Anticoagulant Therapy Flashcards
Steps of hemostasis 5
Vasoconstriction, plt plug, activate clotting cascade, fibrin clot forms, clot retracting and lysis
Primary hemostasis
What it is
Occurs sec-min, plt plug in response to injury. Subendothelial collagen that is exposed attracts platelets
Primary hemostasis: promoted by which pro coagulants, causes what to occur
VWF, factor 8, ADP
Localized vasoconstriction
Primary hemostasis
What adhered plt do 3
Activate to pseudopod shape and release TXA2.
Plt degranulate, releasing chemicals.
Plt aggreg begins, using fibrinogen and VWF
Agents released in degranulation and their roles
5
Serotonin and histamine: vasoconstrict. Thromboxane: vasoconstrict and degranulate plt. ADP- adherence and degranulation, cases plt stickiness. Clotting factors 5a, 8a, 9a. Plt factor 4 enhances clot formation
Extrinsic pathway: starts with what, where it connects to final common pathway
Thromboplastin. Converts factor 7 to factor 7a. To factor 10. To factor 10a where it connects to intrinsic pathway.
Intrinsic pathway: process start and where it becomes common
Collagen, goes from factor: 12 to 12a, 11 to 11a, 9 to 9a, 10 to 10a where it connects
Final common pathway
10a to prothrombin becomes thrombin, fibrinogen becomes fibrin
Secondary hemostasis
Process and what it forms
Min to hrs. Fibrin clot formation, stabilizes plt plug. End of coag cascade where factors converted to each active form
Which end of hemostasis humans tilt slightly towards
More towards coagulation vs anticoagulation
Arterial thrombosis: 3
MI, arterial thrombosis, CVA
Venous thrombosis
DVT and PE
Natural anticoagulants
What they are and their role 5 total
Once coag process activated they regulate process
Prostacyclin, antithrombin 3, heparin, protein c, protein s
What happens in clot retraction and lysis
After clot forms it retracts (fibrin strands shorten). Plt trapped in mesh, have actinomyosin like proteins. Begins in mins and most protein free in an hr
Lysis is carried out by what, mediated by what, activated by what
Process
Carried by fibrinolytic sys, mediated by plasmin, activ by coagulation and inflammation substances. Plasmin splits fibrin and fibrinogen into FDPs
Oral antiplt aggregation
5
Aspirin, ticlopidine, clopidogrel, prasugrel, ticagrelor
IV antiplt therapy 3
Abciximab, eptifibatide, tirofiban
Aspirin: what class, moa
Cox inhibitor, prevents form of TXA2 and degranulation of platelets. Action is irreversible and for plt life, 10-14d
Aspirin: indication. Dose.
Prevention of recurrent ischemic events: stroke, mi, symptomatic pad. 80 mg, 325 mg if active mi
Aspirin: precautions 5
Children (Reyes swelling in liver/brain after virus), pregnant, cv disease (bb/ace/diuretic med fx from prostaglandin inhib, mediates vasodil), asthmatics (leukotrienes), inc bleeding w other anticoags (tx- plt)
Ticlid
Name, moa
Thienopyridine, blocks ADP receptor on plt and inhib fibrinogen binding
Ticlid
Indication
Use restricted due to which SE
Prevents recurrent ischemic events esp if ASA intolerant
Neutropenia, TTP, GI upset, teratogenesis
Plavix
Name and moa
Thienopuridine- irreversibly blocks ADP receptor on plt and inhibits fibrinogen binding
Plavix
Indication
Recurrent ischemic events: stroke prevent, recent ACS, post PCI
ACS triggers
5
HLD, HTN, tobacco use, chronic inflammatory response, infection
Clopidogrel
Which therapy preferable
Clopidogrel > aspirin. Dual preferred
Clopidogrel
Precautions
Metab by CYP2C19, poor metab, req inc dose. Inhib CYP450. Dose adjust for renal or hepatic disease. Use w other anticoags.
