ummD - Anticoagulation

Anticoagulation

Assessing thrombotic risk

Atrial fibrillation - CHA₂DS₂VASC

Prosthetic heart valves

Bioprosthetic valves - lower risk than mechanical; anticoagulate for 3 mo (INR goal 2.5), then follow with antiplatelet
Mechanical valves - high risk, long-term anticoagulation (INR goal 3.0)

Prior hx of VTE (venous thromboembolism)

Annual risk of VTE
Low (< 5%)	VTE was > 12 mo ago
Intermediate (5-10%)	VTE in past 3-12 mo; active cancer (tx within last 6 mo or palliative tx); non-severe thrombophilia (e.g. Factor V Leiden)
High (> 10%)	VTE < 3 mo ago; severe thrombophilia (e.g. Protein C/S deficiency, antiphospholipid)

Risk factors for VTE (venous thromboembolism)

Hospitalized medical (non-surgical) patients

Padua Prediction Score risk assessment for risk over 90 days
High risk of VTE is score ≥ 4 - recommend pharmacologic prophylaxis (heparin, lovenox) for those without contraindications (e.g. major bleeding, low platelets, CrCl < 30 ml/min)

Risk Factor	Points
Active cancer	3
Previous VTE (with the exclusion of superficial vein thrombosis)	3
Reduced mobility* (bed rest ≥ 3 days, with bathroom privileges)	3
Already known thrombophilic condition	3
Recent (≤ 1 mo) trauma and/or surgery	2
Elderly age (≥ 70 y)	1
Heart and/or respiratory failure	1
Acute myocardial infarction or ischemic stroke	1
Acute infection and/or rheumatologic disorder	1
Obesity (BMI ≥ 30)	1
Ongoing hormonal treatment	1

Surgical patients

Generally higher risk for VTE than non-surgical patients
Caprini score (long questionnaire)
Very low risk (< 0.5%)

Low risk (1.5%)

High risk

Risk of bleeding with anticoagulation

Heparin/lovenox - maybe 2-fold increase in minor bleeding (e.g. not major intracranial hemorrhage, etc.)

Increase INR with warfarin		DECREASE INR with warfarin
Cephalosporins	NSAIDS/COX-2 inhibitors	Rifampin
Macrolides	Amiodarone	Barbiturates
Fluoroquinolones	Alcohol	Carbamazepine
Fluconazole	Fluva/lova/rosuva/simva-statin	Phenytoin
INH	Omperazole
Metronidazole	Tamoxifen
Trimethoprim-sulfa	Allopurinol
ASA	Losartan
Flagyl	Alcohol

Supratherapeutic Warfarin

Warfarin inhibits synthesis of vitamin K-dependent clotting factors: II, VII, IX, X

INR <4.5	hold/lower dose Pre-op: hold dose; PO or IV vitamin K 2.5mg, check INR in 12-24 hrs
>4.5 INR <9	No bleed risk: hold doses; monitor Risk for bleed: PO vitamin K 2.5mg, hold doses Pre-op: PO or IV vitamin K 5mg; recheck INR in 12-24 hrs
INR >9	Hold dose; give PO vitamin K 2.5-5mg; redose vitamin K q12-24 hrs as needed
Serious Bleeding	Hold warfarin; Give FFP or PCC Also give vitamin K 5-10mg IV (slowly over 30 min); redose q 12 hrs prn hide(half-life of clotting factors is less than that of warfarin, so give vit K to prevent recurrence of coagulopathy)

4T’s - pretest probability of HIT (low 0-3, intermed 4-5, high 6-7) Don’t send HIT Ab for low prob!

