Atnicoagulant, antiplatelet, thrombolytic Flashcards
2 stages of hemostasis
Formation of platelet plug
Reinforcement with fibrin
Platelet plug formation
Platelet aggregation occurs when they come in contact with exposed collagen on damaged vessel.
Glycoprotein IIb/IIIa receptors on platelet surface form bridges with other platelets made of fibrinogen
Each IIb/IIIa receptor must first undergo activation, activation is from thromboxane A2, thrombin, collagen, platelet activation factor, ADP.
Aggregation allows for platelet plug to form, must be reinforced with fibrin to last
Coagulation
Coagulation is the production of fibrin, which is a thread like protein that reinforces platelet plug. Fibrin is produced through two pathways, intrinsic and extrinsic
Extrinsic factor from tissue factor (tissue thromboplastin) release
Tissue factor released from damaged epithelium.
TF activates VII turns into X
X causes conversion of prothrombin (factor II) to thrombin (factor IIa)
Thrombin causes 3 things to happen
Fibrinogen –> fibrin
Factor V –> Va
Factor VIII –> VIIIa
Intrinsic pathway (contact activation pathway)
Blood exposed to collagen of vessel wall. Collagen causes factor XII to be converted to XIIa
XIIa activates XI which activates IX which activates X
X converted to Xa and clotting cascade is finished
Coagulation occurs with activation of X into Xa
Inactivation of clots is achieved with
Antithrombin.
Enzyme used to breakdown fibrin meshwork of clot
Plasmin. Produced through activation of plasminogen
Fibrinolytic drugs work by
Converting plasminogen to plasmin
3 main categories of fibrinolytics
Anticoagulants: disrupt coagulation cascade, thereby suppressing production of fibrin
Antiplatelets: Inhibit platelet aggregation
Thrombolytics: Promote lysis of fibrin, causing dissolution of thrombi
Anticoagulants reduce
Formation of fibrin
Anticoagulant mechanisms
Inhibition of synthesis of clotting factors, X and thrombin
Inhibition of clotting factors Xa and thrombin
Heparin (unfractionated)
Suppresses formation of fibrin Enhances antithrombin (helps antithrombin to inactivate clotting factors thrombin and factor X)
Sources of heparin
Cattle lungs, pig intestines. Administered by rapid-acting anticoagulant administered IV or SQ
Heparin therapeutic uses
Preferred during pregnancy when rapid anticoag required PE, DVT, evolving stroke Open heart surg, post op, renal dialysis DIC Adjunct to thrombolytic therapy
LMW heparins
Heparin preparations composed of molecules that are shorter than those found in unfractionated heparin
For:
DVT after surg
TX of established DVT
Prevention of ischemic complications (UA, MI, STEMI)
LMW pros and cons
SQ based on body weight Antidote for protamine sulfate toxicity Costs more than unfractionated No monitoring after Adverse effects include bleeding (less than unfractionated heparin, immune-mediated thrombocytopenia, severe neuro injury for pts undergoing spinal epidural anesthesia)
Thrombocytopenia
Low levels of thrombocytes (platelets)
Three common LMWs
Enoxaparin
Dalteparin
Tinzaparin
Enoxaparin (lovenox)
LMW heparin, anticoag
Indications: STEMI
Enoxaparin (lovenox) contras
Hypersens to heparins or pork Active major bleeding Bacterial endocarditis Thrombocytopenia Suspected intracranial bleeding
Enoxaparin (lovenox) dose
IV - BLUE 75 or less - 30mg IV Over 75 - withhold Adult SC (black) 75 or less 1mg/kg Over 75 0.75mg/kg
Warfarin is an
anticoagulant. Vit K antagonist.
