Anticoagulants Flashcards
4 main steps in hemostasis
- vasoconstriction
- platelet aggregation (plug)
- coagulation (clot)
- thrombolysis
what allows for platelet aggregation
platelets cross-linked by fibrinogen binding to GPIIb/IIIa
platelet activation happens when bound to what
collagen
only molecule of coagulation cascade made by EC
vWF
clotting factors of coagulation cascade besides vWF made by what
liver hepatocytes
direct binding of platelet to collagen by what
GPVI
indirect binding of platelet to collagen
vWF: GPIIb/GPIIIa
cytokines inhibit antithrombotic factor and promote thrombotic factors
septic shock thrombosis pathogenesis
heparan sulfate
PGI2
NO
Adenosine
t-PA
thrombomodulin
anti-thrombotic factors produced from EC
vWF
PAI1 (Ang IV receptor)
tissue factor (factor III)
thrombotic factors produced from EC
thrombin receptor that activates protein C and turns thrombin into anti-coagulant
thrombomodulin
found in blood that will be used in platelet aggregation
fibrinogen
what happens for platelets to degranulate
they bind with GPIIb/GPIIIa and GPVI to vWF on subendothelium
how platelet is activated by TXA2 and 5-HT (serotonin)
TXA2 and 5-HT bind Gq receptor on platelet and cause increase in Ca2+
increased Ca2+ from TXA2 and 5-HT binding to Gq on platelet allows for what
activation of GPIIb/IIIa to bind to fibrinogen
how ADP activates platelet
binds P2Y12 (Gi) and decreases cAMP and activates GpIIb/IIIa
crosslinking by fibrinogen via GPIIb/IIIa
platelet aggregation
tissue factor (factor III) so powerful it does what when bound to platelet
directly activates GPIIb/GPIIIa
how thrombin activates platelet
thrombin binds PAR1 (Gq) and leads to degranulation
when platelets are activated what happens
degranulation and ready to bind fibrinogen (step 1 achieved)
lack of vWF (EC problem); mucosal bleeds (nose); most common bleeding disorder; AD
vWD
nose bleeds
epistaxis
stabilizes factor VIII and protects it from inactivation by Protein C
vWF
2 main functions of vWF
platelet aggregation and saving factor VIII
lack of vWF will affect what stages of coagulation
increased (PTT)
2nd most common bleeding disorder; x-linked recessive
Hemophilia A
males of Royal family were affected by this bleeding disorder
Hemophilia B
mutation in Factor V causes it to not be inactivated by protein C; propensity to form clots (thrombosis)
Factor V Leiden
GpIb deficiency (platelet problem)
Bernard-Soulier
Gp IIb/IIIa deficiency
Glanzmann thromboasthenia
made by Stellate cells in the liver
ADAMTS13
multimeric vWF used for adhesion is degraded by what
ADAMTS13
Ab against ADAMTS13, causes accumulation of vWF and thrombosis (TTP)
Ticlopidine
abnormal function of this makes collagen (can lead to cirrhosis of liver)
Stellate cells of liver
endothelial cell exocytotic bodies
Weibel-Palade body
cAMP associated exocytosis when V2 (Gq) is bound
Weibel-Palade body exocytosis
what is carried in the Weibel-Palade body
vWF
V2 receptor agonist (increases release of vWF from EC Weibel-Palade Body)
Desmopressin
what to administer in patient w/ DIC that has no platelets available and clotting factors being used in the disseminated clots
Desmopressin
no platelets available and clotting factors being used in the disseminated clots
consumption coagulopathy
defective platelet aggregation due to absent fibrinogen
Afibrinogenemia
what test to use to tell if vWF or GpIb is deficient
Ristocetin induced platelet aggregation (RIPA)
plant based molecule that directly binds to vWF
Ristocetin
no aggregation means what if both RIPA and RCA tests were used
vWF is absent or not active
RIPA no aggregation, but RCA aggregation (means vWF present)
absent or inactive GpIb
multiple platelets joined together