Clopidogrel
Toxicities- most common in who
Tx
Inc risk of bleeding (mostly in elderly, underwt, and prev hx stroke/tia). Stop drug (at least temporarily), transfuse plt
Prasugrel (effient)
Comparison to clopidogrel
Popular w who
Greater prev of plt agg, reduced risk of MI/in stent thrombosis. Greater risk of bleeding and greater # of fatal events. In clopidogrel non responders
Prasugrel precautions: 5
Dont use when
Active bleed, prev stroke/TIA, underwt, older than 75 y/o (dec dose), 4x greater risk of bleed in cv surgery than clopidogrel
Dont use pre cardiac cath
Ticagrelor (brillianta)
MOA
Comparison to clopidogrel
Blocks ADP receptors from diff binding site (allosteric)
Greater reduction of death rates post MI r/t vascular causes (MI/stroke). Higher rate of non procedure related bleed and higher fatal intracranial hemorrhage
Ticagrelor
Indication
How its always given
Prevent recurrent ischemic events post MI (stroke, ACS, post PCI).
Dual therapy w ASA unless ASA contraindicated
Ticagrelor
Precautions: 4
Contraindications: 2
Prec: Hepatic dysfunc, ASA >100mg/d, hold 5 days before surgery, BID dosing compliance issue
Contra: active bleed, hx intracranial hemorrhage
GIIb/IIIa inhibitors
MOA
Uses
3 drugs
Blocks IIbIIIa receptor preventing fibrinogen binding. Use: ACS, PCI. Reopro, integrillin, agrastat.
GPIIbIIIa Inhibitors: Abciximab
Indication
If used w heparin do what
2 other defining traits
ACS w planned PCI. W hep keep aptt 60-85 sec. most expensive drug, most prolonged effects
GPIIbIIIa: eptifibatide
Indications
Gtt rate based on
ACS and/or PCI bolus then gtt. Drip rate based on creatinine level
GP IIB IIIA
Toxicities which/what
Interactions w
Bleeding: abciximab (reverse w plt), eptifibatide and tirofiban (d/c drug)
Other antiplt and anticoag drugs potentiate effects
Antiplt therapy post STEMI
What is usually given
What for PCI/stent pts
Fibrinolysis pts
ASA as mono lifetime therapy for CAD/prior MI to prevent repeat.
PCI- dual therapy w ASA and other antiplt for one year
Fibrin- ASA for life and at least 14d of clopidogrel
Antiplt peri op
When to d/c and restart
Pt high risk for cv events should do what
D/c 7-10 days before. Resume next day post op if hemostasis achieved.
Risk: continue ASA continue through OR, clopidogrel stopped at least 5d before
Heparin (unfrac)
What’s in it
MOA
Heterogeneous mix of polysaccharide chains.
Activ antirhombin III: inc inhib of thrombin IIa and Factor Xa by 1000 fold
Unfrac hep
Uses
DVT prophylaxis, VTE tx, ACS, when warfarin started or contraindicated
Unfrac hep
DVT prophylaxis dose
5000 units sq q8. Poor kidney less frequently. Q12 if neurosurgery and ESRD
Unfrac hep
IV infusions based/adjustments
Weight based bolus and infusion. Adjusted on aPTT or anti Xa values q6hrs until stable then QD
Unfrac hep
Interactions
Drawback of drug
Inc risk of bleeding when used w other anticoags/antiplt.
Variable anticoag effects, inability to inhibit clot bound thrombin
Unfrac hep
Toxicities
Bleed: stop gtt, reverse w protamine. Benign thrombocytopenia or HIT
HIT
What it is, type 1
Non immune mediated. Benign. Mild plt drop usually within 4d of start of hep tx. Not progressive or assoc w thrombosis
HIT type 2
Immune mediated. Typical onset. Follows heparin exposure (prophylactic or full), reduce ct to <150k or dec 50% from baseline pre heparin. 5-14d after exposure
HIT
Occurs more in who. Typical plt ct.
