Coagulation Flashcards
4 steps of hemostasis
- vascular spasm
- formation of platlet plug (primary hemostasis)
- coagulation & Fibrin Formation (seconday hemostasis)
- Fibrinolysis when clot is no longer needed
Clotting to death is an issue when blank predomindates
procoagulants
what are the risks when procoagulatns dominate?
risk of stroke, MI, thrombosis elsewhere in body
blank and blank favor clot formation
procoagulants and antifibrinolytics
bleeding to death is an issue when blank and blank predominate
anticoagulants and fibrinolytics
name the procoagulants and their function
coagulation factors: coagulation
collagen: tensile strength
wVF: platelet adhesion
Fibronectin: cell adhesion
Name the anticoagulants and their function
protein C: degrade Factors 5a and 8a
protein S: cofactor for protein C
antithrombin: inactivates 2a (thrombin) 9a, 10a, 11a, 12a
tissue pathway factor inhibitor: inhibits tissue factor
thrombomodulin: regulates naturally occurring anticoagulants
Name the fibrinolytics and their function
plasminogen: precursor to plasmin (breaks down fibrin)
tPa: activates plasmin
urokinase: activates plasmin
Name the antifibrinolytics and their function
alpha 2 antiplasmin: inhibits free plasmin in the blood
plasminogen activator inhibitor: bind to tpa and urokinse to accelerate clearance
List the vasoactive mediators and their function
Vascular smooth muscle constriction:
thromboxane A2
ADP
serotonin
Vascular smooth muscle relaxation:
Nitric Oxide
Prostacyclin
where are platelets produced?
megakarocytes in bone marrow
normal platelet count
150,000 - 300,000 /mm^3
platelet lifespan
8-12 days or 1-2 weeks
what body organ can sequester platelets for later use?
spleen
because of platelets small size where do they end up in vasculature?
pushed toward the vessel wall which strategically places them close to their site of action
which cells make up the structural component of clots?
platelets
besides forming the structural component of blood clots, what other function to platelets perfrom?
deliver many substrates necessary for clot formation
waht two things are found on platelets membranes and what is their function?
glycoproteins - repelled by healthy vascular endothelium and adhere to injured endothelium , collagen, and fibrinogen
phospholipids: produce thromboxane A2 that activates platelets
what role do platelet GpIb receptors play in clot formation?
hooks activated platelets to vWF
what role do platelet GpIIb-IIIa receptors play in clot formation?
links platelets together to form a plug
in the absence of vascular injury endothelium inhibits platelets by?
secreting prostaglandin I2 and nitric oxide
name the platelet receptors
GPIb
ADP
TxA2
Thrombin
GPIIb-IIIa
explain the mechanism of action of the vascular spasm, the first step of hemostasis
SNS reflexes
myogenic response
release of vasoactive substances
common sources that can cause vascular spasm
surgery
trauma
plaque dislodgement
spontaneous microvascular injury (this occurs many times a day)
vascular spasms serve two purposes:
- decrease blood loss
- help pro-coagulants stay at affected area to do their job
what are the three steps of Primary hemostasis, or platelet plug formation
- Adhesion
- Activation
- Aggregation
what do platelets adhere to during adhesion
collagen
blank binds blank to the subendothelium during platelet adhesion
vWF binds GPIb receptor to the sub endothelium during adhesion
von willebrand disease is a disorder of…
platelet adhesion
which two things activate platelets
collagen and thrombin
activated platelets release what? what is their function?
ADP and thromboxane A2
both serve to activate nearby platelets and platelet aggregation
thromboxane A2 also serves as vasoconstrictor
once activated how do platelets shape change?
they become swollen, irreguarly shaped, and sticky
this helps them stick together and stick to site of injury
activated platelets express which two glycoproteins on their surface?