platelet plug
antiaggregant drug that is a COX I/II irreversible inhibitor (blocks TXA2)
Aspirin
(-GREL)
P2Y12 inhibitors (stops activation of GpIIb)
PDE inhibitor (cAMP increased and GpIIb not activated)
ABCIXIMAB
mab that blocks fibrinogen from binding GpIIb/IIIa
GpIIb/IIIa inhibitors (blocks FIBrinogen from binding)
VORAPAXAR
PAR1 inhibitor (prevents binding of thrombin)
SE of Ticlopidine (P2Y12 inhibitor)
neutropenia, TTP
contraindication for Clopidogrel
breast feeding (can get into breast milk
most liked P2Y12 inhibitor now
Prasugrel
____ when converted to ____forms the structural meshwork that consolidates an initial platelet plug into a solid hemostatic clot
fibrinogen to fibrin
what is required for the clotting factors to be activated
factor IV (Ca2+)
protein C can deactivate which 2 factors
factor VIII and V
when deactivated by thrombomodulin, ____ can help protein C deactivate VIII and V
thrombin
what factor from extrinsic side activates factor X
VIIa
what factors from intrinsic side activate factor X
VIIIa and IXa
way to measure functionality of extrinsic arm
PT (N 11-15 s)
way to measure functionality of intrinsic arm
PTT (N 25-40 s)
TT normal length (time to convert fibrinogen to fibrin)
<2
INR normal length (patient PT/normal PT)
1
PTT increases with what
vWFD, Heparin and Hemaphilia
PT increases with what
Warfarin and Vitamin K deficiency
what to check for thrombosis in the body
D-dimer
vitamin K antagonist; oral anticoagulant
Warfarin
ingesting Vitamin K can decrease effects of what
Warfarin
very effective drugs that block factor Xa
Warfarin and Dicumarol
block Epoxide reductase (VKORC1 gene); blocks formation of Vitamin K
Warfarin and Dicumarol
target INR for patients on Warfarin
2.5
warfarin used for
Atrial fibrillation
WARNING for warfarin
TERATOGEN
SE’s of warfarin
bleeding and skin necrosis
how microthrombosis and then skin necrosis is induced with patient on warfarin
Protein C depletes before factor II or X and before warfarin can reduce their production
what do you prescribe with warfarin to prevent microthrombosis
Heparin
antidote of warfarin serious bleeding
FFP (fresh frozen plasma)
vitamin K
indirect inhibitor of factor IIa (thrombin) and factor Xa
heparin
indirect effect of heparin due to what
they amplify action of antithrombin III
high molecular weight heparin
Heparin
low molecular weight heparin
Enoxaparin
minimalistic heparin
Fondaparinux
main factors antithrombin III inhibits
IIa (thrombin)
Xa
heparin is safe to use in patient’s with what 2 things
pregnancy
or
renal failure
SE of heparin
heparin induced thrombocytopenia (HIT)
antibodies against platelet 4 leads to what
HIT (heparin induced thrombocytopenia)
antidote for heparin
protamine sulfate
specific heparin that inactivates factor Xa
ENOXAPARIN
heparins that activate antithrombin III and inhibit only Xa
Enoxaparin
Fondaparinux
this specific type of heparin activates antithrombin III and inhibits Xa AND IIa
unfractionated heparin
(-RUDIN)
inactivate IIa (thrombin)
antidote of -RUDINs (thrombin inactivators)
IDARUCIZUMAB
drug from leech saliva that blocks thrombin
HIRUDIN
(-XABAN)
factor Xa inhibitors
more effective and safer than warfarin
direct factor Xa inhibitors
antidote for direct factor Xa inhibitors
ANDEXANET
major 2 fibrinolytic agents
t-PA
urokinase
clot buster
plasmin
natural in our bodies and blocks plasmin
alpha2-antiplasmin
inhibits t-PA and urokinase
PAI-1and2
drug that inhibits plasmin
AMINOCAPROIC ACID
initial Rx of venous thromboembolism
heparins
-RUDINS (direct IIa inhibitors)
secondary Rx for venous thromboembolism
Warfarin
-XABAN (direct Xa inhibitors)
2 main drugs used to treat arterial thrombosis
Aspirin
t-PA