UF > LMWH. Surgery > medical > obstetric
HIT
Typical onset
Delayed
Rapid
Typical- 66%, 5-14d
Delayed- 3-5%, 2-6 wks
Rapid- 25-30%, hrs to days. D/t residual circulating antibodies from heparin exposure past 100 days
HITT
What it is
Which is more common
Thrombocytopenia w thromboembolism, 10-25% of cases
Venous 4x more common
HITT
Venous
Arterial
Mortality, amputation
V: DVT, PE, venous limb gangrene, dural sinuous thrombosis
A: cerebral infarct, limb ischemia, skin necrosis, MI, mesenteric ischemia, adrenal/renal/spinal artery infractions
30% mort, 25% amp rate
HIT lab testing
ELISA: what it measures, s/s
Measures IgG antibody to heparin PF4 complex. Easy to do. Sens 90% spec 80%
HIT lab testing
SRA: what it detects, availability, s/s, dont do what
Plt activation. Not readily available. 95%. Confirmatory test. Dont delay tx waiting for result
HIT clinical management
Stop all drugs known to cause thrombocytopenia. Stop heparin start non hep anticoag (argatroban). Look for hx heparin exposure. Look for hep sources in flush bags/catheters/prophylactic SQ
Lmwh
What it is, action, uses
Saccharide chains, 5k daltons
Binds w antithrombin III, inhibits factor 10a
DVT prophylaxis, ACS, VTE tx
LMWH
Dose depends on
Dose effects checked how
Indication of prophylaxis/tx/ACS
Not routinely monitored, can check anti xa levels
LMWH
Precautions: 4
Tx if bleed
Pregnant (monitor anti xa), obese (wt based dosing), not recc if cr cl <30 ml/min (if no alt reduce dose by 1/2), dont use for spinal surgery pts or w epidurals. Protamine, 60% reversal
Fondaparinux (Arixtra)
What it is
MOA
What it doesnt affect
Synthetic factor 10a inhib. Binds w anti-thrombin 3 to potentiate xa inhibition 300x. No direct effect on 2a (thrombin)
Arixtra indications
ACS, PE/DVT prophylaxis, DVT tx
Arixtra
Contraindications
Tx of bleeding
Cr cl <30 ml/min, spinal anesthesia/lumbar puncture
No known reversal, FFP doesnt work. D/c drug
IV direct thrombin IIa inhib
Don’t require what
Examples 6, which is reversible
Antithrombin 3
Hirudin, lepirudin, desirudin, hirulog, argatroban (reversible), bivalirudin
Direct thrombin inhib
Uses and which specifically for each use 2
HIT (argatroban, lepirudin)
PCI (bivalirudin)
Direct thrombin inhib
Toxicities, which
Bleeding. Lepirudin and desirudin can only be used once d/t anaphylaxis risk
Direct thrombin inhib
Interactions
Tx of bleeding
Inc bleeding w other anticoags, thrombolytics, or antiplt.
Stop gtt, may respond to combo of: factor 7, FFP, and cryo
Warfarin
MOA
Interferes w production of vit k dep clotting factors (2, 7, 9, 10). Interferes w carboxylation of natural anticoags protein c and protein s
Warfarin
Indications: 4
Prevention of thrombosis/embolism in: dvt, afib, mechanical heart valves. Long term tx of vte
Warfarin
Dose based on what
INR goal. High risk pts (which 3), goal of what
Inr. 2-3. Mechanical valve, previous thrombus, anti-phospholipid syndrome. 2.5-3
Warfarin
Overlap w LMWH for how long
Duration of therapy for ___ DVT and PE how long
1-2 days
Uncomplicated, 3 months
Warfarin
Toxicities: 3
Interactions: 4 that increase effect
Bleeding, birth defects, cutaneous necrosis
Inc effect from: amio, cimetidine, tyelenol, phenylbutazone
Warfarin
Decreased effect from 5
Precautions 2
Sucralfate, cholestyramine, spironolactone, barbiturates, vitamin k foods
Concomitant anti plt therapy and/or nsaid use
Warfarin
Sub therapeutic inr:
Super therapeutic inr w/o bleeding:
Reversal/tx of bleeding:
Continue same dose, re-check 1-2 weeks
Hold next dose, check in 1 week
Vitamin k oral or iv, ffp
Periop warfarin
When it needs to be held
When resumed
Do what for high risk pts
5 days before OR to normalize INR. Resume 12-24 hrs postop if hemostasis achieved.
