Anticoagulation Flashcards
How do anticoagulants work?
prevent clots from forming and to keep existing clots from becoming larger; they DO NOT break down clots
What 3 main factors contribute to thrombosis (blood clots) forming (Virchow’s triad)?
- blood vessel (endothelial) injury
- blood stasis (stopping/slowing of blood flow)
- pro-thrombotic conditions (hypercoagulability)
What conditions are anticoagulants used to prevent?
- venous thromboembolism (VTE)
–> DVT/ PE - cardioembolic stroke
What conditions are anticoagulants used to treat?
- immediate treatment of acute coronary syndrome (ACS)
- venous thromboembolism (VTE)
–> DVT/ PE
Where do blood clots form?
anywhere in the body
When do blood clots become dangerous?
when they become an embolus (a clot/ piece of clot that travels somewhere), blocking blood flow to the lungs, heart, or brain
Where are coagulation (clotting) factors made?
liver
Which clotting factors are vitamin K dependent?
II (2)
VII (7)
IX (9)
X (10)
At which factor do the intrinsic and extrinsic pathways meet?
X (10)
What is the outcome of clotting factor activation beginning from either pathway?
activate the next clotting factor in the cascade until fibrin is formed
What is the body’s natural, endogenous anticoagulant?
Antithrombin
Which anticoagulants inhibit the clotting cascade indirectly via antithrombin?
- Fondaparinux
- LMWHs
- UFH
What factors does heparin inhibit?
IIa (thrombin)
Xa
What factors do LMWHs inhibit?
Xa > IIa (thrombin)
Which medications directly inhibit factor Xa?
- apixaban (Eliquis)
- edoxaban (Savaysa)
- rivaroxaban (Xarelto)
What is the MOA of warfarin?
vitamin K antagonist; coagulation factors are still made but have reduced coagulation activity
What medications are DOACs (direct-acting oral anticoagulants)?
- apixaban
- rivaroxaban
- edoxaban
- dabigatran (direct thrombin inhibitor)
When is warfarin preferred over DOACs?
- stroke prevention in Afib WITH moderate to severe mitral stenosis or mechanical heart valve
- VTE treatment in patients WITH triple-positive antiphospholipid syndrome or mechanical heart valve
What agents directly inhibit thrombin, decreasing the amount of fibrin available for clot formation?
- Argatroban (IV)
- Bivalirudin (IV)
- Dabigatran (PO)
What conditions require more anti-platelet action vs. anticoagulation?
- coronary artery disease
- acute coronary syndromes
- PREVENTION of ischemic stroke/ TIA
What conditions are fibrinolytics appropriate for?
- acute ischemic stroke
- STEMI
What is the biggest side effect of anticoagulants?
bleeding
A drop ≥2 g/dL in what lab value could signify internal or external bleeding?
Hemoglobin
What can cause epistaxis (nose bleeds)?
- drugs
- dry nasal mucosa
- nose blowing
What can cause bleeding gums?
- new or worse than usual gingivitis
–> counsel patients to use soft toothbrushes
What can cause bruising?
- drugs (chronic steroids)
- thrombocytopenia/ clotting disorder
- Cushing’s syndrome
- malnutrition
- fracture/sprain
- infection
- physical abuse
What can cause hematoma (internal bleeding from broken blood vessels; deep bruise)?
- can occur on the abdomen from LMWH injection that was rubbed
- epidural/spinal hematomas can occur in patients using LMWH or DOACs getting neuraxial anesthesia or spinal puncture
What can cause hematuria (blood in urine)?
- UTIs
- kidney stones
- prostatitis
- kidney disease
What can cause hematemesis (blood in the vomit)?
- esophageal (varices, chronic reflux)
- stomach/ duodenum (ulcer)
What can cause hematochezia (blood from the anus)?
- esophageal (varices, chronic reflux)
- stomach/ duodenum (ulcer)
- rectum (hemorrhoid, rectal tear)
- diverticulosis
- colon cancer
- IBD
- colon polyps
What infections can cause bloody diarrhea (dysentery)?