GpIIb and GpIIIa
for what kind of injury is platelet plug sufficent without activation of coagulation cascade?
micro injuries
for micro injuries the coagulation cascade is not needed to stop bleeding and the platelet plug is sufficient
why is coagulation cascade needed in addition to platelet plug for significatn vascular injuries?
platelet plug only forms loose, fragile, temporary fix and coagulation cascade is required to form fibirin threads that strengthen the clot
what is the primary purpose of the coagulation cascade?
produce fibrin and form stabilized clot
what is the classical coagulation cascade model
intrinsic, extrinsic, and final common pathways
what is the cell based coagulation model?
modern hybrid understanding
coagulation is initiated by extrinsic pathway with release of Tissue Factor 3
intrinsic pathway amplifies the thrombin generating effects of the extrinsic pathway
List each clotting factor and the mnemonic to remember them
Foolish people try climbing long slopes after Christmas some people have fallen
- Fibrinogen
- Prothrombin
- Tissue Factor
- Calcium ions
- Labile Factor
- Stable Factor
- Anti-hemophilic Factor
- Christmas Factor
- Stuart-Power Factor
- Plasma thromboplastin antecedent
- hageman Factor
- Fibrin stabilizing Factor
draw the clotting cascade
what three points go along with clotting cascade drawing?
8 and 5 are cofactors
2,7,9,10 are circled beause Vit K Dependent
3&4 are not blood proteins
explain the steps in the extrinsic pathway
tissue trauma liberates TF from subendothelium
TF activates Factor 7
7 activates 10 in the presence of Ca++
prothrombin activator and platelet phospholipids activate factor 2
factor 5 is positive feedback mechanism to accelerate continued production of prothrombin activator
what is prothrombin activator?
name for all the factors that lead to thrombin activation
how fast does extrinsic pathway happen?
only needs 15 seconds
which factor has the shortest half life? how short is it? when is this important?
factor 7
4-6 hrs
will be the first factor to become deficient in:
liver failure
Vit K Deficiency
those on warfarin
List the steps of the intrinsic pathway
blood trauma exposure to collagen activates Factor 12
12a activates 11
(this requires HMW Kininogen)
(accelerated by prekallikrein)
11a activates 9
9a & 8 activates 10
prothrombin activator and phospholipid activate thrombin (2a)
(this is the same last step as in extrinsic pathway)
in what disease is factor 8 missing?
hemophilia A
which step in intrinsic pathway requires HMW Kininogen
12a activation of 11
prekallikrein acceleartes which step in intrinsic cascade?
12a activation of 11
what is the final goal of both the inrinsic and extrinsic pathways?
create prothrombin activator (prothrombinase)
what is prothrombinase / prothrombin activator?
10a + 5a + 4
explain the steps of the final common pathway
Promthrombinase / prothrombin activator coverts prothrombin (2) to thrombin (2a)
thrombin changes fibrinogen to fibrinogen monomer in the presence of Ca++ Fibrin fibers are created
after platelets aggregate fibrin is incorporated into platelet plug. Activated fibrin stabilizing factor (13a) facilitates cross linkage of fibrin fibers. This completes the clot
how long does the final blood clot (from final common pathway) stay in place?
until the underlying tissue has repaired itself
what factors limit the size of clot formation?
vasodilation and washout of ADP and TxA2
antithrombin - inactivates 2a, 9a,10a,11a,12a
tissue factor pathway neutralizes tissue factor
protein C and S inhibit factors 5a and 8a
when are clots broken down?
once the body has healed itself, at this point the clot is no longer needed
describe the process of fibrinolysis
- plasminogen is incorported into clot as it is built, but lays dormant until activated
- plasminogen is converted to plasmin by tPA and urokinase
- plasmin breaks fibrin down into fibrin split products
how are fibrin split products measured?
d-dimer
where is plasminogen sythesized?
in the liver
where does tPA come from? is it a major or minor mechanism of plasminogen activation?
released from injured tissue over days to months and is a major mechanism
where does urokinase come from and is it a major or minor mechanism?
produced by kidneys and released into circulation it is a minor mechanism
what else can activate plasminogen to plasmin and where does it come from?
streptokinase from streptococi this is situation specific
what are the two off switches for fibrinolyis?
alpha 2 antiplasmin
plasminogen activator inhibitor
what does alpha 2 antiplasmin do?
inhibits plasmin
what does plasminogen activator inhibitor do?
inhibits conversion of plasminogen to plasmin
what is the main idea of the contemporary cell based coagulation cascade?
coagulation takes place on the surface of a cell that expresses tissue factor
what are the three main steps of the contemporary cell based coagulation cascade?
