defect
Liver disease
Inhibitor present
Factor deficiency common pathway
APTT abnormal
PT normal
Factor deficiency - intrinsic
Lupus anticoagulant
Specific factor inhibitor (ex: VIII)
APTT normal
PT abnormal
Factor deficiency extrinsic pathway
Specific factor inhibitor
APTT abnormal
PT abnormal
TT abnormal
Factor deficiency I
Severe liver disease
DIC
Potent inhibitor
Hypofibrinogenemia/dysfibrinogenemia
fibrinogen normal range
200-400mg/dL
High fibrinogen
low TT
low fibrinogen
high TT
Factor XIII screening test
Measures XIII presence
- only presence in pathways is crosslinkong fibrin monomers to stabilize fibrin clot
- not effectively measured in PT, APTT, TT
Factor XIII screening test principle
in the absence of XIII fibrin is soluble in 5 M Urea or 1% monocholreacetic acid
dissolution of clot indicates factor deficiency