- C. diff
- Shigella
- Entamoeba hitsolytica
How can we tell where a GI bleed might be based on visual appearance?
the darker the bleeding site is away from the anus, the darker the stool; rectal bleeding from polyps might be occult; need fecal occult test to identify
Which medications do not cross-react with HIT antibodies?
IV direct thrombin inhibitors
What is the MOA of unfractionated heparin?
binds to antithrombin and potentiates its ability to inactivate thrombin (IIa), Xa, and other clotting factors (IXa, XIa, XIIa, and plasmin); prevents conversion of fibrinogen to fibrin
What is the dosing of heparin for VTE prophylaxis?
5000 units SQ Q8-12H
What is the dosing of heparin for VTE treatment?
80 units/kg IV bolus –> 18 units/kg/h
What is the dosing of heparin for ACS/STEMI?
60 units/kg IV bolus –> 12 units/kg/h
Heparin treatments are dosed off of which weight in kg?
total body weight
Why should heparin not be administered IM?
hematoma risk
What are CIs to heparin?
- uncontrolled active bleed (intracranial hemorrhage)
- severe thrombocytopenia (low platelets)
- history of HIT
- benzyl alcohol formulations in neonates, pregnancy, breastfeeding, and infants
- pork containing products in those with pork hypersensitivity
What are the warnings with heparin?
fatal medication errors; verify the correct concentration is chosen
What are SEs with heparin?
- bleeding (epistaxis, bruising, gingival, GI)
- thrombocytopenia
- HIT
- hyperkalemia
- alopecia
- osteoporosis (long-term use)
What should be monitored while on heparin treatment?
- aPTT or anti-Xa level (Q6H until therapeutic, at every dose change, and daily)
- platelets (baseline and daily)
- Hgb (baseline and daily)
- Hct ( baseline and daily)
What should be monitored while on VTE prophylaxis with SQ heparin?
- platelets (baseline and daily)
- Hgb (baseline and daily)
- Hct ( baseline and daily)
What is a therapeutic aPTT range while on heparin?
1.5 -2.5x control (per specific institutional protocol
What is a therapeutic anti-Xa range while on heparin?
0.3-0.7 units/mL
What lab value suggests HIT?
a drop in platelets >50% from baseline
Why is heparin dosed IV for VTE and ACS treatment?
rapid onset and short half life (1.5h)
Why is heparin dosed SQ for VTE prophyaxis?
longer onset (20-30 minutes) vs. IV administration
What dosage form of heparin is only used to keep IV lines open?
heparin lock-flushes (HepFlush)
Which dosages of heparin are look alike and sound alike and has been fatal especially in neonates?
heparin injection (10,000 units/mL)
and heparin flushes (10-100 units/mL)
What is the MOA of LMWHs?
binds to antithrombin and potentiates its ability to inactivate thrombin (IIa) and Xa; prevents the conversion of fibrinogen to fibrin; factor Xa inhibition is much greater than IIa
What is the antidote for UFH and LMWHs?
protamine
What is the dosing of enoxaparin for VTE prophylaxis in those with normal renal function?
- 30mg SQ BID
- 40mg SQ QD
What is the dosing of enoxaparin for VTE prophylaxis when CrCl <30 ml/min?
30mg SQ QD
What is the dosing of enoxaparin for VTE, unstable angina, and NSTEMI treatment?
- 1 mg/kg SQ Q12H
- 1.5 mg/kg SQ QD (only for inpatient VTE treatment)
- CrCl <30 ml/min: 1 mg/kg SQ QD
What is the dosing of enoxaparin for STEMI in patients <75 y/o?
- 30mg IV bolus + 1 mg/kg SQ dose (MAX 100mg for the first IV+SQ doses only), followed by 1 mg/kg SQ Q12H
- CrCl <30: 30mg IV bolus + 1 mg/kg SQ dose followed by 1 mg/kg SQ QD
What is the dosing of enoxaparin for STEMI in patients >75 y/o?