- Initiation
- amplification
- propagation
describe the initiation phase of the contemporary cell based coagulation cascade
started by factors 3 and 7
small amount of thrombin is created but not enough to activate fibrin
describe the amplification phase of the contemporary cell based coagulation cascade
platelets, factors 5 and 11 activated
describe the propagation phase of the contemporary cell based coagulation cascade
starts with factor 10 activation
positive feedback so enough thrombin is produced to activate fibrin
why do thrombin levels stay low during initiation phase?
because tissue factor pathway inhibitor limits the amount of tissue factor released
which pathways does aPTT measure?
intrinsic and final common pathway
what medications does aPTT monitor?
unfractionated heparin
NOT LMWH
normal aPTT value?
25-35 seconds
remember this will be longer than PT because PT monitors extrinsic pathway which is faster than intrinsic pathway
how much must coagulation factors decrease by before a change in aPTT is noted?
must decrease by more than 30% before aPTT will be affected
which clotting pathways does PT measure?
extrinsic and final common pathways
PT monitors for therapeutic response to which drug?
warfarin
normal PT
12-14 seconds
how much must coagulation factors decrease before PT will be affected?
must decrease by MORE than 30% before PT will be affected
what is INR?
standardizes PT measurements so that PT values can be compared from lab to lab
what is a normal INR and what is the goal for therapeutic warfarin?
1 is normal
2-3 control is the goal for warfarin therapy
what is ACT used for?
to guide heparin dosing
normal ACT value?
90-120 seconds
what ACT do you need before initiating cardiac bypass?
ACT >400
when do you measure ACT?
before heparin
3min after giving heparin
every 30min thereafter
which is more accurate PTT or ACT? and when?
ACT is more accurate when large doses of heparin are used, i.e cardiac bypass
what does a platelet count give us? what does it not tell us?
only number of platelets, not platelet function
normal platelet count
150,000-300,000 mm^3
platelet count less than x increases risk of surgical bleeding
< 50,000
platelet count less than x increases risk of spontaneous bleeding
20,000
what does bleeding time monitor? is it used often?
platelet function
no, not used often clinically
what is a normal bleeding time?
2-10min
what drugs prolong bleeding time? I.e. affect platelet function
Aspirin
NSAIDs
what does D-dimer monitor?
fibrinolysis
what does elevated d-dimer indicate?
that a thrombus is likely present somewhere in the body
what is a normal d-dimer value?
< 500mg/ml
differential for elevated d-dimer should include what?
DVT, PE, DIC
what is the definition of R/CT on TEG/ROTEM and what does it indicate? what is the normal value?
time to begin clot formation
4-8min
what is the definition of K/CFT on TEG/ROTEM and what is the normal time
time until clot has reachd fixed strength
1-4min
what does the A angle on TEG/ROTEM show
what is normal?
speed of fibrin accumulation
53-72 degrees
what is MA/MCF on TEG/ROTEM
what is normal value?
greatest vertical angle
50-70mm
what is LY30 / LI30 on TEG/ROTEM what is normal and what does it tell us?
% decrease in MA or MCF
0-8%
shows fibrinolysis
normal teg
factor deficiency or anticoagulation
impaired platelet count or function
primary fibrinolysis
hypercoagulation
DIC stage 1
hyper-coagulable state with 2ndary fibrinolysis
DIC stage 2
hypo-coagulable state
Identify the part of the coagulation system that is assessed by each color from left to right and the associated treatment
Which sections measure coagulation and which sections measure fibrinolysis?
coagulation factors : FFP
fibrinogen : Cryo
thrombin generation and fibrin deposition : Cryo
platelets : plateletes / DDAVP
plasmin : TXA / Amicar
first three measure coagulation
last two measure fibrinolysis