Unfractionated heparin - 0-30% have low platelets; 1-2% have true HIT
LMWH (e.g. Lovenox) - < 1% incidence of HIT, but still don't use it if they have a h/o of HIT

	2 points	1 point	0 points
Thrombocytopenia	>50% ↓ & nadir >20	30-50% ↓OR nadir 10-19	<30% ↓OR nadir <10
Timing of plt drop	Clear onset day 5-14 OR <1 day if recent heparin within 30 days	C/w onset 5-14 days but not clear OR onset after day 14 OR <1 day (prior exposure 30-100 days ago)	Drop <4 days without prior exposure
Thrombosis or other sequelae	New thrombosis Skin necrosis at heparin injection sites Anaphylactoid rxn after IV heparin	Progressive or recurrent thrombosis Non-necrotizing (erythematous) skin lesions Suspected thrombosis	None
oTher causes of low plts	None apparent	Possible	Definite

BJH heparin nomogram (Use your institution’s nomogram!)

Check PTT q6
Adjust to target of 1.5-2x upper limit of control via your institution’s PTT/nomogram
Once 2 consecutive PTT’s are therapeutic, monitor PTT daily

PTT <40 sec	Bolus 3000 units and increase drip by 3 units/kg/hr
PTT 40-50 sec	Bolus 2000 units and increase drip by 2 units/kg/hr
PTT 50-59 sec	No bolus, increase drip by 1 unit/kg/hr
PTT 60-94 sec	No change
PTT 95-104 sec	Decrease drip by 1 unit/kg/hr
PTT 105-114 sec	Hold drip 30 minutes, then decrease drip by 2 units/kg/hr
PTT >114 sec	Hold drip 1 hour, then decrease drip by 3 units/kg/hr

Notes

Bridging

Heparin for 1st 5 days of warfarin until therapeutic INR
Not necessary for NOAC (immediately therapeutic) - no bridging in PE was studied for Xarelto, Eliquis
Transitioning from one agent to another

Warfarin vs. NOAC

NOACs lack reversal agents (t_1/2 8-15 hrs, avoid in those with high risk of bleeding, e.g. fall risk), but in general less risk of major bleeding than warfarin
NOACs are not good for CrCl < 30
NOACs don't require INR monitoring; can prescribe a standard dose
RCTs (patient population - non-valvular AF; end point of stroke/systemic embolism)

RE-LY (dabigatran/Pradaxa vs. warfarin) - dabigatran 150 mg BID superior to warfarin (RR 0.64 for stroke)
ROCKET-AF (rivaroxaban/Xarelto vs. warfarin) - rivaroxaban non-inferior to warfarin, but less risk of major bleeding
ARISTOTLE (apixaban/Eliqiuis vs. warfarin) - apixaban superior to warfarin (HR 0.79), less major bleeding, also only study to show reduction in all-cause mortality (HR 0.89)

