Hemostasis Flashcards
Hemostasis involves a complex, rapid, localized, integrated interaction between what four processes
blood vessels
platelets
coagualtion cascade
fibrinolysis
What are the four components of hemostasis activated by endothelial disruption
rapid vasoconstriciton
immediate platelet adherence to collagen
coagulation (intrinsic/extrinsic)
fibrnolysis via tPA
Platelets are formed by —–, where?
megakaryocytes in bone marrow
What is the normal platelet amount in plasma
150,000-300,000/uL
What is the platelet half-life
9-10 days
What three types of storage granules are released when platelet secretion occurs
alpha granules
dense granules
lysosomal vesicles
What are the four distinct functions of platelets in response to vascular damage
places seal over endothelium (maintains integrity)
stops initial bleeding via formation of platelet plugs
stabilizes platelet plug
promotes vascular healing
List the events of platelet adhesion
damaged endothelium with exposed collagen»factor VIII:vWF complex binds exposed collagen to platelet surface receptor (GP Ib)
List the three main events of platelet aggregation
damaged endothelim initiates coagulation
activation of platelets via dense granule release of ADP»>promotes platelet aggregation
platelet shape change, decreased cAMP activity»exposed GPIIb and GPIIIa receptors for fibrinogen binding sites (calcium dependent)
increased phosphoplipase activity»thromboxane A2 formation
What are the two pathways of the coagulation pathway that leads to fibrin formation
contact activation pathway (intrinsic)
tissue factor pathway (extrinsic)
*both pathways activate the COMMON FINAL pathway of FACTOR Xa
What are coagulation factors
serine proteases which act by cleaving downstream proteins
What are the four clotting factors with calcium-binding properties that are vitamin K dependent
II, VII, IX, X
What is factor IV
calcium ion
What test is used to measure the extrinsic pathway
PT
What test is used to measure the intrinsic pathway
PTT
What serine protease does factor Xa activate
Thrombin
*prothrombin»>thrombin
What serine protease does thrombin activate
Fibrin
*fibrinogen»>fibrin
What four biological mechanisms are in place to control excess coagulation
increased blood flow (washout excess factors)
antithrombin III via heparin induced activity
prostacyclin via inhibiting thromboxane A2
protein C activation»fibinolysis
What serine proteases does ATIII inhibit
IX, X, XI, XII
Plasminogen activation results in
formation of plasmin (serine protease) which lyse fibrin clots
How are the endogenous plasminogen activators classified
intrinsic and extrinsic
Name the three intrinsic plasminogen activators
factor XIIa
kallikrein
protein C
Name the two extrinsic plasminogen activators
tPa
urokinase
Name the two Exogenous plasminogen activators
streptokinase
rt-PA
How is thrombin involved in fibrinolysis
thrombin in the presence of thrombomodulin activates protein C
What is the main MOA of protein C
inactivates the inhibitor of plasminogen activator
*allows plasminogen»>plasmin conversion
Plasmin has what effect on clots and platelets
lysis of clots (fibrin)»fibrin split products
- cleaves GP receptors
Heparin is classified as an
anticoagulant
What is the MOA of heparin
binds to ATIII causing a conformational change»>1000X more potent
ATIII inhibits IX, X, XII, XII clotting proteases by forming stable complexes with them
Heparin dosaging depends upon
the desired effect
The desired effect of heparin can be classifed as
partial heparinziation
complete heparinization
partial heparinization is used in what type of procedure
vascular (CEA, AAA resections)
dose generally 100 units/kg
Complete heparinization is used in what type of procedure
CPB
dose generally 300-400 unis/kg
1 unit of heparin is equal to ____mg
1
Heparin follows zero order kinetics, what does this mean for how it is eliminated
a constant AMOUNT of drug is eliminated per unit of time»>linear rate of elimination and NON-linear decrease in plasma concentration
What enzyme metabolizes heparin and where is it located
heparinase, located in the liver
What tests determine the degree of heparinization
PTT»for low doses (1.5-2 times pre-heparin value)
ACT»for high doses (400-500 seconds)
What are the three SE of heparin administration
Hemorrhage
Allergic rxn (beef/pork preparations)
Thrombocytopenia (encourages clot formation)
Thrombocytopenia induced heparin administration is categorized as
mild thrombocytopenia
Heparin-induced Thrombocytopenia and Thrombosis (HITT) syndrome
Mild thrombocytopenia caused by heparin results when
platelets drop below 100,000
*resolves on own
HITT syndrome caused by heparin results when
platelets drop below 50,000
HITT occurs do to the formation of
antibodies that attack platelets
*large doses of heparin causes upregulation of platelets»>antibodies attack platelets»>increased activation»>thrombosis and thrombocytopenia
Are patient’s who receive heparin candidates for regional anesthesia
NOOO!!!!
Fractionated (LMWH) heparins display what type of activity
Antifactor Xa/Antifactor IIa
- more pronounced AF Xa activity
What is a prototype of fractionated heparin
enoxaparin
“parins”
Factor Xa inhibitors are classifed as
direct
indirect
Name one direct factor Xa inhibitor
Rivaro-Xa-ban
*propphylactic prevention of VTE
Name one indirect factor Xa inhibitor
Fondaparinu-X
*DVT prophylaxis
Name one Vitamin K antagonist
Warfarin
What is the MOA of Warfarin
nucleus of warfarin is similar to vitamin K so it binds to VK binding site preventing formation of calcium binding sites on clotting factors II, VII, IX, and X
Warfarin is administered
Orally ONLY
What is used to monitor effects of warfarin
PT
*effective anticoagulation when PT is twice precoumadin PT
Name a class of drugs that are direct thrombin IIa inhibitors
“aTRoban”
Argatroban
What are the three MOA of thrombin inhibitors (IIa)
direct thrombin inhibition
inhibition of protein C (fibrinolysis)
promotes NO release»vasodilation
Name three common drugs used as procoagulants
protamine sulfate
vitamin K
conjugated estrogen
Protamine is a specific antagonist to
heparin
Protamine in the absence of heparin acts as a
anticoagulant
Why must protamine be administered slowly
causes histamine release»>venodilation»>decreased SVR
Protamine should not be given when
those taking protamine containing insulins
allergic to fish
males with vasectomy or infertility
What are the four classification of AntiPlatelet drugs
Cox inhibitors
GP IIb/IIIa inhibitors
PDE inhibitors
ADP antagonists
*given to patient’s with too many platelets
Name an antiplatelet COX inhibitor
Aspirin
*inhibits prostaglandin synthesis by irreversibly inhibiting COX I
Name three anitplatelet GP IIb/IIIa inhibitor
Tirofiban
Eptifibatide
Abcixmab
Name one antiplatelet PDE inhibitor
Dipyridamole
Name three antiplatelet ADP antagonists
Ticlopidine
Clopidogrel
Prasugrel
Name a drug that promotes platelet aggregation
Desmopression (DDAVP)
*increases the release of factor VIII:vWF from vascular endothelium
Name three antifibrinolytics
E-Aminocaproic Acid (amicar)
Tranexamic Acid
Aprotinin
Antifibrinolytics should not be given to patients with
DIC
Name the classes of drugs classified as thrombolytics
“KINASE”
“TEPLASE”