Warfarin works for
Blocks biosynthesis of factors VII, IX, X and prothrombin
It has a delayed onset
Anticoagulants
Not useful in emergencies
Long-term prophylaxis of thrombosis
Prevention of thromboembolism (pts with prosthetic heart valves)
Prevention of thrombosis during a-fib
Antiplatelet drugs 3 major categories
These drugs suppress platelet aggregation
P2Y12 ADP receptor antagonist
GP IIb/IIIa inhibitors
Cyclooxygenase inhibitor (ASA)
ASA effects
ASA is a nonselective cyclooxygenase (COX) inhibitor
It reduces inflammation, fever and pain (COX 2 inhibition)
Protects against MI and ischemic stroke (COX 1 inhibition)
ASA antiplatelet effects
Suppresses aggregation by causing irreversible inhibition of COX 1 which makes TXA2. TXA 2 (thromboxane A2) in platelets promotes aggregation
Class and indications for ASA
Antiplatelet, thromboxane A2 inhibitor
ACS
ASA contras and dose
Hypersens, active GI bleed, asthmatic with hx of ASA,NSAID sensitivity
Adult dose is 160mg PO
Clopidogrel (plavix) blocks
P2Y12ADP receptors on platelet surface, preventing ADP-stimulated aggregation`
Clopidogrel uses
Blockage of coronary artery stents
Reduces thrombotic events in pts with acute coronary syndromes
Prevents stenosis of coronary stents, also for secondary prevention of MI, ischemic stroke and other vascular events.
Similar adverse effects as ASA
Clopidogrel (plavix) class
Platelet inhibitor, P2Y12ADP receptor inhibitor
Indications STEMI-VHR protocol
Clopidogrel (plavix) conras
Hyper sense
Active bleed
Liver dysfunction/jaundice, cirrhosis, alcoholism
Suspected aortic dissection
Clopidogrel (plavix) dose
75 or less 300mg PO
Over 75 75mg PO
Ticagrelor (brilinta) class
Platelet inhibitor, P2Y12ADP receptor inhibitor
Ticagrelor contras
Hypersens
HX of intracranial hemorrhage
Hepatic dysfunction
Active bleeding
Ticagrelor dose
180mg PO (given if getting PCI)
VHR if 75 or less with TNK
TNK weight based dose
Enoxparain 30mg IV - Blue
Clopidogrel (plavix) 300mg PO
Enoxaparin 1mg/kg sub q - black
VHR if over 75 with TNK
TNK weight based dose
NO IV enoxaparin
Clopidogrel 75mg PO
Enoxaparin (lovenox) 0.75mg/kg
VHR for PCI
Enoxaparin 30mg IV
Ticagrelor 180mg PO
Enoxaparin 1mg/kg sub Q
GP IIb/IIIa receptor antagonsits
Most effective antiplatelet drugs
“super aspirin”
Reversible blockade of platelet GP IIb/IIIa receptors
Therapeutic uses include ACS and PCI
Eptifibatide (integrilin)
Small peptide that causes reversible and highly selective inhibition of GP IIb/IIIa receptors
For:
ACS, PCI
Antiplatelet effects reverse within 4 hours of stopping infusion
Tenecteplase (TNK)
Variant of human tissue plasminogen activator (tPA, alteplase)
Approved for acute MI only
How to minimize bleeding risk
Minimize physical manipulation of pt
Avoid subQ and IM injections
Minimize invasive procedures
Minimizes concurrent use of anticoags (heparin, warfarin, dabigatran)
Minimize conccurent use of antiplatelet drugs (ASA, clopidogrel)
Tenecteplase (TNKase) class
Thrombolytic, fibrinolytic
for STEMI
Tenecteplase (TNKase) contras
Hypersen
Active bleeding
Brain tumor
Ischemic CVA within 3 months
Significant closed head/facial trauma within 3 months
Intracranial or spinal surg within 2 months
Suspected aortic dissection
Teneceteplase (TNKase) dose
30-50mg over 5 seconds <60k 30mg 60-70kg 35mg 70-80kg 40mg 80-90kg 45mg 90kg or more 50mg