Duration of therapy for DVTs

Provoked () - 3 mo
Unprovoked (higher risk of recurrence) -

Perioperative anticoagulation/anti-platelet therapy

Drug	Typical Use	DVT ppx dosing	Therapeutic Dosing	Dose adjust	Duration/Reversal
IV Unfractionated Heparin	DVT/PE ACS Valve bridge		MI/USA: 60 units/kg (max: 4000 units), then drip 12 units/kg/hour DVT/PE: 80 units/kg (or 5000 units) then drip 18 units/kg/hour		Usually 4-6 hours Turn off drip Protamine
SQ Unfractionated Heparin	DVT ppx CAN use for DVT/PE	5000 units SQ q 12 hrs or q8 hrs >100 kg: 7500 units SQ q 8 hours	DVT/PE: 333 units/kg then 250 units/kg every 12 hours		~8-12 hrs Protamine
Low MW Heparin
Enoxaparin (Lovenox)	DVT/PE ACS DVT ppx	Med: 40 mg SQ q24hrs Ortho:30mg SQ q12 hrs BMI >40-increase 30%	DVT/PE/ACS: 1 mg/kg SQ Q 12 hours OR 1.5 mg/kg subq daily. (ACTUAL body weight)	Cl_cr <30: dose q day ESRD/HD: no use BMI >40: monitor anti-Xa levels, poss starting dose of 0.75mg/kg SQ q 12	Effects for ~12 hours (protamine)
Dalteparin	DVT/PE (cancer pts) DVT ppx	-variable depending on risk of DVT	DVT/PE (cancer pts): 200 int. units/kg SQ (maximum dose: 18,000 int. units) once daily for 30 days, then reduce	Cl_cr <30, monitor anti-Xa levels to determine appropriate dose	Effects for ~24 hrs (protamine)
Xa inhibitors
Fondaparinux (Arixtra)	DVT/PE DVT ppx	Adults ≥50 kg: 2.5 mg SQ daily. No use for ppx in patients <50 kg	<50 kg: 5 mg SQ once daily 50-100 kg: 7.5 mg SQ once daily >100 kg: 10 mg SQ once daily	Cl_cr 30-50: caution Cl_cr <30: no use	t_1/217-22 hrs Possible benefit of rFVIIa
Rivaroxaban (Xarelto)	Non-valve Afib DVT/PE DVT ppx	(only for knee/hip replacement pts) 10 mg po daily	DVT/PE (acute): 15 mg po q12 hrs for 3 wks, then 20 mg po daily Afib: 20 mg po daily	Cl_cr 15-50: Afib 15 mg po daily Cl_cr <15: avoid use for Afib Cl_cr <30: avoid use for DVT/ppx	t_1/25-9h PCC may help HD/protamine/vit K no help
Apixaban (Eliquis)	Non- valve Afib DVT/PE DVT ppx	(only for hip/knee replacement pts) 2.5 mg PO BID	Afib: 5 mg po BID DVT/PE: 10 mg po BID x 7 days, then 5 mg BID; >6 months later 2.5 mg BID	Afib: if >2 of: Cr > 1.5/HD, wt < 60kg, age > 80): 2.5 mg BID DVT/PE: no adjustment, BUT no trial data with Cr >2.5/CrCl <25	t_1/2 8 hrs for 2.5mg; 12-15hrs for 5mg HD no help; no trials of PCC/rFVIIa Charcoal ( 2-6 hrs)
Edoxaban (Savaysa)	Non-valve Afib DVT/PE		Afib: 60 mg po daily DVT/PE: 60 mg po daily (AFTER 5-10 day bridge)	Cl_cr 15-50: 30mg daily Cl_cr <15-avoid use Cl_cr >95-avoid use for Afib DVT/PE: 30 mg daily if wt <60kg or if on P-gp inhibitor (verapamil/azithro)	t_1/2 10-14 hrs
Direct thrombin inhibitors
Dabigatran (Pradaxa)	Non-valve Afib DVT/PE		Afib: 150mg po BID DVT/PE: 150mg po BID (AFTER 5-10 day bridge)	Afib: Cl_cr 15-30: 75mg PO BID HD/Cl_cr <15: avoid use DVT/PE: Cl_cr <30: avoid use Avoid use if Cl_cr <50 + p-GP inhibitors: (amio/clarithro/verapamil)	t_1/212-14h Idarucizumab (Praxbind) HD may help
Bivalirudin	Anticoag for HIT (unlabeled)		IV gtt 0.15-0.2 mg/kg/hour; adjust to PTT 1.5-2.5 times baseline value (no starting bolus)	Reduce dose in renal failure	t_1/225-57 min Turn off drip
Argatroban	Anticoag for HIT		2 mcg/kg/min, check PTT after 2 hours; adjust dose until the steady-state PTT is 1.5-3 times initial value; keep dosage < 10 mcg/kg/minute	Reduce dose (or avoid) in liver disease Critically ill patients may require lower doses	t_1/239-51 min Turn off drip
Warfarin	DVT/PE Valves Afib HIT	Ortho patients only	DVT/PE, Afib: INR 2-3 Mechanical valves: goal INR may be higher	Warfarindosing.org	Lasts 2-5 days FFP/PCC Vitamin K

author: admin | last edited: April 19, 2022, 6:21 p.m. | pk: 109