- 0.75 mg/kg SQ Q12H (no bolus); (MAX 75mg for first 2 SQ doses)
- CrCl <30: 1 mg/kg SQ QD (no bolus)
LMWHs are dosed based off of which weight in kg?
total body weight
What is the dosing of dalteparin for VTE prophylaxis?
2500-5000 units SQ QD
What is the dosing of dalteparin for unstable angina/NSTEMI treatment?
120 units/kg SQ Q12H (MAX 10,000 units)
What are boxed warnings for LMWHs?
patients undergoing neuraxial anesthesia (epidural/spinal) or undergoing spinal puncture are at risk of hematomas and subsequent paralysis
What are CIs to using LMWHs?
- Hx of HIT
- active major bleed
- hypersensitivity to pork
What should be monitored on LMWHs?
- platelets
- Hgb
- Hct
- SCr
In what populations is it recommended that anti-Xa levels for LMWHs be monitored?
- pregnancy
- renal insufficiency
- obesity
- low body weight
When should anti-Xa levels be obtained in special populations taking LMWHs?
peak anti-Xa levels 4 hours post-SQ dose
What are important storage and administration requirements for LMWHs?
- store at room temperature
- do not administer in patients with HIT, antibodies will cross-react
- do not expel air bubble prior to administration (can cause loss of drug)
- do not administer IM
What drugs interact with LMWHs?
drugs that can increase bleeding risk:
1. NSAIDs
2. SSRIs/SNRIs
3. fibrinolytics
4. anticoagulants/antiplatelets
5. some herbal supplements
Enoxaparin
Lovenox
Dalteparin
Fragmin
What is the MOA of HIT?
- the immune system forms IgG antibodies against heparin bound to platelet factor 4
- the antibodies join with heparin and PF4 to make a complex
- complex binds to Fc receptors on platelets
- platelet activation band release of pro-coagulant microparticles
- pro-thrombotic state
How is the probability of HIT assessed?
4 Ts:
1. Thrombocytopenia
2. Timing of platelet drop (hours up to 5-10 days after starting heparin)
3. Thrombosis (or skin lesions that are necrotizing or non-necrotizing)
4. oTher causes
How is HIT confirmed?
- heparin-PF4 antibody enzyme-linked immunosorbent assay (ELISA) test
- functional assay (serotonin release assay or heparin-induced platelet aggregation assay)
How is HIT managed/treated?
- stop all forms of heparin and LMWH (if on warfarin D/C and administer vitamin K)
- immediately treat with non-heparin anticoagulants (Argatroban)
- DO NOT start warfarin therapy until platelets ≥ 150,000 cells/mm3 and should be initiated at lower doses
- overlap warfarin with a non-heparin anticoagulant for at least 5 days and after the INR is in target for >24 hours
- if urgent cardiac surgery or PCI is required use Bivalrudin
What is the MOA of PO factor Xa inhibitors?
directly inhibit factor Xa
What is the MOA of Fondaparinux (SQ factor Xa inhibitor)?
injectible synthetic pentasaccharide that selectively and indirectly inhibits factor Xa by binding to anti-thrombin
What are boxed warnings with PO factor Xa inhibitors?
- patients undergoing neuraxial anesthesia (epidural/spinal) or undergoing spinal puncture are at risk of hematomas and subsequent paralysis
- premature discontinuation increases risk of thrombotic events
What are boxed warnings unique to edoxaban?
reduced efficacy in nonvalvular AF patients with CrCl >95 ; DO NOT USE
What are CIs with PO factor Xa inhibitors?
active pathological bleeding
What are general warnings with PO factor Xa inhibitors?
- not recommended with prosthetic heart valves or triple-positive antiphospholipid syndrome (all 3 antibodies positive)
- avoid in patients with moderate to severe hepatic impairment
What are SEs with PO factor Xa inhibitors?
generally well tolerated unless bleeding occurs
What are unique SEs with edoxaban?