Bridge w heparin until 4-6 hrs of surgery
Novel oral anticoags
Also known as what
Where they work
Contraindicated in who and why 2
Direct oral anticoags. Enzymatic activity of thrombin and factor 10a. Prosthetic heart valves (greater thrombosis risk) and pregnancy (lack of clinical evidence)
Oral direct thrombin inhibitor
Dabigatran (Pradaxa)
MOA
Uses: 4
Inactivates circulating and clot bound thrombin (factor Iia). Stroke and embolism prevention in NON-VALVULAR afib. Prevents DVT after hip or knee replacement surgery. Tx PE/DVT.
Pradaxa
Lower dose for who: 3
Bleeding, elderly, mod-severe renal impairment
Pradaxa
Comparison to warfarin based on 2 doses
Higher dose- superior to warf in reduction of stroke and embolism w no diff in major bleed. Lower dose non inferior for prevention w a 20% relative risk reduction for major bleed
Dabigatran
Advantages 4
No routine monitoring needed, predictable pharmacokinetics. Less influenced by diet and drugs. Peak action 1 hr (fast). Short 1/2 life 12-24h in pts w normal renal func
Dabigatran
Disadvantages 3
Use what for which cases of bleeding
High cost and BID dosing. May req adjustment for renal ins and obesity. No antidote, Fab used if life threat bleed. Non specific pro coagulant agents pt complex conc or factor 7a also can be used in serious bleed.
Dabigatran
Disadvantages
2
No assay for monitoring of effect. No long term data, some fatal bleed cases
No parental versions avail for which inhibitor, moa
Direct factor 10a, inactivate circulating and clot bound 10a
Xarelto
Class
Uses 3
Direct factor 10a inhibitors. Uses: stroke and systemic embolism prevention in non-valvular afib, prevent dvt post hip/knee replacement, tx pe/dvt
Xarelto
Comparison to warfarin
Non inferior for preventing stroke or embolism. Overal bleed risk about same, decreased risk of intracranial and fatal bleed w rivaroxaban
Rivaroxaban
Advantages 5
No routine monitoring needed/predictable kinetics, less influenced by diet/drugs,QD, rapid peak 2-4h, short 1/2t 7-11h
Rivaroxaban
Disadvantages
3
High cost, not rec for VTE proph/tx or secondary prevention w impaired creatinine clearance. No current antidote. Praxbind/10a decoy under investigation, shown to reduce 10a inhibitor activity
Rivaroxaban
What for bleeding
No data on
Non specific pro coagulant agents (pt complex or 7a) can be used for fatal bleed. No long term data
Apixaban
Class
Uses 3
Direct factor 10a inhib. Stroke/systemic embolism prevention in non valvular afib, prevent dvt after hip/knee replacement, tx pe/dvt
Apixaban
Comparison to ASA in who
Comparison to warfarin
Benefit over ASA if not candidate for warfarin.
Superior to warf for prevention of stroke/embolism. Decrease in bleeding risk, ICH, and mortality
Apixaban
Advantages 4
No routine monitoring needed/predictable, less influence by diet/drugs, fast peak 3h, short 1/2 life 12h
Apixaban
Cons
3
High cost/bid dose. Dose adjust for age, weight, renal func. No antidote. Praxbind under investigation
Apixaban
Use what in serious bleed
No what
Pt complex concentrate/factor 7a
No assay to monitor, no long term data
Aripazine
What it is and what it does
Reversal for oral dabigatran, apixaban, rivaroxaban, sq lovenox, sq fondaparinux
Fibrinolytics
Action
Plasminogen activators convert plasminogen to plasmin which causes fibronolysis
Fibrinolytics
Uses 3
Acute STEMI, acute ischemic stroke (within 6 hrs of symptom onset, tpa, urokinase (de-clog CVL, pe)
Fibrinolytics
Absolute contraindications 6
Previous hemorrhagic stroke, ischemic stroke last 3 months, known intracranial tumor, active internal bleed, suspected aortic dissection, significant closed head/facial trauma last 3 months
Fibrinolytics
Relative contraindications 5
Severe uncontrolled htn 180/110, severe chronic htn hx, current use anticoags/inr >2.5, known bleeding disorder, non compressible vascular puncture
Fibrinolytics
5 more relative contraindications
Trauma in 2-4 wks (cpr too), surgery last 3 weeks, recent 2-4 internal bleed, pregnancy, streptokinase- allergy or prior exposure (5d-2yrs)
