Flashcards in Hemodynamics Part I: hemostasis Deck (92):
hemostasis occurs as the result of ...
well regulated and balanced process of maintaining blood in a fluid state while allowing for controlled and focused clotting to prevent blood loss
3 general components that contribute to hemostasis
sequence of clot formation (5)
1. brief vasoconstriction
2. endothelial damage exposes subendothelium casuing platelts to become activated and adhere.
3. TF is released and activates the coagulation cascade forming fibrin
4. platelet activation furthers coagulation
5. fibrin and platelets form a clot thereby plugging the defect to prevent blood loss
factors which activate endothelium and shift the function to the procoagulant state include (4)
antithrombotic mechanisms of the endothelium
- acts as barrier to suendothelium
- prostacyclin PGI2 and NO inhibit platelet aggregation (thrombin and several cytokines stimulate PGI2 and NO synthesis)
- adenosine diphosphatase degrades ADP thereby inhibiting platelet aggregation
anticoagulant activites of endothelium
- heparin-like molecules are cofactors to antithrombin
-thrombomodlin converts thrombin to an anticoagulant
- fibrinolytic (endothelial cells make tPA)
prothrombotic mechanisms of the endothelium
- endothelial cells synthesize von Willebrand factor, which serves to firmly bind platelets to the subendothelium
- endotoxin and some cytokines induce enothelial cells to make tissue factor
- endothelial cells secrete plasminogen activator inhibitor
under normal conditions, endothelial cells inhibit platelet adherence and blood clotting
injury or activation of endothelial cells results in procoagulant state
from what do platelet cells derive?
platelet adhesion: vWF links the subenothellium to _________ on platelets
glycoprotein Ib receptors
this mediates firma dherence of platelets to vessel wall
_____- activates the platelets causing the release of their granules
platelet granule contents
platelet factor 4
function of calcium
critical coagulation cascade
function of ADP
mediates platelet aggregation which drives increasing platelet aggregation at the site (along with thromboxane)
function of platelet factor 4
binding of heparin by platelet factor 4 results in its inactivation
function of serotonin
fibrinogen links platelets via _____
GpIIb - IIIa inhibitors are used to -------
where does thrombin bind
platelet activation causes expression of __________ on surface of platelets
phospholipid complexes on suface of platelts which act as surfaces to bind coagulation factors and calcium --> promotes coagulation
actions of thrombin
thrombin converts fibrinogen to fibrin monomer but also effects local vasculature, inflammation and fibrinolysis
forms glue for platelet plug
when is tissue factor released?
when tissue is injured
where do the intrinsic and extrinsic pathways converge?
factors IX and X
what surface is best for maximum coagulation factor activity?
prolongs prothrombin time PT (extrinsic)
prolongs partial thromboplastin time PTT (intrinsic )
intrinsic longer pathway PTT
fibrinogen --> fibrin
action of antithrombin III
directly inactivates serine proteases thrombin and Xa (also IXa, XIa and XIIa)
what potentiates the action of antithrombin III
cleaves the cofactors Va and VIIIa
breaks down fibrin
enhances the activity of protein C
activates protein C
activated by thrombin
binds to thrombin to alter its conformation
inhibits VIIa tissue factor complex (extrinsic arm)
tissue pathway factor inhibitor
where is plasmin activity optimized?
at sites of fibrin deposition
how is free plasmin inactivated
by circulating alpha2 antiplasmin
what inactivates tPA
PAI plasminogen activator inhibitor
how do endothelial cells modulate coagulation/anticoagulation balance?
by releasing PAI
what increases PAI?
thrombin and various cytokines
what breaks down fibrin?
plasmin (from plasminogen)
what 3 substance activate plasminogen?
prevent clot formation and extension
interfere with platelet activty
dissolve existing thrombi
blood clot that forms abnormally within a blood vessel
a dislodged blood clot which travels through the bloodstream
naturally occurring anticoagulant produced by basophils and mast cells to prevent formation and extension of blood clots
does heparin disintegrate clots that have already formed?
how is heparin given?
intravenously or by subcutaneous injection
how does heparin work?
binds and activates antithrombin III (inhibits thrombin, factor IXa, factor Xa)
how is warfarin administered?
how does warfarin decrease blood coagulation?
by interfering with vitamin K metabolism
what are the vitamin K dependent clotting factors>
what clotting factors does heparin attack?
what clotting factors does coumadin attack?
direct thrombin inhibitor
direct factor Xa inhibitor
direct factor Xa inhibitor
TFPI tissue factor pathway inhibitor
new anticoagulation drug
extrinsic assessment of coagulation
prothrombin time PT
what drug increased the prothrombin time
which factors require vitamin K for synthesis
factors II, VII, IX, X, protein C and protein S
describe the international normalized ratio INR
compares patient PT to the normal PT which compensates for differences in tissue factor
intrinsic assessment of coagulation
partial thromboplastin time PTT
what prolongs the PTT
what are the only factors not included in PTT
factors VII and XIII
how would you distinguish between an inhibitor and factor deficiency
mixing pt sample with normal plasma:
if inhibitor: no clotting
if deficiency: clotting
low dose heparin PT and PTT
high dose heparin PT and PTT
low dose warfarin PT adn PTT
high dose warfarin PT and PTT
what is warfarin necrosis?
thighs, breasts, and buttocks multiple or single lesion, with localized pain and erythema that develops into a painful necrotic eschar
low levels of protein C --> transient hypercoagulable state causing local thrombosis of dermal vessels
describe heparin induced thrombocytopenia
platelet factor 4 is released by plateltes and bidns heparin thus blocking its action and pormoting coagulation
antibodies to heparin bind heparin/platelet factor 4 complex ----> endothelila injury and platelet activation (prothombotic state)
defect of platelet adhesion
lacking glycoprotein Ib
platelet abnormality: defect of platelet aggregation
lacking glycoprotein IIb/IIIA
TTP thrombotic thrombocytopenic Purpura
platelet abnormality: antibodies direct against the von Willebrand factor cleaving protease, ADAMTS-13
Idiopathic thrombocytopenic purpura ITP
antibodies directly agianst platelets
aplastic anemia/ pancytopenia
all the cell lines are gone- marrow destroyed
von Willerbrand's disease
deficiency of von Willebrand's antigen
easily bruised, nosebleed, etc.
most common bleeding disorder
factor VIII deficiency
x-linked recessive most common hemophilia
factor IX deficiency
x-linked recessive coagulopathy
factor XI deficiency
mildest hemophilia associated with the EJws
factor XII deficiency
not clinically important
neither is the presence of lupus anticoagulant
purpura petechia and ecchymoses are most likely
trouble stopping blleding most likely
coagulation factor deficiency
NOT a specific diagnosis
widespread activation of the caogulation system (thrombin) that from tiny thrombi throughout body leading to thrombocytopenia and consumptive coagulopathy (organ failure and bleeding)
peripheral blood smear of DIC
observe sheared RBC