- rash
- elevated LFTs
What is monitored with PO factor Xa inhibitors?
- Hgb
- Hct
- SCr
- LFTs
How can PO factor Xa inhibitors be administered if patients have trouble swallowing or have an NG tube?
all can be crushed and put on applesauce or suspended in water
How can apixaban be administered if patients have trouble swallowing or have an NG tube?
can be crushed and mixed with D5W, water, or applesauce
How long before elective surgery shoud PO factor Xa inhibitors be discontinued?
rivaroxiban: 24 hours prior
edoxaban: 24 hours prior
apixaban: 48 hours prior with mod-high bleeding risk; 24 hours prior with low bleeding risk
What is the dosing of apixaban for nonvalvular AF (stroke prophylaxis)?
- 5mg PO BID
- if 2/3 conditions met (≥80 y/o, ≤60mg TBW, SCr ≥1.5); 2.5mg PO BID
What is the dosing of apixaban for DVT/PE treatment?
Initial: 10mg PO BID x 7days, then 5mg PO BID (Eliquis DVT/PE started pack)
Extended (≥ 6 months of initial treatment): 2.5 mg PO BID
What is the dosing of apixaban for DVT prophylaxis post hip/knee replacement?
Knee: 2.5mg PO BD x 12 days; give first dose 12-24 hours after surgery
Hip: 2.5mg Po BID x 35 days ; give first dose 12-24 hours after surgeryv
What should a patient do if they miss a dose of apixaban?
take immediately on the same day, then resume BID dosing; DO NOT double the dose to make up for a missed dose
Which PO Xa-inhibitor is available as a suspension?
rivaroxaban
What should doses of rivaroxiban ≥15 mg be administered with?
food
What is dosing of rivaroxaban for nonvalvular AF (stroke prophylaxis)?
CrCl>50: 20mg PO QD with evening meal
CrCl 15-50: 15mg PO QD with evening meal
CrCl <15: 15 mg PO QD (per manufacturer, but limited data)
What is the dosing of rivaroxaban for DVT/PE treatment?
Initial: 15mg PO BID x 21 days, then 20mg PO QD with food
Extended (≥ 6 months of initial treatment): 10mg PO QD
CrCl 15-30: use caution
CrCl<15: DO NOT USE
What is dosing of rivaroxaban for DVT prophylaxis (after hip/knee replacement) and VTE prophylaxis in acutely ill medical patients)?
knee: 10mg PO QD x 12 days
hip: 10mg PO QD x 35 days
acutely ill: 10mg PO QD x 31-39 days
CrCl 15-30: use caution
CrCl<15: DO NOT USE
What is dosing of rivaroxaban for risk reduction of major CVD events in PAD/CAD?
2.5 mg PO BIS in combination with low dose aspirin
CrCl< 15: 15mg PO QD (per manufacturer)
What should be done if a dose of rivaroxaban is missed?
If taking 15mg BID: take immediately to ensure intake of 30mg/day (2 tablets can be taken at once) then resume regular schedule the following day
If taking 10,15,20mg QD: take immediately on the same day, otherwise skip (DO NOT DOUBLE UP)
What is andexanet alfa (Andexxa) an antidote for?
apixaban and rivaroxaban
What is the dosing of edoxaban for nonvalvular AF (stroke prevention) ?
CrCl> 95: DO NOT USE
CrCl 51-95: 60mg PO QD
CrCl: 15-50: 30mg PO QD
CrCl< 15: not recommended
What is the dosing of edoxaban for the treatment of DVT/PE?
60mg QD after 5-10 days of parenteral anticoagulation
CrCl 15-50, TBW ≤60kg, or certain P-gp inhibitors: 30mg QD
CrCl<15: not recommended
What should be done if a dose of edoxaban is missed?
take immediately on the same day; DO NOT DOUBLE UP
Apixaban
Eliquis